bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Ageing and Gender on Naturally Acquired Antibodies to Pneumococcal Capsular Polysaccharides and Virulence-Associated Proteins
Authors: Simell Birgit , Lahdenkari Mika , Reunanen Antti , Käyhty Helena , Väkeväinen Merja
Published: July 2008

Elderly individuals are susceptible to pneumococcal infections. Although factors contributing to the increased susceptibility of the elderly to bacterial infections may be several, compromised immune function, a consequence of normal human ageing, is widely accepted to play a role. We evaluated the effect of ageing on the concentrations of naturally acquired antibodies to pneumococcal capsular polysaccharides (PPS) and protein antigens. The concentrations of immunoglobulin G (IgG) and IgM antibodies to the PPS of serotypes 3, 4, 6B, 9V, 14, and 23F and IgG antibodies to the pneumococcal virulence-associated proteins CbpA, LytC, PhtD and its C-terminal fragment (PhtD C), NanA, PspA fam1, and PspA fam2 were measured by enzyme immunoassay in the sera of younger (30 to 64 years of age) and elderly (65 to 97 years of age) adults. The concentrations of anti-PPS IgG against serotypes 3 and 6B, of anti-PPS IgM against serotypes 3, 4, 6B, 9V, and 23F, and of anti-protein IgG against all tested antigens were significantly lower in the elderly than in younger adults. A stronger decline in anti-PPS antibody concentrations was seen with age in women compared to men, while anti-protein antibody concentrations were mainly similar between the genders. Age, gender, and the nature of the antigen have substantial and varying effects on the antibody concentrations in the sera of adults.
VanB Phenotype-
vanA
Genotype
Enterococcus faecium
with Heterogeneous Expression of Teicoplanin Resistance
Authors: Park Il Joong , Lee Wee Gyo , Shin Jong Hee , Lee Kyung Won , Woo Gun Jo
Published: July 2008

Six VanB phenotype-
vanA
genotype isolates of
Enterococcus faecium
with heterogeneous expression of teicoplanin resistance which gave rise to an outbreak at a Korean tertiary care teaching hospital have IS
1216V
in the coding region of
vanS
. This could be the underlying cause of the VanB phenotype-
vanA
genotype with heterogeneous expression of teicoplanin resistance.
Functional Analysis of the Complextrans-Activating Response Element RNA Structure in Simian Immunodeficiency Virus
Authors: Centlivre Mireille , Klaver Bep , Berkhout Ben , Das Atze T.
Published: July 2008

Transcription of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) is activated through binding of the viral Tat protein to thetrans-activating response (TAR) element at the 5′ end of the nascent transcript. Whereas HIV type 1 (HIV-1) TAR folds a simple hairpin structure, the corresponding domains of HIV-2 and SIVmac exhibit a more complex structure composed of three stem-loops. This structural polymorphism may be attributed to additional functions of TAR in HIV-2/SIVmac replication. We recently constructed an SIVmac variant that does not require the Tat-TAR interaction for transcription. We used this variant to study additional roles of TAR in SIVmac replication and generated mutants with a truncated TAR structure. We demonstrate that partial or nearly complete removal of TAR does not impair viral transcription, RNA processing, and translation. Moreover, these deletions do not significantly affect virus replication in the PM1 T-cell line and macaque peripheral blood mononuclear cells. These results demonstrate that the complex TAR structure in SIVmac has no other essential function in virus replication in vitro besides its role in Tat-mediated activation of transcription.
Central Role of Reverting Mutations in HLA Associations with Human Immunodeficiency Virus Set Point
Authors: Matthews Philippa C. , Prendergast Andrew , Leslie Alasdair , Crawford Hayley , Payne Rebecca , Rousseau Christine , Rolland Morgane , Honeyborne Isobella , Carlson Jonathan , Kadie Carl , Brander Christian , Bishop Karen , Mlotshwa Nonkululeko , Mullins James I. , Coovadia Hoosen , Ndung'u Thumbi , Walker Bruce D. , Heckerman David , Goulder Philip J. R.
Published: July 2008

Much uncertainty still exists over what T-cell responses need to be induced by an effective human immunodeficiency virus (HIV) vaccine. Previous studies have hypothesized that the effective CD8
+
T-cell responses are those driving the selection of escape mutations that reduce viral fitness and therefore revert posttransmission. In this study, we adopted a novel approach to define better the role of reverting escape mutations in immune control of HIV infection. This analysis of sequences from 710 study subjects with chronic C-clade HIV type 1 infection demonstrates the importance of mutations that impose a fitness cost in the control of viremia. Consistent with previous studies, the viral set points associated with each HLA-B allele are strongly correlated with the number of Gag-specific polymorphisms associated with the relevant HLA-B allele (
r
= −0.56,
P
= 0.0034). The viral set points associated with each HLA-C allele were also strongly correlated with the number of Pol-specific polymorphisms associated with the relevant HLA-C allele (
r
= −0.67,
P
= 0.0047). However, critically, both these correlations were dependent solely on the polymorphisms identified as reverting. Therefore, despite the inevitable evolution of viral escape, viremia can be controlled through the selection of mutations that are detrimental to viral fitness. The significance of these results is in highlighting the rationale for an HIV vaccine that can induce these broad responses.
S Acylation of the Hemagglutinin of Influenza Viruses: Mass Spectrometry Reveals Site-Specific Attachment of Stearic Acid to a Transmembrane Cysteine
Authors: Kordyukova Larisa V. , Serebryakova Marina V. , Baratova Ludmila A. , Veit Michael
Published: July 2008

S acylation of cysteines located in the transmembrane and/or cytoplasmic region of influenza virus hemagglutinins (HA) contributes to the membrane fusion and assembly of virions. Our results from using mass spectrometry (MS) show that influenza B virus HA possessing two cytoplasmic cysteines contains palmitate, whereas HA-esterase-fusion glycoprotein of influenza C virus having one transmembrane cysteine is stearoylated. HAs of influenza A virus having one transmembrane and two cytoplasmic cysteines contain both palmitate and stearate. MS analysis of recombinant viruses with deletions of individual cysteines, as well as tandem-MS sequencing, revealed the surprising result that stearate is exclusively attached to the cysteine positioned in the transmembrane region of HA.
The Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 4E10 Monoclonal Antibody Is Better Adapted to Membrane-Bound Epitope Recognition and Blocking than 2F5
Authors: Huarte Nerea , Lorizate Maier , Maeso Rubén , Kunert Renate , Arranz Rocio , Valpuesta José M. , Nieva José L.
Published: July 2008

The broadly neutralizing 2F5 and 4E10 monoclonal antibodies (MAbs) recognize epitopes within the membrane-proximal external region (MPER) that connects the human immunodeficiency virus type 1 (HIV-1) envelope gp41 ectodomain with the transmembrane anchor. By adopting different conformations that stably insert into the virion external membrane interface, such as helical structures, a conserved aromatic-rich sequence within the MPER is thought to participate in HIV-1-cell fusion. Recent experimental evidence suggests that the neutralizing activity of 2F5 and 4E10 might correlate with the MAbs' capacity to recognize epitopes inserted into the viral membrane, thereby impairing MPER fusogenic activity. To gain new insights into the molecular mechanism underlying viral neutralization by these antibodies, we have compared the capacities of 2F5 and 4E10 to block the membrane-disorganizing activity of MPER peptides inserted into the surface bilayer of solution-diffusing unilamellar vesicles. Both MAbs inhibited leakage of vesicular aqueous contents (membrane permeabilization) and intervesicular lipid mixing (membrane fusion) promoted by MPER-derived peptides. Thus, our data support the idea that antibody binding to a membrane-inserted epitope may interfere with the function of the MPER during gp41-induced fusion. Antibody insertion into a cholesterol-containing, uncharged virion-like membrane is mediated by specific epitope recognition, and moreover, partitioning-coupled folding into a helix reduces the efficiency of 2F5 MAb binding to its epitope in the membrane. We conclude that the capacity to interfere with the membrane activity of conserved MPER sequences is best correlated with the broad neutralization of the 4E10 MAb.
Comparative Aspects of Animal Regeneration
Authors: Brockes Jeremy P. , Kumar Anoop
Published: July 2008

Most but not all phyla include examples of species that are able to regenerate large sections of the body plan. The mechanisms underlying regeneration on this scale are currently being studied in a variety of contexts in both vertebrates and invertebrates. Regeneration generally involves the formation of a wound epithelium after transection or injury, followed by the generation of regenerative progenitor cells and morphogenesis to give the regenerate. Common mechanisms may exist in relation to each of these aspects. For example, the initial proliferation of progenitor cells often depends on the nerve supply, whereas morphogenesis reflects the generation of positional disparity between adjacent cells—the principle of intercalation. These mechanisms are reviewed here across a range of contexts. We also consider the evolutionary origins of regeneration and how regeneration may relate to both agametic reproduction and to ontogeny.
Purinergic and nitrergic junction potential in the human colon
Authors: Gallego Diana , Gil Víctor , Aleu Jordi , Aulí Mariona , Clavé Pere , Jiménez Marcel
Published: July 2008

The aim of the present work is to investigate a putative junction transmission [nitric oxide (NO) and ATP] in the human colon and to characterize the electrophysiological and mechanical responses that might explain different functions from both neurotransmitters. Muscle bath and microelectrode techniques were performed on human colonic circular muscle strips. The NO donor sodium nitroprusside (10 μM), but not the P2Y receptor agonist adenosine 5′-O-2-thiodiphosphate (10 μM), was able to cause a sustained relaxation. NG-nitro-l-arginine (l-NNA) (1 mM), a NO synthase inhibitor, but not 2′-deoxy- N6-methyl adenosine 3′,5′-diphosphate tetraammonium salt (MRS 2179) (10 μM), a P2Y antagonist, increased spontaneous motility. Electrical field stimulation (EFS) at 1 Hz caused fast inhibitory junction potentials (fIJPs) and a relaxation sensitive to MRS 2179 (10 μM). EFS at higher frequencies (5 Hz) showed biphasic IJP with fast hyperpolarization sensitive to MRS 2179 followed by sustained hyperpolarization sensitive to l-NNA; both drugs were needed to fully block the EFS relaxation at 2 and 5 Hz. Two consecutive single pulses induced MRS 2179-sensitive fIJPs that showed a rundown. The rundown mechanism was not dependent on the degree of hyperpolarization and was present after incubation with l-NNA (1 mM), hexamethonium (100 μM), MRS 2179 (1 μM), and NF023 (10 μM). We concluded that single pulses elicit ATP release from enteric motor neurons that cause a fIJP and a transient relaxation that is difficult to maintain over time; also, NO is released at higher frequencies causing a sustained hyperpolarization and relaxation. These differences might be responsible for complementary mechanisms of relaxation being phasic (ATP) and tonic (NO).
Lung EC-SOD overexpression attenuates hypoxic induction of Egr-1 and chronic hypoxic pulmonary vascular remodeling
Authors: Nozik-Grayck Eva , Suliman Hagir B. , Majka Susan , Albietz Joseph , Van Rheen Zachary , Roush Kevin , Stenmark Kurt R.
Published: July 2008

Although production of reactive oxygen species (ROS) such as superoxide (O2·−) has been implicated in chronic hypoxia-induced pulmonary hypertension (PH) and pulmonary vascular remodeling, the transcription factors and gene targets through which ROS exert their effects have not been completely identified. We used mice overexpressing the extracellular antioxidant enzyme extracellular superoxide dismutase (EC-SOD TG) to test the hypothesis that O2·− generated in the extracellular compartment under hypoxic conditions contributes to PH through the induction of the transcription factor, early growth response-1 (Egr-1), and its downstream gene target, tissue factor (TF). We found that chronic hypoxia decreased lung EC-SOD activity and protein expression in wild-type mice, but that EC-SOD activity remained five to seven times higher in EC-SOD TG mice under hypoxic conditions. EC-SOD overexpression attenuated chronic hypoxic PH, and vascular remodeling, measured by right ventricular systolic pressures, proliferation of cells in the vessel wall, muscularization of small pulmonary vessels, and collagen deposition. EC-SOD overexpression also prevented the early hypoxia-dependent upregulation of the redox-sensitive transcription factor Egr-1 and the procoagulant protein TF. These data provide the first evidence that EC-SOD activity is disrupted in chronic hypoxia, and increased EC-SOD activity can attenuate chronic hypoxic PH by limiting the hypoxic upregulation of redox-sensitive genes.
Subfornical organ differentially modulates baroreflex function in normotensive and two-kidney, one-clip hypertensive rats
Authors: Maliszewska-Scislo Maria , Chen Haiping , Augustyniak Robert A. , Seth Dale , Rossi Noreen F.
Published: July 2008

During activation of the renin-angiotensin system, hindbrain circumventricular organs such as the area postrema have been implicated in modulating the arterial baroreflex. This study was undertaken to test the hypothesis that the subfornical organ (SFO), a forebrain circumventricular structure, may also modulate the baroreflex. Studies were performed in rats with two-kidney, one-clip (2K,1C) hypertension as a model of endogenously activated renin-angiotensin system. Baroreflex function was ascertained during ramp infusions of phenylephrine and nitroprusside in conscious sham-clipped and 5-wk 2K,1C rats with either a sham or electrolytically lesioned SFO. Lesioning significantly decreased mean arterial pressure in 2K,1C rats from 158 ± 7 to 131 ± 4 mmHg but not in sham-clipped rats. SFO-lesioned, sham-clipped rats had a significantly higher upper plateau and range of the renal sympathetic nerve activity-mean arterial pressure relationship compared with sham-clipped rats with SFO ablation. In contrast, lesioning the SFO in 2K,1C rats significantly decreased both the upper plateau and range of the baroreflex control of renal sympathetic nerve activity, but only the range of the baroreflex response of heart rate decreased. Thus, during unloading of the baroreceptors, the SFO differentially modulates the baroreflex responses in sham-clipped vs. 2K,1C rats. Since lesioning the SFO did not influence plasma angiotensin II (ANG II), the effects of the SFO lesion are not caused by changes in circulating levels of ANG II. These findings support a pivotal role for the SFO in the sympathoexcitation observed in renovascular hypertension and in baroreflex regulation of sympathetic activity in both normal and hypertensive states.
Modulation of Phasic and Tonic Muscle Synergies With Reaching Direction and Speed
Authors: d'Avella Andrea , Fernandez Laure , Portone Alessandro , Lacquaniti Francesco
Published: July 2008

How the CNS masters the many degrees of freedom of the musculoskeletal system to control goal-directed movements is a long-standing question. We have recently provided support to the hypothesis that the CNS relies on a modular control architecture by showing that the phasic muscle patterns for fast reaching movements in different directions are generated by combinations of a few time-varying muscle synergies: coordinated recruitment of groups of muscles with specific activation profiles. However, natural reaching movements occur at different speeds and require the control of both movement and posture. Thus we have investigated whether muscle synergies also underlie reaching at different speeds as well as the maintenance of stable arm postures. Hand kinematics and shoulder and elbow muscle surface EMGs were recorded in five subjects during reaches to eight targets in the frontal plane at different speeds. We found that the amplitude modulation of three time-invariant synergies captured the variations in the postural muscle patterns at the end of the movement. During movement, three phasic and three tonic time-varying synergies could reconstruct the time-normalized muscle pattern in all conditions. Phasic synergies were modulated in both amplitude and timing by direction and speed. Tonic synergies were modulated only in amplitude by direction. The directional tuning of both types of synergies was well described by a single or a double cosine function. These results suggest that muscle synergies are basic control modules that allow generating the appropriate muscle patterns through simple modulation and combination rules.
Tone-Specific and Nonspecific Plasticity of the Auditory Cortex Elicited by Pseudoconditioning: Role of Acetylcholine Receptors and the Somatosensory Cortex
Authors: Ji Weiqing , Suga Nobuo
Published: July 2008

Experience-dependent plastic changes in the central sensory systems are due to activation of both the sensory and neuromodulatory systems. Nonspecific changes of cortical auditory neurons elicited by pseudoconditioning are quite different from tone-specific changes of the neurons elicited by auditory fear conditioning. Therefore the neural circuit evoking the nonspecific changes must also be different from that evoking the tone-specific changes. We first examined changes in the response properties of cortical auditory neurons of the big brown bat elicited by pseudoconditioning with unpaired tonal (CSu) and electric leg (USu) stimuli and found that it elicited nonspecific changes to CSu (a heart-rate decrease, an auditory response increase, a broadening of frequency tuning, and a decrease in threshold) and, in addition, a small tone-specific change to CSu (a small short-lasting best-frequency shift) only when CSu frequency was 5 kHz lower than the best frequency of a recorded neuron. We then examined the effects of drugs on the cortical changes elicited by the pseudoconditioning. The development of the nonspecific changes was scarcely affected by atropine (a muscarinic cholinergic receptor antagonist) and mecamylamine (a nicotinic cholinergic receptor antagonist) applied to the auditory cortex and by muscimol (a GABAA-receptor agonist) applied to the somatosensory cortex. However, these drugs abolished the small short-lasting tone-specific change as they abolished the large long-lasting tone-specific change elicited by auditory fear conditioning. Our current results indicate that, different from the tone-specific change, the nonspecific changes depend on neither the cholinergic neuromodulator nor the somatosensory cortex.
The PPAR‐γ Agonist 15‐Deoxy‐Δ12,14‐Prostaglandin J2 Attenuates Microglial Production of IL‐12 Family Cytokines: Potential Relevance to Alzheimer′s Disease
Authors: Xu Jihong , Barger Steven W. , Drew Paul D.
Published: July 2008

Accumulation of amyloid‐β peptide (Aβ) appears to contribute to the pathogenesis of Alzheimer′s disease (AD). Therapeutic hope for the prevention or removal of
Aβ deposits has been placed in strategies involving immunization against the Aβ peptide. Initial Aβ immunization studies in animal models of AD showed great promise. However, when this strategy was attempted in human subjects with AD, an unacceptable degree of meningoencephalitis occurred. It is generally believed that this adverse outcome resulted from a T‐cell response to Aβ. Specifically, CD4+ Th1 and Th17 cells may contribute to severe CNS inflammation and limit the utility of Aβ immunization in the treatment of AD. Interleukin (IL)‐12 and IL‐23 play critical roles in the development of Th1 and Th17 cells, respectively. In the present study, Aβ1−42 synergistically elevated the expression of IL‐12 and IL‐23 triggered by inflammatory activation of microglia, and the peroxisome proliferator‐activated receptor (PPAR)‐γ agonist 15‐deoxy‐Δ12,14‐PGJ2 (15d‐PGJ2) effectively blocked the elevation of these proinflammatory cytokines. Furthermore, 15d‐PGJ2 suppressed the Aβ‐related synergistic induction of CD14, MyD88, and Toll‐like receptor 2, molecules that play critical roles in neuroinflammatory conditions. Collectively, these studies suggest that PPAR‐γ agonists may be effective in modulating the development of AD.
Anticancer Activity of Ag(I) N-Heterocyclic Carbene Complexes Derived from 4,5-Dichloro-1H-Imidazole
Authors: Medvetz Doug A. , Hindi Khadijah M. , Panzner Matthew J. , Ditto Andrew J. , Yun Yang H. , Youngs Wiley J.
Published: July 2008

A class of Ag(I) N-heterocyclic carbene silver complexes, 1–3, derived from 4,5-dichloro-1H-imidazole has been evaluated for their anticancer activity against the human cancer cell lines OVCAR-3 (ovarian), MB157 (breast), and Hela (cervical). Silver complexes 1–3 are active against the ovarian and breast cancer cell lines. A preliminary in vivo study shows 1 to be active against ovarian cancer in mice. The results obtained in these studies warrant further investigation of these compounds in vivo.
Vesicoureteral Reflux in the Child with Lazy Bladder Syndrome: The Infrequent Voider
Authors: Grasso Marco , Torelli Fabrizio , Blanco Salvatore , Fortuna Flavio , Baruffi Marco
Published: July 2008

The Infrequent Voider Syndrome or Lazy Bladder Syndrome in children is characterized by a large capacity bladder, frequently associated with a significant volume of residual urine. Usually these patients arrive at medical examination with a history of recurrent urinary infections but without anomalies in the upper urinary tract. We report about a young girl affected by one-sided degree vesico-ureteral reflux due to Lazy Bladder Syndrome that had never been diagnosed before. This patient has been submitted to a prompt bladder training and seems presently to have at last gained a physiological micturition after 9 months of follow-up, without actual evidence of vesicoureteral reflux. Therefore we must stress that it is prominently important considering about infrequent micturition in a paediatric case history or a large capacity bladder, possible presence of bladder dysfunction and vesicoureteral reflux too.
The Achievements and Challenges of Silicon Photonics
Authors: Soref Richard
Published: July 2008

A brief overview of silicon photonics is given here in order to provide a context for invited and contributed papers in this special issue. Recent progress on silicon‐based photonic components, photonic integrated circuits, and optoelectronic integrated circuits is surveyed. Present and potential applications are identified along with the scientific and engineering challenges that must be met in order to actualize applications. Some on‐going government‐sponsored projects in silicon optoelectronics are also described.
Anxiety in Children Undergoing VCUG: Sedation or No Sedation?
Authors: Herd David W.
Published: July 2008

Background. Voiding cystourethrograms are distressing for children and parents. Nonpharmacological methods reduce distress. Pharmacological interventions for VCUG focus on sedation as well as analgesia, anxiolysis, and amnesia. Sedation has cost, time, and safety issues. Which agents and route should we use? Are we sure that sedation does not influence the ability to diagnose vesicoureteric reflux?Methods. Literature search of Medline, EMBASE, and the Cochrane Database. Review of comparative studies found.Results. Seven comparative studies including two randomised controlled trials were reviewed. Midazolam given orally (0.5-0.6 mg/kg) or intranasally (0.2 mg/kg) is effective with no apparent effect on voiding dynamics. Insufficient evidence to recommend other sedating agents was found. Deeper sedating agents may interfere with voiding dynamics.Conclusion. Midazolam reduces the VCUG distress, causes amnesia, and does not appear to interfere with voiding dynamics. Midazolam combined with simple analgesia is an effective method to reduce distress to children undergoing VCUG.
PPARγ and Apoptosis in Cancer
Authors: Elrod Heath A. , Sun Shi-Yong
Published: July 2008

Peroxisome proliferator‐activated receptors (PPARs) are ligand binding transcription factors which function in many physiological roles including lipid metabolism, cell growth, differentiation, and apoptosis. PPARs and their ligands have been shown to play a role in cancer. In particular, PPARγ ligands including endogenous prostaglandins and the synthetic thiazolidinediones (TZDs) can induce apoptosis of cancer cells with antitumor activity. Thus, PPARγ ligands have a potential in both chemoprevention and therapy of several types of cancer either as single agents or in combination with other antitumor agents. Accordingly, the involvement of PPARγ and its ligands in regulation of apoptosis of cancer cells have been extensively studied. Depending on cell types or ligands, induction of apoptosis in cancer cells by PPARγ ligands can be either PPARγ‐dependent or ‐independent. Through increasing our understanding of the mechanisms of PPARγ ligand‐induced apoptosis, we can develop better strategies which may include combining other antitumor agents for PPARγ‐targeted cancer chemoprevention and therapy. This review will highlight recent research advances on PPARγ and apoptosis in cancer.
Use of a Smartphone for Improved Self-Management of Pulmonary Rehabilitation
Authors: Marshall A. , Medvedev O. , Antonov A.
Published: July 2008

Patients suffering from chronic respiratory disease need to follow a rehabilitative exercise programme, in order to self-manage their illness and improve quality of life. Adherence to the programme is highly dependent on professional support from a physiotherapist and hence declines when patients seek to self-manage in the home. A number of requirements were identified for a Smartphone-based application in which patients are supported remotely and given automatic feedback during exercise. An application is described which will improve adherence during pulmonary rehabilitation.
Plasmin System Regulation in an Ovalbumin-Induced Rat Model of Asthma
Authors: Kucharewicz I. , Mogielnicki A. , Kasacka I. , Buczko W. , Bodzenta-Łukaszyk A.
Published: July 2008

Background: So far studies showing the role of the plasmin system in airway remodelling have been conducted using in vitro models. The aim of the present study was to determine plasmin system regulation in an in vivo rat model of asthma. Methods: Asthma in Wistar rats was induced by ovalbumin (OVA) sensitization followed by an OVA challenge (OVA/OVA, n = 6). Control groups were saline-sensitized challenged with OVA (VEH/OVA, n = 6) and OVA-sensitized challenged with saline (OVA/VEH, n = 6). Plasmin system components were determined in the plasma by ELISA. Plasminogen activator inhibitor-1 (PAI-1) was localized by an immunohistochemical reaction. Results: Sensitization and challenge with OVA caused thickening of the airway wall, hypertrophy of smooth muscle cells, infiltration of inflammatory cells, subepithelial fibrosis, epithelial and endothelial lesions.Serum total IgE was significantly higher in OVA-sensitized rats as compared to VEH-sensitized control groups. Tissue plasminogen activator activity was significantly decreased in asthmatic animals (4.48 ± 0.4 vs. 6.7 ± 0.3 ng/ml for OVA/OVA and OVA/VEH; p < 0.05), and PAI-1 activity was statistically significantly higher in asthma rats (0.8 ± 0.05 vs. 0.5 ± 0.03 ng/ml for OVA/OVA vs. OVA/VEH; p < 0.05). α2-Antiplasmin was higher in rats receiving OVA sensitization than in those that were sham sensitized (p < 0.05). Immunohistochemical staining for PAI-1in the lungs of asthmatic animals showed very strong PAI-1 expression in lung inflammatory cells. Conclusions: We have demonstrated for the first time the existence of PAI-1 in lung inflammatory cells of rats with asthma. This finding was consistent with the superiority of plasmin system inhibition over activation in plasma.
Effects of Repeated Respiratory Syncytial Virus Infections on Pulmonary Dendritic Cells in a Murine Model of Allergic Asthma
Authors: Hirose Hiroko , Matsuse Hiroto , Fukahori Susumu , Tsuchida Tomoko , Tomari Shinya , Kawano Tetsuya , Fukushima Chizu , Mizuta Yohei , Kohno Shigeru
Published: July 2008

Background: Primary and secondary respiratory syncytial virus (RSV) infection differentially regulates preexisting allergic airway inflammation. Objectives: The present study was designed to determine the effects of primary and secondary low-grade RSV infections on pulmonary dendritic cell (DC) functions. Methods: Eight groups of BALB/c mice were used: one group each for control primary and secondary sensitization, primary and secondary sensitization to Dermatophagoides farinae (Derf) allergen, primary and secondary infection with RSV, and primary and secondary sensitization to Derf plus infection with RSV. CD11c+ pulmonary DCs were isolated from these mice and then transferred to naïve mice followed by intranasal Derf challenge. Furthermore, either anti-IL-12 monoclonal antibody (αIL-12 mAb) or anti-IL-10 (αIL-10) mAb were injected into donor mice after Derf challenge and during RSV infection to determine the involvement of IL-12 and IL-10. Results: Primary RSV infection failed to induce polarization in DCs since it failed to induce IL-10 and IL-12 production in Derf-sensitized donor lung. In contrast, secondary RSV infection significantly enhanced IL-12 production from Derf-sensitized donor lung, thereby enhancing both Th1 and Th2 responses. During RSV infection, αIL-12 but not αIL-10 mAb treatment blocked these immunological effects. Conclusion: Via IL-12, DCs may play a critical role in shifting the immune response in this experimental model of repeated respiratory viral infection in allergic asthma.
Endogenous IL-17 Does Not Play a Significant Role in the Development of Experimental Murine Allergic Conjunctivitis
Authors: Fukushima Atsuki , Sumi Tamaki , Ishida Waka , Yamada Jun , Iwakura Yoichiro , Ueno Hisayuki
Published: July 2008

Background: Endogenous IL-17 is needed for the Ag sensitization that results in murine allergic asthma, a Th2-mediated disease. Here, we aimed to investigate the role IL-17 plays in the development of murine experimental allergic conjunctivitis (EC) which is also a Th2-mediated disease.Methods:To induce EC, wild-type (WT) and IL-17-deficient (IL-17 KO) mice on the BALB/c and C57BL/6 backgrounds were immunized with ragweed (RW) in alum and challenged with RW in eye drops. Alternatively, EC was induced by adoptively transferring RW-primed splenocytes followed by challenge with RW-containing eye drops. Twenty-four hours after the RW challenge, the conjunctivas and spleens were harvested for histological analyses and cytokine assays, respectively. Results: The WT and IL-17 KO mice on both backgrounds did not differ in terms of the severity of actively induced EC, as evaluated by the conjunctival eosinophil infiltration. They also did not differ with regard to the phenotypes of the inflammatory cells infiltrating the conjunctivas, although primed IL-17 KO splenocytes stimulated in vitro with RW extract did produce significantly higher amounts of IL-4, IL-13 and IFN-γ than WT splenocytes. Reciprocal adoptive transfer experiments also demonstrated that the IL-17 from both the donor splenocytes and the recipient mice is not involved in the development of EC. Conclusions: Endogenous IL-17 does not appear to play a significant role in the development of EC.
Procyanidin C1 from Apple Extracts Inhibits FcεRI-Mediated Mast Cell Activation
Authors: Nakano Nobuhiro , Nishiyama Chiharu , Tokura Tomoko , Nagasako-Akazome Yoko , Ohtake Yasuyuki , Okumura Ko , Ogawa Hideoki
Published: July 2008

Background: Polyphenol-enriched fractions, which are extracted from unripe apples (Rosaceae, Malus spp.), consisting of procyanidins (polymers of catechins) are known to have an anti-allergenic effect on patients with various allergic diseases. Although it has been reported that apple extracts inhibit histamine release from mast cells, the molecular mechanisms for this anti-allergenic effect are not well understood. To elucidate the molecular mechanisms by which apple extracts induce their anti-allergenic effects, the effects of purified apple extract components on high-affinity receptors for IgE (FcΕRI)-mediated mast cell activation were investigated. Methods: The anti-allergic effect of oral administration of apple procyanidin extracts on passive cutaneous anaphylactic responses of BALB/c mice was assessed. We evaluated the effects of procyanidin C1 (PC1) [epicatechin-(4β→8)-epicatechin-(4β→8)-epicatechin], a component of the procyanidin fraction, on mouse bone-marrow-derived mast cell degranulation, cytokine production, protein tyrosine phosphorylation and on the generation of intracellular reactive oxygen species (ROS) of cells stimulated by FcΕRI cross-linking in vitro. Results: In an in vivo study, oral administration of the procyanidin fraction suppressed the mast-cell-dependent allergic reaction. In in vitro studies, PC1 dose-dependently decreased FcΕRI-mediated degranulation and cytokine production of mast cells. Furthermore, PC1 inhibited tyrosine phosphorylation of Syk and linker for activation of T cells, and the ROS generation in stimulated mast cells. Conclusions: PC1 suppresses FcΕRI-mediated mast cell activation by inhibiting intracellular signaling pathways. These observations provide evidence for the anti-allergenic effects of the procyanidin-enriched apple extract.
The Clinical Characteristics of Respiratory Allergy in Immigrants in Northern Italy
Authors: Lombardi Carlo , Penagos Martin , Senna Gianenrico , Canonica Giorgio Walter , Passalacqua Giovanni
Published: July 2008

Background: Respiratory allergy is influenced and determined by genetic and environmental factors. Migration is a good epidemiological model to indirectly assess the influence of the environment. We assessed the clinical characteristics of respiratory allergy in immigrants in Brescia, Italy. Methods: We prospectively collected the data of all immigrants referred to our allergy service for respiratory complaints since 1992. All patients underwent a standard diagnostic workup. The records of a matched Italian population of 1,534 patients were examined for comparison. Results: Two hundred and thirty-seven patients were evaluated (108 male, mean age 36.3 years). Their countries of origin were uniformly distributed among 4 macroareas (Asia, Africa, South America, Eastern Europe). All patients were referred less than 1 month after the onset of symptoms. Family history for atopy was positive in 9% and clinical history of respiratory allergy was positive in 2%. The mean time of onset of symptoms after immigration was 5.21 years, and the onset symptoms were rhinitis and asthma in 68% patients. Twenty-five percent were monosensitized subjects and 20% of patients had cockroach positivity. Some characteristics (family history, previous clinical history and severity of rhinitis) were clearly different from those of the Italian control population. Conclusion: In this population of immigrants, it seems that environmental factors, more than genetic ones, play a role in the onset of respiratory allergy.
Analysis of Safety, Risk Factors and Pretreatment Methods during Rush Hymenoptera Venom Immunotherapy
Authors: Gorska Lucyna , Chelminska Marta , Kuziemski Krzysztof , Skrzypski Marcin , Niedoszytko Marek , Damps-Konstanska Iwona , Szymanowska Amelia , Siemińska Alicja , Wajda Beata , Drozdowska Adrianna , Jutel Marek , Jassem Ewa
Published: July 2008

Background: The safety profile of venom immunotherapy is a relevant issue. We evaluated the frequency of severe adverse events (SAE), associated risk factors, retrospective comparison of pretreatment protocols including solely H1 receptor blockers and a combination of H1 and H2 receptor blockers during rush Hymenoptera venom immunotherapy. Methods: The study group comprised 118 patients. The treatment was initiated according to a 5-day rush protocol with the use of standardized venom allergens of either wasp or honeybee. Results: During the rush induction, side effects occurred in 18 patients (15.2%), whereas SAE were present in 7 patients (5.9%). Twelve out of 18 (66.6%) developed anaphylactic reactions on the fourth day of the rush protocol, with the majority of cases at a dose of 40 or 60 µg of the venom extract (p = 0.001). The frequency of SAE was also significantly higher on the fourth day than thereafter (p = 0.0001) as well as in patients allergic to bee venom (p = 0.049). All systemic side effects were more frequent in women (p = 0.0065). However, this relation was not true when SAE were consider (p = 0.11). A higher percentage of SAE was observed in the subjects pretreated with both H1 and H2 receptor antagonists than in those pretreated with H1 blocker only (8.8 vs. 4.1%); however, the difference was not significant. Conclusions: Considerable severity of allergic adverse events requires particular attention to patients allergic to bee venom and during rush phase, especially when rapidly increasing doses are administered. Pretreatment with H2 blockers is debatable and warrants further investigation.
Low Erythropoietin Production in Familial Amyloidosis TTR V30M Is Not Related with Renal Congophilic Amyloid Deposition
Authors: Beirão Idalina , Moreira Luciana , Porto Graça , Lobato Luísa , Fonseca Isabel , Cabrita António , Costa P.M.P.
Published: July 2008

Background: Anemia with low serum erythropoietin (EPO) is common in Portuguese transthyretin V30M amyloid polyneuropathy (FAP). Low EPO production can be observed before clinical disease. Renal amyloidosis is observed in FAP, mainly in the medulla. Renal manifestations correlate with glomerular and vascular involvement, but not with tubulointerstitial deposition. To evaluate the potential role of renal amyloid deposits in the genesis of the EPO defect in FAP, we analyzed the renal biopsies of 12 patients (5 males, 7 females, aged from 29 to 54 years) with a clinical evolution varying from 3 to 12 (mean 5.4 ± 2.8) years. Methods: Formalin-fixed, paraffin-embedded sections of renal biopsies were stained by Congo red. Amyloid deposits were assessed by a semiquantitative method based on the percentage of amyloid deposition in each renal structure. Hemoglobin, creatinine, urea, EPO and proteinuria were concomitantly evaluated and correlated with the pathological findings. Results: Renal amyloid deposits were observed in all biopsies analyzed, independently of the neuropathy score. Low serum EPO levels were not related with either the amount of amyloid deposition or the renal clinical manifestations. Conclusion: Impairment of EPO production in FAP is not directly related to renal amyloid deposits and more studies are needed to clarify this question.
Development of the Human Parvocellular Red Nucleus
Authors: Yamaguchi Katsuyuki , Goto Noboru
Published: July 2008

Morphology of the human parvocellular red nucleus (RNp) was investigated in 14 fetuses aged from 12 to 39 weeks of gestation (WG). The brains were processed into celloidin-embedded serial sections. At 12 WG, the anlage of RNp was observed as an ovoid mass of immature neurons clustering into some groups. Lobular appearance in cross-sectional images was conspicuous during the early stages (12–23 WG), particularly at rostral levels. The fasciculus retroflexus of Meynert was seen as a prominent bundle of fibers surrounded by the most rostral part of RNp. Two types of neurons were identified: large and small neurons. Large neurons were earlier observed at 16 WG, and had a polygonal or multipolar perikaryon with abundant Nissl bodies from 28 WG onwards. Small neurons later appeared among large neurons at 21 WG, and had a triangular or ovoid perikaryon with scanty Nissl bodies. The volume of RNp showed an exponential increase with age during 20–39 WG. The mean of neuronal perikaryonal areas showed a linear increase with age in both types during 16–39 WG, although the degree of change was much greater in large neurons than small neurons. The current study has clearly demonstrated the presence of two neuronal populations and their differential growth in developing human RNp.
Comparison of Cause Distribution between Elderly and Non-Elderly Patients with Chronic Cough
Authors: Wei Weili , Yu Li , Lü Hanjing , Wang Lan , Shi Cuiqin , Ma Wei , Huang Yang , Qiu Zhongmin
Published: July 2008

Background: The causes of chronic cough in elderly patients have not been specifically investigated. Therefore, it remains to be determined whether chronic cough differs between elderly and non-elderly patients. Objectives: To investigate the distribution of causes of chronic cough in elderly patients in comparison with etiologies of chronic cough observed in non-elderly patients. Methods: From 2,989 new patients presenting consecutively to the Department of Respiratory Medicine of the Tongji Hospital over a 1.5-year period, 287 patients with chronic cough were enrolled in the study. Patients aged ≥60 years were assigned to the elderly group. The elderly group comprised 104 patients and the non-elderly group the remaining 183 patients. The causes of cough were primarily evaluated according to a modification of Irwin’s anatomic diagnostic protocol which included induced sputum cytology, verified by the specific therapy. Results: Cough-variant asthma (34.6 vs. 41.5%) and upper airway cough syndrome (19.3 vs. 23.5%) were the most common causes of chronic cough both in the elderly and non-elderly groups. The distribution of causes and frequency were significantly different between elderly and non-elderly groups: angiotensin-converting enzyme inhibitor (ACEI)-induced cough (16.3 vs. 1.7%, χ2 value = 22.12, p < 0.001) and gastroesophageal reflux disease (GERD; 10.6 vs. 3.7%, χ2 value = 5.14, p = 0.02) were more common in the elderly group. Conclusions: A more frequent incidence of ACEI-induced cough and GERD is the distinctive feature in the cause distribution between elderly and non-elderly patients with chronic cough.
What Silicon Nanocluster is Most Likely Formed in Etching Experiments? Theoretical DFT Study
Authors: Zhanpeisov Nurbosyn U. , Fukumura Hiroshi
Published: July 2008

Density functional calculations at the B3LYP/6-31G* level were performed for Si nanoclusters of ca.1 nm in size. The structural, energetic, electronic as well as the estimated absorption spectra by the time-dependent DFT (TDDFT) calculations using varied functionals and basis sets
for the representative cluster models are all in favor of the formation of most probable Si35H36 nanocluster in recent electrochemical etching experiments. The nanostructure has a complete H-termination at the borderline regions and lacks from the presence of any defects
like surface Si—Si dimer units formed via self-healing of dangling Si—Si bonds or from any relatively short H…H contacts.
Molecular Ordering in Layer-by-Layer Polyelectrolyte Films Studied by Sum-Frequency Vibrational Spectroscopy: The Effects of Drying Procedures
Authors: Silva Heurison S. , Uehara Thiers M. , Bergamaski Kleber , Miranda Paulo B.
Published: July 2008

Sum-Frequency Vibrational Spectroscopy (SFVS) has been used to investigate the effect of nitrogen-flow drying on the molecular ordering of Layer-by-Layer (LbL) films of poly(allylamine hydrochloride) (PAH) alternated with poly(styrene sulfonate) (PSS). We find that films dried by spontaneous
water evaporation are more ordered and homogeneous than films dried by nitrogen flow. The latter are quite inhomogeneous and may have regions with highly disordered polymer conformation. We propose that drying by spontaneous water evaporation reduces the effect of drag by the drying front,
while during nitrogen-flow drying the fast evaporation of water "freezes" the disordered conformation of adsorbed polyelectrolyte molecules. These findings are important for many applications of LbL films, since device performance usually depends on film morphology and its molecular structure.
On the Use of Neumann's Principle for the Calculation of the Polarizability Tensor of Nanostructures
Authors: Oliveira Micael J. T. , Castro Alberto , Marques Miguel A. L. , Rubio Angel
Published: July 2008

The polarizability measures how the system responds to an applied electrical field. Computationally, there are many different ways to evaluate this tensorial quantity, some of which rely on the explicit use of the external perturbation and require several individual calculations to
obtain the full tensor. In this work, we present some considerations about symmetry that allow us to take full advantage of Neumann's principle and decrease the number of calculations required by these methods. We illustrate the approach with two examples, the use of the symmetries in real
space and in spin space in the calculation of the electrical or the spin response.
Immobilization of Catalysts of Biological Interest on Porous Oxidized Silicon Surfaces
Authors: Alves Wendel A. , Fiorito Pablo A. , Froyer Gerard , Haber Fady El , Vellutini Luc , Torresi Roberto M. , Córdoba de Torresi Susana I.
Published: July 2008

The present paper deals with the immobilization of redox mediators and proteins onto protected porous silicon surfaces to obtain their direct electrochemical reactions and to retain their bioactivities. This paper shows that MP-11 and viologens are able to establish chemical bonds with
3-aminopropyltriethoxylsilane-modified porous silicon surface. The functionalization of the surfaces have been fully characterized by energy dispersive X-ray analysis (EDX) and X-ray photoelectron spectroscopy (XPS) to examine the immobilization of these mediators onto the solid surface. Amperometric
and open circuit potential measurements have shown the direct electron transfer between glucose oxidase and the electrode in the presence of the viologen mediator covalently linked to the 3-aminopropyltriethoxylsilane (APTES)-modified porous silicon surfaces.
Nanofluid Two-Phase Flow and Thermal Physics: A New Research Frontier of Nanotechnology and Its Challenges
Authors: Cheng Lixin , Bandarra Filho Enio P. , Thome John R.
Published: July 2008

Nanofluids are a new class of fluids engineered by dispersing nanometer-size solid particles in base fluids. As a new research frontier, nanofluid two-phase flow and thermal physics have the potential to improve heat transfer and energy efficiency in thermal management systems for many
applications, such as microelectronics, power electronics, transportation, nuclear engineering, heat pipes, refrigeration, air-conditioning and heat pump systems. So far, the study of nanofluid two-phase flow and thermal physics is still in its infancy. This field of research provides many
opportunities to study new frontiers but also poses great challenges. To summarize the current status of research in this newly developing interdisciplinary field and to identify the future research needs as well, this paper focuses on presenting a comprehensive review of nucleate pool boiling,
flow boiling, critical heat flux, condensation and two-phase flow of nanofluids. Even for the limited studies done so far, there are some controversies. Conclusions and contradictions on the available nanofluid studies on physical properties, two-phase flow, heat transfer and critical heat
flux(CHF) are presented. Based on a comprehensive analysis, it has been realized that the physical properties of nanofluids such as surface tension, liquid thermal conductivity, viscosity and density have significant effects on the nanofluid two-phase flow and heat transfer characteristics
but the lack of the accurate knowledge of these physical properties has greatly limited the study in this interdisciplinary field. Therefore, effort should be made to contribute to the physical property database of nanofluids as a first priority. Secondly, in particular, research on nanofluid
two-phase flow and heat transfer in microchannels should be emphasized in the future.