Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Bacterial OmpA and Host Cytoskeleton in the Invasion of Human Intestinal Epithelial Cells by Enterobacter sakazakii

Enterobacter sakazakii is an emerging pathogen in neonates and infants. Interactions of E. sakazakii with intestinal epithelium could be vital in the pathogenesis of enteric infections and in its systemic dissemination. The present study investigated the interaction of E. sakazakii with human intestinal epithelial (INT407) cells and the role of bacterial outer membrane protein A (OmpA) and host cytoskeleton in these interactions. E. sakazakii invaded INT407 cells with moderate efficiency. An ompA– mutant of E. sakazakii was significantly attenuated in its invasiveness, and complementation restored the invasive phenotype significantly. Drugs acting on host cell microfilaments (MF) and microtubules (MT) significantly inhibited bacterial invasion. Localization of both microfilaments (MF) and microtubules (MT) was observed in INT407 cells following E. sakazakii infection. The results suggest that E. sakazakii invasion of INT407 cells involves participation of both MF and MT and bacterial OmpA plays a critical role in invasion.
Large-Scale Sequence Analysis of M Gene of Influenza A Viruses from Different Species: Mechanisms for Emergence and Spread of Amantadine Resistance

ABSTRACT Influenza A virus infects many species, and amantadine is used as an antiviral agent. Recently, a substantial increase in amantadine-resistant strains has been reported, most of which have a substitution at amino acid position 31 in the M2 gene. Understanding the mechanism responsible for the emergence and spread of antiviral resistance is important for developing a treatment protocol for seasonal influenza and for deciding on a policy for antiviral stockpiling for pandemic influenza. The present study was conducted to identify the existence of drug pressure on the emergence and spread of amantadine-resistant influenza A viruses. We analyzed data on more than 5,000 virus sequences and constructed a phylogenetic tree to calculate selective pressures on sites in the M2 gene associated with amantadine resistance (positions 26, 27, 30, and 31) among different hosts. The phylogenetic tree revealed that the emergence and spread of the drug-resistant M gene in different hosts and subtypes were independent and not through reassortment. For human influenza virus, positive selection was detected only at position 27. Selective pressures on the sites were not always higher for human influenza virus than for viruses of other hosts. Additionally, selective pressure on position 31 did not increase after the introduction of amantadine. Although there is a possibility of drug pressure on human influenza virus, we could not find positive pressure on position 31. Because the recent rapid increase in drug-resistant virus is associated with the substitution at position 31, the resistance may not be related to drug use.
Capsulelike surface material of Mycoplasma dispar induced by in vitro growth in culture with bovine cells is antigenically related to similar structures expressed in vivo

Electron microscopy has been used to show that Mycoplasma dispar produces an external capsulelike material in vivo that has an affinity for both ruthenium red and polycationic ferritin. This extracellular material is lost upon passage in culture medium but can be regained with a single passage on bovine lung fibroblast (BLF) cells. To confirm that the extracellular material associated with cell-grown mycoplasmas was the same as that observed in infected calves, rabbit antibodies were produced to purified capsulelike material isolated by protease digestion of cell-grown organisms. These antibodies bound to capsulelike material on the surface of M. dispar cells colonizing the bronchial epithelium of infected calves and to capsulelike material from cell-grown mycoplasmas. Calves infected with M. dispar produced antibodies in lung secretions that were capable of binding to the purified capsulelike material. The Fab fragments of rabbit antibodies to in vitro-produced capsulelike material could block this binding, indicating that the capsulelike material was similar in both in vivo-grown and cell-grown organisms. The carbohydrate nature of the capsular material suggested by the ruthenium red and polycationic staining characteristics was confirmed by its binding to Ricinus communis agglutinin, a galactose-specific lectin. These studies confirm that capsule material produced during infections with M. dispar share antigenic determinants with the material produced under in vitro conditions and that association with mammalian cells induces production of this material.
Epidural Morphine Improves Pain Relief and Maintains Sensory Analgesia during Continuous Epidural Bupivacaine after Abdominal Surgery

Twenty patients scheduled for elective major abdominal surgery were matched into two groups with regard to age, sex, height, body weight, and surgical procedure. Both groups received general anesthesia plus lumbar epidural analgesia with similar loading doses of bupivacaine 0.5% (23.1 ± 1.0 and 23.3 ± 0.8 ml) (mean ± SEM) followed by continuous infusion of plain bupivacaine 0.5% (8 ml/hr) plus, in one group, epidural morphine (0.5 mg/hr). Pain score on a 5-point scale and sensory analgesia (pin prick) were assessed hourly for 16 hours after skin incision. If sensory analgesia decreased more than 5 segments from preoperative levels or if pain scores reached 2 (moderate pain), the patients were removed from the study, and pain was treated with other methods.Preoperative mean (± SEM) sensory levels of analgesia were similar in the bupivacaine and the bupivacainemorphine groups (T3.4 ± 0.5 and T3.3 ± 0.4, respectively). In the group receiving only bupivacaine, sensory analgesia regressed over time with a simultaneous increase in pain score. Thus, within 10 hr after skin incision, seven patients in this group were discharged from the study, and 16 hr after incision only one patient maintained initial level of sensory analgesia. In contrast, each patient receiving bupivacaine plus morphine had stable sensory analgesia and was completely free of pain as indicated by a mean pain score of zero during the 16-hr observation period. Thus epidural morphine may improve pain relief and maintain analgesia during continuous epidural bupivacaine administration after abdominal surgery.
Variation in Its C-Terminal Amino Acids Determines Whether Endo-β-Mannanase Is Active or Inactive in Ripening Tomato Fruits of Different Cultivars1

Endo-β-mannanase cDNAs were cloned and characterized from ripening tomato (Lycopersicon esculentum Mill. cv Trust) fruit, which produces an active enzyme, and from the tomato cv Walter, which produces an inactive enzyme. There is a two-nucleotide deletion in the gene from tomato cv Walter, which results in a frame shift and the deletion of four amino acids at the C terminus of the full-length protein. Other cultivars that produce either active or inactive enzyme show the same absence or presence of the two-nucleotide deletion. The endo-β-mannanase enzyme protein was purified and characterized from ripe fruit to ensure that cDNA codes for the enzyme from fruit. Immunoblot analysis demonstrated that non-ripening mutants, which also fail to exhibit endo-β-mannanase activity, do so because they fail to express the protein. In a two-way genetic cross between tomato cvs Walter and Trust, all F1 progeny from both crosses produced fruit with active enzyme, suggesting that this form is dominant and homozygous in tomato cv Trust. Self-pollination of a plant from the heterozygous F1 generation yielded F2 plants that bear fruit with and without active enzyme at a ratio appropriate to Mendelian genetic segregation of alleles. Heterologous expression of the two endo-β-mannanase genes in Escherichia coliresulted in active enzyme being produced from cultures containing the tomato cv Trust gene and inactive enzyme being produced from those containing the tomato cv Walter gene. Site-directed mutagenesis was used to establish key elements in the C terminus of the endo-β-mannanase protein that are essential for full enzyme activity.
Are halocarboranes suitable for substitution reactions? The case for 3-I-1,2-closo-C(2)B(10)H(11): molecular orbital calculations, aryldehalogenation reactions, (11)B NMR interpretation of closo-carboranes, and molecular structures of 1-Ph-3-Br-1,2-closo-C(2)B(10)H(10) and 3-Ph-1,2-closo-C(2)B(10)H(

In this paper, the chemistry of 3-X-1,2-closo-C(2)B(10)H(11) (X = halogen) derivatives is extended. Molecular orbital and (11)B and (13)C NMR calculations on these species are presented. A qualitative interpretation of the (11)B NMR spectra of closo o-carborane derivatives is also provided. The synthesis of 3-X-1-R-o-carborane (X = I, Br and R = Me, Ph) derivatives is reported, and aryldehalogenation at the B3 position is reported for the first time. The molecular and crystal structures of 1-phenyl-3-bromo-1,2-dicarba-closo-dodecaborane and 3-phenyl-1,2-dicarba-closo-dodecaborane are described.
Event‐related potential and eye tracking evidence of the developmental dynamics of face processing

Although the wide neural network and specific processes related to faces have been revealed, the process by which face‐processing ability develops remains unclear. An interest in faces appears early in infancy, and developmental findings to date have suggested a long maturation process of the mechanisms involved in face processing. These developmental changes may be supported by the acquisition of more efficient strategies to process faces (theory of expertise) and by the maturation of the face neural network identified in adults. This study aimed to clarify the link between event‐related potential (ERP) development in response to faces and the behavioral changes in the way faces are scanned throughout childhood. Twenty‐six young children (4–10 years of age) were included in two experimental paradigms, the first exploring ERPs during face processing, the second investigating the visual exploration of faces using an eye‐tracking system. The results confirmed significant age‐related changes in visual ERPs (P1, N170 and P2). Moreover, an increased interest in the eye region and an attentional shift from the mouth to the eyes were also revealed. The proportion of early fixations on the eye region was correlated with N170 and P2 characteristics, highlighting a link between the development of ERPs and gaze behavior. We suggest that these overall developmental dynamics may be sustained by a gradual, experience‐dependent specialization in face processing (i.e. acquisition of face expertise), which produces a more automatic and efficient network associated with effortless identification of faces, and allows the emergence of human‐specific social and communication skills.
Synthesis and Biological Activity of Peptide Derivatives of Iodoquinazolinones/Nitroimidazoles

Two substituted quinazolinyl/imidazolyl-salicylic acids 5, 6 were synthesized by the reaction of 6-iodo-2-methylbenzoxazin-4-one/5-nitroimidazole with 5-aminosalicylic acid (5-ASA). Coupling of compounds 5 and 6 with different amino acid ester hydrochlorides, dipeptide and tripeptide methyl esters yielded novel quinazolino/imidazolopeptide derivatives 5a-f and 6a-g. The chemical structures of all newly synthesized compounds were confirmed by means of FT-IR, 1H- and 13C-NMR, MS and elemental analysis. Selected peptide ester derivatives were further hydrolyzed by using lithium hydroxide (LiOH) to afford the corresponding acid derivatives 5ba-da and 6ea-ga. All peptide derivatives were assayed for antimicrobial and anthelmintic activities against eight pathogenic microbes and three earthworm species. Among the tested compounds, 5e, 5d, 6e and their hydrolyzed analogs 5da and 6ea exhibited higher antimicrobial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans, and 5a, 6g and 6ga displayed better antifungal activity against the dermatophytes Trichophyton mentagrophytes and Microsporum audouinii. Moreover, 6f and its hydrolyzed derivative 6fa showed good anthelmintic activity against Megascoplex konkanensis, Pontoscotex corethruses and Eudrilus eugeniea at dose of 2 mg mL–1.
Validity study of head and neck flexion-extension motion comparing measurements of a pendulum goniometer and roentgenograms.

Study completed in partial fulfillment of requirements for Master of Health Sciences Degree, Physical Therapy, Washington University, St. Louis, MO. Physical therapists measure head and neck flexion-extension with goniometers, assuming that such measures are an accurate appraisal of joint motion. The only universally accepted, reliable, and objective method of measuring joint motion, however, is by roentgenograms, which have potentially harmful effects and are too expensive to be used routinely for assessing changes in motion. A method is discussed for computing head-tilt on neck and neck flexion-extension motion from roentgenograms. Radiographic measures were compared to pendulum goniometer measures for total head and neck motion (i.e., head-tilt on neck plus neck motion in both the flexed and extended positions) showing good correlation (Pearson = 0.97) and good agreement [intraclass correlation (ICC) = 0.98] between measures. This study validated that the pendulum goniometer and roentgenograms obtain the same measures for head and neck motion in the sagittal plane. J Orthop Sports Phys Ther 1990;11(9):414-418.
Magnetoencephalographic Infraslow Activity: A Feasibility Study

Purpose: To explore if background infraslow activity (ISA) can be retrieved from archived magnetoencephalographic (MEG) recordings and its potential clinical relevance. Methods: Archived recordings of 15 patients with epilepsy and 10 normal subjects were evaluated for MEG/EEG delta (0.5–3 Hz) and ISA (0.01–0.1 Hz). The data were obtained on a Neuromag/Elekta system with 204 planar gradiometers and 102 magnetometer sensors and also 60 EEG channels. To remove artifacts, all MEG files were temporal signal space separation filtered. The data were then analyzed with the BESA Research software. Results: Infraslow activity was present in all files for MEG and EEG. Good concordance between EEG and MEG ISA was seen with delta for laterality and with clinical features. Delta frequencies were always less than 2 Hz. During sleep, an inverse relationship between delta and ISA occurred. With increasing depth of sleep, delta activity increased while ISA decreased and vice versa. Intermittent higher amplitude transients, arising from background, were also seen but their nature is at present unknown. Clinically relevant ictal onset baseline shifts were likewise observed. Conclusion: Infraslow activity is a normal segment of the cerebral electromagnetic frequency spectrum. It follows physiologic rules and can be related to areas of pathology. This is in accord with previously published EEG observations and further studies of this segment of the electromagnetic frequency spectrum for its origin and changes in health and disease are indicated.
The dissolution enhancement of piroxicam in its physical mixtures and solid dispersion formulations using gluconolactone and glucosamine hydrochloride as potential carriers

Abstract The solid dispersion technique is one of the most effective methods for improving the dissolution rate of poorly water-soluble drugs; however this is reliant on a suitable carrier and solvent being selected. The work presented explores amino sugars (d-glucosamine HCl and d-gluconolactone) as potential hydrophilic carriers to improve dissolution rate of a poorly water-soluble drug, piroxicam, from physical mixtures and solid dispersion formulations. Solid dispersions of the drug and carrier were prepared using different ratios by the conventional solvent evaporation method. Acetone was used as solvent in the preparation of solid dispersions. Physical mixtures of piroxicam and carrier were also prepared for comparison. The properties of all solid dispersions and physical mixtures were studied using a dissolution tester, Fourier transform infrared, XRD, SEM and differential scanning calorimetry. These results showed that the presence of glucosamine or gluconolactone can increase dissolution rate of piroxicam compared to pure piroxicam. Glucosamine or Gluconolactone could be used as carrier in solid dispersion formulations and physical mixtures to enhance the dissolution rate. Solid state studies showed that no significant changes occurred for piroxicam in physical mixtures and solid dispersion.
Demonstration of vasorelaxant activity with an A1-selective adenosine agonist in porcine coronary artery: involvement of potassium channels.

The vasodilator activity of adenosine has been associated with selective stimulation of A2 receptors. In the present study, the vasorelaxant (VR) activity of an A1-selective agonist, CPA (cyclopentyladenosine), was examined in isolated porcine coronary arterial rings precontracted with prostaglandin F2 alpha and compared to the A2-selective agonist DPMA (N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl] adenosine). DPMA, approximately 13-fold selective for the rat brain A2 receptor, relaxed isolated coronary arterial rings with an EC50 of 0.59 +/- 0.19 microM (n = 23) whereas CPA, 2200-fold selective for the rat brain A1 receptor, was approximately 5-fold less potent with an EC50 of 3.18 +/- 0.6 microM (n = 11). At low concentrations (10-300 nM) CPA caused vasoconstriction, indicative of the A1-selective nature of this agonist. CGS 15943 (100 nM), a nonselective adenosine antagonist, attenuated the VR activity of DPMA and CPA, causing a 9- and 12-fold rightward shift of the dose-response curves, respectively, whereas 8-cyclopentyl-1,3-dipropylxanthine (20 nM), a highly A1-selective blocker, had no such effect. Both adenosine antagonists abolished the vasoconstrictor response of CPA at low concentrations. The contributions of the cyclic GMP pathway to adenosine-induced VR was assessed using an inhibitor of endothelium-dependent relaxing factor (L-nitroarginine). L-nitroarginine had no effect on the EC50 for CPA-induced VR and, marginally, but not significantly, attenuated DPMA effects. Moreover, no elevation in cyclic GMP levels could be observed in tissues stimulated with CPA or DPMA. (ABSTRACT TRUNCATED AT 250 WORDS)
Evaluation of the safety and efficacy of sibutramine, orlistat and metformin in the treatment of obesity

Aim: Some of our obese patients who were receiving 10 mg/day sibutramine reported feeling hunger at night. To address this, we designed a randomized, prospective clinical trial to study the efficacy and safety of 10 mg sibutramine twice daily (bid), and compare this treatment with 120 mg orlistat three times daily (tid) and 850 mg metformin (bid).
Post‐mortem diagnosis of encephalitis in a 75‐year‐old man associated with human herpesvirus‐6 variant A

An HHV‐6 variant A infection is described in a 75 year‐old man in association with meningoencephalitis identified at autopsy. The patient presented with fever and anorexia, then he developed altered consciousness, motor weakness, progressive lethargy, and coma, and died 21 days after hospital admission. Histopathological examination showed perivascular lymphocytic infiltrates in the central nervous system (CNS). Serum and cerebral spinal fluid (CSF) samples drawn from the patient were tested for viruses by a nested polymerase chain reaction (nPCR). HHV‐6 primers A and C [Aubin et al., 1991 : J Clin Microb 29: 367–372] and HS6AE and HS6AF from [Dewhurst et al. ( 1993 ): J Clin Microb 31: 416–418] disclosed a 750 bp genomic product of HHV‐6 in both types of biological samples. Restricted site analysis showed that the HHV‐6 DNA amplified belonged to the variant A of the virus. Short sequences of HHV‐6 DNA could also be detected in the DNA extracted from formalin‐fixed, paraffin‐embedded sections of CNS tissues by use of one (GM5 and GM6) of three pairs of HHV‐6 primers that were selected. Immunohistochemical examination of brain sections, employing a specific monoclonal antibody directed against the HHV‐6 gp 102 protein, detected the viral antigen in neurons and glial cells. J. Med. Virol. 77:244–248, 2005. © 2005 Wiley‐Liss, Inc.
PIOGLITAZONE INHIBITS HOMOCYSTEINE‐INDUCED MIGRATION OF VASCULAR SMOOTH MUSCLE CELLS THROUGH A PEROXISOME PROLIFERATOR‐ACTIVATED RECEPTOR γ‐INDEPENDENT MECHANISM

1 Peroxisome proliferator‐activated receptor (PPAR)‐γ agonists have been demonstrated to exert protective effects against homocysteine (Hcy)‐induced pathogenesis. However, the effects of PPAR‐γ agonists on Hcy‐induced migration are unknown. In the present study, we examined the effect of pioglitazone on the migration of vascular smooth muscle cells (VSMC) induced by Hcy and the possible mechanism involved. 2 Vascular smooth muscle cells were isolated from the thoracic aortas of male Sprague‐Dawley rats. The migration of VSMC was examined using a transwell technique. The generation of intracellular reactive oxygen species (ROS) was measured using the ROS‐sensitive fluoroprobe 2′,7′‐dichlorodihydrofluorescein diacetate. The activity of NAD(P)H oxidase was assessed by lucigenin enhanced chemiluminescence. Activation of p38 mitogen‐activated protein kinase (MAPK) was determined by western blotting. 3 The results showed that pioglitazone dose‐dependently inhibited the migration of VSMC induced by Hcy. This was not reversed by the PPAR‐γ antagonist GW9662. In addition, pretreatment with the NAD(P)H oxidase inhibitor diphenylene iodonium (DPI), the free radical scavenger N‐acetylcysteine and the p38 MAPK inhibitor SB202190 blocked Hcy‐induced VSMC migration. Furthermore, we observed that pioglitazone suppressed Hcy‐induced intracellular ROS production; similar effects were observed with DPI and NAC. Pioglitazone attenuated Hcy‐induced activation of NAD(P)H oxidase. Moreover, pioglitazone blocked Hcy‐induced p38 MAPK phosphorylation; similar effects were observed for DPI, NAC and SB202190. 4 The data demonstrate that pioglitazone inhibits Hcy‐induced VSMC migration that is independent of PPAR‐γ. Furthermore, part of the biological effect of pioglitazone involves a decrease in the levels of NAD(P)H oxidase derived‐ROS and p38 MAPK activation.
Multiple imputation to estimate the association between eyes in disease progression with interval‐censored data

In many ophthalmologic studies, progression of diseases such as diabetic retinopathy, age‐related maculopathy, cataract, and glaucoma is only noted when each eye is examined at intervals that commonly vary between subjects. Such data are often analysed using continuous time survival methods with observed progression assumed to occur at the end of the interval. Tied times of progression can lead to substantial bias in estimation of the association between progression in right and left eyes. We describe a multiple imputation strategy to create multiple data sets without ties, based on drawing interval‐censored progression times from a parametric gamma frailty model that accounts for continuous and discrete covariates. We illustrate the method with data from 478 patients with insulin‐dependent diabetes mellitus who were followed for progression of diabetic retinopathy in the Sorbinil Retinopathy Trial. Resolution of tied failure times allows for valid estimation of the hazard of progression in one eye given the progression status of the other eye. A simulation study suggests that the method performs well. Results highlight the advantage of multiple imputation that data imputed under one model can be analysed under several alternative models. Copyright © 2004 John Wiley & Sons, Ltd.
New High Directivity Coupler Design Using Feed-forward Compensation Technique

In this paper, an original high directivity directional coupler is presented. The proposed structure consists of a dual-directional coupler connected at its coupled terminations to a feed-forward compensation circuit. The compensation circuit is used to increase the coupler isolation factor of the obtained directional coupler. The directivity of a commercial dual-directional coupler has been improved by 40 dB using the proposed method.