bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeated Balloon Inflations Do Not Diminish ST Segment Elevation even though Coronary Collateral Recruitment Is Promoted in Pigs
Authors: Lyras Theodore , Papalois Apostolos , Klamargias Lykourgos , Kyrzopoulos Stamatis , Dafnomili Paraskevi , Kyriakides Zenon S.
Published: February 2007

Objective: Attempts to demonstrate preconditioning during repeated angioplasty balloon inflations (BIs) have not been universally successful. The main obstacle is that the first BI is unreliable, due to the variable degrees of occlusion by the deflated balloon. In the present study, we examined whether ST segment elevation decreases and evaluated its relation to collateral recruitment during repeated angioplasty BIs in the pig. Methods and Results: Twenty male pigs, 7 months old, under general anesthesia, underwent 3 repeated BIs of 120 s, with a 5-min interval between them, in the left anterior descending artery or the right coronary artery. A pressure wave wire was used for the measurement of coronary wedge pressure and to obtain the intracoronary ST segment elevation. Intracoronary ST segment elevation was 1.97 ± 0.76 mV during the 1st BI, 2.09 ± 0.82 mV during the 2nd BI and 1.84 ± 0.82 mV during the 3rd BI (p = n.s.). Coronary wedge pressure was 12 ± 6, 18 ± 18 and 20 ± 20 mm Hg (p < 0.05 vs. 1st BI) during the 3 BIs, respectively. Conclusion: Repeated BIs do not diminish ST segment elevation in the pig model, even though coronary collateral recruitment is promoted.
WITHDRAWN: Cardiac Troponin T: An Early Molecule Marker of Normalization of Left Ventricular Ejection Fraction in Patients with Peripartum Cardiomyopathy
Authors: Li Yan-Bo , Hu Cheng-Lin , Zhang Jia-Ming , Zou Yong-Guang , Tang Yan-Hong , Chen Jiang-Bing , Tang Qi-Zhu , Huang Cong-Xin
Published: February 2007

The article entitled, "Cardiac Troponin T: An Early Molecule Marker of Normalization of Left Ventricular Ejection Fraction in Patients with Peripartum Cardiomyopathy", by Li et al, which originally was published in this space, has been removed because an article by the same authors and reporting very similar work already has been published in HEART [Published Online First: 25 October 2006], entitled, "Troponin T measurement can predict persistent left ventricular dysfunction in peripartum cardiomyopathy", by Hu et al. The printed version of the article in HEART can be found at Heart 2007;93:488-490.
Open-Heart Surgery in Patients with Liver Cirrhosis: Indications, Risk Factors, and Clinical Outcomes
Authors: An Y. , Xiao Y.B. , Zhong Q.J.
Published: February 2007

Background: Because of recent advances in cardiopulmonary bypass (CPB) surgery, there are broadened indications to approach patients with a high operative risk. Meanwhile, there is an increasing number of patients with severe liver dysfunction subjected to open-heart surgery. This retrospective study was designed to evaluate the operative indications and clinical outcomes in patients with liver cirrhosis (LC) undergoing open-heart surgery. In addition, determinants influencing their prognosis were assessed. Patients and Methods: Between May 1996 and June 2005, 24 patients with LC underwent CPB open-heart surgery in our institution. The preoperative severity of the LC was determined according to the Child-Pugh classification. Their perioperative data were analyzed. Several perioperative factors were compared by multivariate logistic regression analysis between survivors and nonsurvivors to determine possible risk factors contributing to mortality. Results:There were 14 females and 10 males. Their age ranged from 36 to 72 (mean 53 ± 13) years. Seventeen cases were classified as having Child-Pugh class A LC, 6 as having Child-Pugh class B, and 1 as having Child-Pugh class C LC. All patients underwent CPB surgery. The mean operation time and the cross-clamp time were 160 ± 53 and 90 ± 42 min, respectively. During the first 24 h after the operation, the mean chest tube output was 1,080 ± 320 ml. The mean duration of mechanical ventilation was 32 ± 22 h, and the mean intensive care unit stay was 11 ± 8 days. Sixty-six percent of the patients experienced significant morbidity. Fifty-three percent of the patients with Child-Pugh class A LC and 100% of those with Child-Pugh class B and C LC suffered postoperative complications. The overall mortality rate was 25%. The postoperative mortality rates of the patients with Child-Pugh class A, B, and C LC were 6, 67, and 100%, respectively. Preoperative serum total bilirubin and cholinesterase levels and EuroSCORE (European System for Cardiac Operative Risk Evaluation) values along with CPB time were identified as the important predictors to differentiate between survivors and nonsurvivors by multivariate logistic regression analysis. Conclusions: The Child-Pugh class is associated with hepatic decompensation and mortality after open-heart CPB surgery in patients with LC. Such surgery can be performed safely in patients with a Child-Pugh class A LC. But cardiac interventions using CPB in patients with more advanced LC are associated with high mortality and morbidity rates. The preoperative total plasma bilirubin and cholinesterase concentrations as well as the EuroSCORE along with the CPB time are identified as statistically significant predictors of mortality after open-heart surgery in patients with LC. Our findings indicate that patients with chronic liver disease scheduled for open-heart surgery should be carefully evaluated before the operation and that the CPB duration should be as short as possible.
Improved Neovascularization of PEGT/PBT Copolymer Matrices in Response to Surface Modification by Biomimetic Coating
Authors: Ring A. , Steinstraesser L. , Muhr G. , Steinau H.-U. , Hauser J. , Langer S.
Published: February 2007

PEGT/PBT (polyethylene glycol terephthalate/polybutylene terephthalate) copolymer matrices with three different surface coatings [calcium-phosphate (Ca-P), collagen, and gas plasma] were placed into dorsal skinfold chambers of 24 balb/c mice. Untreated PEGT/PBT matrices served as the controls. The basal surfaces of the implants directly contacted the striated skin muscle. Neovascularization of the implants was analyzed by intravital fluorescence microscopy. Microcirculatory observations were performed in the surrounding skin muscle, at the border zone of the implant, and in the center of the implant. The functional vessel density (FVD; mm/mm2), as the length of perfused microvessels per observation area, was measured by computer-assisted analysis. The FVD served as the parameter of neovascularization. At the end of the protocol, histological observation of hematoxylin/eosin-standard-stained sections was performed by light microscopy. The FVD in the center of the implant on day 8 was only observed in gas-plasma-coated (8.8 ± 10.2 mm/mm2) and Ca-P-coated implants (0.8 ± 2.0 mm/mm2). None of the other groups showed perfused microvessels in the center of the implant on day 8 (p < 0.05). The FVD values in the center of the gas-plasma-coated and the Ca-P-coated implants were 20.7 ± 8.2 and 19.2 ± 15.5 mm/mm2 as compared with 7.1 ± 17.4 and 7.7 ± 5.9 mm/mm2 for collagen-coated and untreated implants on day 16. The histological examination confirmed the profound microvascular ingrowth into the matrix pores of the gas-plasma-treated and the Ca-P-coated copolymer matrices in the center of the implants. The study showed that the ingrowth of microvessels into PEGT/PBT matrices can be accelerated by Ca-P coating and gas plasma treatment in the dorsal skinfold chamber in mice.
Effect of Cytochrome c Peroxidase on the Corneal Epithelial Healing Process after Excimer Laser Photo-Ablation in Transgenic Mice
Authors: Scorolli L. , Meduri A. , Morara M. , Scalinci S.Z. , Meduri R.A.
Published: February 2007

Aim: To evaluate the role of commercially prepared cytochrome c peroxidase eye drops in corneal epithelial healing of transgenic B6(A)-Rpe65rd12/J mice after excimer laser photo-ablation. Materials and Methods: In our prospective animal series, 72 eyes of 36 mice had uneventful bilateral excimer laser photo-ablation. In each mouse, one eye received standard topical postoperative therapy with tobramycin, diclofenac, and dexamethasone eye drops plus cytochrome c peroxidase eye drops (two drops three times a day for 1 week or until corneal re-epithelialization was complete, corresponding to 15,000 IU/day). The fellow eye served as the control and received standard postoperative therapy plus placebo. The mice were monitored daily, commencing on the day after surgery, for 7 days to evaluate the corneal re-epithelialization rate using a video slit lamp camera with cobalt blue light. The mean diameter of the corneal wounds was measured. Videotaped images were recorded and analyzed by computer planimetry. Results: All eyes treated with cytochrome c peroxidase eye drops healed completely before day 5 after surgery, with a mean re-epithelialization time of 92 ± (SD) 10 h; the mean re-epithelialization time was 121 ± 8 h in the eyes receiving placebo (p < 0.05). There were no statistically significant differences between the two groups in corneal haze presentation during the follow-up period (p = 0.70), perhaps because the observation period was too short (7 days). However, the corneal clarity, on slit lamp biomicroscopy, in the study group was higher than that in the control group. No side effects or toxic effects were observed. Conclusions: These data suggest that cytochrome c peroxidase significantly accelerates epithelial healing after phototherapeutic keratectomy. Further clinical studies should be performed to prove the results obtained in this study and the long-term efficacy of cytochrome c peroxidase to prevent corneal haze.
The Role of Simvastatin on Postoperative Peritoneal Adhesion Formation in an Animal Model
Authors: Kucuk Hasan Fehmi , Kaptanoglu Levent , Kurt Necmi , Uzun Huseyin , Eser Mehmet , Bingul Sadık , Torlak Oguzhan Aziz , Akyol Huseyin
Published: February 2007

Aim: The aim of this study is to show the effect of simvastatin on intra-abdominal adhesion formation. Method: Adhesion formation was achieved by scratching the cecum and anterior abdominal wall following median laparotomy. Three different groups of 10 rats each were formed. In group I, 0.57 mg/kg/day simvastatin was injected intraperitoneally right after the operation and for 5 days thereafter. In group II, an equal dose of simvastatin to that used in group I was given via gavage. A physiological saline solution was given to group III for the same period of time. On the 6th and 14th day, blood samples were taken and peritoneal lavage was performed to measure the tissue-type plasminogen activator (t-PA) activity. Adhesions were graded via re-laparotomies on the 14th day after the first operation. Results: The adhesion scores were 1.40 ± 0.22, 1.50 ± 0.26, and 2.90 ± 0.34 in groups I, II, and III, respectively (p = 0.007), and the score was higher in group III than in the other groups (p = 0.005, p = 0.011). Conclusion: Intraperitoneal simvastatin application decreases adhesion formation by increasing the t-PA level in abdominal surgery.
Selective Decline in Information Processing in Subgroups of Multiple Sclerosis: An 8-Year Longitudinal Study
Authors: Bergendal G. , Fredrikson S. , Almkvist O.
Published: February 2007

Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system (CNS) that causes white matter and cortical lesions over many years. The CNS is selectively affected by the disease with a great variety of symptoms between patients. In this study, we describe the impact on various aspects of cognition over an 8-year follow-up period in 31 consecutive MS patients subgrouped as relapsing remitting (RR) MS, secondary progressive (SP) MS, and primary progressive (PP) MS. Results showed a differential pattern of cognitive decline already at baseline in speed of information processing. During the follow-up, a pronounced decline occurred in speed of information processing, finger-motor speed, copying geometrical designs, episodic memory, and visuospatial short-term memory. A striking difference was observed between a marked decline in visual reaction time, whereas no significant change was seen in auditory reaction time. In contrast, there was no time-related decline in verbal abilities. However, an initial marked cognitive impairment predicted further cognitive decline over the 8-year follow-up. Information-processing tests were found to be an especially strong predictor of long-term cognitive decline. In addition, high EDSS score at follow-up was associated with decline in information processes. Results also showed that SP-MS patients deteriorated significantly more than the other two groups, particularly in visual compared to auditory information processing. To conclude, cognitive decline appeared particularly in SP-MS patients and in visual information processing.
Tumor Necrosis Factor-α-308 Gene Polymorphism in Croatian and Slovenian Multiple Sclerosis Patients
Authors: Ristić Smiljana , Lovrečić Luca , Starčević-Čizmarević Nada , Brajenović-Milić Bojana , Šega Jazbec Saša , Sepčić Juraj , Kapović Miljenko , Peterlin Borut
Published: February 2007

Previous findings regarding the role of TNF-α-308 gene polymorphism in multiple sclerosis (MS) are contradictory. The aim of this study was to investigate the possible influence of TNF-α-308 polymorphism on MS susceptibility and the MS disease process in a Croatian and Slovenian population. Genotyping was performed in 338 patients and 460 healthy controls. The TNF2 allele was present in 123 (26.8%) healthy controls vs. 67 (19.9%) MS patients (p = 0.023, odds ratio = 0.68, 95% confidence interval = 0.48–0.95), suggesting that carriage of the TNF2 allele might decrease MS risk. The difference in TNF2 allele carrier frequency between patients and controls was identified in the relapsing-remitting MS group. There was no association between TNF2 allele carrier status and age at disease onset or disease progression. Our results suggest that, in the study populations, the TNF-α-308 polymorphism may play a role in MS susceptibility.
Causes of Ischemic Stroke in Young Adults, and Evolution of the Etiological Diagnosis over the Long Term
Authors: Varona J.F. , Guerra J.M. , Bermejo F. , Molina J.A. , Gomez de la Cámara A.
Published: February 2007

Background: Causes of ischemic stroke in young adults (15–45 years) are diverse, but undetermined etiology is common in a majority of studies. Aims: The present series study aims to evaluate causes and changes in the etiological diagnosis of ischemic stroke in young adult patients admitted to a tertiary medical center over a period of 27 years. Methods: We retrospectively reviewed the records of patients with a first-ever stroke in the age range of 15–45 years who were admitted to the ‘12 de Octubre’ University Hospital between 1974 and 2002. Results: 272 young adults with ischemic stroke were identified. The etiological diagnoses were: undetermined in 36% of patients, large-artery atherosclerosis in 21%, cardioembolism in 17%, non-atherosclerotic vasculopathy in 17%, and other specific etiologies in 9%. While in the first study period (1974–1988) 45% of patients were diagnosed with uncertain etiology, in the last period (1989–2002) only 26% were diagnosed with cryptogenic stroke (45% with two or more potential etiologies identified; 45% with no identified cause despite complete evaluation, and 10% with incomplete evaluation). Conclusions: The etiological diagnosis of stroke in young adults has changed over time as a result of improvements in diagnostic workup. While cryptogenic stroke was the most frequent diagnosis in the past, today specific causes (non-atherosclerotic vasculopathy, large-artery atherosclerosis, cardioembolism and hematological disorder) are identified in the majority of patients.
Strategy for Detecting Susceptibility Genes with Weak or No Marginal Effect
Authors: Kotti S. , Bickeböller H. , Clerget-Darpoux F.
Published: February 2007

Most human diseases result from complex interactions among multiple genes that yield weak or modest effects. Despite the growing awareness of the importance of gene-gene interactions, the paradigm of detectable effects of individual variants remains the cornerstone of genome association studies with tagSNPs. The interactive effect of two variants is only tested once the individual effect of one variant is detected. Both genes, however, may have at the same time a weak (or even no) marginal effect but an important effect through their interaction. In such a situation, current approaches may fail to detect variants having a crucial role in the causal chain. Here, we propose a new strategy: the 2-locus TDT. It allows the detection of the involvement of two genes without individual effect. Our strategy simultaneously uses information on biallelic candidate polymorphisms in two genes M and N. We first estimate the relative marginal penetrances of the genotype at each locus and of the joint (two-locus) genotype and then we test for the interactive effect of the two genes using a likelihood ratio test. We show that our approach has good power to detect the effect of two genes in situations for which a locus-by-locus strategy would have been unsuccessful. At a time where genome-wide association studies are fashionable, we think it is important to consider the strategy of studying good candidate pathways with our approach.
The Use of the Restricted Partition Method with Case-Control Data
Authors: Culverhouse R.
Published: February 2007

Background/Aims: Many diseases important to public health are not due solely to a single mutation or environmental insult. Instead, complex interactions among multiple genes and environmental exposures likely play crucial roles in the etiology of diverse phenotypes from schizophrenia to chemotherapy response. The Restricted Partition Method (RPM) was designed to detect qualitative genetic and environmental factors contributing to a quantitative trait, even if the contribution is predominantly presented as an interaction (displaying little or no signal in univariate analyses). Although the RPM was developed with the expectation that trait values would be drawn from normal distributions, the algorithm will function if the quantitative trait values are replaced with 0’s or 1’s indicating control or case status. The aim of this study is to evaluate the performance of the RPM on case-control data. Methods: Case-control data simulated for this study and data provided to the Pharmcogenetics Research Network Analysis Workshop 2005 were used to assess power and type I error for the RPM in this setting. Results: For the tested data, the RPM displayed good power and type I error very close to nominal rates. Conclusions: The RPM is an appropriate method for the analysis of case-control data.
The Impact of Genotype Misclassification Errors on the Power to Detect a Gene-Environment Interaction Using Cox Proportional Hazards Modeling
Authors: Tung Lin , Gordon Derek , Finch Stephen J.
Published: February 2007

This paper extends gene-environment (G × E) interaction study designs in which the gene (G) is known and the environmental variable (E) is specified to the analysis of ‘time-to-event’ data, using Cox proportional hazards (PH) modeling. The objectives are to assess whether a random sample of subjects can be used to detect a specific G × E interaction and to study the sensitivity of the power of PH modeling to genotype misclassification. We find that a random sample of 2,100 is sufficient to detect a moderate G × E interaction. The increase in sample size necessary (SSN) to maintain Type I and Type II error rates is calculated for each of the 6 genotyping errors for both dominant and recessive modes of inheritance (MOI). The increase in SSN required is relatively small when each genotyping error rate is less than 1% and the disease allele frequency is between 0.2 and 0.5. The genotyping errors that require the greatest increase in SSN are any misclassification of a subject without the at-risk genotype as having the at-risk genotype. Such errors require an indefinitely large increase in SSN as the disease allele frequency approaches 0, suggesting that it is especially important that subjects recorded as having the at-risk genotype be correctly genotyped. Additionally, for a dominant MOI, large increases in SSN can occur with large disease allele frequency.
Exploiting Gene-Environment Interaction to Detect Genetic Associations
Authors: Kraft Peter , Yen Yu-Chun , Stram Daniel O. , Morrison John , Gauderman W. James
Published: February 2007

Complex disease by definition results from the interplay of genetic and environmental factors. However, it is currently unclear how gene-environment interaction can best be used to locate complex disease susceptibility loci, particularly in the context of studies where between 1,000 and 1,000,000 markers are scanned for association with disease. We present a joint test of marginal association and gene-environment interaction for case-control data. We compare the power and sample size requirements of this joint test to other analyses: the marginal test of genetic association, the standard test for gene-environment interaction based on logistic regression, and the case-only test for interaction that exploits gene-environment independence. Although for many penetrance models the joint test of genetic marginal effect and interaction is not the most powerful, it is nearly optimal across all penetrance models we considered. In particular, it generally has better power than the marginal test when the genetic effect is restricted to exposed subjects and much better power than the tests of gene-environment interaction when the genetic effect is not restricted to a particular exposure level. This makes the joint test an attractive tool for large-scale association scans where the true gene-environment interaction model is unknown.
Assessing Environmental Modifiers of Disease Risk Associated with Rare Mutations
Authors: Whittemore Alice S.
Published: February 2007

Objective: As disease-predisposing mutations are increasingly identified, there is growing need to assess the effects of lifestyle and environmental factors on disease risks in mutation carriers. Such assessment is difficult when the mutations are rare and evaluating them in large population samples is costly. Methods: This paper describes four study designs for evaluating the effects of environmental exposures in carriers of rare disease-predisposing mutations. Results: The strengths and weaknesses of the designs are assessed, and strategies for analyzing the data obtained from such designs are considered. Conclusions: When exposure effects in noncarriers are well-established and exposure is independent of carrier status in the population of disease-free controls, the case-only design provides a feasible and efficient method for inferring effects in carriers. When exposure effects in noncarriers are not well established, the most feasible design options are those that compare exposures in carrier cases to either untyped controls or to carrier controls. These two designs have complementary strengths and weaknesses; thus inferences are stronger when measures of association estimated using the two designs are consistent.
Novel Single Nucleotide Polymorphisms in the Specific Protein 1 Binding Site of the Bovine PRNP Promoter in Japanese Black Cattle: Impairment of Its Promoter Activity
Authors: Nakamura Izuru , Xue Guangai , Sakudo Akikazu , Saeki Keiichi , Matsumoto Yoshitsugu , Ikuta Kazuyoshi , Onodera Takashi
Published: February 2007

Susceptibility to transmissible spongiform encephalopathy and different alleles of the prion protein gene (PRNP) of humans and sheep are associated. A tentative association between PRNP promoter polymorphisms and bovine spongiform encephalopathy (BSE) susceptibility has been reported in German cattle, whereas none of the known polymorphisms within the bovine PRNP-coding sequence affect BSE susceptibility. In the present study, novel single nucleotide polymorphisms located in the 5′-flanking region of bovine PRNP affecting its expression were demonstrated in Japanese Black cattle. We sequenced exon 1, and the approximately 200-bp 5′-flanking region of the PRNP translation initiation site containing the proximal promoter of PRNP was harvested. We identified 7 single nucleotide polymorphisms: –184A→G, –141T→C, –85T→G, –47C→A, –6C→T, +17C→T and +43C→T. Six segregated haplotypes in the population were cloned into luciferase-expressing plasmids, transfected into N2a cells, and their reporter activities were measured 48 h after transfection. Six haplotypes showed a decreased expression level including –6C→T in specific protein 1 binding site (p < 0.05) or –141T→C (p < 0.01) at 48 h compared with the wild-type haplotype. These results advocate that certain polymorphisms such as specific protein 1 binding site polymorphisms in the bovine PRNP promoter region in Japanese Black cattle could influence promoter activity, suggesting that breeding cattle with such substitutions may be a useful approach in reducing BSE risk.
Reliable Generation of Stable High Titer Producer Cell Lines for Gene Therapy
Authors: Rattmann Ina , Kleff Veronika , Feldmann Anja , Ludwig Carsten , Sorg Ursula Regina , Opalka Bertram , Moritz Thomas , Flasshove Michael
Published: February 2007

Objective: Retroviral vectors represent one of the most robust technologies for in vivo expression of heterologous gene sequences and are still the most commonly used vectors in clinical gene therapy trials. The production of high titer retroviral preparations, however, can be a problematic procedure for certain constructs. Methods: GALV- or RD114-pseudotyped retroviral particles carrying selectable fluorescence markers or drug resistance genes, such as the green fluorescent protein (GFP) or the O6-methylguanine-DNA-methyltransferase (MGMT) mutants, were used to stably transduce Phoenix-(FNX-)eco cells. Thereafter, a polyclonal population of producer cells was generated by enriching cells with high marker gene expression. In addition, single producer clones were selected by limiting dilution. Results: Retroviral titers were increased 1–2 logs by enriching for a polyclonal population of producer cells, and selection of single producer clones allowed another 1- to 2-log increase in titers. Using this method, reproducibly high titer viral preparations allowing efficient transduction of hematopoietic stem cells were generated. Conclusion: A reliable and time-effective method to generate stable high titer producer cells based on the FNX-cell line for problematic retroviral vector constructs is described.
Circulating Hepatitis B Virus RNA in Newborns from Carrier Mothers
Authors: Zhu Shao-Jun , Li Yan-Hong , Wang Qing-Tu , Guo Yong , Cui Yun , Su Qin , Hacker Hans Jörg , Schröder Claus H. , Feng Ying-Ming , Zhang Wei
Published: February 2007

Objective: Despite intermittent flares, progression of chronic infection with hepatitis B virus has generally been related to a decrease in replication levels. In our laboratory, this decrease has been found to be associated with a decline in circulating full-length transcripts (fRNA) and to a shift to truncated transcripts (trRNA). Monitoring fRNA and trRNA as markers allows a more detailed analysis of high or low or non-replicative HBV infection stages. Methods: Here, we determined circulating HBV RNA in newborns from a total of 69 HBsAg-positive carrier mothers with and without immunotherapy administered during the last 3 months of pregnancy. Results: In line with previous observations, serum HBV DNA in newborns was only found when their mothers had not been treated (7/23). HBV RNA measured as trRNA was detected both in the presence and in apparent absence of serum HBV DNA. fRNA (coexisting with HBV DNA and HBeAg) was detected only in newborns from untreated mothers (8/23) and was always combined with trRNA. In contrast, trRNA was found in newborns from both untreated (20/23) and treated mothers (26/46). Conclusions: Our data strongly suggest a direct intrauterine transmission of a low-replicative (unapparent) HBV infection stage. However, a feto-maternal transfer of trRNA (transfer of a marker) rather than transmission of the infectious virus cannot be excluded.
In vitro Interaction of Poliovirus with Cytoplasmic Dynein
Authors: González Durán Elizabeth , del Angel Rosa M. , Salas Benito Juan Santiago
Published: February 2007

Objective: Poliovirus (PV) enters the host by the oral route and can infect the central nervous system (CNS) by two mechanisms: crossing the blood-brain barrier and traveling along the nerves from the muscle to the spinal cord. In the latter mechanism, the PV receptor, CD155, and the motor protein, dynein, have been implicated in the transport of PV to the CNS. In this work we analyzed the possible interaction of PV with dynein. Methods: PV was bound to a Sepharose 4B beads and they were used to analyze the interaction of PV with cytoplasmic proteins from neuroblastoma cells by affinity chromatography and Western blot. Results: The interaction with cytoplasmic dynein was observed only when the Sepharose beads bound to PV were used and not in the control ones, where proteins from uninfected cells were coupled. Conclusion: These preliminary results open the possibility that PV uses the dynein directly in its retrograde axonal transport.
Neuroprotective and Intraocular Pressure-Lowering Effects of (–)Δ9-Tetrahydrocannabinol in a Rat Model of Glaucoma
Authors: Crandall James , Matragoon Suraporn , Khalifa Yousuf M. , Borlongan Caesar , Tsai Nai-Tse , Caldwell Ruth B. , Liou Gregory I.
Published: February 2007

In glaucoma, retinal ganglion cell (RGC) death is induced by many risk factors, including ocular hypertension. It has been proposed that glutamate-mediated oxidative stress may also contribute to this RGC death. Cannabinoids are known to possess therapeutic properties including ocular hypotension and antioxidation. In this study, we test the hypothesis that (–)Δ9-tetrahydrocannabinol (THC) lowers intraocular pressure (IOP) and prevents RGC death in a rat model of glaucoma. Arat model of experimental glaucoma with chronic, moderately elevated IOP was produced unilaterally by cauterization of episcleral vessels. Rats received weekly injections of THC at a level of 5 mg/kg or vehicle for 20 weeks. IOP of both eyes was measured weekly on anesthetized animals immediately before THC treatment. RGCs were labeled in a retrograde fashion and counted in whole-mounted retinas. IOP was elevated in all operated eyes 1 day after the operation and remained elevated in the vehicle-treated rats throughout 20 weeks. In THC-treated rats, IOP elevation in operated eyes was diminished 2 weeks after operation and remained reduced. IOP in the contralateral control eyes was not affected by THC. In the operated eyes of vehicle-treated animals, there was a loss of ∼50 and 40% of the RGCs in the peripheral and central retina, respectively. The RGC loss in the operated eyes of the THC-treated animals was reduced to 10–20%. These results demonstrate that THC is a neuroprotectant that preserves RGCs in an experimental model of glaucoma, possibly through a reduction in IOP.
The Response of Retrobulbar Vasculature to Hypercapnia in Primary Open-Angle Glaucoma and Ocular Hypertension
Authors: Sines D. , Harris A. , Siesky B. , Januleviciene I. , Haine C.L. , Yung C.W. , Catoira Y. , Garzozi H.J.
Published: February 2007

Purpose: To evaluate the physiological effects of hypercapnia on the retrobulbar vasculature in ocular hypertension (OH) and open-angle glaucoma (OAG). Methods: Peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistive index (RI) of the ophthalmic (OA) and central retinal arteries (CRA) were evaluated in 12 eyes with OH and 8 eyes with OAG using color Doppler imaging. Measurements were taken before and during hypercapnia. Results: Patients with OAG were found to have increased EDV (p < 0.035) of the CRA, and decreased PSV (p < 0.097) and EDV (p < 0.098) of the OA, during hypercapnia. Patients with OH had increased PSV (p < 0.062) and EDV (p < 0.072) of the CRA during hypercapnia. Patients with OH also demonstrated a greater percent change in the calculated RI (p < 0.065) of the CRA in response to hypercapnia when compared to OAG. The mean RI of the CRA decreased during hypercapnia. Discussion: Patients with OH were found to have a normal vasodilatory response within the retrobulbar vasculature during hypercapnia resulting in increased volumetric blood flow to the retina while patients with OAG did not, suggesting there is vasospasm at or downstream from the CRA resulting in decreased volumetric blood flow to the retina.
AP-1 Expression in Ethanol-Treated Corneal Epithelium in vivo
Authors: Okada Yuka , Saika Shizuya , Miyamoto Takeshi , Shirai Kumi , Ueyama Takashi , Senba Emiko , Ohnishi Yoshitaka
Published: February 2007

Purpose: To examine the expression pattern of stress-related genes, c-fos and c-jun, both the major components of activator protein-1 (AP-1), in rat corneal epithelium treated with a short-term ethanol exposure. The purpose of the current study was to examine if the ethanol exposure during laser epithelial keratomileusis (LASEK) may stimulate or damage the corneal epithelial cells. Method: Sixty male Wistar rats were used. Fifty microliters of 20% ethanol was placed onto a surface 2.4 mm in diameter of the central corneal epithelium for 30 s. The affected eyes, washed with saline, were then enucleated after various intervals of healing. To know the expression pattern of c-fos and c-jun mRNAs and c-Fos, c-Jun and Jun D proteins, in situ hybridization and immunohistochemistry were carried out. The expression level of c-fos and c-jun mRNAs was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Apoptotic nuclei in the tissue sections were identified by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. Results: Thirty to 60 min after the treatment, c-fos and c-jun mRNAs were detected in the corneal epithelium. These signals were no longer evident at 90 min. c-Fos protein was detected in the corneal epithelium around the area of ethanol exposure from 60 to 120 min after the treatment, while c-Jun protein was not detected. Jun D protein was detected in control whole corneal epithelium and not affected by ethanol exposure in the periphery. The levels of c-fos and c-jun mRNAs were increased approximately 8 times at 30 min compared with the control level. TUNEL-positive apoptotic nuclei in the tissue sections were identified. Conclusion: Corneal epithelial cells, especially those surrounding the ethanol-exposed area, are transiently transcriptionally activated at a very early phase after the ethanol exposure. mRNA expression for c-fos is followed by protein synthesis, but that of c-jun is not followed by protein synthesis. Resistance of Jun D protein expression to ethanol suggests that it might be a candidate for an AP-1 complex with c-Fos.
Pigment-Epithelium-Derived Factor Suppresses Expression of Receptor for Advanced Glycation End Products in the Eye of Diabetic Rats
Authors: Yamagishi Sho-ichi , Matsui Takanori , Nakamura Kazuo , Yoshida Takafumi , Takeuchi Masayoshi , Inoue Hiroyoshi , Yoshida Yumiko , Imaizumi Tsutomu
Published: February 2007

The interaction of advanced glycation end products (AGEs) and their receptor (RAGE) elicits inflammatory and proliferative responses in retinal vascular wall cells, thereby being involved in the pathogenesis of diabetic retinopathy. Recently, pigment-epithelium-derived factor (PEDF) has also been shown to play a role in diabetic retinopathy. However, the effects of PEDF on RAGE gene expression remain to be elucidated. Therefore, we investigated here whether PEDF could prevent diabetes- or AGE-induced RAGE gene expression and the way that it might achieve this effect. Administration of PEDF or pyridoxal phosphate, an AGE inhibitor, suppressed RAGE gene expression in the eye of streptozotocin-induced diabetic rats. Further, intravenous injection of AGEs to normal rats increased RAGE gene expression, which was also blocked by PEDF. In vitro, PEDF or an antioxidant N-acetylcysteine blocked the AGE-induced RAGE gene induction in microvascular endothelial cells. In addition, PEDF completely inhibited superoxide generation and NF-ĸB activation in AGE-exposed endothelial cells. These results demonstrated that PEDF could inhibit diabetes- or AGE-induced RAGE gene expression by blocking the superoxide-mediated NF-ĸB activation. Our present study suggests that pharmacological upregulation or substitution of PEDF may play a protective role against diabetic retinopathy by attenuating the deleterious effect of AGEs.
Fluorescein Angiography Compared to Three-Dimensional Measurements by the Retinal Thickness Analyzer in Classic Choroidal Neovascularization
Authors: Strauss R.W. , Rombold F. , Kampik A. , Neubauer A.S.
Published: February 2007

Purpose: To compare and correlate imaging of classic subfoveal choroidal neovascularization (CNV) with noninvasive 3-dimensional imaging by the retinal thickness analyzer (RTA) to conventional fluorescein angiography (FA). Methods: A total of 29 eyes of 29 consecutive patients with predominantly classic CNV eligible for photodynamic therapy underwent FA and RTA imaging. The FA dimensions of the CNV were measured independently by two graders. With the RTA, masked to FA the size of the CNV itself as imaged in 3-dimensional reconstruction, the size of significantly thickened retina overlying the CNV and the maximum retinal thickness were measured. Results: The mean diameter of the CNV determined from 3-dimensional RTA reconstructions showed an excellent correlation with measurements from FA (r = 0.91, p < 0.001). The area of retinal thickening was by a mean of 0.7 mm in diameter larger and correlated moderately well with the size of the CNV on FA (r = 0.65, p < 0.001). In contrast, there was no correlation between the absolute retinal thickness and the CNV size on FA. Conclusions: Noninvasive quantitative mapping of predominantly classic CNV by RTA is feasible and also allows 3-dimensional measurement of the lesion itself. The results correlate well with FA assessment but visualize different properties of the disease.
Chorioretinal Vascular Oxygen Tension in Spontaneously Breathing Anesthetized Rats
Authors: Shakoor A. , Gupta M. , Blair N.P. , Shahidi M.
Published: February 2007

Purpose: To establish baseline and variability of oxygen tension (PO2) measurements in the choroid, retinal arteries, capillaries, and veins of spontaneously breathing anesthetized rats and determine the effect of a moderate surgical procedure on the chorioretinal PO2. Methods: Our previously established optical section phosphorescence imaging technique was utilized to measure PO2 in the chorioretinal vasculatures. Imaging was performed in 29 spontaneously breathing rats under ketamine/xylazine anesthesia. In 7 rats, blood was drawn using a surgically implanted femoral arterial catheter and analyzed to determine the systemic arterial PO2. The PO2 measurements in 22 rats without surgery (group 1) and 7 surgically instrumented rats (group 2) were statistically compared. The intrasubject variability was calculated by the average standard deviation (SD) of repeated measurements. Results: The average systemic arterial PO2 was 52 ± 7 mm Hg (mean ± SD) in group 2. In group 1, the average PO2 measurements in the choroid, retinal arteries, capillaries, and veins were 50 ± 11, 40 ± 5, 39 ± 6, and 30 ± 5 mm Hg, respectively. No statistically significant PO2 differences in any of the chorioretinal vasculatures were found between the two groups (p > 0.4). The intrasubject variability was 3 mm Hg in the choroid, retinal arteries, capillaries, and veins. Conclusions: Chorioretinal PO2 measurements in spontaneously breathing anesthetized rats have a relatively low variability, indicating that PO2 changes due to various physiological alterations can be reliably assessed.
VEGF-Targeted RNA Interference Suppresses Angiogenesis and Tumor Growth of Retinoblastoma
Authors: Jia R.B. , Zhang P. , Zhou Y.X. , Song X. , Liu H.Y. , Wang L.Z. , Luo M. , Lu J. , Ge S.F. , Fan X.Q.
Published: February 2007

Vascular endothelial growth factor (VEGF) is one of the most important angiogenic growth factors for tumor angiogenesis which has been verified to be involved in neovascularization of retinoblastoma. Here, we sought to explore whether RNA interference (RNAi) targeting VEGF could inhibit retinoblastoma angiogenesis and tumor growth. Stable transfection of the two human retinoblastoma cell lines SO-RB50 and HXO-RB44 with VEGF-targeted small interfering RNA (siRNA) expression plasmid significantly inhibited VEGF expression determined by real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay and Western blot, whereas the control transfection showed no effects. The chemically synthesized VEGF siRNA dramatically suppressed tumor angiogenesis (CD34 immunohistochemistry) and tumor growth in the SO-RB50 subcutaneous xenograft model. Significant downregulation of VEGF expression both on messenger RNA and protein levels in VEGF-siRNA-treated SO-RB50 subcutaneous xenograft was confirmed by real-time PCR and Western blot compared to control. Our data demonstrate the suppression function on angiogenesis and tumor growth of retinoblastoma by VEGF-targeted RNAi. This novel therapeutic strategy promises to play a part in the clinical management of retinoblastoma.
Intravitreal Bevacizumab for Filtering Surgery
Authors: Jonas Jost B. , Spandau Ulrich H. , Schlichtenbrede Frank
Published: February 2007

Background: It was the aim of this study to report on the intravitreal use of bevacizumab as antiproliferative agent in combination with filtering surgery. Methods: The clinical interventional case series study included 2 patients (2 eyes) who underwent standard antiglaucomatous penetrating filtering surgery combined with an intravitreal application of 1.5 mg bevacizumab. The intraocular pressure was elevated due to an intravitreal triamcinolone injection as treatment of exudative age-related macular degeneration (patient No. 1) or due to neovascular glaucoma (patient No. 2) after an ischemic retinal branch vein occlusion. Results: At 4 and 12 weeks after surgery, intraocular pressure was reduced in both patients to 10 and 14 mm Hg with functioning filtering blebs. Conclusions: Intravitreal bevacizumab may potentially be helpful as addition to antiglaucomatous filtering surgery, particularly in neovascular glaucoma.
Caregiver Burden Associated with Behavioral and Psychological Symptoms of Dementia in Elderly People in the Local Community
Authors: Matsumoto Naomi , Ikeda Manabu , Fukuhara Ryuji , Shinagawa Shunichiro , Ishikawa Tomohisa , Mori Takaaki , Toyota Yasutaka , Matsumoto Teruhisa , Adachi Hiroyoshi , Hirono Nobutsugu , Tanabe Hirotaka
Published: February 2007

Background: Despite many studies about the association between caregiver burden and behavioral and psychological symptoms of dementia (BPSD), there have been no population-based studies to evaluate caregiver burden associated with each BPSD. Objective: To evaluate caregiver burden associated with the individual BPSD in elderly people living in the community. Methods: The subjects were 67 participants with dementia living with their caregivers (diagnosed in the third Nakayama study): 51 Alzheimer’s disease, 5 vascular dementia and 11 other. The Neuropsychiatric Inventory (NPI) and NPI Caregiver Distress Scale (NPI-D) were used to assess subjects’ BPSD and related caregiver distress, respectively. Results: In the subjects exhibiting BPSD, aberrant motor behavior had the highest mean NPI score, and depression/dysphoria had the lowest. Agitation/aggression had the highest mean NPI-D score, and euphoria/elation had the lowest. Delusion, agitation/aggression, apathy/indifference, irritability/lability and aberrant motor behavior showed a correlation between the NPI and NPI-D scores. Conclusion: The burden associated with BPSD is different for each symptom and does not always depend on frequency and severity of BPSD. These findings suggest that some symptoms, such as agitation/aggression and irritability/lability, may affect the caregivers significantly, although their frequency and severity are low.
Novel Immunosuppressant Agents Targeting Activated Lymphocytes by Biocompatible MPC Polymer Conjugated with Interleukin-2
Authors: Chiba N. , Ueda M. , Shimada T. , Jinno H. , Watanabe J. , Ishihara K. , Kitajima M.
Published: February 2007

The immunopharmacological profile of novel biocompatible water-soluble interleukin-2 (IL-2)-conjugated 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer immunosuppressive agents was established. MPC-co-n- butyl methacrylate (BMA)-co-p-nitrophenylcarbonyloxyethyl methacrylate (NPMA) (PMBN) was prepared as a backbone for these novel agents. PMBN contained MPC as a biocompatible unit, BMA as a hydrophobic domain in water, and NPMA as an immobilizable unit with IL-2. This research showed that proliferation of cell lines with high-affinity IL-2 receptors derived from T cell malignancies were suppressed by the PMBN conjugated with IL-2 (PMBN-IL2 conjugate) incorporating paclitaxel (PTX) and cyclosporin A at lower concentrations than used conventionally. PMBN-IL2 conjugates incorporating PTX also inhibited the proliferation of responder cells in a human mixed lymphocyte culture at a lower concentration than unconjugated drug. However, PMBN-IL2 conjugates incorporating FK506 inhibited proliferation no more than FK506 alone. The PMBN-IL2 conjugate with PTX may therefore be useful for selectively eliminating activated lymphocytes that hyperproduce high-affinity IL-2 receptors. As an entirely human ‘immunotoxin analogue’ it may not be associated with the dose-limiting toxicity and immunogenicity of conventional immunotoxins.
Investment Bust in Post-Crisis Korea: Fact or Fiction?
Authors: Lim Kyung-Mook , Lim Wonhyuk
Published: February 2007

In post-crisis Korea, facility (equipment) investment shows the worrisome trends of a slowdown in investment growth and a decline in investment propensity. We marshal micro and macro data to examine four major explanations for these important developments. Our analysis: (a) finds that cyclical factors such as depressed private consumption in 2003 and 2004 did lead to lower investments in automobiles, hence dragging down total investment growth in these years; (b) rejects the claim that investment was lowered by an “anti-chaebol environment” created by the Roh Moo-hyun government (facility investment by large firms actually increased by a great deal in 2003 and 2004, whereas aggregate investment in the national account showed anemic growth); (c) supports the “moral hazard” hypothesis, which states that chaebol investment in the pre-crisis period was abnormally high because of implicit state guarantees (the chaebol dummy in our investment equations was no longer statistically significant in the post-crisis period, in the aftermath of large-scale bankruptcies); and (d) supports the “hollowing-out” hypothesis, which holds that outward foreign direct investment has reduced domestic facility investment because the price competitiveness of final assembly and other labor-intensive sectors in Korea has been eroded by the rise of late-developing countries such as China and Vietnam.