bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Detection and Typing of Strains ofMycobacterium aviumsubsp.paratuberculosisfrom Broth Cultures
Authors: Motiwala Alifiya S. , Strother Megan , Theus Natalie E. , Stich Roger W. , Byrum Beverly , Shulaw William P. , Kapur Vivek , Sreevatsan Srinand
Published: May 2005

A liquid culture followed by molecular confirmation was evaluated for potential to improve sensitivity and reduce time to diagnosis ofMycobacterium aviumsubsp.paratuberculosisinfection. Fecal samples from 240 animals from Ohio farms were assessed for presence ofM. aviumsubsp.paratuberculosisusing four different protocols: (i) sedimentation processing followed by inoculation on Herrold's Egg Yolk media (HEYM) slants (monitored biweekly up to 16 weeks), (ii) double centrifugation processing followed by inoculation on HEYM slants (monitored biweekly up to 16 weeks), (iii) liquid-solid double culture method using modified 7H9 broth (8 weeks) followed by subculture on HEYM slants (monitored up to 8 weeks), and (iv) liquid culture using modified 7H9 broth (8 weeks) followed by molecular assays for the presence of twoM. aviumsubsp.paratuberculosis-specific targets. The number of positive samples detected by each protocol was 37, 53, 65, and 76, respectively. Twenty-seven samples were positive by all four methods. Based on samples positive by at least one method (n= 81), the sensitivities for sedimentation processing, double centrifugation processing, liquid-solid double culture, and liquid culture followed by molecular confirmation were 46%, 65%, 80%, and 94%, respectively. Fingerprinting of the positive samples using two polymorphic (G and GGT) short sequence repeat regions identified varying levels of within-farm and between-farm diversity. Our data indicate that liquid culture followed by molecular confirmation can significantly improve sensitivity and reduce time-to-diagnosis (from 16 to 8 weeks) ofM. aviumsubsp.paratuberculosisinfection and can also be efficiently employed for the systematic differentiation ofM. aviumsubsp.paratuberculosisstrains to understand the epidemiology of Johne's disease.
Effect of Prophylactic Valacyclovir on the Presence of Human Herpesvirus DNA in Saliva of Healthy Individuals after Dental Treatment
Authors: Miller Craig S. , Avdiushko Sergei A. , Kryscio Richard J. , Danaher Robert J. , Jacob Robert J.
Published: May 2005

Human herpesviruses (HHVs) are ubiquitous pathogens that intermittently reactivate from latency. Transmission is believed to be facilitated by their frequent appearance in saliva. This study sought to understand the factors that influence the appearance of these viruses in saliva by examining the prevalence, pattern, and quantity of all eight HHVs in saliva of immunocompetent adults with a history of recurrent oral herpes simplex virus (HSV) infections following dental treatment and antiviral therapy. Valacyclovir or matched placebo was given (2 g twice on the day of treatment and 1 g twice the following day) to 125 patients in a randomized, double-blind controlled trial. Saliva, collected on the day of dental treatment and 3 and 7 days later, was analyzed using real-time quantitative PCR. At all visits, HHVs coinfected saliva. Over the course of the week, the DNAs of HHV-6 and HHV-7 were detected significantly more often (97% to 99% of patients) than Epstein-Barr virus (EBV; 64.8%), HSV-1 (13.0%), HHV-8 (3.2%), cytomegalovirus (2.4%), HSV-2 (0%), and varicella-zoster virus (0%), irrespective of drug treatment (P< 0.002). Mean genome copy numbers were highest for HSV-1 and HHV-6. Dental treatment did not influence asymptomatic viral shedding patterns. However, valacyclovir treatment resulted in significantly fewer patients shedding EBV at both postoperative visits compared with placebo (P< 0.008). These results suggest that HHVs are simultaneously present in the saliva of healthy adults at levels that could facilitate transmission, and valacyclovir therapy decreases the prevalence of EBV in saliva but has little effect on HHV-6 and HHV-7.
Population Structure, Antimicrobial Resistance, and Mutation Frequencies of
Streptococcus pneumoniae
Isolates from Cystic Fibrosis Patients
Authors: del Campo Rosa , Morosini María-Isabel , de la Pedrosa Elia Gómez-G. , Fenoll Asunción , Muñoz-Almagro Carmen , Máiz Luis , Baquero Fernando , Cantón Rafael ,   the Spanish Pneumococcal Infection Study Network
Published: May 2005

Forty-eight
Streptococcus pneumoniae
isolates recovered from sputum samples from 26 cystic fibrosis (CF) patients attending our CF unit (1995 to 2003) were studied. Mean yearly incidence of isolation was 5.5%, and all were strains recovered from young patients (≤12 years). The isolation was linked to clinical exacerbation in 35% of the cases, but only 27% of these were not accompanied by other CF pathogens. Fifty percent of the patients presented with two to four isolates over the studied period. Pulsed-field gel electrophoresis-SmaI digestion revealed a high heterogeneity (32 pulsotypes among 48 isolates) and the persistence over a 6-month period of a single clone (clone A) in two patients. This clone, presenting a varied multiresistance phenotype, was identified as the Spain
23F
-1 clone and was also recognized in six other patients, including two out of nine patients from the CF unit of Sant Joan de Dèu Hospital, Barcelona, Spain. In our isolates, 16 different serotypes were recognized, the most frequent being 23F (33.3%), 19F (18.8%), 6A (6.2%), and 6B (6.2%). High overall resistance rates were observed: to penicillin, 73%; to cefotaxime, 33%; to erythromycin, 42%; to tetracycline, 58%; to chloramphenicol, 48%; and to trimethoprim-sulfamethoxazole, 67%. Resistance to fluoroquinolones was not detected. Multiresistance was a common feature (60%). The percentage of
S. pneumoniae
strains with increased frequencies of mutation to rifampin resistance (≥7.5 × 10
−8
) was significantly higher (
P
= 0.02) in CF (60%) than among non-CF (37%) isolates in the same institution (M. I. Morosini et al., Antimicrob. Agents Chemother. 47:1464-1467, 2003). Even though a clear association with acute exacerbations could not be observed, long-term clonal persistence and variability, high frequency of antibiotic resistance, and hypermutability indicate the plasticity for adaptation of
S. pneumoniae
to the CF lung environment.
Detection of Bacteria in Red Blood Cell Concentrates by the Scansystem Method
Authors: Ribault S. , Faucon A. , Grave L. , Nannini P. , Faure I. Besson
Published: May 2005

Bacterial contamination remains one of the major risks associated with blood product transfusion. The kinetics of bacterial growth in red blood cell concentrates (RBCC) is different than otherwise due to storage at 4°C, conditions in which most bacteria do not survive. Psychrophilic bacteria such as
Yersinia enterocolitica
, however, can proliferate from a very low level of contamination to clinically significant levels at 4°C and are known to cause severe transfusion-related infections. A screening method allowing the early detection of very low levels of bacteria in RBCC would improve transfusion safety. The Scansystem method has been previously described for detection of bacteria in platelet concentrates. We present here a modification of the system for detection of low levels of bacteria in RBCC. The Scansystem RBC kit protocol requires three steps, i.e., the agglutination and selective removal of RBCs, a labeling stage during which bacteria are labeled with a DNA-specific fluorophore, and finally recovery of bacteria on the surface of a black membrane for analysis using the Scansystem. The entire procedure from sampling to result can be completed in 90 min. Both gram-negative and gram-positive bacteria in RBCC are detected with a higher sensitivity than with currently available culture-based methods. The Scansystem RBC kit is shown to be sensitive enough to identify low-level bacterial contamination in a single unit tested in a pool of up to 20 RBCC samples (detection limit of between 1 and 10 CFU/ml depending on the bacterial strain). The method therefore lends itself to incorporation into high-sample-throughput screening programs.
Immunofluorescence Assay for Detection of the Nucleocapsid Antigen of the Severe Acute Respiratory Syndrome (SARS)-Associated Coronavirus in Cells Derived from Throat Wash Samples of Patients with SARS
Authors: Liu I-Jung , Chen Pei-Jer , Yeh Shiou-Hwei , Chiang Yu-Ping , Huang Li-Min , Chang Ming-Fu , Chen Shey-Ying , Yang Pan-Chyr , Chang Shan-Chwen , Wang Wei-Kung ,   the SARS Research Group of the National Taiwan University College of Medicine-National Taiwan University Hospital
Published: May 2005

An antigen detection assay for severe acute respiratory syndrome (SARS) coronavirus was established in this study by an indirect immunofluorescence test, which utilized cells derived from throat wash samples of patients with SARS and a rabbit serum that recognized the nucleocapsid protein of SARS-associated coronavirus (SARS-CoV) but not that of other human coronavirus tested. It detected SARS-CoV in 11 of 17 (65%) samples from SARS patients as early as day 2 of illness but in none of the 10 samples from healthy controls. Compared with other diagnostic modalities for detecting SARS-CoV, this assay is simpler, more convenient, and economical. It could be an alternative for early and rapid diagnosis, should SARS return in the future.
Efficiency of the Ortho VITROS Assay for Detection of Hepatitis C Virus-Specific Antibodies Increased by Elimination of Supplemental Testing of Samples with Very Low Sample-to-Cutoff Ratios
Authors: Oethinger Margret , Mayo Donald R. , Falcone JoAnne , Barua Pankaj K. , Griffith Brigitte P.
Published: May 2005

The clinical significance of specimens with low sample-to-cutoff (S/Co) ratios in the Ortho VITROS chemiluminescence assay (CIA) for detection of antibodies to hepatitis C virus (HCV) was evaluated. In one study of 482 CIA-reactive samples, none of the 83 samples with S/Co ratios of <5 was HCV RNA positive. In a subsequent study, 332 samples with S/Co ratios of between 1 and 20 were tested with the recombinant immunoblot assay (RIBA). None of the 163 samples with S/Co ratios of <5 was RIBA positive, 83% were RIBA negative, and 28 samples (18%) were RIBA indeterminate. HCV RNA and/or clinical evidence of hepatitis was not found in the 27 indeterminate cases examined. These results show that over 99% of samples with very low S/Co ratios (≤5) have no evidence of HCV infection. Therefore, we suggest that the HCV antibody testing algorithm for the VITROS assay might be modified to eliminate supplemental testing of samples with very low S/Co ratios.
Isothermal RNA Sequence Amplification Method for Rapid Antituberculosis Drug Susceptibility Testing of
Mycobacterium tuberculosis
Authors: Takakura Shunji , Tsuchiya Shigeo , Fujihara Naoko , Kudo Toyoichiro , Iinuma Yoshitsugu , Mitarai Satoshi , Ichiyama Satoshi , Yasukawa Kiyoshi , Ishiguro Takahiko
Published: May 2005

RNA transcript quantification by an isothermal sequence amplification reaction was evaluated for susceptibility testing of 15
Mycobacterium tuberculosis
strains. Agreement with the proportion method on Ogawa egg medium and the BACTEC MGIT 960 system was 100 and 87% for rifampin, 93 and 100% for isoniazid, 60 and 53% for ethambutol, and 80 and 80% for streptomycin, respectively.
The anti-inflammatory effect of inhaled nitric oxide on pulmonary inflammation in a swine model
Authors: El Kebir D , Taha R , Hubert B , Gauvin D , Gangal M , Blaise G
Published: May 2005

Cardiopulmonary bypass (CPB) is associated with an inflammatory process that leads to lung injury. In this study, we hypothesized that inhaled nitric oxide (INO) possesses the ability to modulate CPB-induced inflammation. Fifteen male pigs were randomly divided into 3 groups: Sham, CPB+LPS (CPB and lipopolysaccharide), and CPB+LPS+INO. INO (20 parts per million) was administered for 24 h after anesthesia. CPB was performed for 90 min, and LPS was infused (1 µg/kg) after CPB. Bronchoalveolar lavage (BAL) fluid and blood were collected at T0(before CPB), at 4 h, and at 24 h. At 24 h, BAL interleukin-8 (IL-8) levels were not increased as expected in the CPB+LPS group compared with the Sham group, but they were reduced significantly in the CPB+LPS+INO group. Cell hypo reactivity observed in the groups receiving LPS also seemed to downregulate endothelial nitric oxide synthase NOS protein expression relative to the Sham group. Nitrite and nitrate (NOx) concentrations were decreased significantly in the groups without INO. Moreover, animals treated with INO showed higher rates of pulmonary apoptosis compared with their respective controls. These results demonstrate that NOx production is reduced after CPB and that INO acts on the inflammatory process by diminishing neutrophils and their major chemoattractant, IL-8. INO also increases cell apoptosis in the lungs under inflammatory conditions, which may explain, in part, how it resolves pulmonary inflammation.Key words: CPB, nitric oxide, apoptosis, LPS, IL-8.
Effects of dopamine, SKF-38393 and R(-)-NPA on ATP-activated currents in rat DRG neurons
Authors: Li Guo-Hua , Guan Bing-Cai , Li Zhi-Wang
Published: May 2005

This study aimed to investigate the effect of the activation of dopamine (DA) receptors on ATP-activated currents (IATP) in freshly isolated dorsal root ganglion (DRG) neurons of rats using whole-cell patch clamp technique in combination with intracellular dialysis. Extracellular application of DA inhibited IATP in half of the neurons tested (39/77, 50.6%), enhanced IATP in a small subset of the neurons (22/77, 28.6%), and had no effect on IATP in the rest (16/77, 20.8%). To investigate the DA receptor subtypes that mediate these modulations, the effects of R(-)-NPA, a D2 receptor agonist, and SKF-38393, a D1 receptor agonist, were examined. Preapplication of R(-)-NPA inhibited IATP in most of the cells tested (53/57, 93.0%) and had no effect in the rest (4/57, 7.0%); no potentiating effect was observed. Preapplication of SKF-38393 inhibited IATP in a majority of the cells tested (57/77, 74.0%), potentiated IATP in some cells (12/77, 15.6%), and had no effect in the remainder (8/77, 10.4%). Further study of the inhibitory effect of R(-)-NPA and SKF-38393 revealed that both of them acted in a noncompetitive manner, shifting the concentration-response curve for IATP downwards with the maximal response markedly reduced and EC50 basically unchanged; and the inhibition was independent of the holding potential. Intracellular dialysis of GDP-β-S and H-7 abolished R(-)-NPA inhibition of IATP completely, and SKF-38393 inhibition of IATP was removed by intracellular application of H-7 but not by H-9. These results suggest that the activation of DA receptors dominantly inhibits IATP in dorsal root ganglion cells, and this inhibition may be involved in the modulation of afferent information by the diencephalon-derived DA in the primary sensory neurons.Key words: dopamine, ATP, R(-)-NPA, SKF-38393, dorsal root ganglion, whole-cell patch clamp recording, intracellular dialysis.
A SEMI-CLASSICAL ANALYSIS OF THE PROTON SEQUENTIAL EMISSION IN 16O+58Ni DEEP INELASTIC COLLISIONS
Authors: AUDITORE L. , BARNÁ R. , DE PASQUALE D. , ITALIANO A. , TRIFIRÓ A. , TRIMARCHI M. , RAUCH V. , BECK C. , BELLOT T. , BHATTACHARYA C. , DISDIER D. , FREEMAN R. M. , HAAS F. , NOUICER R. , PAPKA P. , ROUSSEAU M. , ZAFRA A. SÀNCHEZ I. , STEZOWSKI O. , STRAZZERI A.
Published: May 2005

We study the 16 O +58 Ni deep inelastic reaction by using coincident charged techniques. Inclusive as well as exclusive data of the C , N , and O fully-damped fragments and their associated light charged particles ( p , d , t , and α-particles) have been collected at the IReS Strasbourg VIVITRON Tandem facility. The velocity distributions of the emitted protons and the associated multiplicity polar plots are analyzed by means of a model which describes simultaneously the nonequilibrium and the evaporative (equilibrated) components of a deep inelastic reaction mechanism. Estimates on polarization phenomena as well as the associated "decay times" of the reaction have been obtained. The hypothesis of a new "fan effect" is proposed for the proton sequential emission in the deep inelastic scattering of 16 O +58 Ni at 8.25 MeV/nucleon.
A NATURAL RENORMALIZATION OF THE ONE-LOOP EFFECTIVE ACTION FOR SCALAR FIELD IN CURVED SPACETIME
Authors: TAKOOK MOHAMMAD VAHID
Published: May 2005

It has been shown that the negative norm states necessarily appear in a covariant quantization of the free minimally coupled scalar field in de Sitter space.1,2 In this process, ultraviolet and infrared divergences have been automatically eliminated.3 A natural renormalization of the one-loop interacting quantum field in Minkowski spacetime (λϕ4 theory) has been achieved through the consideration of the negative norm states.4 The one-loop effective action for scalar field in a general curved space-time has been calculated by this method, and a natural renormalization procedure in the one-loop approximation has been established.
CLUSTER–CLUSTER POTENTIALS FOR THE LITHIUM NUCLEI
Authors: DOMA S. B. , EL-ZEBIDY ABDEL FATTAH M.
Published: May 2005

Two types of cluster–cluster potentials are obtained for the lithium nuclei. The first is an attractive one and the second is a superposition of repulsive and attractive Gaussian forces. The ground-state wave functions of the lithium nuclei 6 Li , 7 Li , 8 Li , and 9 Li are expanded in terms of products of two wave functions: the first represents the set of A-4 nucleons and the second represents the set of the last four nucleons. In the construction of these wave functions, we have used the basis functions of the translation-invariant shell model. The expansion coefficients of the factorizations of these wave functions are products of four-particle orbital and spin-isospin fractional parentage coefficients. Two least-square formulas for the cluster–cluster potentials, which depend on the mass number A, are fitted for the lithium nuclei.
DIRAC OPERATOR IN MATRIX GEOMETRY
Authors: AVRAMIDI IVAN G.
Published: May 2005

We review the construction of the Dirac operator and its properties in Riemannian geometry, and show how the asymptotic expansion of the trace of the heat kernel determines the spectral invariants of the Dirac operator and its index. We also point out that the Einstein–Hilbert functional can be obtained as a linear combination of the first two spectral invariants of the Dirac operator. Next, we report on our previous attempts to generalize the notion of the Dirac operator to the case of Matrix Geometry, where, instead of a Riemannian metric there is a matrix valued self-adjoint symmetric two-tensor that plays a role of a "non-commutative" metric. We construct invariant first-order and second-order self-adjoint elliptic partial differential operators, which can be called "non-commutative" Dirac operators and non-commutative Laplace operators. We construct the corresponding heat kernel for the non-commutative Laplace type operator and compute its first two spectral invariants. A linear combination of these two spectral invariants gives a functional that can be considered as a non-commutative generalization of the Einstein–Hilbert action.
MITOCHONDRIAL DNA AND HUMAN EVOLUTION
Authors: Pakendorf Brigitte , Stoneking Mark
Published: May 2005

▪ Abstract  Several unique properties of human mitochondrial DNA (mtDNA), including its high copy number, maternal inheritance, lack of recombination, and high mutation rate, have made it the molecule of choice for studies of human population history and evolution. Here we review the current state of knowledge concerning these properties, how mtDNA variation is studied, what we have learned, and what the future likely holds. We conclude that increasingly, mtDNA studies are (and should be) supplemented with analyses of the Y-chromosome and other nuclear DNA variation. Some serious issues need to be addressed concerning nuclear inserts, database quality, and the possible influence of selection on mtDNA variation. Nonetheless, mtDNA studies will continue to play an important role in such areas as examining socio-cultural influences on human genetic variation, ancient DNA, certain forensic DNA applications, and in tracing personal genetic history.
Mutually dependent localization of megalin and Dab2 in the renal proximal tubule
Authors: Nagai J. , Christensen E. I. , Morris S. M. , Willnow T. E. , Cooper J. A. , Nielsen R.
Published: May 2005

Disabled-2 (Dab2) is a cytoplasmic adaptor protein that binds to the cytoplasmic tail of the multiligand endocytic receptor megalin, abundantly expressed in renal proximal tubules. Deletion of Dab2 induces a urinary increase in specific plasma proteins such as vitamin D binding protein and retinol binding protein (Morris SM, Tallquist MD, Rock CO, and Cooper JA. EMBO J 21: 1555–1564, 2002). However, the subcellular localization of Dab2 in the renal proximal tubule and its function have not been fully elucidated yet. Here, we report the characterization of Dab2 in the renal proximal tubule. Immunohistocytochemistry revealed colocalization with megalin in coated pits and vesicles but not in dense apical tubules and the brush border. Kidney-specific megalin knockout almost abolished Dab2 staining, indicating that Dab2 subcellular localization requires megalin in the proximal tubule. Reciprocally, knockout of Dab2 led to a redistribution of megalin from endosomes to microvilli. In addition, there was an overall decrease in levels of megalin protein observed by immunoblotting but no decrease in clathrin or α-adaptin protein levels or in megalin mRNA. In rat yolk sac epithelial BN16 cells, Dab2 was present apically and colocalized with megalin. Introduction of anti-Dab2 antibody into BN16 cells decreased the internalization of125I-labeled receptor-associated protein, substantiating the role of Dab2 in megalin-mediated endocytosis. The present study shows that Dab2 is localized in the apical endocytic apparatus of the renal proximal tubule and that this localization requires megalin. Furthermore, the study suggests that the urinary loss of megalin ligands observed in Dab2 knockout mice is caused by suboptimal trafficking of megalin, leading to decreased megalin levels.
AT1receptor-mediated enhancement of collecting duct renin in angiotensin II-dependent hypertensive rats
Authors: Prieto-Carrasquero Minolfa C. , Kobori Hiroyuki , Ozawa Yuri , Gutiérrez Astrid , Seth Dale , Navar L. Gabriel
Published: May 2005

Angiotensin II (ANG II)-infused rats exhibit increases in distal nephron renin expressed in principal cells of connecting tubules and collecting ducts. This study was performed to determine whether the augmentation of distal nephron renin involves ANG II type 1 (AT1) receptor activation. Male Sprague-Dawley rats (200–220 g) were divided into three groups: 1) sham operated ( n = 8); 2) ANG II infused (80 ng/min, 13 days, n = 8); and 3) ANG II infused plus AT1receptor blocker (ARB), olmesartan (5 mg/days, n = 8). ANG II infusion increased systolic blood pressure (BP; 178 ± 4 vs. 122 ± 1 mmHg; P < 0.001) and suppressed plasma renin activity (PRA; 0.08 ± 0.1 vs. 5.3 ± 0.8 ng ANG I·ml−1·h−1). ARB treatment prevented the increase in BP (113 ± 6 mmHg) and led to increases in PRA (15.8 ± 1.5 ng ANG I·ml−1·h−1). Renin protein levels measured in the kidney medulla, to avoid contribution from juxtaglomerular appartus cells, were higher in ANG II-infused rats [1.64 ± 0.3 vs. 1.00 ± 0.1 densitometric units (DU) compared with sham-operated rats; P < 0.05], and ARB treatment prevented this increase (1.01 ± 0.1). Similarly, renin immunoreactivity increased in medullary collecting ducts of ANG II-infused compared with sham-operated rats (2.5 ± 0.3 vs. 1.0 ± 0.2 DU; P < 0.001), which was also prevented by ARB (1.01 ± 0.06). Renin qRTPCR in ANG II-infused rats showed higher mRNA levels in the kidney medulla compared with sham-operated rats (5.5 ± 2.3 vs. 0.04 ± 0.02 ratio to GAPDH mRNA levels; P < 0.001); however, renin transcript levels were normalized in the ARB-treated rats. These data demonstrate that the augmentation of distal nephron renin in ANG II-infused hypertensive rats is AT1receptor mediated. The augmented distal tubular renin may contribute to increased intratubular ANG II levels and distal nephron sodium reabsorption in ANG II-dependent hypertension.
Profiling of differentially expressed genes in wound margin biopsies of horses using suppression subtractive hybridization
Authors: Lefebvre-Lavoie Josiane , Lussier Jacques G. , Theoret Christine L.
Published: May 2005

Disturbed gene expression may disrupt the normal process of repair and lead to pathological situations resulting in excessive scarring. To prevent and treat impaired healing, it is necessary to first define baseline gene expression during normal repair. The objective of this study was to compare gene expression in normal intact skin (IS) and wound margin (WM) biopsies using suppression subtractive hybridization (SSH) to identify genes differentially expressed during wound repair in horses. Tissue samples included both normal IS and biopsies from 7-day-old wounds. IS cDNAs were subtracted from WM cDNAs to establish a subtracted (WM-IS) cDNA library; 226 nonredundant cDNAs were identified. Detection of genes previously shown to be expressed 7 days after trauma, including the pro-α2-chain of type 1 pro-collagen (COL1A2), annexin A2, the pro-α3-chain of type 6 pro-collagen, β-actin, fibroblast growth factor 7, laminin receptor 1, matrix metalloproteinase 1 (MMP1), secreted protein acidic cystein rich, and tissue inhibitor of metalloproteinase 2, supported the validity of the experimental design. A RT-PCR assay confirmed an increase or induction of the cDNAs of specific genes (COL1A2, MMP1, dermatan sulfate proteoglycan 2, cluster differentiation 68, cluster differentiation 163, and disintegrin and metalloproteinase domain 9) within wound biopsies. Among these, COL1A2 and MMP1 had previously been documented in horses; 68.8% of the cDNAs had not previously been attributed a role during wound repair, of which spermidine/spermine- N-acetyltransferase, serin proteinase inhibitor B10, and sorting nexin 9 were highly expressed and whose known functions in other processes made them potential candidates in regulating the proliferative response to wounding. In conclusion, we identified novel genes that are differentially expressed in equine wound biopsies and that may modulate repair. Future experiments must correlate changes in mRNA levels for precise molecules with spatiotemporal protein expression within tissues.
Double‐coset enumeration algorithm for symmetrically generated groups
Authors: Sayed Mohamed
Published: May 2005

A double‐coset enumeration algorithm for groups generated by
symmetric sets of involutions together with its computer implementation is described.
A generalization of a contraction principle in probabilisticmetric spaces. Part II
Authors: Miheţ Dorel
Published: May 2005

A fixed point theorem concerning probabilistic contractions
satisfying an implicit relation, which generalizes a well‐known result of Hadžić, is proved.
Water waves generated by disturbances at an ice cover
Authors: Maiti Paramita , Mandal B. N.
Published: May 2005

This paper is concerned with two‐dimensional unsteady motion of
water waves generated by an initial disturbance created at an ice sheet covering the water. The ice cover is modeled as a thin elastic plate. Using linear theory, the problem is formulated as an initial value problem for the velocity potential describing the motion in the liquid. In the mathematical analysis, the Laplace and Fourier transform techniques have been utilized to obtain the depression of the ice‐covered surface in the form of an infinite
integral. For the special case of initial disturbance concentrated at the origin, taken on the ice cover, this integral is evaluated asymptotically by the method of a stationary phase for a long time and large distance from the origin. The form of the ice‐covered
surface is graphically depicted for two types of initial disturbances.
Semicompatibility and fixed point theorems in an unbounded D‐metric space
Authors: Singh Bijendra , Jain Shishir , Jain Shobha
Published: May 2005

Rhoades (1996) proved a fixed point theorem in a bounded D‐metric space for a contractive self‐map with applications. Here we establish a more general fixed point theorem in an unbounded D‐metric space, for two self‐maps satisfying a general contractive condition with a restricted domain of x and y. This has been done by using the notion of semicompatible maps in D‐metric space. These results generalize and improve the results of Rhoades (1996), Dhage et al. (2000), and Veerapandi and Rao (1996). These results also underline the necessity and importance of semicompatibility in fixed point theory of D‐metric spaces. All the results of this paper are new.
The Mayo Clinic Family Study of Parkinson’s Disease: Study Design, Instruments, and Sample Characteristics
Authors: Rocca Walter A. , Peterson Brett J. , McDonnell Shannon K. , Bower James H. , Ahlskog J. Eric , Schaid Daniel J. , Maraganore Demetrius M.
Published: May 2005

We describe here the Mayo Clinic Family Study of Parkinson’s disease (PD), including the overall study design (historical cohort study of relatives from birth to onset of PD or censoring), the data collection instruments, the strategies implemented to prevent or measure biases, and the sample obtained. These methodological details may provide assistance to other investigators designing studies of the familial aggregation of PD or other aging-related chronic diseases. We investigated the incidence of PD and other neurodegenerative diseases among 1,001 first-degree relatives of 162 patients with PD and 851 relatives of 147 controls representative of the population of Olmsted County, Minn., USA. In addition, we studied 2,713 first-degree relatives of 411 patients with PD referred to the Mayo Clinic. Finally, we studied a group of 625 spouses of either cases or controls. Relatives with PD or other neurodegenerative diseases were ascertained using the family study method.
Visual Information Processing in the Lion-Tailed Macaque (Macaca silenus): Mental Rotation or Rotational Invariance?
Authors: Burmann Britta , Dehnhardt Guido , Mauck Björn
Published: May 2005

Mental rotation is a widely accepted concept indicating an image-like mental representation of visual information and an analogue mode of information processing in certain visuospatial tasks. In the task of discriminating between image and mirror-image of rotated figures, human reaction times increase with the angular disparity between the figures. In animals, tests of this kind yield inconsistent results. Pigeons were found to use a time-independent rotational invariance, possibly indicating a non-analogue information processing system that evolved in response to the horizontal plane of reference birds perceive during flight. Despite similar ecological demands concerning the visual reference plane, a sea lion was found to use mental rotation in similar tasks, but its processing speed while rotating three-dimensional stimuli seemed to depend on the axis of rotation in a different way than found for humans in similar tasks. If ecological demands influence the way information processing systems evolve, hominids might have secondarily lost the ability of rotational invariance while retreating from arboreal living and evolving an upright gait in which the vertical reference plane is more important. We therefore conducted mental rotation experiments with an arboreal living primate species, the lion-tailed macaque. Performing a two-alternative matching-to-sample procedure, the animal had to decide between rotated figures representing image and mirror-image of a previously shown upright sample. Although non-rotated stimuli were recognized faster than rotated ones, the animal’s mean reaction times did not clearly increase with the angle of rotation. These results are inconsistent with the mental rotation concept but also cannot be explained assuming a mere rotational invariance. Our study thus seems to support the idea of information processing systems evolving gradually in response to specific ecological demands.
Reduction of Soluble E-Selectin after Combined Treatment with Simvastatin and Vitamins C and E
Authors: Burger Peter Christian , Schoeberlein Andreina , Seifert Burkhardt , Zund Gregor
Published: May 2005

Objective: We investigated the influence of treatment with simvastatin and vitamins C and E on serum levels of soluble cell adhesion molecules (sCAM) as markers of atherosclerosis and endothelial activation. Methods: In 11 hypercholesterolemic patients, serum levels of sCAM were measured by enzyme immunoassay before and after 6 weeks of treatment with either simvastatin (20 mg) or vitamin C (1 g) plus vitamin E (600 mg) and after an additional 6 weeks of combined treatment. In 8 of the patients angiography was performed at study entry. Results: Baseline levels of soluble intercellular adhesion molecule-1 (sICAM-1) showed an age-dependent increase (coefficient of correlation 0.71, p = 0.014) and were higher in patients with established atherosclerotic lesions than in patients with no such lesions (369.5 ± 61.8 vs. 238.4 ± 56.4 ng/ml, p = 0.023). Whereas either treatment alone had no influence on the serum levels of sCAM, combined treatment with simvastatin and vitamins C and E reduced serum levels of soluble E-selectin from 43.2 ± 18.9 ng/ml at baseline to 39.7 ± 16.5 ng/ml (p = 0.027) at study end. Although not significant, levels of soluble P-selectin were also reduced from a mean of 125.9 ± 64.1 ng/ml at baseline to 115 ± 64.9 ng/ml (p = 0.1). Serum levels of sICAM-1 and soluble vascular cell adhesion molecule-1 (sVCAM-1) remained unchanged by this treatment. Conclusion: Combined treatment with simvastatin and vitamins C and E reduced serum levels of soluble E-selectin but had no influence on sICAM-1 and sVCAM-1 levels.
Comparison of Epoetin Alfa and Darbepoetin Alfa Biological Activity under Different Administration Schedules in Normal Mice
Authors: Sasu Barbra J. , Hartley Cynthia , Schultz Henry , McElroy Patricia , Khaja Raheemuddin , Elliott Steven , Egrie Joan C. , Browne Jeffrey K. , Begley C. Glenn , Molineux Graham
Published: May 2005

The unit of erythropoietic activity has long been the standard by which erythropoietic agents are judged, but the development of long-acting agents such as darbepoetin alfa has highlighted the shortcomings of this approach. To this point, we compared the in vivo activity of Epoetin alfa and darbepoetin alfa per microgram of protein core. Using the established mass-to-unit conversion for Epoetin alfa (1 µg ≅ 200 U), we then calculated darbepoetin alfa activity in units. Activity varied with treatment regimen (1 µg darbepoetin alfa ≅ 800 U for 3 times weekly dosing to 8,000 U for a single injection). This analysis reveals the inadequacy of evaluating darbepoetin alfa activity in terms of standard erythropoietic units. We therefore propose that for molecules with heightened biological activity, a more legitimate basis for comparison is the protein mass.
Molecular Basis of Thalassemia Syndromes in Serbia and Montenegro
Authors: Pavlovic S. , Urosevic J. , Poznanic J. , Perisic L.J. , Petrucev B. , Tosic N. , Krivokapic-Dokmanovic L. , Janic D. , Cvorkov-Drazic M. , Bunjevacki G.
Published: May 2005

This study reports the molecular characterization of thalassemia syndromes in Serbian and Montenegrin populations. We identified eight β-thalassemia mutations [codon 39 (C→T), IVS-I-110 (G→A), IVS-II-745 (C→G), codon 44 (-C), –87 (C→G), IVS-II-1 (G→A), IVS-I-6 (T→C), IVS I-1 (G→A)] in 70 members of 29 families using polymerase chain reaction, reverse dot blot, amplification refractory mutation system and direct sequencing analysis. Hemoglobin (Hb) Lepore was found to be the most common cause of the thalassemia phenotype. Hb Sabine and α-thalassemia were detected as well. We also studied β-globin gene cluster haplotypes and their association with the most common mutations. A novel haplotype associated with the Hb Lepore gene was identified. The results presented herein allowed the implementation of a prenatal diagnosis program in Serbia and Montenegro.
Philadelphia-Chromosome-Positive T-Lymphoblastic Leukemia: Acute Leukemia or Chronic Myelogenous Leukemia Blastic Crisis
Authors: Raanani Pia , Trakhtenbrot Luba , Rechavi Gideon , Rosenthal Esther , Avigdor Abraham , Brok-Simoni Frida , Leiba Merav , Amariglio Ninette , Nagler Arnon , Ben-Bassat Isaac
Published: May 2005

The Ph1 chromosome has rarely been reported in T-lineage acute lymphoblastic leukemia (T-ALL), and the clinical relevance of this translocation in T-ALL is currently unknown. In chronic myelogenous leukemia (CML) some data indicate derivation of T-cells from the leukemic clone and only a few cases of T-derived blastic crisis have been reported and quite often disputed. Particularly in cases identified initially in blastic crisis it may be difficult to distinguish those from Ph1-positive T-ALL. We herein report 2 patients who presented with a clinical picture of Ph1-positive T-ALL and who raised a differential diagnosis from T-cell blastic crisis of CML. We review the literature and suggest clinical and laboratory features that can help in the diagnosis. According to our literature review, 23 cases of Ph1-positive T-ALL and 44 cases of T-cell blastic crisis of CML, including ours, were reported. Some major differences between the two entities could help in establishing a diagnosis of Ph1-positive T-cell blastic crisis of CML vs. Ph1-positive T-ALL: Male sex and younger age was more predominant in T-ALL. While in most cases of CML blastic crisis there was a history of CML there was no such history in the T-ALL cases. Medullary involvement with lymphoblastic leukemia was present in all cases of T-ALL but only in about half of the cases of CML blastic crisis. None of the CML-blastic crisis cases tested by RT-PCR showed the minor breakpoint transcript, while 2 cases with T-ALL had the minor breakpoint transcript and 1 had both transcripts. Combined morphologic and FISH analysis can help to distinguish between the two entities and was applied in one of our cases. Although both entities carry a severe prognosis, differentiating between them might have clinical relevance, especially in the imatinib era.
Postnatal Expression of the Serotonin Transporter in Auditory Brainstem Neurons
Authors: Thompson A.M. , Lauder J.M.
Published: May 2005

To investigate the putative role of serotonin (5-HT) in auditory brainstem development, the expression of the 5-HT transporter (5-HTT) was evaluated in the normal mouse brainstem at 6 different postnatal ages. The brains of C3H/HeJ mice at birth (P0) and P1, P8–P9, P13, P21–P22, P35–P36 and P48–P50 were collected and processed immunohistochemically with an antibody raised against the 5-HTT. 5-HTT immunoreactivity (5-HTT-IR) was first observed in P8 mice and was localized to cell bodies in the ventral cochlear nucleus (VCN) and principal nuclei of the superior olivary complex, including the medial nucleus of the trapezoid body. Labeled neurons were found in similar regions in older mice except at P48–50, where labeled neurons were observed in the VCN only. 5-HTT-IR was especially prominent in VCN neurons at P21 and was observed in all of the brains examined at this age. These results indicate that auditory brainstem neurons of the normal inbred mouse express the 5-HTT postnatally. The presence of 5-HTT-IR in neurons located in the VCN indicates a regional expression of the 5-HTT that is related to the ascending auditory pathway. The timing of 5-HTT expression indicates that 5-HT may modulate developmental processes that rely on cochlear input.
Individual Analysis of EEG Band Power and Clinical Drug Response in Schizophrenia
Authors: Kikuchi Mitsuru , Wada Yuji , Higashima Masato , Nagasawa Tatsuya , Takeda Tsutomu , Koshino Yoshifumi
Published: May 2005

The main purpose of this study was to investigate the relationship between short-term clinical outcome and changes in electroencephalogram (EEG) power after drug treatment in patients with schizophrenia, and also to compare two different methods for quantitative EEG analysis. EEG power analysis was performed by both conventional fixed frequency band and adjusted frequency band based on individual alpha frequency (IAF) in 16 drug-naive patients before and after drug administration. In the theta bands determined by both conventional fixed band and IAF methods, the EEG power after treatment was larger than that before treatment. In addition, there was a correlation between EEG power and clinical drug response evaluated by changes in BPRS score. With regard to this correlation, IAF methods showed no apparent advantage over methods using conventional fixed frequency bands. Conventional quantitative EEG analysis can still serve as a useful tool for the assessment of short-term outcome of drug treatment.
Contributions of Depressive Mood and Circulating Inflammatory Markers to Coronary Heart Disease in Healthy European Men
Authors: Empana J.P. , Sykes D.H. , Luc G. , Juhan-Vague I. , Arveiler D. , Ferrieres J. , Amouyel P. , Bingham A. , Montaye M. , Ruidavets J.B. , Haas B. , Evans A. , Jouven X. , Ducimetiere P.
Published: May 2005

Background—

Data on the possible association between depressive disorders and inflammatory markers are scarce and inconsistent. We investigated whether subjects with depressive mood had higher levels of a wide range of inflammatory markers involved in coronary heart disease (CHD) incidence and examined the contribution of these inflammatory markers and depressive mood to CHD outcome.

Methods and Results—

We built a nested case-referent study within the Prospective Epidemiological Study of Myocardial Infarction (PRIME) study of healthy middle-aged men from Belfast and France. We considered the baseline plasma sample from 335 future cases (angina pectoris, nonfatal myocardial infarction, coronary death) and 670 matched controls (2 controls per case). Depressive mood characterized men whose baseline depression score (13-item modification of the Welsh depression subscale) was in the fourth quartile (mean score, 5.75; range, 4 to 12). On average, men with depressive mood had 46%, 16%, and 10% higher C-reactive protein, interleukin-6, and intercellular adhesion molecule-1 levels, respectively, independently of case-control status, social characteristics, and classic cardiovascular risk factors; no statistical difference was found for fibrinogen. The odds ratios of depressive mood for CHD were 1.35 (95% CI, 1.05 to 1.73) in univariate analysis and 1.50 (95% CI, 1.04 to 2.15) after adjustment for social characteristics and classic cardiovascular risk factors. The latter odds ratio remained unchanged when each inflammatory marker was added separately, and in this analysis, each inflammatory marker contributed significantly to CHD event risk.

Conclusions—

These data support an association of depressive mood with inflammatory markers and suggest that depressive mood is related to CHD even after adjustment for these inflammatory markers.
Forced Expression of α-Myosin Heavy Chain in the Rabbit Ventricle Results in Cardioprotection Under Cardiomyopathic Conditions
Authors: James Jeanne , Martin Lisa , Krenz Maike , Quatman Carmen , Jones Fred , Klevitsky Raisa , Gulick James , Robbins Jeffrey
Published: May 2005

Background—

The biochemical differences between the 2 mammalian cardiac myosin heavy chains (MHCs), α-MHC and β-MHC, are well described, but the physiological consequences of basal isoform expression and isoform shifts in response to altered cardiac load are not clearly understood. Mature human ventricle contains primarily the β-MHC isoform. However, the α-MHC isoform can be detected in healthy human ventricle and appears to be significantly downregulated in failing hearts. The unique biochemical properties of the α-MHC isoform might offer functional advantages in a failing heart that is expressing only the β-MHC isoform. This hypothesis cannot be tested in mice or rats because both species express α-MHC as the predominant isoform.

Methods and Results—

To test the effects of persistent α-MHC expression on the background of β-MHC, we made transgenic (TG) rabbits that expressed rabbit α-MHC cDNA in the ventricle so that the endogenous myosin was partially replaced by the transgenically encoded species. Molecular, histological, and functional analyses showed no significant baseline effects in the TG rabbits compared with nontransgenic (NTG) littermates. To determine whether α-MHC expression afforded any advantages to stressed myocardium, a cohort of TG and NTG rabbits was subjected to rapid ventricular pacing. Although both the TG and NTG rabbits developed dilated cardiomyopathy, the TG rabbits had a higher shortening fraction, less septal thinning, and more normal ±dP/dt than paced NTG rabbits.

Conclusions—

Transgenic expression of α-MHC does not have any apparent detrimental effects under basal conditions and is cardioprotective in experimental tachycardia-induced cardiomyopathy.
Transgenic Rabbit Model for Human Troponin I–Based Hypertrophic Cardiomyopathy
Authors: Sanbe Atsushi , James Jeanne , Tuzcu Volkan , Nas Selman , Martin Lisa , Gulick James , Osinska Hanna , Sakthivel Sadayappan , Klevitsky Raisa , Ginsburg Kenneth S. , Bers Donald M. , Zinman Bruce , Lakatta Edward G. , Robbins Jeffrey
Published: May 2005

Background—

Transgenic and gene-targeted models have focused on the mouse. Fundamental differences between the mouse and human exist in Ca
2+
handling during contraction/relaxation and in alterations in Ca
2+
flux during heart failure, with the rabbit more accurately reflecting the human system.

Methods and Results—

Cardiac troponin I (cTnI) mutations can cause familial hypertrophic cardiomyopathy. An inhibitory domain mutation, arginine146→glycine (cTnI
146Gly
), was modeled with the use of transgenic expression in the rabbit ventricle. cTnI
146Gly
levels >40% of total cTnI were perinatally lethal, whereas replacement levels of 15% to 25% were well tolerated. cTnI
146Gly
expression led to a leftward shift in the force-pCa
2+
curves with cardiomyocyte disarray, fibrosis, and altered connexin43 organization. In isolated cTnI
146Gly
myocytes, twitch relaxation amplitudes were smaller than in normal cells, but [Ca]
i
transients and sarcoplasmic reticulum Ca
2+
load were not different. Detrended fluctuation analysis of the QT
max
intervals was used to evaluate the cardiac repolarization phase and showed a significantly higher scaling exponent in the transgenic animals.

Conclusions—

Expression of modest amounts of cTnI
146Gly
led to subtle defects without severely affecting cardiac function. Aberrant connexin organization, subtle morphological deficits, and an altered fractal pattern of the repolarization phase of transgenic rabbits, in the absence of entropy or other ECG abnormalities, may indicate an early developing pathology before the onset of more obvious repolarization abnormalities or major alterations in cardiac mechanics.