bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of transition from cognitive impairment to senile dementia: a prospective, longitudinal study
Authors: Artero S. , Tierney M. C. , Touchon J. , Ritchie K. 
Published: May 2003

Objective: The purpose of this investigation was to replicate the statistical approach used in a previous investigation (Toronto study) within a French population to determine the best predictive model for Alzheimer's disease (AD).Method: Data from neuropsychological tests from two prospective studies were entered into a regression model.Results: Replication of the statistical approach in the Montpellier sample produced a three‐test model with a specificity of 99% and sensitivity of 73%. This model consisted of a delayed auditory verbal recall test, a construction test, a category fluency test and provides probability estimates for the transition to dementia in individual cases.Conclusion: The models derived from these two longitudinal studies provide an empirical basis for the selection of tests for the definition of mild cognitive impairment of the Alzheimer type (MCI‐A). The small set of tests derived are suitable for use in general practice.
The effect of melatonin administration on pituitary hormone secretion in man
Authors: Forsling Mary L. , Wheeler M. J. , Williams A. J. 
Published: May 2003

OBJECTIVEEvidence is accumulating that the nocturnal increase in melatonin may influence pituitary hormone secretion. The aim of this study was to determine the effect of exogenous melatonin, in concencetrations spanning the physiological range, on the release of pituitary hormones in man during daylight hoursDESIGNA double blind, randomized, crossover study.SUBJECTSEight healthy male volunteers with a mean age of 21 ± 0.5 years were studied on four occasions, observations being made after the adminstration of melatonin in doses of 0.05, 0.5 or 5.0 mg or placebo. They refrained from taking heavy exercise, alcohol and from smoking for 24 h prior to the study.MEASUREMENTSSerum cortisol, growth hormone, prolactin and plasma oxytocin, vasopressin, sodium, osmolality and packed cell volume were measured in samples taken at 30 minutes intervals for 150 minutes after the administration of melatonin.RESULTSMelatonin produced dose‐dependent changes in circulating concentrations of oxytocin and vasopressin, the 0.5 mg dose being stimulatory, while 5.0 mg was inhibitory. These two doses stimulated growth hormone release, while there was no significant effect on prolactin or cortisol release.CONCLUSIONSThese results confirm that the nocturnal increase in melatonin could contribute to the patterns of oxytocin, vasopressin and growth hormone release seen over 24 h.
ACTH and cortisol release following intravenous desmopressin: a dose–response study
Authors: Scott Lucinda V. , Medbak Sami , Dinan Timothy G. 
Published: May 2003

OBJECTIVEDesmopressin (DDAVP) is a synthetic analogue of AVP, the companion regulator of corticotrophin‐releasing hormone (CRH) in the control of ACTH synthesis and release from the pituitary corticotrophs. The body of evidence from human studies suggests that DDAVP alone, unlike AVP, does not bring about ACTH release, although recent evidence suggests idiosyncracies of response in healthy subjects. We examined whether DDAVP exerted any consistent effect on ACTH and cortisol release, and also if this occurred in a dose‐dependant manner.DESIGN AND SUBJECTSA total of 18 subjects participated in the study. Saline, 5 μg, 10 μg and 15 μg DDAVP were administered as an intravenous bolus at 1300 h; 5, 7, 18 and 8 subjects, respectively, participated in each arm of the study. Plasma ACTH and cortisol responses were measured over a 120‐minutes period.RESULTSSignificant between group comparisons were demonstrated for both ACTH (P < 0.05) and cortisol responses (P < 0.005) measured as maximum increment from baseline. The ACTH response to 5, 10 and 15 μg DDAVP was significantly greater than saline at all three doses, whilst maximal responses were seen at 10 μg. The cortisol responses to 10 and 15 μg DDAVP doses, but not 5 μg, were significantly greater than following saline. 11/18 subjects were deemed ‘responders’ following 10μg DDAVP on the basis of both ACTH and cortisol output.CONCLUSIONSThis data suggests that DDAVP is capable of stimulating ACTH and cortisol release when administered alone as a bolus in over 50% of healthy subjects. This is in contrast to much of the extant literature. The mode of administration may be pertinent to this effect. This finding has implications for the recent focus on DDAVP as a diagnostic tool in disorders such as Cushing's Disease.
A new system for laser‐UVA‐microirradiation of living cells
Authors: Walter J. , Cremer T. , Miyagawa K. , Tashiro S. 
Published: May 2003

SummaryLocal nuclear irradiation of living cells has been used to gain insight into the dynamic changes that cell nuclei undergo in response to DNA damage. In particular, the effects of DNA double‐strand breaks (DSBs), a major threat to the genomic integrity of cells, have been studied by local nuclear irradiation with ionizing radiation. This method has the disadvantage that it requires expensive equipment to generate a sufficiently high density of focused or collimated ionizing radiation. After appropriate sensitization of the cellular DNA, nuclear microirradiation with UVA can also produce DSBs. In this communication we present a semi‐automatic system for laser‐UVA‐microirradiation based on a commercial laser scanning microscope. The system allows the convenient selection and precise irradiation of living cells, and could provide the basis for a more widespread availability of microirradiation facilities for DNA‐repair research.
Reducing image distortions due to temperature‐related microscope stage drift
Authors: Adler J. , Pagakis S. N. 
Published: May 2003

SummaryDistortions in confocal 3D image data sets were related to movements of the microscope stage that matched fluctuations in laboratory temperature. Movement was apparent in all three axes. Adding a draught‐proof enclosure, covering the stage, objective lenses and supporting structures, minimized these short‐term fluctuations. However, the stage still tracked slow changes in laboratory temperature and was sensitive to heat sources mounted on the microscope. Suggestions are made about microscope design.
Cardiac autonomic characteristics in infants sleeping with their head covered by bedclothes
Authors: Franco Patricia , Lipshut Willy , Valente Filomena , Adams Stephan , Groswasser José , Kahn André 
Published: May 2003

SummaryThe risk of Sudden Infant Death Syndrome is increased in infants sleeping with their head covered by bedding items. This study was designed to evaluate cardiac autonomic nervous controls in infants sleeping with the head covered by bedclothes. Sixteen healthy infants with a median age of 12 weeks (range 9–13 weeks) were recorded polygraphically for one night. While they slept in their usual supine position, a bedsheet was placed over their head for about 45 min. All infants were challenged with the head covered and with the head free during both rapid eye movement (REM) and non‐rapid eye movement (NREM) sleep. Sleep, breathing and heart rate (HR) characteristics were recorded simultaneously, together with rectal and pericephalic temperatures. In both head‐free and head‐covered conditions, autoregressive spectral analysis of HR was evaluated as a function of sleep stages. During the head‐covered periods, parasympathetic tonus decreased and sympathetic activity increased in both REM and NREM sleep. Compared with the head‐free periods, the head‐covered sleep periods were characterized by greater rectal (P = 0.012) and pericephalic temperatures (P = 0.002). Covering the infant's head with a bedsheet was associated with significant changes in autonomic balance. The finding could be related to an elevation in temperatures within the infant's microenvironment.
Change in the Retrograde Atrial Activation Sequence Following Radiofrequency Modification of the Atrioventricular Node:
Authors: Dizon José , Reiffel James , Kassotis John , Woollett Ian , Garan Hasan 
Published: May 2003

Introduction: Despite the great success in treating AV nodal reentrant tachycardia (AVNRT) with radiofrequency modification of the AV node, the dimensions of the electrophysiologic circuit of this arrhythmia remain unclear, and simple models fail to explain all tachycardia‐related phenomena.
Methods and Results: We describe three unusual cases of supraventricular tachycardia (SVT). In all three cases, retrograde atrial activation during ventricular pacing or during SVT manifested local left atrial electrograms recorded from the coronary sinus preceding the septal atrial electrograms (eccentric activation), with earliest atrial activity at the lateral or posterolateral mitral annulus. Electrophysiologic maneuvers and observations were consistent with AVNRT as the mechanism in each case. In all cases, radiofrequency modification of the AV node eliminated inducible SVT and abolished dual pathway AV nodal physiology. The retrograde atrial activation sequence during ventricular pacing changed after ablation in each case, with septal atrial electrograms preceding left atrial electrograms recorded from the coronary sinus (concentric activation).
Conclusion: The observations in these cases cannot be explained by the traditional model of slow, fast, and intermediate AV nodal pathways. A model incorporating a circuit close to the AV node with left atrial and coronary sinus connections is proposed.
(J Cardiovasc Electrophysiol, Vol. 14, pp. 461‐466, May 2003)
Effect of Amiodarone on Dispersion of Atrial Refractoriness and Cycle Length in Patients with Atrial Fibrillation
Authors: Fynn Simon P. , Todd Derick M. , Julian W. , Hobbs C. , Armstrong Karen L. , Fitzpatrick P. , Garratt Clifford J. 
Published: May 2003

Introduction: Amiodarone is effective in preventing the recurrence of atrial fibrillation (AF) after cardioversion (CV). Dispersion of atrial refractoriness may be relevant to the generation of AF. We designed a study to determine the electrophysiologic effects of amiodarone in patients with previous early recurrence of AF after CV.
Methods and Results: Fifteen patients with previous AF recurrence (without antiarrhythmic drugs) after CV (CV1) were selected for amiodarone therapy and repeat CV (CVamio). Prior to CV1, mean AF cycle length (AFCL) had been recorded at four atrial sites (right atrial appendage [RAA], distal coronary sinus [DCS], right atrial lateral wall [LAT], and interatrial septum [IAS]) and dispersion of AFCL had been calculated. These patients were treated with amiodarone and, prior to CVamio, AFCL was recorded at the four atrial sites as for CV1. Between CV1 and CVamio, AFCL increased at all atrial sites:

153 ± 13 msec

to

179 ± 14 msec

at RAA,

144 ± 12 msec

to

174 ± 18 msec

at DCS,

158 ± 13 msec

to

182 ± 16 msec

at LAT, and

161 ± 18 msec

to

181 ± 17 msec

at IAS. Dispersion of AFCL decreased from

24 ± 10 msec

at CV1 to

15 ± 11 msec

at

CVamio (P = 0.01)

. The median time in sinus rhythm increased from 3.12 hours post CV1 to 28 days post

CVamio (P < 0.02)
.
Conclusion: Amiodarone causes a reduction in the dispersion of AFCL. This action may be relevant to the beneficial effects of amiodarone in patients with AF.
(J Cardiovasc Electrophysiol, Vol. 14, pp. 485‐491, May 2003)
Characterization of Sustained Atrial Tachycardia in Dogs with Rapid Ventricular Pacing‐Induced Heart Failure
Authors: Stambler Bruce S. , Fenelon Guilherme , Shepard Richard K. , Clemo Henry F. , Guiraudon Colette M. 
Published: May 2003

Introduction: Atrial arrhythmias often complicate congestive heart failure (CHF). We characterized inducible atrial tachyarrhythmias and electrophysiologic alterations in dogs with CHF and atrial enlargement produced by rapid ventricular pacing.
Methods and Results: Endocardial pacing leads were implanted in the right ventricle, right atrium, and coronary sinus in 18 dogs. The right ventricular lead was connected to an implanted pacemaker capable of rapid ventricular pacing. The atrial leads were used to perform electrophysiologic studies in conscious animals at baseline in all dogs, during CHF induced by rapid ventricular pacing at 235 beats/min in 15 dogs, and during recovery from CHF in 6 dogs. After

20 ± 7 days

of rapid ventricular pacing, inducibility of sustained atrial tachycardia (cycle length

120 ± 12 msec

) was enhanced in dogs with CHF. Atrial tachycardia required a critical decrease in atrial burst pacing cycle length (≤130 msec) for induction and often could be terminated by overdrive pacing. Calcium antagonists (verapamil, flunarizine, ryanodine) terminated atrial tachycardia and suppressed inducibility. Effective refractory periods at 400‐ and 300‐msec cycle lengths in the right atrium and coronary sinus were prolonged in dogs with CHF. Atrial cells from dogs with CHF had prolonged action potential durations and reduced resting potentials and delayed afterdepolarizations (DADs). Mitochondria from atrial tissue from dogs with CHF were enlarged and had internal cristae disorganization.
Conclusions: CHF promotes inducibility of sustained atrial tachycardia. Based on the mode of tachycardia induction, responses to pacing and calcium antagonists, and presence of DADs, atrial tachycardia in this CHF model has a mechanism most consistent with DAD‐induced triggered activity resulting from intracellular calcium overload.
(J Cardiovasc Electrophysiol, Vol. 14, pp. 499‐507, May 2003)
Axonal Transport and Sorting of Herpes Simplex Virus Components in a Mature Mouse Visual System
Authors: LaVail Jennifer H. , Tauscher Andrew N. , Aghaian Elda , Harrabi Ons , Sidhu Sukhvinder S. 
Published: May 2003

ABSTRACT
The time course for delivery and transport of two major proteins of herpes simplex virus (HSV) has been determined for mature mouse retinal ganglion cell axons in vivo. Twenty-four hours after intravitreal injection of HSV, valacyclovir was introduced into the drinking water of the mice to inhibit subsequent viral replication. Without treatment, viral spread and replication in periaxonal glial cells confound study of axonal transport. At 2 to 5 days after infection, the animals were sacrificed and contiguous segments of the optic pathway were removed. Immunofluorescence microscopy indicated that the number of infected astrocytes was reduced in the proximal optic nerve and eliminated in the optic tract. Western blots of the retina with antibodies for envelope and capsid components, glycoprotein D (gD) and VP5, respectively, revealed that both components were expressed in retinal homogenates by 2 days. Results of reverse transcription-PCR indicated that there was no gD mRNA present in the treated optic tract 5 days after infection. Therefore, we conclude that gD is transcribed from viral mRNA in the retinal ganglion cell bodies. The gD accumulated in the proximal ganglion cell axon by 2 days and reached the most distal segment after 3 days. The VP5 first appeared in the proximal axons at 4 days, about 48 h after the appearance of gD. Thus, gD entered the axon earlier and independent of VP5. These finding confirm the subassembly model of viral transport in neurons and suggest that there is a 4- to 5-day window for initiation of effective antiviral treatment with valacyclovir.
Expression and Immunogenicity of Sequence-Modified Human Immunodeficiency Virus Type 1 Subtype BpolandgagpolDNA Vaccines
Authors: zur Megede Jan , Otten Gillis R. , Doe Barbara , Liu Hong , Leung Louisa , Ulmer Jeffrey B. , Donnelly John J. , Barnett Susan W. 
Published: May 2003

ABSTRACTControl of the worldwide AIDS pandemic may require not only preventive but also therapeutic immunization strategies. To meet this challenge, the next generation of human immunodeficiency virus type 1 (HIV-1) vaccines must stimulate broad and durable cellular immune responses to multiple HIV antigens. Results of both natural history studies and virus challenge studies with macaques indicate that responses to both Gag and Pol antigens are important for the control of viremia. Previously, we reported increased Rev-independent expression and improved immunogenicity of DNA vaccines encoding sequence-modified Gag derived from the HIV-1SF2strain (J. zur Megede, M. C. Chen, B. Doe, M. Schaefer, C. E. Greer, M. Selby, G. R. Otten, and S. W. Barnett, J. Virol. 74: 2628-2635, 2000). Here we describe results of expression and immunogenicity studies conducted with novel sequence-modified HIV-1SF2GagPol and Pol vaccine antigens. These Pol antigens contain deletions in the integrase coding region and were mutated in the reverse transcriptase (RT) coding region to remove potentially deleterious enzymatic activities. The resulting Pol sequences were used alone or in combination with sequence-modified Gag. In the latter, the natural translational frameshift between the Gag and Pol coding sequences was either retained or removed. Smaller, in-frame fusion gene cassettes expressing Gag plus RT or protease plus RT also were evaluated. Expression of Gag and Pol from GagPol fusion gene cassettes appeared to be reduced when the HIV protease was active. Therefore, additional constructs were evaluated in which mutations were introduced to attenuate or inactivate the protease activity. Nevertheless, when these constructs were delivered to mice as DNA vaccines, similar levels of CD8+T-cell responses to Gag and Pol epitopes were observed regardless of the level of protease activity. Overall, the cellular immune responses against Gag induced in mice immunized with multigenicgagpolplasmids were similar to those observed in mice immunized with the plasmid encoding Gag alone. Furthermore, all of the sequence-modifiedpolandgagpolplasmids expressed high levels of Pol-specific antigens in a Rev-independent fashion and were able to induce potent Pol-specific T- and B-cell responses in mice. These results support the inclusion of agagpolin-frame fusion gene in future HIV vaccine approaches.
Human Rhinovirus Type 16: Mutant V1210A Requires Capsid-Binding Drug for Assembly of Pentamers To Form Virions during Morphogenesis
Authors: Lee Wai-Ming , Wang Wensheng 
Published: May 2003

ABSTRACT
Our laboratory has previously reported isolation of human rhinovirus type 16 (HRV16) mutants which depend on WIN 52035 to grow. A rapid rise of progeny virus infectivity occurred when drug was added late in growth cycles, suggesting that the drug-dependence lesion was at the step of virus assembly (W. Wang et al., J. Virol. 72:1210-1218, 1998). Here, we report that capsid subunits, 5S protomers and 14S pentamers, of a drug-dependent mutant were produced normally in the absence of drug, but mutant 80S empty capsids and 150S provirions were not formed, maturation cleavage of provirions (VP0 → VP2 + VP4) did not occur, and the unassembled mutant capsid subunits were degraded with a half-life of 15 min. Drug was not required by mutant virus for attachment, uncoating, RNA synthesis and protein synthesis, and polyprotein processing except maturation cleavage. The requirement of drug for assembly of mutant pentamers to form provirions and the rapid assembly of preformed subunits (synthesized in the absence of drug) after drug addition suggested that after native pentamers (P5) have been formed they must be converted to an assembly active state (P5∗), possibly by a conformational change induced by the binding of drug. We propose that pocket factor plays the same role in wild-type virus. In addition, we also report the construction and the properties of a full-length cDNA clone of HRV16, pR16.11, which produces in vitro transcripts with infectivity similar to that of virion RNA. This cDNA clone is available at the American Type Culture Collection.
Binding of CCAAT Displacement Protein CDP to Adenovirus Packaging Sequences
Authors: Erturk Ece , Ostapchuk Philomena , Wells Susanne I. , Yang Jihong , Gregg Keqin , Nepveu Alain , Dudley Jaquelin P. , Hearing Patrick 
Published: May 2003

ABSTRACT

Adenovirus (Ad) type 5 DNA packaging is initiated in a polar fashion from the left end of the genome. The packaging process is dependent upon the
cis
-acting packaging domain located between nucleotides 194 and 380. Seven A/T-rich repeats have been identified within this domain that direct packaging. A1, A2, A5, and A6 are the most important repeats functionally and share a bipartite sequence motif. Several lines of evidence suggest that there is a limiting
trans
-acting factor(s) that plays a role in packaging. Two cellular activities that bind to minimal packaging domains in vitro have been previously identified. These binding activities are P complex, an uncharacterized protein(s), and chicken ovalbumin upstream promoter transcription factor (COUP-TF). In this work, we report that a third cellular protein, octamer-1 protein (Oct-1), binds to minimal packaging domains. In vitro binding analyses and in vivo packaging assays were used to examine the relevance of these DNA binding activities to Ad DNA packaging. The results of these experiments reveal that COUP-TF and Oct-1 binding does not play a functional role in Ad packaging, whereas P-complex binding directly correlates with packaging function. We demonstrate that P complex contains the cellular protein CCAAT displacement protein (CDP) and that full-length CDP is found in purified virus particles. In addition to cellular factors, previous evidence indicates that viral factors play a role in the initiation of viral DNA packaging. We propose that CDP, in conjunction with one or more viral proteins, binds to the packaging sequences of Ad to initiate the encapsidation process.
Comparative Immunogenicity in Rhesus Monkeys of DNA Plasmid, Recombinant Vaccinia Virus, and Replication-Defective Adenovirus Vectors Expressing a Human Immunodeficiency Virus Type 1
gag
Gene
Authors: Casimiro Danilo R. , Chen Ling , Fu Tong-Ming , Evans Robert K. , Caulfield Michael J. , Davies Mary-Ellen , Tang Aimin , Chen Minchun , Huang Lingyi , Harris Virginia , Freed Daniel C. , Wilson Keith A. , Dubey Sheri , Zhu De-Min , Nawrocki Denise , Mach Henryk , Troutman Robert , Isopi Lynne , Williams Donna , Hurni William , Xu Zheng , Smith Jeffrey G. , Wang Su , Liu Xu , Guan Liming , Long Romnie , Trigona Wendy , Heidecker Gwendolyn J. , Perry Helen C. , Persaud Natasha , Toner Timothy J. , Su Qin , Liang Xiaoping , Youil Rima , Chastain Michael , Bett Andrew J. , Volkin David B. , Emini Emilio A. , Shiver John W. 
Published: May 2003

ABSTRACT

Cellular immune responses, particularly those associated with CD3
+
CD8
+
cytotoxic T lymphocytes (CTL), play a primary role in controlling viral infection, including persistent infection with human immunodeficiency virus type 1 (HIV-1). Accordingly, recent HIV-1 vaccine research efforts have focused on establishing the optimal means of eliciting such antiviral CTL immune responses. We evaluated several DNA vaccine formulations, a modified vaccinia virus Ankara vector, and a replication-defective adenovirus serotype 5 (Ad5) vector, each expressing the same codon-optimized HIV-1
gag
gene for immunogenicity in rhesus monkeys. The DNA vaccines were formulated with and without one of two chemical adjuvants (aluminum phosphate and CRL1005). The Ad5-
gag
vector was the most effective in eliciting anti-Gag CTL. The vaccine produced both CD4
+
and CD8
+
T-cell responses, with the latter consistently being the dominant component. To determine the effect of existing antiadenovirus immunity on Ad5-
gag
-induced immune responses, monkeys were exposed to adenovirus subtype 5 that did not encode antigen prior to immunization with Ad5-
gag
. The resulting anti-Gag T-cell responses were attenuated but not abolished. Regimens that involved priming with different DNA vaccine formulations followed by boosting with the adenovirus vector were also compared. Of the formulations tested, the DNA-CRL1005 vaccine primed T-cell responses most effectively and provided the best overall immune responses after boosting with Ad5-
gag
. These results are suggestive of an immunization strategy for humans that are centered on use of the adenovirus vector and in which existing adenovirus immunity may be overcome by combined immunization with adjuvanted DNA and adenovirus vector boosting.