bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing automobile head restraint positioning in Portland, Oregon
Authors: Young A L , Ragel B T , Su E , Mann C N , Frank E H
Published: April 2005

Objective:Automobile head restraints, when used properly, have been shown to decrease the incidence and severity of whiplash injuries to the neck. Before the development of a public campaign on proper head restraint positioning, the authors assessed head restraint positioning and public understanding.

Design:Over a one month period, the position of the vehicle head restraint of drivers was observed in moving cars in the city of Portland, Oregon (population 530 000). Optimal position was defined as having the head restraint above the ears with the back of the head touching the head restraint. A questionnaire on head restraint understanding was administered to people during jury service.

Results:Of the 4287 drivers observed, 1% (n = 30) had no head restraint on their seat, 4% (n = 158) had a fixed head restraint, and 95% (n = 4099) had an adjustable head restraint. Among the fixed head restraints, 21% (33/158) were positioned optimally with no horizontal gap. Among the adjustable head restraints, only 7% (280/4099) had optimal head restraint positioning. Overall, 93% (3974/4287) of all head restraints observed were suboptimally positioned. Seventy five percent (38/51) of polled Portland residents identified safety as the primary head restraint function.

Conclusion:Ninety three percent of all head restraints observed were suboptimally positioned. Fixed head restraints were three times more likely to be in optimal position than adjustable head restraints (21%v7%). Most polled Portland residents understood the proper function and positioning of head restraints. This discrepancy between actual practice and understanding should be addressed with public education and manufacturer design changes.
Effects on alcohol related fatal crashes of a community based initiative to increase substance abuse treatment and reduce alcohol availability
Authors: Hingson R W , Zakocs R C , Heeren T , Winter M R , Rosenbloom D , DeJong W
Published: April 2005

Objective:This analysis tested whether comprehensive community interventions that focus on reducing alcohol availability and increasing substance abuse treatment can reduce alcohol related fatal traffic crashes.

Intervention:Five of 14 communities awarded Fighting Back grants by The Robert Wood Johnson Foundation to reduce substance abuse and related problems attempted to reduce availability of alcohol and expand substance abuse treatment programs (FBAT communities). Program implementation began on 1 January 1992.

Design:A quasi-experimental design matched each program community to two or three other communities of similar demographic composition in the same state.

Main outcome measures:The ratio of fatal crashes involving a driver or pedestrian with a blood alcohol concentration of 0.01% or higher, 0.08% or higher, or 0.15% or higher were examined relative to fatal crashes where no alcohol was involved for 10 years preceding and 10 years following program initiation.

Results:Relative to their comparison communities, the five FBAT communities experienced significant declines of 22% in alcohol related fatal crashes at 0.01% BAC or higher, 20% at 0.08% or higher, and 17% at 0.15% or higher relative to fatal crashes not involving alcohol.

Conclusions:Community interventions to reduce alcohol availability and increase substance abuse treatment can reduce alcohol related fatal traffic crashes.
Long term effects of a home visit to prevent childhood injury: three year follow up of a randomized trial
Authors: King W J , LeBlanc J C , Barrowman N J , Klassen T P , Bernard-Bonnin A-C , Robitaille Y , Tenenbein M , Pless I B
Published: April 2005

Objective:To assess the long term effect of a home safety visit on the rate of home injury.

Design:Telephone survey conducted 36 months after participation in a randomized controlled trial of a home safety intervention. A structured interview assessed participant knowledge, beliefs, or practices around injury prevention and the number of injuries requiring medical attention.

Setting:Five pediatric teaching hospitals in four Canadian urban centres.

Participants:Children less than 8 years of age presenting to an emergency department with a targeted home injury (fall, scald, burn, poisoning or ingestion, choking, or head injury while riding a bicycle), a non-targeted injury, or a medical illness.

Results:We contacted 774 (66%) of the 1172 original participants. A higher proportion of participants in the intervention group (63%) reported that home visits changed their knowledge, beliefs, or practices around the prevention of home injuries compared with those in the non-intervention group (43%; p<0.001). Over the 36 month follow up period the rate of injury visits to the doctor was significantly less for the intervention group (rate ratio = 0.74; 95% CI 0.63 to 0.87), consistent with the original (12 month) study results (rate ratio = 0.69; 95% CI 0.54 to 0.88). However, the effectiveness of the intervention appears to be diminishing with time (rate ratio for the 12–36 month study interval = 0.80; 95% CI 0.64 to 1.00).

Conclusions:A home safety visit was able to demonstrate sustained, but modest, effectiveness of an intervention aimed at improving home safety and reducing injury. This study reinforces the need of home safety programs to focus on passive intervention and a simple well defined message.
An evaluation of state firearm regulations and homicide and suicide death rates
Authors: Rosengart M , Cummings P , Nathens A , Heagerty P , Maier R , Rivara F
Published: April 2005

Objective:To determine if any of five different state gun laws were associated with firearm mortality: (1) “shall issue” laws permitting an individual to carry a concealed weapon unless restricted by another statute; (2) a minimum age of 21 years for handgun purchase; (3) a minimum age of 21 years for private handgun possession; (4) one gun a month laws which restrict handgun purchase frequency; and (5) junk gun laws which ban the sale of certain cheaply constructed handguns.

Design:A cross sectional time series study of firearm mortality from 1979 to 1998.

Setting:All 50 states and the District of Columbia.

Subjects:All residents of the United States.

Main outcome measures:Firearm homicides, all homicides, firearm suicides, and all suicides.

Results:When a “shall issue” law was present, the rate of firearm homicides was greater, RR 1.11 (95% confidence interval 0.99 to 1.24), than when the law was not present, as was the rate of all homicides, RR 1.08 (95% CI 0.98 to 1.17), although this was not statistically significant. No law was associated with a statistically significant decrease in the rates of firearm homicides or total homicides. No law was associated with a statistically significant change in firearm suicide rates.

Conclusion:A “shall issue” law that eliminates most restrictions on carrying a concealed weapon may be associated with increased firearm homicide rates. No law was associated with a statistically significant reduction in firearm homicide or suicide rates.
Out on a limb: risk factors for arm fracture in playground equipment falls
Authors: Sherker S , Ozanne-Smith J , Rechnitzer G , Grzebieta R
Published: April 2005

Objectives:To investigate and quantify fall height, surface depth, and surface impact attenuation as risk factors for arm fracture in children who fall from playground equipment.

Design:Unmatched case control study.

Setting:Five case hospitals and 78 randomly selected control schools.

Participants:Children aged less than 13 years in Victoria, Australia who fell from school playground equipment and landed on their arm. Cases sustained an upper limb fracture and controls had minor or no injury. A total of 402 cases and 283 controls were included.

Interventions:Children were interviewed in the playground as soon as possible after their fall.

Main outcome measures:Falls were recreated on site using two validated impact test devices: a headform (measuring peak G and HIC) and a novel anthropometric arm load dummy. Equipment and fall heights, as well as surface depth and substrate were measured.

Results:Arm fracture risk was greatest for critical equipment heights above 1.5 m (OR 2.39, 95% CI 1.49 to 3.84, p<0.01), and critical fall heights above 1.0 m (OR 2.96, 95% CI 1.71 to 5.15, p<0.01). Peak headform deceleration below 100G was protective (OR 0.67, 95% CI 0.45 to 0.99, p = 0.04). Compliance with 20 cm surface depth recommendation was poor for both cases and controls.

Conclusions:Arm fracture-specific criteria should be considered for future standards. These include surface and height conditions where critical headform deceleration is less than 100G. Consideration should also be given to reducing maximum equipment height to 1.5 m. Improved surface depth compliance and, in particular, guidelines for surface maintenance are required.
CONTINUOUS FEEDBACK CONTROL STRATEGY WITH MAXIMAL CAPTURE ZONE IN A CLASS OF PURSUIT GAMES
Authors: TURETSKY VLADIMIR , GLIZER VALERY Y.
Published: April 2005

An interception problem of a highly maneuverable target is considered using a linearized kinematical model with first order acceleration dynamics of the interceptor and the target. The problem is interpreted as a differential game of pursuit. An admissible pursuer (interceptor) feedback strategy, continuous with respect to the state variables and having a maximal capture zone, is constructed. This strategy is the saturated version of a linear feedback control, obtained from the solution of an auxiliary linear-quadratic differential game with cheap controls. This strategy is evaluated by Monte-Carlo simulation of the interception with noisy measurements.
CONVEXITY IN STOCHASTIC COOPERATIVE SITUATIONS
Authors: TIMMER JUDITH , BORM PETER , TIJS STEF
Published: April 2005

This paper introduces a new model concerning cooperative situations in which the payoffs are modeled by random variables. We analyze these situations by means of cooperative games with random payoffs. Special attention is paid to three types of convexity, namely coalitional-merge, individual-merge and marginal convexity. The relations between these types are studied and in particular, as opposed to their deterministic counterparts for TU games, we show that these three types of convexity are not equivalent. However, all types imply that the core of the game is nonempty. Sufficient conditions on the preferences are derived such that the Shapley value, defined as the average of the marginal vectors, is an element of the core of a convex game.
AN AXIOM SYSTEM FOR A VALUE FOR GAMES IN PARTITION FUNCTION FORM
Authors: ALBIZURI M. J. , ARIN J. , RUBIO J.
Published: April 2005

Lucas and Trall (1963) defined the games in partition function form as a generalization of the cooperative games with transferable utility. In our work we propose by means of an axiomatic characterization a solution for such games in partition function form. This solution will be a generalization of the Shapley value (1953).
A HISTORICAL OVERVIEW OF FUZZY MATHEMATICS
Authors: KERRE ETIENNE E. , MORDESON JOHN N.
Published: April 2005

In this paper, we present a historical overview of the development of fuzzy mathematics. We mainly concentrate on the evolution of the mathematical representation of fuzziness by means of fuzzy set theory. From the many remaining recently introduced models to represent imprecise and uncertain information, we briefly treat rough set theory.
EXTENDED DAILY EXCHANGE RATES FORECASTS USING WAVELET TEMPORAL RESOLUTIONS
Authors: KABOUDAN MAK
Published: April 2005

Applying genetic programming and artificial neural networks to raw as well as wavelet-transformed exchange rate data showed that genetic programming may have good extended forecasting abilities. Although it is well known that most predictions of exchange rates using many alternative techniques could not deliver better forecasts than the random walk model, in this paper employing natural computational strategies to forecast three different exchange rates produced two extended forecasts (that go beyond one-step-ahead) that are better than naïve random walk predictions. Sixteen-step-ahead forecasts obtained using genetic programming outperformed the one- and sixteen-step-ahead random walk US dollar/Taiwan dollar exchange rate predictions. Further, sixteen-step-ahead forecasts of the wavelet-transformed US dollar/Japanese Yen exchange rate also using genetic programming outperformed the sixteen-step-ahead random walk predictions of the exchange rate. However, random walk predictions of the US dollar/British pound exchange rate outperformed all forecasts obtained using genetic programming. Random walk predictions of the same three exchange rates employing raw and wavelet-transformed data also outperformed all forecasts obtained using artificial neural networks.
GENE SELECTION USING LOGISTIC REGRESSIONS BASED ON AIC, BIC AND MDL CRITERIA
Authors: ZHOU XIAOBO , WANG XIAODONG , DOUGHERTY EDWARD R.
Published: April 2005

In microarray-based cancer classification, gene selection is an important issue owing to the large number of variables (gene expressions) and the small number of experimental conditions. Many gene-selection and classification methods have been proposed; however most of these treat gene selection and classification separately, and not under the same model. We propose a Bayesian approach to gene selection using the logistic regression model. The Akaike information criterion (AIC), the Bayesian information criterion (BIC) and the minimum description length (MDL) principle are used in constructing the posterior distribution of the chosen genes. The same logistic regression model is then used for cancer classification. Fast implementation issues for these methods are discussed. The proposed methods are tested on several data sets including those arising from hereditary breast cancer, small round blue-cell tumors, lymphoma, and acute leukemia. The experimental results indicate that the proposed methods show high classification accuracies on these data sets. Some robustness and sensitivity properties of the proposed methods are also discussed. Finally, mixing logistic-regression based gene selection with other classification methods and mixing logistic-regression-based classification with other gene-selection methods are considered.
Effects of white adipose tissue grafts on total body fat and cellularity are dependent on graft type and location
Authors: Lacy Eva L. , Bartness Timothy J.
Published: April 2005

Surgical removal of body fat (lipectomy) triggers compensatory increases in nonexcised white adipose tissue (WAT), thus restoring adiposity levels in many species, including Siberian hamsters. In Siberian hamsters, when their lipectomized WAT is transplanted to another site (autologous grafts, no net change in body fat), healthy grafts result, but the lipectomy-induced compensatory increases in nonexcised WAT masses are exaggerated, an effect that apparently occurs only when the grafts contact intact WAT. When WAT is added to nonlipectomized hamsters to increase body fat, native WAT pads do not decrease. Thus WAT addition or removal-replacement does not induce compensatory WAT responses consistent with total body fat regulation as does WAT subtraction. Therefore, we tested whether the exaggerated response to lipectomy occurring with autologous WAT transplantation is dependent on graft site placement and whether the donor graft source [inguinal or epididymal WAT (IWAT, EWAT), sibling vs. nonsibling] affected body fat responses to WAT additions in nonlipectomized hamsters. Lipectomized hamsters received subcutaneous autologous EWAT grafts placed remotely from other WAT (ventrum) or in contact with intact WAT (dorsum), whereas intact hamsters received EWAT or IWAT grafts from sibling or nonsibling donors. The exaggerated response to lipectomy only occurred when grafts were in contact with intact WAT. EWAT, but not IWAT, additions to nonlipectomized siblings or nonsiblings increased native IWAT and retroperitoneal WAT mass but not EWAT mass compared with controls. Collectively, WAT transplantation to either lipectomized or nonlipectomized hamsters increased body fat contingent on graft contact with intact or native WAT.
Anteroposterior somatotopy of innocuous cooling activation focus in human dorsal posterior insular cortex
Authors: Hua Le H. , Strigo Irina A. , Baxter Leslie C. , Johnson Sterling C. , Craig A. D. (Bud)
Published: April 2005

Prior data indicate that graded activation by innocuous thermal stimuli occurs in the dorsal posterior insular (dpIns) cortex of humans, rather than the parietal somatosensory regions traditionally thought necessary for discriminative somatic sensations. We hypothesized that if the dpIns subserves the haptic capacity of localization in addition to discrimination, then it should be somatotopically organized. Using functional magnetic resonance imaging to detect activation in the dpIns by graded cooling stimuli applied to the hand and neck, we found unimodal foci arranged in an anteroposterior somatotopographic pattern, consistent with participation of the dpIns in localization as well as discrimination. This gradient is orthogonal to the mediolateral somatotopy of parietal somatosensory regions, which supports the fundamental conceptual differentiation of the interoceptive somatic representation in the dpIns from the parietal exteroceptive representations. These data also support the suggestion that the poststroke central pain syndrome associated with lesions of the dpIns is a thermoregulatory dysfunction. Finally, another focus of strongly graded activation, which we interpret to represent thermoregulatory behavioral motivation elicited by dynamic cooling, was observed in the dorsal medial cortex.
LPS-activated complement, not LPS per se, triggers the early release of PGE2by Kupffer cells
Authors: Perlik Vit , Li Zhongua , Goorha Sarita , Ballou Leslie R. , Blatteis Clark M.
Published: April 2005

The intravenous injection of LPS rapidly evokes fever. We have hypothesized that its onset is mediated by prostaglandin (PG)E2quickly released by Kupffer cells (Kc). LPS, however, does not stimulate PGE2production by Kc as rapidly as it induces fever; but complement (C) activated by LPS could be the exciting agent. To test this hypothesis, we injected LPS (2 or 8 μg/kg) or cobra venom factor (CVF, an immediate activator of the C cascade that depletes its substrate, ultimately causing hypocomplementemia; 25 U/animal) into the portal vein of anesthetized guinea pigs and measured the appearance of PGE2, TNF-α, IL-1β, and IL-6 in the inferior vena cava (IVC) over the following 60 min. LPS (at both doses) and CVF induced similar rises in PGE2within the first 5 min after treatment; the rises in PGE2due to CVF returned to control in 15 min, whereas PGE2rises due to LPS increased further, then stabilized. LPS given 3 h after CVF to the same animals also elevated PGE2, but after a 30- to 45-min delay. CVF per se did not alter basal PGE2and cytokine levels and their responses to LPS. These in vivo effects were substantiated by the in vitro responses of primary Kc from guinea pigs to C (0.116 U/ml) and LPS (200 ng/ml). These results indicate that LPS-activated C rather than LPS itself triggers the early release of PGE2by Kc.
Activation of 5-HT1A receptors in the medullary raphe reduces cardiovascular changes elicited by acute psychological and inflammatory stresses in rabbits
Authors: Nalivaiko Eugene , Ootsuka Youichirou , Blessing William W.
Published: April 2005

The present strategy for the prevention of excessive sympathetic neural traffic to the heart relies on the use of beta-blockers, drugs that act at the heart end of the brain-heart axis. In the present study, we attempted to suppress cardiac sympathetic nerve activity by affecting the relevant cardiomotoneurons in the brain using the selective serotonin-1A (5-HT1A) receptor agonist 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT). In conscious, unrestrained rabbits, instrumented for recordings of heart rate, arterial pressure, or cardiac output, we provoked increases in cardiac sympathetic activity by psychological (loud sound, pinprick, and air jet) or inflammatory (0.5 μg/kg iv lipopolysaccharide) stresses. Pinprick and air-jet stresses elicited transient increases in heart rate (+50 ± 7 and +38 ± 4 beats/min, respectively) and in mean arterial pressure (+16 ± 2 and +15 ± 3 mmHg, respectively). Lipopolysaccharide injection caused sustained increases in heart rate (from 210 ± 3 to 268 ± 10 beats/min) and in arterial pressure (from 74 ± 3 to 92 ± 4 mmHg). Systemically administered 8-OH-DPAT (0.004–0.1 mg/kg) substantially attenuated these responses in a dose-dependent manner. Drug effects were prevented by a selective 5-HT1A receptor antagonist, WAY-100635 (0.1 mg/kg iv). Similarly to systemic administration, microinjection of 8-OH-DPAT (500 nl of 10 mM solution) into the medullary raphe-parapyramidal region caused antitachycardic effects during stressful stimulation and during lipopolysaccharide-elicited tachycardia. This is the first demonstration that activation of 5-HT1A receptors in the medullary raphe-parapyramidal area causes suppression of neurally mediated cardiovascular changes during acute psychological and immune stresses.
Impact of aging on muscle blood flow in chronic heart failure
Authors: Eklund Kevin E. , Hageman K. Sue , Poole David C. , Musch Timothy I.
Published: April 2005

Chronic heart failure (CHF) is manifested principally in the elderly population. Therefore, to understand the causes of exercise intolerance in CHF patients, it is imperative to resolve the effects of aging on muscle blood flow (BF) in CHF. To address this issue, we determined the muscle BF response to submaximal treadmill exercise (20 m/min, 5% grade) in young (YCHF: 6–8 mo, 412 ± 11 g, n = 11) and old (OCHF: 27–29 mo, 494 ± 10 g, n = 8) Fischer 344 × Brown Norway rats with similar degrees of myocardial infarction-induced left ventricular (LV) dysfunction [resting LV end-diastolic pressure: YCHF= 24 ± 2, OCHF= 22 ± 2 mmHg; derivative of LV pressure over time: YCHF= 5,168 ± 285; OCHF= 5,050 ± 165 mmHg/s; lung weight normalized to body weight: YCHF= 9.14 ± 0.72; OCHF= 8.21 ± 0.29 mg/g (all P > 0.05)]. The exercising heart rate response was blunted in OCHFcompared with YCHFrats (YCHF= 454 ± 8, OCHF= 395 ± 9 beats/min; P < 0.05). BF (radiolabeled microspheres) to the total hindlimb musculature and to each of the 28 individual muscles examined was similar between YCHFand OCHFrats under resting conditions. During exercise, BF to five of the hindlimb muscles that normally possess a majority of slow-twitch oxidative and fast-twitch oxidative glycolytic muscle fibers increased significantly less (−25 to −42%) for OCHFcompared with YCHFrats. In contrast, BF to 14 of the hindlimb muscles that normally possess a majority of fast-twitch glycolytic muscle fibers was increased (+22 to +337%) for OCHFvs. YCHFrats, which contributed to a greater mass-specific total hindlimb BF response in OCHFrats (YCHF= 78 ± 5, OCHF= 100 ± 11 ml·min−1·100 g−1; P < 0.05) and coincided with greater reductions in BF to the kidneys and splanchnic organs during exercise in OCHFvs. YCHF. In conclusion, there appears to be a profound age-related redistribution of BF from the highly oxidative to the highly glycolytic muscles of the hindlimb during exercise in OCHFcompared with YCHFrats. This phenomenon is qualitatively similar to that reported previously for healthy young and old rats.
The role of carbonic anhydrase in the recovery of skeletal muscle from anoxia
Authors: Wroblewski Krzysztof , Spalthoff Simon , Zimmerman Un-Jin , Post Robert L. , Sanger Joseph W. , Forster Robert E.
Published: April 2005

To investigate the role of carbonic anhydrase in the recovery of skeletal muscle from anoxia, pH and cell phosphates were measured by31P-nuclear magnetic resonance in superfused newborn rabbit myotubes and cultured mouse soleus cells (H-2Kb-ts a58) after ∼2–3.5 h without superfusion. In control studies, pH and phosphocreatine fell and Pirose during anoxia and recovered within <10 min after reperfusion began. A carbonic anhydrase inhibitor, acetazolamide, and dimethylamiloride, an inhibitor of the Na+/H+antiporter NHE1, delayed the recoveries of pH, phosphocreatine, and Pifor >10 min, but the rate of recovery, once initiated, was unchanged. In the presence of the inhibitors, after reperfusion started, the pH did not rise immediately, despite a large inwardly directed HCO3−gradient, suggesting that HCO3−movement was unimportant in acid elimination. Lactate, measured by its methyl protons, rose during anoxia and did not fall after 1 h of reperfusion and could not have eliminated protons by cotransport. We conclude that NHE1 is the major exporter of protons by skeletal muscle in recovery from a period of anoxia and that it is essential for functioning carbonic anhydrase to be attached to NHE1 to activate it. The mechanism of late recovery of pH could be the mobilization of another proton transporter or removal of the inhibition of the Na+/H+antiporter. Inhibition of carbonic anhydrase in skeletal muscle retards acid removal and modifies muscle metabolism significantly after anoxia.
Removal of Hepatitis C Virus by G-1 Beads in Sera from Patients with Chronic Hepatitis C
Authors: Moriyama Mitsuhiko , Kaneko Miki , Matsumura Hiroshi , Fukushima Akiko , Aoki Hiroshi , Tanaka Naohide , Kuroda Kazumichi , Shimizu Kazufumi , Hiraishi Katsuya , Arakawa Yasuyuki
Published: April 2005

Recently, a new method of extracorporeal granulocyte depletion apheresis has been developed to treat inflammatory systemic diseases using an Adacolumn (Japan Immunoresearch Laboratories, Takasaki, Japan) that is filled with acetate cellulose beads (G-1 beads) to adsorb the granulocytes. We examined whether hepatitis C virus (HCV) is adsorbed after incubation of the Adacolumn with the sera from patients with HCV-RNA-positive chronic hepatitis C. Patients and Methods: A total of 10 patients with chronic hepatitis C, whose levels of HCV RNA were greater than 800 kIU/ml were examined. The serum was incubated with 500 G-1 beads in a syringe at 37°C for 1 h. After removal of the serum, the beads were washed with RNase-free water. The G-1 beads were removed from the syringe after centrifugation. RNA was extracted from 200 µl of the wash waste and from 10, 50, 100 and 200 beads, respectively, using TRIZol regent. Detection of HCV RNA was performed using the nested PCR method. Results: HCV RNA was detected from as few as 10 G-1 beads. HCV RNA was not detected from waste fluid collected after the last wash from any of the patients. Further, HCV RNA was detected in the initial waste fluid after the 37°C incubation with serum in all of the patients. Since HCV RNA was detected on the G-1 beads, but not from the last washing solution in the current examination, these results suggest that the G-1 beads adsorbed HCV RNA. Conclusions: Our in vitro study confirmed that G-1 beads adsorbed HCV; therefore, apheresis using a column filled with G-1 beads may reduce the HCV RNA load in the blood of patients with chronic hepatitis C.
Molecular Characterization of Jurkat Cells Persistently Infected with Vaccinia Virus Mutant Vp811
Authors: Melana S.M. , Pogo B.G.T.
Published: April 2005

Previous reports from this laboratory demonstrated that persistent infections could be established in Jurkat cells with wild-type vaccinia virus (Jvac). The infected cells elicit increased expression of IL-2, IL-2Rα and IL-6 but not of IL-1β nor of interferon-γ. The persistently infected cells are also capable to transactivate the LTR gene of HIV-1 virus (HIV-1LTR). In addition, NFĸβ and NFAT are found activated in Jvac. To find out whether the gene(s) responsible for establishment, maintenance and molecular characteristics of persistently infected cells are located in the terminal ends of the molecule, Jurkat cells were infected with a deletion mutant Vp811 that lacks 32.7 and 14.9 kb at the left and right terminal, respectively. The results indicate that the deletion mutant is capable of establishing persistent infections. The persistently infected cells show a similar pattern of expression to that observed in Jvac cells. It is concluded that the viral gene(s) involved in persistence and molecular cellular changes is (are) present in the mutant.
Characterization of Nonpolio Enteroviruses Recovered from Patients with Aseptic Meningitis in Korea
Authors: Joo Chul Hyun , Ahn Jeonghyun , Seo Ilsun , Kim Yoo Kyum , Kim DongHou , Hong HeaNam , Lee Heuiran
Published: April 2005

Objectives: We attempted to characterize nonpolio enteroviruses recovered from Korean patients with aseptic meningitis. Methods: We performed RT-PCR on the 5′-nontranslated region using clinical specimens. Infectious clinical isolates were amplified by infecting Vero cells with RT-PCR-positive clinical specimens. We then investigated the direct effect in primary neuronal cells or cardiomyocytes following virus infection. Results: Total 12 clinical isolates were subtypically analyzed by both RT-PCR/sequencing comparison of the VP-1 region and neutralization assay. 43-2, 43-2S, 57 and 58 were found to be coxsackievirus B1 (CVB1), 312 to be CVB5, 14-2S and 327 to be echovirus 6, 165 to be echovirus 9, 337 to be echovirus 11, and 270 to be echovirus 30. All the clinical isolates tested showed profound cytotoxicity to various degrees in the primary neuronal cells within 24 h postinfection at 10 MOI. By contrast, a significant cytopathic effect was observed in the primary cardiomyocytes at 3–5 days postinfection at 50 MOI. Conclusions: The present study suggests that the clinical isolates recovered from Korean patients belonged to different CVB or echovirus serotypes and that these viruses showed diversities in their virulence in primary neuronal cells and cardiomyocytes.
Analysis of the 5’ End Structure of HCV Subgenomic RNA Replicated in a Huh7 Cell Line
Authors: Takahashi Hitoshi , Yamaji Masashi , Hosaka Masahiro , Kishine Hiroe , Hijikata Makoto , Shimotohno Kunitada
Published: April 2005

Objective: Recently, HCV subgenomic RNA that replicates in vitro in a certain cell line have been elucidated. Since the 5′ end of the genome of positive strand RNA viruses is often modified with a cap structure or a covalently linked protein, we have assessed structural feature of the HCV genome obtained from Huh7 cells in which HCV subgenomic RNA has been shown to efficiently self-replicate. Methods: HCV subgenomic RNA was obtained from the Huh7 and was analyzed for its 5′ end. Results: Phosphorylation of the genomic RNA by polynucleotide kinase was observed only after treatment with phosphatase. The labeling efficiency of the genome with polynucleotide kinase was not enhanced by treatment with pyrophosphatase. Conclusion: It is suggested that the 5′ end of HCV genomic RNA obtained from HCV replicon cells is not modified except phosphorylation. Furthermore, analysis of the 5′ end of the HCV RNA obtained from the HCV subgenome self-replicating cells revealed the presence of two types of subgenomic RNA that contained either guanylate or adenylate at the 5′ end. This result indicates that the 5′ end of the subgenome in Huh7 cells is redundant and there is no significant evolutionary advantage between the two genomes.
Suckling Mice Were Used to Detect Infectious Dengue-2 Viruses by Intracerebral Injection of the Full-Length RNA Transcript
Authors: Lee Ying-Ray , Huang Kao-Jean , Lei Huan-Yao , Chen Shun-Hua , Lin Yee-Shin , Yeh Trai-Ming , Liu Hsiao-Sheng
Published: April 2005

Objective: In this study we established a mouse brain injection system to detect infectious dengue-2 virus produced from the full-length RNA transcripts.Methods: In vitrotranscription was usedto synthesizefull-length dengue-2 virus RNA from the plasmid pRS424FLDEN2NGC, which was intracerebrally injected into the 6-day-old suckling mice (ICR strains). Engineered dengue-2 viruses were detected in the brain sections using immunohistochemistry staining. RT-PCR followed by restriction endonuclease BstEII digestion was used to confirm the mosquito C6/36 cells cocultured with the mouse brain extract. Results: The mice inoculated with the full-length dengue-2 viral RNA transcript showed paralysis symptoms and died between day 10 and 13 postinjection. The dengue-2 virus-specific antigens (E, Core and NS1) were detected in all the brain and part of the liver sections of the paralyzed mice by immunohistochemistry staining, indicating the existence of dengue-2 virus in these tissues of the suckling mice. The viruses detected in the brains of suckling mice were indeed infectious, which was further confirmed by coculturing mosquito C6/36 cells with the brain extract of the injected mice. Conclusions: Wedeveloped an in vivo approach to detect and produce engineered dengue viruses with infectivity from the full-length plasmid cDNA. This suckling mice system will also aid in screening the infectious viruses that are created by site-directed mutagenesis and is useful for the studies of dengue virus gene function and pathogenesis in the host.
Hepatitis B and C Virus Variants in Long-Term Immunosuppressed Renal Transplant Patients in Latvia
Authors: Sominskaya Irina , Mihailova Marija , Jansons Juris , Emelyanova Viktorija , Folkmane Inese , Smagris Eriks , Dumpis Uga , Rozentals Rafails , Pumpens Paul
Published: April 2005

The incidence of genome variants of hepatitis B and hepatitis C viruses among 38 long-term (2–15 years) immunosuppressed patients after renal transplantation and 10 patients undergoing dialysis was investigated. Twelve patients had only HBV infection, 9 had only HCV infection and 14 were co-infected. Regions corresponding to the HBV X/EnII/BCP, preC/C, preS/S and to the HCV core were sequenced for molecular characterization of the HBV and HCV genomes. Fifty-seven percent of HBV DNA isolates belonged to genotype D and 42% to genotype A, whereas 77% of HCV RNA isolates belonged to genotype 1b and only 17% to genotype 3a. One sample (6%) was of genotype 2c. Detailed analysis of the above-mentioned HBV genome regions revealed the presence of nucleotide point mutations, which, in some cases, resulted in amino acid substitutions. The clinical significance of such mutations is discussed.
Analysis of Human Cytomegalovirus UL144 Variability in Low-Passage Clinical Isolates in Japan
Authors: Murayama Tsugiya , Takegoshi Masataka , Tanuma Junichi , Eizuru Yoshito
Published: April 2005

To explore a possible role for viral genes as determinants of virulence, portions of the UL144 tumor necrosis factor-like receptor gene and the UL55 envelope glycoprotein B gene from 42 patients with congenital human cytomegalovirus (HCMV) infection or other diseases were sequenced. Of the 42 patients, 16 (38%) had UL144 group 1 [group 1A, 15 of 16 (94%); group 1B, 1 of 16 (6%); group 1C, 0 of 16 (0%)], 5 patients (12%) had UL144 group 2, and 21 patients (50%) had UL144 group 3. Although group 1C was not found in Japan strains (0%), it was found in USA strains (22%). Other HCMV polymorphisms should be further evaluated for their potential relevance to neonatal infection, and acquired immunodeficiency syndrome-associated HCMV diseases.
Optical Coherence Tomography Measurement of the Retinal Nerve Fiber Layer in Normal and Juvenile Glaucomatous Eyes
Authors: Mrugacz Malgorzata , Bakunowicz-Lazarczyk Alina
Published: April 2005

The aim of this study was to quantitatively assess and compare the thickness of the retinal nerve fiber layer (RNFL) in normal and glaucomatous eyes of children using the optical coherence tomograph. The mean RNFL thickness of normal eyes (n = 26) was compared with that of glaucomatous eyes (n = 26). The eyes were classified into diagnostic groups based on conventional ophthalmological physical examination, Humphrey 30-2 visual fields, stereoscopic optic nerve head photography, and optical coherence tomography. The mean RNFL was significantly thinner in glaucomatous eyes than in normal eyes: 95 ± 26.3 and 132 ± 24.5 µm, respectively. More specifically, the RNFL was significantly thinner in glaucomatous eyes than in normal eyes in the inferior quadrant: 87 ± 23.5 and 122 ± 24.2 µm, respectively. The mean and inferior quadrant RFNL thicknesses as measured by the optical coherence tomograph showed a statistically significant correlation with glaucoma. Optical coherence tomography may contribute to tracking of juvenile glaucoma progression.
Subepidermal Calcified Nodules
Authors: Carvounis Petros E. , Santi Mariarita , Stern Jere B. , Miller Marijean
Published: April 2005

Subepidermal calcified nodules (SCNs) are uncommon, benign lesions usually presenting in childhood which occasionally involve the eyelids. Only a handful of cases have been reported in the ophthalmologic literature. We present 2 cases, one in a 7-year-old Hispanic boy, the other in a 13-year-old African American boy, with eyelid lesions which were clinically thought to be possible juvenile xanthogranuloma, but which on histopathologic examination showed the characteristic features of SCNs.
Influenza Retinitis: Association with Influenza Encephalitis
Authors: Fukami Shin , Wakakura Masato , Inouye Jiro
Published: April 2005

Purpose: To report an unusual case of retinitis caused by influenza virus. Case: A 30-year-old male claimed partial color blindness after recovery from influenza encephalitis. Visual acuity was 0.3 in the right eye and 0.03 in the left. An ophthalmoscopic fundus examination looked normal, but fluorescein angiography revealed granular hyperfluorescence with multiple dark circular lesions at the posterior pole of both eyes. Serological testing revealed an influenza A virus infection. With corticosteroid pulse therapy (3 days) followed by oral methyl prednisolone for 1 month, visual acuity gradually recovered. Over the following 2-year period, visual acuity has recovered to 1.2 in both eyes, but color sensation still remains impaired. Conclusions: Influenza encephalitis can cause visual loss due to retinitis at the posterior pole.
Non-Hodgkin’s Lymphomas in Greece according to the WHO Classification of Lymphoid Neoplasms
Authors: Economopoulos T. , Papageorgiou S. , Dimopoulos M.A. , Pavlidis N. , Tsatalas C. , Symeonidis A. , Foudoulakis A. , Pectasides D. , Rontogianni D. , Rizos E. , Chalkia P. , Anagnostopoulos A. , Melachrinou M. , Papageorgiou E. , Fountzilas G.
Published: April 2005

The purpose of this retrospective study, the largest unselected series in our country, was to illustrate the clinicopathological features of non-Hodgkin’s lymphoma (NHL) classified according to the World Health Organization (WHO) classification of lymphoid neoplasms. A retrospective analysis was conducted and clinical features of histological subtypes were established in 810 patients (age ≧15 years) with NHL who were treated at 8 major centers representative of Greece. There were 435 males and 375 females 95% of them aged >30 years. B symptoms were present in 34% of the patients, while 45.3% had stages I–II and 54.6% had stages III–IV. LDH was increased in 37% of the patients. B cell lymphomas formed 88% of the cases whereas T cell lymphomas formed 12% of the total. Indolent lymphomas accounted for 31.1%, aggressive ones for 66.7% and very aggressive ones for 2.4% of all NHLs. Among indolent lymphomas extranodal ones (MALT B cell lymphoma) were the most common subset while follicular lymphoma grade I and II and small lymphocytic ones presented with equal frequency. Among the aggressive lymphomas diffuse large cell lymphoma (DLCL) was the most common subtype; this entity along with large-cell immunoblastic lymphomas accounted for 45.2% of all B cell lymphomas. Among the T cell lymphomas, peripheral T cell lymphomas and anaplastic large cell lymphomas of the T/null-cell type were the most common subtypes. The most common extranodal presentation was the gastrointestinal tract (GI). Next in frequency were primary extranodal NHL of the head and neck region. MALT B cell lymphomas were found in almost half of the patients with GI tract NHL, whereas in all other extranodal places DLCL was the predominant histological subtype. The median survival for indolent and aggressive NHL was 123.5 and 55.5 months, respectively. This is the first report of a large series of malignant lymphomas in Greece using the WHO classification. It appears that there are no significant differences between NHL in Greece and other large series as far as clinical and extranodal presentation is concerned. The frequency of follicular lymphoma in the current study is comparable to that reported from Asian countries and mainland Europe, but lower than that of US and Northern European series. There were no important differences in the incidence of the remaining histological subtypes between Greece and other European countries.
Haemopoietic Cell Transplantation of Patients with a History of Deep or Invasive Fungal Infection during Prophylaxis with Liposomal Amphotericin B
Authors: Krüger William H. , Rüssmann Bettina , de Wit Maike , Kröger Nicolaus , Renges Helmut , Sobottka Ingo , Zander Axel R.
Published: April 2005

Relapse of a preceding fungal infection is a considerable risk during haemopoietic stem cell transplantation. The optimal secondary prophylaxis has not been found so far since the application of standard drugs is hampered by potential ineffectiveness or intolerable side effects. This investigation describes haemopoietic cell transplantation of patients with a history of invasive or systemic fungal infection (IFI). The strategy was either administration of liposomal amphotericin B as secondary prophylaxis or an early switch to liposomal amphotericin B after administration of azoles. The 43 patients had a history of proven (n = 14), probable (n = 14) and possible (n = 15) IFI. Twenty-eight patients (65%) could be discharged from the BMT ward without signs of mycosis. Transplant-related mortality was 35%. Overall, 12 fungus-related (IFI) deaths (28%) occurred. The percentage of fungus-related deaths was highest in the ‘proven’ group with 43% compared to 20 and 21% in the two other groups. Side effects of liposomal amphotericin B were low. A discontinuation of the drug was not necessary in any patient. Serum creatinine showed a slight increase to 128% (median) of the baseline allowing continuous administration of concomitant nephrotoxic drugs such as cyclosporin A. In conclusion, secondary prophylaxis with or early switch to liposomal amphotericin B facilitates allogeneic stem cell transplantation of patients with a history of IFI with minor side effects. However, fungal infections and transplant-related mortality remain major problems in this often heavily pretreated subgroup of patients.
Absence of Gene Mutation in TRAIL Receptor 1 (TRAIL-R1) and TRAIL Receptor 2 (TRAIL-R2) in Chronic Myelogenous Leukemia and Myelodysplastic Syndrome, and Analysis of mRNA Expressions of TRAIL and TRAIL-Related Genes in Chronic Myelogenous Leukemia
Authors: Liu Li-Gen , Tanaka Hideo , Ito Kinro , Ito Takuo , Sultana Tanvira A. , Kyo Taiichi , Kimura Akiro
Published: April 2005

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an interferon (IFN)-induced molecule with apoptotic activity. We examined gene mutations in the death domains of TRAIL receptor 1 (TRAIL-R1) and TRAIL receptor 2 (TRAIL-R2), and in the TRAIL gene promoter in 46 chronic myelogenous leukemia (CML) patients. In 23 of the 46 patients, all the coding regions of TRAIL-R2 were also examined. However, no mutation or loss of heterozygosity was found. Furthermore, no mutation in the death domains of TRAIL-R1 and TRAIL-R2 genes, which causes amino acid change, was found in 18 myelodysplastic syndrome (MDS) patients. Ribonuclease protection assay (RPA) and real-time quantitative polymerase chain reaction using polymorphonuclear neutrophils of five new CML patients showed that the TRAIL mRNA expression was very low before in vitro IFN-α stimulation and markedly upregulated after IFN-α stimulation. FAS mRNA was also upregulated with IFN-α stimulation but the fold induction was far lower than that of TRAIL mRNA. In addition, RPA revealed that the ratio of (TRAIL-R1 plus TRAIL-R2) to TRAIL-R3 was also increased after IFN-α stimulation. Taken together, gene mutations of TRAIL-R1, TRAIL-R2 are infrequent in patients with CML and MDS. Andso is the TRAIL promoter for CML. These mutations seem unrelated to tumorigenesis, disease progression, and response to IFN-α therapy in CML. A markedly high induction of TRAIL mRNA by IFN-α may have some relevance to IFN-α action in CML patients.
CD20-Negative Pyothorax-Associated B Cell Lymphoma
Authors: Fukuno Kenji , Tsurumi Hisashi , Kanemura Nobuhiro , Nishio Masaru , Tanabashi Shinobu , Okamoto Kiyonao , Moriwaki Hisataka
Published: April 2005

We describe an 86-year-old male who developed CD20-negative pyothorax-associated B cell lymphoma 64 years after he had suffered from tuberculous pleuritis. Therapy with 8 courses of THP-COP at 2-week intervals was followed by involved-field radiotherapy of 30 Gy. Uncertain complete remission was achieved. Thereafter, local recurrence of pyothorax-associated lymphoma (PAL) at the primary site was seen. The patient received salvage radiotherapy of 50 Gy. The patient died of pneumonia during a second uncertain complete remission. The progression-free survival and overall survival of this patient were 10 and 15 months, respectively. When compared with the median survival of 9 months reported in the literature, the adverse effect of CD20 negativity on prognosis may not apply to PAL patients with an occasional aberrant phenotype.
Pathogenesis of Pre-Neoplastic Lesions of the Stomach: Targets for Prevention
Authors: Leung Wai K. , Sung Joseph J.Y.
Published: April 2005

Gastric atrophy and intestinal metaplasia are generally considered to be precancerous lesions of the stomach. Chronic Helicobacter pylori infection is one the most important factors in the development of these pre-malignant gastric lesions. In addition to bacterial factors, polymorphisms in the cytokine genes of the host that modulate inflammatory responses are found to have a synergistic effect in the development of gastric cancer as well as pre-neoplastic lesions. Recently, inappropriate activation of the intestine-specific transcription factor like the homeobox gene complex CDX1 and CDX2 are found to be an important contributing factor in the induction of intestinal metaplasia in the stomach. Aberrant expression of cyclooxygenase-2 and epigenetic changes are also frequently detected in pre-neoplastic gastric lesions. One of the most important questions relating to these pre-neoplastic gastric lesions is that whether H. pylori eradication could reverse these changes. However, most controlled studies showed no or just modest improvement in intestinal metaplasia after H. pylori eradication. Further studies should evaluate the role of other chemopreventive agents, particularly cyclooxygenase-2 inhibitor, on regression of pre-neoplastic lesions.
Prevention of Gastric Cancer by Helicobacter pylori Eradication
Authors: Leodolter A. , Naumann M. , Malfertheiner P.
Published: April 2005

The evidence supporting the important role of Helicobacter pylori causing gastric cancer is getting stronger. The mechanisms by which H. pylori can influence the progression to severe changes in the gastric mucosa are under investigation. An increased gastric epithelial cell proliferation has been observed in individuals infected with H. pylori. This lifelong increased cell turnover is deemed to be a major risk factor for increased mutational changes and may lead to the development of gastric cancer. Successful eradication of H. pylori infection induces the healing of the gastritis and a significant decrease in gastric epithelial cell proliferation. Nevertheless, it is right now unknown at which time the point of no return, meaning at which time an eradication therapy leads to a benefit for the individual to prevent gastric cancer, has been reached. Therefore the major question that arises is to whom an eradication therapy should be offered to prevent gastric cancer. A general elimination of the infection might be worthwhile, but seems to be unrealistic now because of the high prevalence of the infection and the missing of a vaccine. This review reflects possible mechanisms of gastric cancer development induced by chronic H. pylori infection and recent investigational trials for prevention of gastric cancer by H. pylori eradication therapy will be discussed.