bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Alpha/Beta Interferon in Venezuelan Equine Encephalitis Virus Pathogenesis: Effect of an Attenuating Mutation in the 5′ Untranslated Region
Authors: White Laura J. , Wang Jia-Gang , Davis Nancy L. , Johnston Robert E. 
Published: July 2002

ABSTRACT

Venezuelan equine encephalitis virus (VEE) is an important equine and human pathogen of the Americas. In the adult mouse model, cDNA-derived, virulent V3000 inoculated subcutaneously (s.c.) causes high-titer peripheral replication followed by neuroinvasion and lethal encephalitis. A single change (G to A) at nucleotide 3 (nt 3) of the 5′ untranslated region (UTR) of the V3000 genome resulted in a virus (V3043) that was avirulent in mice. The mechanism of attenuation by the V3043 mutation was studied in vivo and in vitro. Kinetic studies of virus spread in adult mice following s.c. inoculation showed that V3043 replication was reduced in peripheral organs compared to that of V3000, titers in serum also were lower, and V3043 was cleared more rapidly from the periphery than V3000. Because clearance of V3043 from serum began 1 to 2 days prior to clearance of V3000, we examined the involvement of alpha/beta interferon (IFN-α/β) activity in VEE pathogenesis. In IFN-α/βR
−/−
mice, the course of the wild-type disease was extremely rapid, with all animals dying within 48 h (average survival time of 30 h compared to 7.7 days in the wild-type mice). The mutant V3043 was as virulent as the wild type (100% mortality, average survival time of 30 h). Virus titers in serum, peripheral organs, and the brain were similar in V3000- and V3043-infected IFN-α/βR
−/−
mice at all time points up until the death of the animals. Consistent with the in vivo data, the mutant virus exhibited reduced growth in vitro in several cell types except in cells that lacked a functional IFN-α/β pathway. In cells derived from IFN-α/βR
−/−
mice, the mutant virus showed no growth disadvantage compared to the wild-type virus, suggesting that IFN-α/β plays a major role in the attenuation of V3043 compared to V3000. There were no differences in the induction of IFN-α/β between V3000 and V3043, but the mutant virus was more sensitive than V3000 to the antiviral actions of IFN-α/β in two separate in vitro assays, suggesting that the increased sensitivity to IFN-α/β plays a major role in the in vivo attenuation of V3043.
Cytokine-Sensitive Replication of Hepatitis B Virus in Immortalized Mouse Hepatocyte Cultures
Authors: Pasquetto Valérie , Wieland Stefan F. , Uprichard Susan L. , Tripodi Marco , Chisari Francis V. 
Published: July 2002

ABSTRACTWe have previously shown that alpha/beta interferon (IFN-α/β) and gamma interferon (IFN-γ) inhibit hepatitis B virus (HBV) replication by eliminating pregenomic RNA containing viral capsids from the hepatocyte. We have also shown that HBV-specific cytotoxic T lymphocytes that induce IFN-γ and tumor necrosis factor alpha (TNF-α) in the liver can inhibit HBV gene expression by destabilizing preformed viral mRNA. In order to further study the antiviral activity of IFN-α/β, IFN-γ, and TNF-α at the molecular level, we sought to reproduce these observations in an in vitro system. Accordingly, hepatocytes were derived from the livers of HBV-transgenic mice that also expressed the constitutively active cytoplasmic domain of the human hepatocyte growth factor receptor (c-Met). Here, we show that the resultant well-differentiated, continuous hepatocyte cell lines (HBV-Met) replicate HBV and that viral replication in these cells is efficiently controlled by IFN-α/β or IFN-γ, which eliminate pregenomic RNA-containing capsids from the cells as they do in the liver. Furthermore, we demonstrate that IFN-γ, but not IFN-α/β, is capable of inhibiting HBV gene expression in this system, especially when it acts synergistically with TNF-α. These cells should facilitate the analysis of the intracellular signaling pathways and effector mechanisms responsible for these antiviral effects.
Ionic Strength- and Temperature-Induced K
Ca
Shifts in the Uncoating Reaction of Rotavirus Strains RF and SA11: Correlation with Membrane Permeabilization
Authors: Martin Sandra , Lorrot Mathie , El Azher Mounia Alaoui , Vasseur Monique 
Published: July 2002

ABSTRACT

The hydrodynamic diameters of native rotavirus particles, bovine RF and simian SA11 strains, were determined by quasielastic light scattering. By using this method and agarose gel electrophoresis, the Ca
2+
dissociation constant, K
Ca
, governing the transition from triple-layer particles (TLPs) to double-layer particles (DLPs), was shown to increase, at constant pH, as the temperature and/or the ionic strength of the incubation medium increased. We report the novel observation that, under physiological conditions, K
Ca
values for both RF and SA11 rotaviruses were well above the intracytoplasmic Ca
2+
concentrations of various cells, which may explain why TLP uncoating takes place within vesicles (possibly endosomes) during the entry process. A correlation between TLP uncoating and cell membrane permeabilization was found, as shown by the release of carboxyfluorescein (CF) from CF-loaded intestinal brush-border membrane vesicles. Conditions stabilizing the virion in the TLP form inhibited CF release, whereas conditions favoring the TLP-to-DLP transformation activated this process. We conclude that membrane permeabilization must be preceded by the loss of the outer-capsid proteins from trypsinized TLP and that physiological ionic strength is required for permeabilization to take place. Finally, the paper develops an alternative explanation for the mechanism of rotavirus entry, compatible with the Ca
2+
-dependent endocytic pathway. We propose that there must be an iterative process involving tight coupling in time between the lowering of endosomal Ca
2+
concentration, virion decapsidation, and membrane permeabilization, which would cause the transcriptionally active DLPs to enter the cytoplasm of cells.
The Solitary Long Terminal Repeats of ERV-9 Endogenous Retrovirus Are Conserved during Primate Evolution and Possess Enhancer Activities in Embryonic and Hematopoietic Cells
Authors: Ling Jianhua , Pi Wenhu , Bollag Roni , Zeng Shan , Keskintepe Meral , Saliman Hatem , Krantz Sanford , Whitney Barry , Tuan Dorothy 
Published: July 2002

ABSTRACT
The solitary long terminal repeats (LTRs) of ERV-9 endogenous retrovirus contain the U3, R, and U5 regions but no internal viral genes. They are middle repetitive DNAs present at 2,000 to 4,000 copies in primate genomes. Sequence analyses of the 5" boundary area of the erythroid β-globin locus control region (β-LCR) and the intron of the embryonic axin gene show that a solitary ERV-9 LTR has been stably integrated in the respective loci for at least 15 million years in the higher primates from orangutan to human. Functional studies utilizing the green fluorescent protein (GFP) gene as the reporter in transfection experiments show that the U3 region of the LTRs possesses strong enhancer activity in embryonic cells of widely different tissue origins and in adult cells of blood lineages. In both the genomic LTRs of embryonic placental cells and erythroid K562 cells and transfected LTRs of recombinant GFP plasmids in K562 cells, the U3 enhancer activates synthesis of RNAs that are initiated from a specific site 25 bases downstream of the AATAAA (TATA) motif in the U3 promoter. A second AATAAA motif in the R region does not serve as the TATA box or as the polyadenylation signal. The LTR-initiated RNAs extend through the R and U5 regions into the downstream genomic DNA. The results suggest that the ERV-9 LTR-initiated transcription process may modulate transcription of the associated gene loci in embryonic and hematopoietic cells.
The Distribution Coefficients of Bis(2-chloroethyl) Sulfide Between Some Organic Solvents and Water
Authors: Lukovic Zoran T. , Jovanovic Bratislav Ž. , Skala Dejan U. 
Published: July 2002

The results of determining the distribution coefficients of bis(2-chloroethyl) sulfide between some organic solvents and water at 25 °C are presented in this paper. Two original methods for determining the distribution coefficients were applied: the kinetic method and the method of hydrolysis blocking. Values of the obtained distribution coefficients are discussed from the aspect of the calculated solubility parameters. The denoted methods can also be applied in a similar fashion to determine the distribution coefficients of other substances of similar properties.
X-Ray Structural Study of Terguride SolvatesTerguride Methanol Solvate
Authors: Kratochvíl Bohumil , Novotný Jiří , Hušák Michal , Had Jiří , Stuchlík Josef , Jegorov Alexandr 
Published: July 2002

The structure of the unstable solvate of the semisynthetic ergot derivate terguride methanol solvate C20H28N4O .CH3OH, was solved by direct methods and refined to an R value of 0.093 for 1 462 unique observed reflections. The title alkaloid crystallizes in the orthorhombic space group P212121 with lattice parameters a = 10.438(1), b = 13.200(4), c = 15.495(5) Å, V = 2 134.8(9) Å3, Z = 4. An indole moiety of the terguride molecule is almost perfect planar, ring C has an E6 envelope conformation and ring D adopts a 1C4 chair shape. As found from X-ray powder diffraction study, terguride methanol solvate completely transforms to terguride monohydrate in air during several hours.
Decreasing landing forces: effect of instruction
Authors: McNair Peter J , Prapavessis Harry , Callender Karen 
Published: July 2002

Objective—To examine the effects of instructions related to joint kinematics, auditory stimuli, and imagery on lowering the vertical ground reaction forces associated with landing from a jump.Study Design—Randomised controlled trial.Setting—A laboratory in an educational institution.Subjects—Eighty asymptomatic subjects (27 men) with a mean age of 24 years.Intervention—Subjects were randomly assigned to the following groups: (1) instruction (limb position instructions); (2) auditory cue (listen to impact sounds); (3) imagery (metaphorical); (4) control. Subjects were required to jump from a box 300 mm in height and land on a force plate. Measures of the ground reaction force were recorded before and after the intervention.Main Outcome Measure—The peak vertical ground reaction force recorded at footstrike.Results—The peak vertical ground reaction forces in the technical instruction and auditory groups were significantly less than those of the control group. There was no significant difference between the auditory and technical instruction groups. There was no significant difference between the imagery and control groups.Conclusions—When an aim of a rehabilitation programme is to minimise forces on the lower limb during landing type activities, the findings support the use of instructions related to kinematics as well as instructions that draw the patient's attention to the sound at impact.
Tai chi: physiological characteristics and beneficial effects on health
Authors: Li J X , Hong Y , Chan K M 
Published: July 2002

Objectives—To assess the characteristic effects of Tai Chi Chuan (TCC) exercise on metabolism and cardiorespiratory response, and to measure its effect on cardiorespiratory function, mental control, immune capacity, and the prevention of falls in elderly people.Design—A review of controlled experimental studies and clinical trials designed with one of two aims: either to assess physiological responses during the performance of TCC or to assess the impact of this exercise on general health and fitness.Main outcome measures—Metabolic rate, heart rate, blood pressure, ventilation, maximal oxygen uptake (V̇o2max), immune capacity, falls, and fall related factors.Subjects—A total of 2216 men and women.Results—Under review were 31 original studies, published in Chinese or English journals, that met the criteria for inclusion. Most of the papers written in Chinese had not been introduced into the Western literature. Nine of these studies showed that TCC can be classified as moderate exercise, as its does not demand more than 55% of maximal oxygen intake. When this form of exercise and others conducted at equal intensity were compared, TCC showed a significantly lower ventilatory equivalent (V̇e/V̇o2max). Evidence provided by cross sectional and longitudinal studies suggests that TCC exercise has beneficial effects on cardiorespiratory and musculoskeletal function, posture control capacity, and the reduction of falls experienced by the elderly.Conclusions—TCC is a moderate intensity exercise that is beneficial to cardiorespiratory function, immune capacity, mental control, flexibility, and balance control; it improves muscle strength and reduces the risk of falls in the elderly.
Dependence of the maximal lactate steady state on the motor pattern of exercise
Authors: Beneke R , Leithäuser R M , Hütler M 
Published: July 2002

Background—Blood lactate concentration (BLC) can be used to monitor relative exercise intensity. The highest BLC representing an equilibrium between lactate production and elimination is termed maximal lactate steady state (MLSS). MLSS is used to discriminate qualitatively between continuous exercise, which is limited by stored energy, from other types of exercise terminated because of disturbance of cellular homoeostasis.Aim—To investigate the hypothesis that MLSS intraindividually depends on the mode of exercise.Methods—Six junior male rowers (16.5 (1.4) years, 181.7 (3.1) cm, 69.8 (3.3) kg) performed incremental and constant load tests on rowing and cycle ergometers. Measurements included BLC, sampled from the hyperaemic ear flap, heart rate, and oxygen uptake. MLSS was defined as the highest BLC that increased by no more than 1.0 mmol/l during the final 20 minutes of constant workload.Results—In all subjects, MLSS was lower (p≤0.05) during rowing (2.7 (0.6) mmol/l) than during cycling (4.5 (1.0) mmol/l). No differences between rowing and cycling were found with respect to MLSS heart rate (169.2 (9.3)v172.3 (6.7) beats/min), MLSS workload (178.7 (29.8)v205.0 (20.7) W), MLSS intensity expressed as a percentage (63.3 (6.6)%v68.6 (3.8)%) of peak workload (280.8 (15.9)v299.2 (28.4) W) or percentage (76.4 (3.4)%v75.1 (3.0)%) of peak oxygen uptake (60.4 (3.4)v57.2 (8.6) ml/kg/min).Conclusions—In rowing and cycling, the MLSS but not MLSS workload and MLSS intensity intraindividually depends on the motor pattern of exercise. MLSS seems to decrease with increasing mass of the primarily engaged muscle. This indicates that task specific levels of MLSS occur at distinct levels of power output per unit of primarily engaged muscle mass.
Lactic acidosis, potassium, and the heart rate deflection point in professional road cyclists
Authors: Lucía A , Hoyos J , Santalla A , Pérez M , Carvajal A , Chicharro J L 
Published: July 2002

Objective: To determine the influence of lactic acidosis, the Bohr effect, and exercise induced hyperkalaemia on the occurrence of the heart rate deflection point (HRDP) in elite (professional) cyclists.Methods: Sixteen professional male road cyclists (mean (SD) age 26 (1) years) performed a ramp test on a cycle ergometer (workload increases of 5 W/12 s, averaging 25 W/min). Heart rate (HR), gas exchange parameters, and blood variables (lactate, pH, P50of the oxyhaemoglobin dissociation curve, and K+) were measured during the tests.Results: A HRDP was shown in 56% of subjects at about 88% of their maximal HR (HRDP group; n = 9) but was linear in the rest (No-HRDP group; n = 7). In the HRDP group, the slope of the HR-workload regression line above the HRDP correlated inversely with levels of K+at the maximal power output (r= −0.67; p<0.05).Conclusions: The HRDP phenomenon is associated, at least partly, with exercise induced hyperkalaemia.
Background electroencephalographic (EEG) activities of very preterm infants born at less than 27 weeks gestation: a study on the degree of continuity
Authors: Hayakawa M , Okumura A , Hayakawa F , Watanabe K , Ohshiro M , Kato Y , Takahashi R , Tauchi N 
Published: July 2002

AIMSTo clarify the features of the background electroencephalographic (EEG) activities in clinically well preterm infants born at less than 27 weeks gestation and to outline their chronological changes with increasing postconceptional age (PCA).METHODSEEGs of clinically well premature infants born at less than 27 weeks gestation were recorded during the early postnatal period. The infants were separated into three groups according to their PCA at the time of EEG recording (21–22 weeks PCA, 23–24 weeks PCA, and 25–26 weeks PCA). The mean and maximum duration of interburst intervals (IBIs), the mean duration of bursts, and the percentage of continuous and discontinuous patterns in each PCA group were evaluated.RESULTSThere were three infants at 21–22 weeks PCA, seven at 23–24 weeks PCA, and five at 25–26 weeks PCA. Eighteen EEG recordings were obtained. The mean and maximum IBI duration decreased with increasing PCA. The percentage of continuous patterns increased with increasing PCA. Conversely, the percentage of discontinuous patterns decreased with increasing PCA.CONCLUSIONSIn premature infants born at less than 27 weeks gestation, the characteristics of the background EEG activities were similar to those of older premature infants. These changes reflect the development of the central nervous system in this period.Key messagesAt less than 27 weeks gestational age, the characteristics of background EEG activities were found to be as follows:the mean and maximum IBI duration decreased with increasing PCAthe percentage of continuous patterns increased with increasing PCAthe percentage of discontinuous patterns increased with increasing PCAthe mean burst duration during discontinuous patterns increased as PCA increased
Erythropoietin acts as a trophic factor in neonatal rat intestine
Authors: Juul S E , Ledbetter D J , Joyce A E , Dame C , Christensen R D , Zhao Y , DeMarco V 
Published: July 2002

BACKGROUNDErythropoietin (Epo) receptors are present on enterocytes of fetal and neonatal small bowel but the role of Epo in the bowel is not known.AIMSWe tested the following hypotheses: (1) enterally dosed Epo is absorbed from the intestines of neonatal rats, (2) Epo acts as a trophic factor in developing small bowel, and (3) the trophic effects of Epo are dependant on the route of administration.METHODSThe dose dependant effects of enterally dosed recombinant human erythropoietin (rEpo 0–1000 U/kg/day) were studied in artificially raised rat pups and compared with dam raised controls and dam raised pups given rEpo in rat milk. After one week, reticulocyte counts, haematocrits, and plasma Epo concentrations were measured, and calibrated morphometric measurements of villi were performed. The effects of route of rEpo administration (enteral v parenteral) on erythropoiesis, bowel growth, and disaccharidase activity were studied in nursing pups treated for one and two weeks.RESULTSSerum Epo concentrations ranged from undetectable (<0.6 mU/ml) to 8.4 mU/ml in control and enterally dosed pups (median 1.8 mU/ml), and from 4.9 to 82.3 mU/ml (median 20.4 mU/ml) in parenterally dosed animals. No increase in haematocrit or reticulocyte count was noted in enterally treated pups compared with controls after up to two weeks of treatment. Small bowel length was greater in rEpo treated pups, and a dose dependent increase in villus surface area which was independent of the route of dosing and associated with increased BrdU uptake was found.CONCLUSIONSrEpo is not enterally absorbed in an intact and functional form from the intestines of neonatal rat pups. Thus enterally dosed rEpo has no erythropoietic effects. However, rEpo acts as a trophic factor in developing rat small bowel whether given enterally or parenterally.
Doctors' and nurses' attitudes towards and experiences of voluntary euthanasia: survey of members of the Japanese Association of Palliative Medicine
Authors: Asai Atsushi , Ohnishi Motoki , Nagata Shizuko K , Tanida Noritoshi , Yamazaki Yasuji 
Published: July 2002

Objective—To demonstrate Japanese doctors' and nurses' attitudes towards and practices of voluntary euthanasia (VE) and to compare their attitudes and practices in this regard.Design—Postal survey, conducted between October and December 1999, using a self-administered questionnaire.Participants—All doctor members and nurse members of the Japanese Association of Palliative Medicine.Main outcome measure—Doctors' and nurses' attitude towards and practices of VE.Results—We received 366 completed questionnaires from 642 doctors surveyed (response rate, 58%) and 145 from 217 nurses surveyed (68%). A total of 54% (95% confidence interval (CI): 49-59) of the responding doctors and 53% (CI: 45-61) of the responding nurses had been asked by patients to hasten death, of whom 5% (CI: 2-8) of the former and none of the latter had taken active steps to bring about death. Although 88% (CI: 83-92) of the doctors and 85% (CI: 77-93) of the nurses answered that a patient's request to hasten death can sometimes be rational, only 33% (CI: 28-38) and 23% (CI: 16-30) respectively regarded VE as ethically right and 22% (CI: 18-36) and 15% (CI: 8-20) respectively would practise VE if it were legal. Logistic regression model analysis showed that the respondents' profession was not a statistically independent factor predicting his or her response to any question regarding attitudes towards VE.Conclusions—A minority of responding doctors and nurses thought VE was ethically or legally acceptable. There seems no significant difference in attitudes towards VE between the doctors and nurses. However, only doctors had practised VE.
The relationship between the arts and medicine
Authors: Scott P Anne 
Published: July 2002

In this paper some of the intriguing links between the arts and medicine are explored. As a starting point I consider the notion of whole person understanding as articulated by Downie in an article entitled “Literature and medicine”, published in the Journal of Medical Ethics in 1991.1I suggest that the arts can contribute to whole person understanding in at least three ways. The arts may stimulate: (a) insight into common patterns of response (shared human experiences); (b) insight into individual difference or uniqueness, and (c) enrichment of the language and thought of the practitioner.Much literature which explores the relationship between the arts and medicine tends to focus on the value of the arts in increasing our understanding of the particular individual, “whole person understanding” in Downie's sense of the word. This, however, assumes that “whole person understanding” should focus only on the unique in the individual. This view is, I think, mistaken. If we take the notion of “whole person” seriously then we must recognise that which is unique but also that which humans may share. I suggest that this broader view is of the greatest importance in any consideration of the relationship between the arts and medicine.