bluuebunny/crossref_metadata_2025 huggingface dataset:
AN AUTOMATED PROCEDURE FOR THE EXTRACTION OF METABOLIC NETWORK INFORMATION FROM TIME SERIES DATA
Authors: MARINO SIMEONE , VOIT EBERHARD O.
Published: September 2006

Novel high-throughput measurement techniques in vivo are beginning to produce dense high-quality time series which can be used to investigate the structure and regulation of biochemical networks. We propose an automated information extraction procedure which takes advantage of the unique S-system structure and supports model building from time traces, curve fitting, model selection, and structure identification based on parameter estimation. The procedure comprises of three modules: model Generation, parameter estimation or model Fitting, and model Selection (GFS algorithm).The GFS algorithm has been implemented in MATLAB and returns a list of candidate S-systems which adequately explain the data and guides the search to the most plausible model for the time series under study. By combining two strategies (namely decoupling and limiting connectivity) with methods of data smoothing, the proposed algorithm is scalable up to realistic situations of moderate size. We illustrate the proposed methodology with a didactic example.
Idiosyncratic Toxicity: A Convergence of Risk Factors
Authors: Ulrich Roger G.
Published: September 2006

The therapeutic margin for any drug is based on both toxicity and efficacy. Generally, toxicity is dose-dependent and is driven either by the therapeutic target or by an untoward target. However, idiosyncratic toxicities are usually not observed until a drug has been on the market and has gained broad exposure. Except in the case of pharmacokinetic interactions, these toxicities are not driven solely by drug exposure but rather depend on several drug- and patient-related risk factors. Drug-related risk factors include metabolism, bioactivation and covalent binding, and the inhibition of key cell functions. Patient-related risk factors include underlying disease, age, gender, comedications, nutritional status, activation of the innate immune system, physical activity, and genetic predispositions. Idiosyncratic toxicity can occur when a convergence of risk factors, including drug exposure, tips the risk-benefit balance away from benefit and toward risk.
Imaging of respiratory-related population activity with single-cell resolution
Authors: Funke Frank , Dutschmann Mathias , Müller Michael
Published: September 2006

The pre-Bötzinger complex (PBC) in the rostral ventrolateral medulla contains a kernel involved in respiratory rhythm generation. So far, its respiratory activity has been analyzed predominantly by electrophysiological approaches. Recent advances in fluorescence imaging now allow for the visualization of neuronal population activity in rhythmogenic networks. In the respiratory network, voltage-sensitive dyes have been used mainly, so far, but their low sensitivity prevents an analysis of activity patterns of single neurons during rhythmogenesis. We now have succeeded in using more sensitive Ca2+ imaging to study respiratory neurons in rhythmically active brain stem slices of neonatal rats. For the visualization of neuronal activity, fluo-3 was suited best in terms of neuronal specificity, minimized background fluorescence, and response magnitude. The tissue penetration of fluo-3 was improved by hyperosmolar treatment (100 mM mannitol) during dye loading. Rhythmic population activity was imaged with single-cell resolution using a sensitive charge-coupled device camera and a ×20 objective, and it was correlated with extracellularly recorded mass activity of the contralateral PBC. Correlated optical neuronal activity was obvious online in 29% of slices. Rhythmic neurons located deeper became detectable during offline image processing. Based on their activity patterns, 74% of rhythmic neurons were classified as inspiratory and 26% as expiratory neurons. Our approach is well suited to visualize and correlate the activity of several single cells with respiratory network activity. We demonstrate that neuronal synchronization and possibly even network configurations can be analyzed in a noninvasive approach with single-cell resolution and at frame rates currently not reached by most scanning-based imaging techniques.
Distinct roles of PMCA isoforms in Ca2+ homeostasis of bladder smooth muscle: evidence from PMCA gene-ablated mice
Authors: Liu Li , Ishida Yukisato , Okunade Gbolahan , Pyne-Geithman Gail J. , Shull Gary E. , Paul Richard J.
Published: September 2006

We previously showed that plasma membrane Ca2+-ATPase (PMCA) activity accounted for 25–30% of relaxation in bladder smooth muscle ( 8 ). Among the four PMCA isoforms only PMCA1 and PMCA4 are expressed in smooth muscle. To address the role of these isoforms, we measured cytosolic Ca2+ ([Ca2+]i) using fura-PE3 and simultaneously measured contractility in bladder smooth muscle from wild-type (WT), Pmca1+/−, Pmca4+/−, Pmca4−/−, and Pmca1+/− Pmca4−/− mice. There were no differences in basal [Ca2+]i values between bladder preparations. KCl (80 mM) elicited both larger forces (150–190%) and increases in [Ca2+]i (130–180%) in smooth muscle from Pmca1+/− and Pmca1+/− Pmca4−/− bladders than those in WT or Pmca4−/−. The responses to carbachol (CCh: 10 μM) were also greater in Pmca1+/− (120–150%) than in WT bladders. In contrast, the responses in Pmca4−/− and Pmca1+/− Pmca4−/− bladders to CCh were significantly smaller (40–50%) than WT. The rise in half-times of force and [Ca2+]i increases in response to KCl and CCh, and the concomitant half-times of their decrease upon washout of agonist were prolonged in Pmca4−/− (130–190%) and Pmca1+/− Pmca4−/− (120–250%) bladders, but not in Pmca1+/− bladders with respect to WT. Our evidence indicates distinct isoform functions with the PMCA1 isoform involved in overall Ca2+ clearance, while PMCA4 is essential for the [Ca2+]i increase and contractile response to the CCh receptor-mediated signal transduction pathway.
Taurine transporter in fetal T lymphocytes and platelets: differential expression and functional activity
Authors: Iruloh C. G. , D'Souza S. W. , Speake P. F. , Crocker I. , Fergusson W. , Baker P. N. , Sibley C. P. , Glazier J. D.
Published: September 2006

Transplacental transfer of taurine, a β-amino acid essential for fetal and neonatal development, constitutes the primary source of taurine for the fetus. Placental transport of taurine is compromised in pregnancies complicated by intrauterine growth restriction, resulting in a reduced concentration of taurine in cord plasma. This could impact on fetal cellular metabolism as taurine represents the most abundant intracellular amino acid in many fetal cell types. In the present study, we have used pure isolates of fetal platelets and T lymphocytes from cord blood of placentas, from normal, term pregnancies, as fetal cell types to examine the cellular uptake mechanisms for taurine by the system β transporter and have compared gene and protein expression for the taurine transporter protein (TAUT) in these two cell types. System β activity in fetal platelets was 15-fold higher compared with fetal T lymphocytes ( P < 0.005), mirroring greater TAUT mRNA expression in platelets than T lymphocytes ( P < 0.005). Cell-specific differences in TAUT protein moieties were detected with a doublet of 75 and 80 kDa in fetal platelets compared with 114 and 120 kDa in fetal T lymphocytes, with relatively higher expression in platelets. We conclude that greater system β activity in fetal platelets compared with T lymphocytes is the result of relatively greater TAUT mRNA and protein expression. This study represents the first characterization of amino acid transporters in fetal T lymphocytes.
Molecular cloning and functional expression of a VIP-specific receptor
Authors: Zhou Huiping , Huang Jiean , Murthy Karnam S.
Published: September 2006

Three receptors for VIP and pituitary adenylate cyclase-activating peptide (PACAP) have been cloned and characterized: PAC1, with high affinity for PACAP, and VPAC1and VPAC2with equally high affinity for VIP and PACAP. The existence of a VIP-specific receptor (VIPs) in guinea pig (GP) teniae coli smooth muscle was previously surmised on the basis of functional studies, and its existence was confirmed by cloning of a partial NH2-terminal sequence. Here we report the cloning of the full-length cDNAs of two receptors, a VPAC2receptor from GP gastric smooth muscle and VIPsfrom GP teniae coli smooth muscle. The cDNA sequence of the VIPsencodes a 437-amino acid protein ( Mr49,560) that possesses 87% similarity to VPAC2receptors in rat and mouse and differs from the VPAC2receptor in GP gastric smooth muscle by only two amino-acid residues, F40F41in lieu of L40L41. In COS-1 cells transfected with the GP teniae coli smooth muscle receptor, only VIP bound with high affinity (IC501.4 nM) and stimulated cAMP formation with high potency (EC501 nM). In contrast, in COS-1 cells transfected with the GP gastric smooth muscle receptor, both VIP and PACAP bound with equally high affinity (IC502.3 nM) and stimulated cAMP with equally high potency (EC501.5 nM). We conclude that the receptor cloned from GP teniae coli smooth muscle is a VIPsdistinct from VPAC1and VPAC2receptors. The ligand specificity in this species is determined by a pair of adjacent phenylalanine residues (L40L41) in the NH2-terminal ligand-binding domain.
Differentiation of the Gastric Mucosa I. Role of histamine in control of function and integrity of oxyntic mucosa: understanding gastric physiology through disruption of targeted genes
Authors: Chen Duan , Aihara Takeshi , Zhao Chun-Mei , Håkanson Rolf , Okabe Susumu
Published: September 2006

Many physiological functions of the stomach depend on an intact mucosal integrity; function reflects structure and vice versa. Histamine in the stomach is synthesized by histidine decarboxylase (HDC), stored in enterochromaffin-like (ECL) cells, and released in response to gastrin, acting on CCK2 receptors on the ECL cells. Mobilized ECL cell histamine stimulates histamine H2 receptors on the parietal cells, resulting in acid secretion. The parietal cells express H2, M3, and CCK2 receptors and somatostatin sst2 receptors. This review discusses the consequences of disrupting genes that are important for ECL cell histamine release and synthesis (HDC, gastrin, and CCK2 receptor genes) and genes that are important for “cross-talk” between H2 receptors and other receptors on the parietal cell (CCK2, M3, and sst2 receptors). Such analysis may provide insight into the functional significance of gastric histamine.
Lymphocyte-mediated regulation of β-endorphin in the myenteric plexus
Authors: Verma-Gandhu Monica , Verdu Elena F. , Cohen-Lyons Daniel , Collins Stephen M.
Published: September 2006

Lymphocytes are antinociceptive and can modulate visceral pain perception in mice. Previously, we have shown that adoptive transfer of CD4+ T cells to severe combined immune-deficient (SCID) mice normalized immunodeficiency-related visceral hyperalgesia. Pain attenuation was associated with an increase in β-endorphin release by T cells and an upregulation of β-endorphin in the enteric nervous system. In this study, we investigated the relationship between T cells and opioid expression in the myenteric plexus. We examined opioid peptide and receptor expression in the myenteric plexus in the presence and absence of mucosal T cells. We found a positive association between T cells and β-endorphin expression; this was accompanied by a downregulation of the μ-opioid receptor (MOR). In vitro, T helper (Th) type 1 and type 2 cytokine stimulation of CD4+ T cells or isolation of T cells from in vivo Th-polarized mice did not increase T cell release of β-endorphin or the induction of β-endorphin expression in the myenteric plexus. However, exogenous β-endorphin did upregulate β-endorphin expression, and both cycloheximide and naloxone methiodide inhibited peptide upregulation. Therefore, our results suggest that nonpolarized CD4+ T cells release β-endorphin, which, through an interaction with MOR, stimulates an upregulation of β-endorphin expression in the myenteric plexus. Thus, we propose that the mechanism underlying lymphocyte modulation of visceral pain involves T cell modulation of opioid expression in the enteric nervous system.
A new model of chronic pancreatitis in rats
Authors: Yamamoto Mitsuyoshi , Otani Munenori , Otsuki Makoto
Published: September 2006

This study was designed to examine whether continuous pancreatic ductal hypertension (PDH) plays an important role in the onset and development of chronic pancreatitis (CP). Pancreatic, biliary, and duodenal cannulas were implanted in male Wistar rats. PDH was induced by vertically raising the free end of the pancreatic duct cannula to exert a hydrostatic pressure and maintained for 2 wk. PDH was gradually increased, but when the pancreatic juice (PJ) flow was interrupted, PDH was decreased to restore PJ flow. The induction of PDH resulted in a marked reduction of amylase activity in PJ and an increase in serum amylase activity. At 2 wk after persistent PDH, pancreatic exocrine function was markedly decreased in response to a bolus injection of secretin (100 pmol/kg) compared with the control group. Histological examination revealed interlobular as well as intralobular fibrosis in the form of nodular pancreatitis at 2 wk after the induction of PDH. Immunohistochemistry revealed the expression of fibronectin and collagen types I and III. Quantitative real-time RT-PCR showed an increase in transforming growth factor-β1mRNA expression in the pancreas during PDH. The present results suggest that PDH plays an important role in the onset and development of CP. Furthermore, our animal model seems useful for investigating the mechanisms of CP in rats.
Ia-afferent input to motoneurons during shortening and lengthening muscle contractions in humans
Authors: Petersen Nicolas T. , Butler Jane E. , Carpenter Mark G. , Cresswell Andrew G.
Published: September 2006

The central nervous system employs different strategies to execute specific motor tasks. Because afferent feedback during shortening and lengthening muscle contractions differs, the neural strategy underlying these tasks may be quite distinct. Cortical drive may be adjusted or afferent input regulated. The exact mechanisms are not clear. Here, we examine the control of synaptic transmission across the Ia synapse during shortening and lengthening muscle contractions. Subjects were instructed to maintain isolated activity in a single tibialis anterior (TA) motor unit while muscle length was varied from flexion to extension and back. At a fixed interval after a firing of the active motor unit, a single electrical stimulus was applied to the common peroneal nerve to activate Ia afferents from the TA muscle. We investigated the stimulus-induced change in firing probability of 19 individual low-threshold TA motor units during shortening and lengthening contractions. Any change in firing probability depends on both pre- and postsynaptic mechanisms. In this experiment, motoneuron firing rate was similar during both contraction types. There was no difference in the firing probability between shortening and lengthening contractions (0.23 ± 0.03 and 0.20 ± 0.02, respectively). We suggest that there is no contraction type-specific control of Ia input to the motoneurons during shortening and lengthening muscle contractions. Cortical adjustments may have occurred.
Mechanical response to methacholine and deep inspiration in supine men
Authors: Meinero Maurizio , Coletta Giuseppe , Dutto Luca , Milanese Manlio , Nova Giorgio , Sciolla Andrea , Pellegrino Riccardo , Brusasco Vito
Published: September 2006

The effects of supine posture on airway responses to inhaled methacholine and deep inspiration (DI) were studied in seven male volunteers. On a control day, subjects were in a seated position during both methacholine inhalation and lung function measurements. On a second occasion, the whole procedure was repeated with the subjects lying supine for the entire duration of the study. On a third occasion, methacholine was inhaled from the seated position and measurements were taken in a supine position. Finally, on a fourth occasion, methacholine was inhaled from the supine position and measurements were taken in the seated position. Going from sitting to supine position, the functional residual capacity decreased by ∼1 liter in all subjects. When lung function measurements (pulmonary resistance, dynamic elastance, residual volume, and maximal flows) were taken in supine position, the response to methacholine was greater than at control, and this was associated with a greater dyspnea and a faster recovery of dynamic elastance after DI. By contrast, when methacholine was inhaled in supine position but measurements were taken in sitting position, the response to methacholine was similar to control day. These findings document the potential of the decrease in the operational lung volumes in eliciting or sustaining airflow obstruction in nocturnal asthma. It is speculated that the exaggerated response to methacholine in the supine posture may variably contribute to airway smooth muscle adaptation to short length, airway wall edema, and faster airway renarrowing after a large inflation.
Bicarbonate infusion and pH clamp moderately reduce hyperventilation during ramp exercise in humans
Authors: Péronnet François , Meyer Tim , Aguilaniu Bernard , Juneau Carl-Étienne , Faude Oliver , Kindermann Wilfried
Published: September 2006

To test the hypothesis that the decrease in plasma pH contributes to the hyperventilation observed in humans in response to exercise at high workloads, five healthy male subjects performed a ramp exercise [maximal workload: 352 W (SD 35)] in a control situation and when arterialized plasma pH was maintained at the resting level (pH clamp) by intravenous infusion of sodium bicarbonate [129 mmol (SD 23), beginning at 59% maximal workload (SD 5)]. Bicarbonate infusion did not modify O2 consumption (V̇o2) but significantly ( P < 0.05) increased arterial Pco2, plasma bicarbonate concentration, and respiratory exchange ratio ( P < 0.05). At the three highest workloads, pulmonary ventilation (V̇e) and V̇e/V̇o2 were ∼5–10% lower ( P < 0.05) when bicarbonate was infused than in the control situation, and hyperventilation was reduced by 15–30%. These data suggest that the decrease in plasma pH is one of the factors that contribute to the hyperventilation observed at high workloads.
Noisy Inputs and the Induction of On–Off Switching Behavior in a Neuronal Pacemaker
Authors: Paydarfar David , Forger Daniel B. , Clay John R.
Published: September 2006

Neuronal oscillators can function as bistable toggle switches, flipping between quiescence and rhythmic firing in response to an input stimulus. In theory, such switching should be sensitive to small noisy inputs if the bistable states are in close proximity, which we test here using a perfused squid axon preparation. We find that small noisy stimulus currents induce a multitude of paths between two nearby stable states: repetitive firing and quiescence. The pattern of on–off switching of the pacemaker depends on the intensity, spectral properties, and phase angle of stimulus current fluctuations. Analysis by spike-triggered averaging of the stimulus currents near the transitions reveals that sinusoidal stimuli timed antiphase or in phase with repetitive firing correlates with switching of the pacemaker off or on, respectively. Our results reveal a distinct form of bistability in which noise can either silence pacemaker activity, trigger repetitive firing, or induce sporadic burst patterns similar to those recorded in a variety of normal and pathological neurons.
Response Properties and Synchronization of Rhythmically Firing Dendritic Neurons
Authors: Goldberg Joshua A. , Deister Chris A. , Wilson Charles J.
Published: September 2006

The responsiveness of rhythmically firing neurons to synaptic inputs is characterized by their phase-response curve (PRC), which relates how weak somatic perturbations affect the timing of the next action potential. The shape of the somatic PRC is an important determinant of collective network dynamics. Here we study theoretically and experimentally the impact of distally located synapses and dendritic nonlinearities on the synchronization properties of rhythmically firing neurons. By combining the theories of quasi-active cables and phase-coupled oscillators we derive an approximation for the dendritic responsiveness, captured by the neuron's dendritic PRC (dPRC). This closed-form expression indicates that the dPRCs are linearly filtered versions of the somatic PRC and that the filter characteristics are determined by the passive and active properties of the dendrite. The passive properties induce leftward shifts in the dPRCs and attenuate them. Our analysis yields a single dimensionless parameter that classifies active dendritic conductances as either regenerative conductances that counter the passive properties by boosting the dPRCs or restorative conductances that high-pass filter the dPRCs. Thus dendritic properties can generate a qualitative difference between the somatic and dendritic PRCs. As a result collective dynamics can be qualitatively different depending on the location of the synapse, the neuronal firing rates, and the dendritic nonlinearities. Finally, we use dual whole cell recordings from the soma and apical dendrite of cortical pyramidal neurons to test these predictions and find that empirical dPRCs are shifted leftward, as predicted, but may also display high-pass characteristics resulting from the restorative dendritic HCN (h) current.
Cytomegalovirus-induced embryopathology: mouse submandibular salivary gland epithelial-mesenchymal ontogeny as a model
Authors: Melnick Michael , Mocarski Edward S , Abichaker George , Huang Jing , Jaskoll Tina
Published: September 2006

Background

Human studies suggest, and mouse models clearly demonstrate, that cytomegalovirus (CMV) is dysmorphic to early organ and tissue development. CMV has a particular tropism for embryonic salivary gland and other head mesenchyme. CMV has evolved to co-opt cell signaling networks so to optimize replication and survival, to the detriment of infected tissues. It has been postulated that mesenchymal infection is the critical step in disrupting organogenesis. If so, organogenesis dependent on epithelial-mesenchymal interactions would be particularly vulnerable. In this study, we chose to model the vulnerability by investigating the cell and molecular pathogenesis of CMV infected mouse embryonic submandibular salivary glands (SMGs).

Results

We infected E15 SMG explants with mouse CMV (mCMV). Active infection for up to 12 days in vitro results in a remarkable cell and molecular pathology characterized by atypical ductal epithelial hyperplasia, apparent epitheliomesenchymal transformation, oncocytic-like stromal metaplasia, β-catenin nuclear localization, and upregulation of Nfkb2, Relb, Il6, Stat3, and Cox2. Rescue with an antiviral nucleoside analogue indicates that mCMV replication is necessary to initiate and maintain SMG dysmorphogenesis.

Conclusion

mCMV infection of embryonic mouse explants results in dysplasia, metaplasia, and, possibly, anaplasia. The molecular pathogenesis appears to center around the activation of canonical and, perhaps more importantly, noncanonical NFκB. Further, COX-2 and IL-6 are important downstream effectors of embryopathology. At the cellular level, there appears to be a consequential interplay between the transformed SMG cells and the surrounding extracellular matrix, resulting in the nuclear translocation of β-catenin. From these studies, a tentative framework has emerged within which additional studies may be planned and performed.
Identification of genes regulated by Wnt/β-catenin pathway and involved in apoptosis via microarray analysis
Authors: Huang Moli , Wang Yihua , Sun Daochun , Zhu Hongxia , Yin Yanbing , Zhang Wei , Yang Shangbin , Quan Lanping , Bai Jinfeng , Wang Shengqi , Chen Quan , Li Songgang , Xu Ningzhi
Published: September 2006

Background

Wnt/β-catenin pathway has critical roles in development and oncogenesis. Although significant progress has been made in understanding the downstream signaling cascade of this pathway, little is known regarding Wnt/β-catenin pathway modification of the cellular apoptosis.

Methods

To identify potential genes regulated by Wnt/β-catenin pathway and involved in apoptosis, we used a stably integrated, inducible RNA interference (RNAi) vector to specific inhibit the expression and the transcriptional activity of β-catenin in HeLa cells. Meanwhile, we designed an oligonucleotide microarray covering 1384 apoptosis-related genes. Using oligonucleotide microarrays, a series of differential expression of genes was identified and further confirmed by RT-PCR.

Results

Stably integrated inducible RNAi vector could effectively suppress β-catenin expression and the transcriptional activity of β-catenin/TCF. Meanwhile, depletion of β-catenin in this manner made the cells more sensitive to apoptosis. 130 genes involved in some important cell-apoptotic pathways, such as PTEN-PI3K-AKT pathway, NF-κB pathway and p53 pathway, showed significant alteration in their expression level after the knockdown of β-catenin.

Conclusion

Coupling RNAi knockdown with microarray and RT-PCR analyses proves to be a versatile strategy for identifying genes regulated by Wnt/β-catenin pathway and for a better understanding the role of this pathway in apoptosis. Some of the identified β-catenin/TCF directed or indirected target genes may represent excellent targets to limit tumor growth.
Fibrillar beta-amyloid peptide Aβ1–40 activates microglial proliferation via stimulating TNF-α release and H2O2 derived from NADPH oxidase: a cell culture study
Authors: Jekabsone Aiste , Mander Palwinder K , Tickler Anna , Sharpe Martyn , Brown Guy C
Published: September 2006

Background

Alzheimer's disease is characterized by the accumulation of neuritic plaques, containing activated microglia and β-amyloid peptides (Aβ). Fibrillar Aβ can activate microglia, resulting in production of toxic and inflammatory mediators like hydrogen peroxide, nitric oxide, and cytokines. We have recently found that microglial proliferation is regulated by hydrogen peroxide derived from NADPH oxidase. Thus, in this study, we investigated whether Aβ can stimulate microglial proliferation and cytokine production via activation of NADPH oxidase to produce hydrogen peroxide.

Methods

Primary mixed glial cultures were prepared from the cerebral cortices of 7-day-old Wistar rats. At confluency, microglial cells were isolated by tapping, replated, and treated either with or without Aβ. Hydrogen peroxide production by cells was measured with Amplex Red and peroxidase. Microglial proliferation was assessed under a microscope 0, 24 and 48 hours after plating. TNF-α and IL-1β levels in the culture medium were assessed by ELISA.

Results

We found that 1 μM fibrillar (but not soluble) Aβ1–40peptide induced microglial proliferation and caused release of hydrogen peroxide, TNF-α and IL-1β from microglial cells. Proliferation was prevented by the NADPH oxidase inhibitor apocynin (10 μM), by the hydrogen peroxide-degrading enzyme catalase (60 U/ml), and by its mimetics EUK-8 and EUK-134 (20 μM); as well as by an antibody against TNF-α and by a soluble TNF receptor inhibitor. Production of TNF-α and IL-1β, measured after 24 hours of Aβ treatment, was also prevented by apocynin, catalase and EUKs, but the early release (measured after 1 hour of Aβ treatment) of TNF-α was insensitive to apocynin or catalase.

Conclusion

These results indicate that Aβ1–40-induced microglial proliferation is mediated both by microglial release of TNF-α and production of hydrogen peroxide from NADPH oxidase. This suggests that TNF-α and NADPH oxidase, and its products, are potential targets to prevent Aβ-induced inflammatory neurodegeneration.
The effect of hip abduction on the EMG activity of vastus medialis obliquus, vastus lateralis longus and vastus lateralis obliquus in healthy subjects
Authors: Bevilaqua-Grossi Débora , Monteiro-Pedro Vanessa , de Vasconcelos Rodrigo Antunes , Arakaki Juliano Coelho , Bérzin Fausto
Published: September 2006

Study design

Controlled laboratory study.

Objectives

The purposes of this paper were to investigate (d) whether vastus medialis obliquus (VMO), vastus lateralis longus (VLL) and vastus lateralis obliquus (VLO) EMG activity can be influenced by hip abduction performed by healthy subjects.

Background

Some clinicians contraindicate hip abduction for patellofemoral patients (with) based on the premise that hip abduction could facilitate the VLL muscle activation leading to a VLL and VMO imbalance

Methods and measures

Twenty-one clinically healthy subjects were involved in the study, 10 women and 11 men (aged X = 23.3 ± 2.9). The EMG signals were collected using a computerized EMG VIKING II, with 8 channels and three pairs of surface electrodes. EMG activity was obtained from MVIC knee extension at 90° of flexion in a seated position and MVIC hip abduction at 0° and 30° with patients in side-lying position with the knee in full extension. The data were normalized in the MVIC knee extension at 50° of flexion in a seated position, and were submitted to ANOVA test with subsequent application of the Bonferroni multiple comparisons analysis test. The level of significance was defined as p ≤ 0.05.

Results

The VLO muscle demonstrated a similar pattern to the VMO muscle showing higher EMG activity in MVIC knee extension at 90° of flexion compared with MVIC hip abduction at 0° and 30° of abduction for male (p < 0.0007) and MVIC hip abduction at 0° of abduction for female subjects (p < 0.02196). There were no statistically significant differences in the VLL EMG activity among the three sets of exercises tested.

Conclusion

The results showed that no selective EMG activation was observed when comparison was made between the VMO, VLL and VLO muscles while performing MVIC hip abduction at 0° and 30° of abduction and MVIC knee extension at 90° of flexion in both male and female subjects. Our findings demonstrate that hip abduction do not facilitated VLL and VLO activity in relation to the VMO, however, this study included only healthy subjects performing maximum voluntary isometric contraction contractions, therefore much remains to be discovered by future research
Altered gene expression in asymptomatic SHIV-infected rhesus macaques (Macacca mulatta)
Authors: Carroll Erica E , Hammamieh Rasha , Chakraborty Nabarun , Phillips Aaron T , Miller Stacy-Ann M , Jett Marti
Published: September 2006

Simian-Human immunodeficiency virus is a chimeric virus which, in rhesus macaques (Macacca mulatta) closely imitates immunodeficiency virus infection in human (HIV). A relatively new way to study pathogenesis of viral infection is to study alterations in host gene expression induced by the virus. SHIV infection with certain strains does not result in clinical signs. We hypothesized that alterations in gene expression relating to the immune system would be present in SHIV-infected animals despite the lack of clinical signs. Splenic tissue from four adult male Indian-origin Rhesus monkeys serologically positive for non-pathogenic SHIV 89.6 was processed by cDNA microarray analysis. Results were compared with the corresponding outcome using splenic tissues from four unexposed adult male Rhesus monkeys. Subsequent gene analysis confirmed statistically significant variations between control and infected samples. Interestingly, SHIV-infected monkeys exhibited altered expression in genes related to apoptosis, signal transduction, T and B lymphocyte activation and importantly, to immune regulation. Although infected animals appeared asymptomatic, our study demonstrated that SHIV-infected monkeys cannot reliably be used in studies of other infectious agents as their baseline gene expression differs from that of normal Rhesus monkeys. The gene expression differences in SHIV-infected animals relative to uninfected animals offer additional clues to the pathogenesis of altered immune function in response to secondary infection.
Toddlers' Empathy‐Related Responding to Distress: Predictions From Negative Emotionality and Maternal Behavior in Infancy
Authors: Spinrad Tracy L. , Stifter Cynthia A.
Published: September 2006

This study focused on the predictive contributions of infants' temperamental negative emotionality (proneness to fear, anger), sex, maternal responsivity, and their interaction on toddlers' empathy‐related responding to distress in 3 contexts. Ninety‐eight infants and their mothers participated in a longitudinal study. When the infants were 10 months of age, mothers completed assessments of infant temperamental anger and fear, and maternal behaviors were observed in a free‐play setting. At 18 months of age, toddlers' empathy‐related responding to the distress of a stranger, a crying baby doll, and the mother was assessed. A series of hierarchical and logistic regressions were performed, and results indicated that infant fear predicted higher concerned awareness toward adults and higher personal distress reactions toward the mother. In addition, maternal responsivity predicted higher concerned attention and lower personal distress reactions toward the baby doll and mother. Findings also revealed several interaction effects to predict toddlers' empathy‐related responding to distress.
Object Function and Categorization in Infancy: Two Mechanisms of Facilitation
Authors: Booth Amy E.
Published: September 2006

Does function facilitate categorization by focusing infants' attention generally on all commonalities among objects or specifically on functionally relevant properties? After familiarization to a novel category, 18‐month‐olds selected another category member from a pair of previously unseen test objects. In Experiments 1 and 2, infants chose globally similar over functionally similar and novel test objects. Functionally similar and novel test objects were chosen equally. These data suggest that function facilitates categorization through a general attention‐enhancing mechanism. However, when functions were more uniquely and transparently tied to object properties in Experiments 3 and 4, infants chose functionally similar over novel test objects. Globally and functionally similar test objects were chosen equally. Therefore, a specific attention‐enhancing mechanism also sometimes supports categorization.
The potential for radiation sensitizers and possible strategy for use
Authors: Whitmore G. F.
Published: September 2006

The search for radiation sensitizers for use in radiotherapy is based on the assumption that proper use of these compounds will provide a differential sensitization of tumor and normal tissue. Based on the evidence that hypoxic cells exist within human tumors but not within normal cell populations, there is reason to believe that specific sensitizers of hypoxic cells might provide useful therapeutic benefit. This paper discusses the possible advantages of such sensitizers, over reliance on the phenomenon of reoxygenation, and describes very briefly the current status of hypoxic cell sensitizers. Finally a proposal is made concerning the way in which such sensitizers might be tested for their efficacy in human radiotherapy.
An epidemiological study of laryngeal cancer in japan (1960‐1969)
Authors: Iwamoto H.
Published: September 2006

This report presents the findings of an epidemiological study of laryngeal cancer in Japan, based on 6,360 cases treated and registered during the 10‐year period from 1960 through 1969.

The number of the patients increased 1.5 times from 1960 to 1969. Geographically the absolute number of recorded cases was proportional to the population density; in other words, it was larger in heavily urbanized areas and smaller in rural regions.

An anatomical classification revealed that the incidence of supraglottic and glottic cancer was about equal (3,121 and 3,176 cases), and subglottic cancer was only 1 percent of the total.

Histologically, 98.6 percent were of the squamous cell carcinoma and 1.4 percent were of the basal cell carcinoma, adenocarcinoma, transitional cell carcinoma, etc.

As to the age and sex distribution, the majority of the patients were 50 to 70 years old, and those in their 60′s were most numerous. The ratio between men and women was 9.6 to 1.

56.1 percent of the patients surveyed were found to have a blood relation with a history of cancer and 31 percent were engaged in occupations where they used their voices frequently.

Smoking habits were found in 96 percent of the patients surveyed and as many as 52 percent came under the category of heavy smokers. Cigarette smoking might be regarded as a significant factor in laryngeal cancer, while alcohol consumption was not as significant a causal factor as smoking.

The living environment had no explicit relationship to laryngeal cancer in the above‐mentioned period of years.
The sequential septo‐rhinoplasty
Authors: Smithdeal Charles D.
Published: September 2006

In septo‐rhinoplastic surgery it is helpful to follow a logical series of stages for correcting abnormalities of various anatomic components of the nose. A suggested order of staging of the typical nasal plastic operation is presented. By following a logical sequence of surgical stages, the least correctible components are modified first, and each successive stage of the procedure is related to the result obtained in the previous stage.

Technical considerations are presented in each stage suggested, and the analysis and correction of intranasal abnormalities to restore normal nasal function is emphasized. Specific preoperative problems and the results of suggested methods of correction are presented.
The Security of Sea Lanes in Southeast Asia
Authors: Ho Joshua H.
Published: September 2006

Asian economies rely heavily on the sea for transportation: analysts have warned that disruption of regional sea lanes by terrorists or pirates can have severe economic repercussions. However, this article contends that the threat has been overstated and measures taken by the littoral countries have further lowered the risk.
Relocating the U.S. Forces in South Korea: Strained Alliance, Emerging Partnership in the Changing Defense Posture
Authors: Nam Chang-hee
Published: September 2006

Relocating the forward-deployed U.S. forces in Korea south of the Han River is part of the Pentagon's Global Defense Posture Review, a process that stems from America's military transformation. This unprecedented move is headed in a direction that simultaneously challenges the half-century-old alliance and promotes a new partnership between the U.S. and South Korea.
Speech in Children with an Isolated Cleft Palate: A Longitudinal Perspective
Authors: Persson Christina , Lohmander Anette , Elander Anna
Published: September 2006

Objective

To describe articulation and speech symptoms related to velopharyngeal impairment in children born with an isolated cleft palate.

Design

Blind assessment of speech at 3, 5, 7, and 10 years of age was performed. Two subgroups were formed based on the results at age 5 years, the no-VPI group and the VPI group, and they were compared with controls.

Setting

A university hospital.

Patients

Twenty-six children born with isolated cleft palate. Seventeen children served as controls.

Interventions

Soft palate closure at 7 months and hard palate closure at a mean age of 3 years and 11 months if the cleft extended into the hard palate.

Main Outcome Measures

Perceptual assessments of four variables related to velopharyngeal function and of articulation errors were performed at all ages. Phonetic transcriptions of target speech sounds were obtained at 5, 7, and 10 years and nasalance scores were obtained at age 10 years.

Results

The no-VPI group continued to have no or minor difficulties. The VPI group improved but continued to have moderate velopharyngeal impairment. Both groups differed significantly from the controls at age 10 years. Persistent velopharyngeal impairment, as well as glottal misarticulation, were mostly found in children with the cleft as a part of a syndrome or together with multiple malformations.

Conclusion

Small changes in velopharyngeal impairment were found across ages. Improvement seemed to be related to surgical intervention, and persistent problems seemed to be related to the presence of additional multiple malformations or syndromes.
Effect of Nasal Decongestion on Nasalance Measures
Authors: Pegoraro-Krook Maria Inês , Dutka-Souza Jeniffer C. R. , Williams William N. , Teles Magalhães Lídia C. , Rossetto Patrícia Cortez , Riski John E.
Published: September 2006

Objective

The purpose of this study was to evaluate the effect of nasal decongestant on nasalance scores for a group of 100 individuals.

Participants

Forty-one subjects with hypernasality and 59 subjects without hypernasality underwent nasometric assessment at the Hospital for Rehabilitation of Craniofacial Anomalies, University of São Paulo, Bauru, Brazil.

Design

Nasalance scores were obtained for each subject before the application of a nasal decongestant and again 10 minutes after subjects received a topical nasal decongestant applied into both nostrils.

Results

The nasalance scores obtained after the application of the nasal decongestant were significantly higher than those obtained before the decongestant.

Conclusions

Nasal decongestion had a small but statistically significant effect on nasalance scores, suggesting that in some individuals, nasal congestion should be a variable of concern when using the Nasometer. Both nasal congestion (i.e., due to nasal rhinitis) and the effects of nasal decongestant sprays may influence Nasometer test results. Interpretation of nasalance scores, therefore, should be done carefully. Furthermore, nasometry, with and without nasal decongestant, can be a valuable clinical tool for screening anterior nasal obstruction, helping to isolate obstruction due to nasal congestion from structural obstruction in the nasal cavities.
Dual Segmental Distraction Osteogenesis of the Midface in a Patient with Apert Syndrome
Authors: Takashima Mariko , Kitai Noriyuki , Murakami Shumei , Takagi Satoshi , Hosokawa Ko , Kreiborg Sven , Takada Kenji
Published: September 2006

Objective

To present orthodontic treatment combined with dual segmental distraction osteogenesis in a patient with Apert syndrome.

Patient

A 15-year-old boy exhibited severe midfacial hypoplasia with retruded and hypoplastic maxilla and anterior open bite. The patient was treated with a rigid external distraction II system for distraction osteogenesis, a preadjusted edgewise appliance, and a modified maxillary protraction headgear. The concave profile with midfacial hypoplasia was improved. A tight occlusal relationship between maxillary and mandibular teeth was achieved. Postoperative treatment results have been stable for 1 year.
The Effect of Cranio-Maxillofacial Osteotomies and Distraction Osteogenesis on Speech and Velopharyngeal Status: A Critical Review
Authors: Chanchareonsook Nattharee , Samman Nabil , Whitehill Tara L.
Published: September 2006

Objectives

To review the impact of maxillary advancement by orthognathic surgery and distraction osteogenesis on speech and velopharyngeal status based on the literature of the past 30+ years, to review the methods employed in previous studies to explain discrepancies in results, and to make recommendations for future studies.

Method

Thirty-nine published articles on the effect of cranio-maxillofacial osteotomies and distraction osteogenesis on speech and velopharyngeal status were identified and were systematically analyzed. A total of 747 cases of cleft and noncleft patients were selected, including craniofacial deformities and syndromes mainly involving maxillary hypoplasia.

Results

Findings varied. Many studies found that surgery had no impact on speech and velopharyngeal status. Some reported worsening only in patients with preexisting velopharyngeal impairment or those with borderline velopharyngeal function before surgery. There was no clear difference in outcome between distraction and conventional osteotomy, although there have been few systematic comparisons. There was great variation among reviewed studies in the number of subjects, speech sample, number and type of listeners, speech outcome measures, and timing of postoperative assessment. Few studies employed reliability measures.

Conclusion

None of the 39 reviewed studies compared conventional osteotomy and distraction by including both groups in a single study. Randomized controlled trials with adequate number of subjects and follow-up duration are needed.
Women, knowing, and authenticity: Living with contradictions
Authors: English Leona M.
Published: September 2006

This chapter examines the myth of “women's learning” and suggests how to develop a teaching practice that is authentic, open to difference, and attentive to power.
Schizophrenia is not associated with the functional candidate gene ERBB3: Results from a case‐control study
Authors: Kanazawa Tetsufumi , Glatt Stephen J. , Tsutsumi Atsushi , Kikuyama Hiroki , Koh Jun , Yoneda Hiroshi , Tsuang Ming T.
Published: September 2006

Increasing evidence has supported the hypothesis of a neurodevelopmental component in the etiology of schizophrenia. Recently, several independent microarray gene expression studies have revealed downregulated expression of myelin‐related genes in the postmortem brains of schizophrenia patients. Complete myelination of the cortex has been observed to occur in late adolescence and early adulthood, which is typically the age of onset of schizophrenia. ERBB3 is a gene which has not only been found to be downregulated in schizophrenia simultaneously in three microarray studies, but also is a strong candidate because of its potential role in neurodevelopment as a receptor of NRG1. Therefore, we performed association analysis of seven nonsynonymous SNPs in this gene. Two SNPs in ERBB3 (rs773123 and rs2271188) were polymorphic in our samples, neither of which showed significant evidence of association with the illness (P = 0.639 and 0.561, respectively). Because replication across such studies is notoriously difficult, the microarray evidence implicating ERBB3 still strongly supports some role of this gene in schizophrenia. However, our failure to find genetic association suggests that the differential expression of ERBB3 in schizophrenia may be environmentally driven, or involve cis‐ or trans‐acting genetic factors beyond the boundaries of the gene itself. © 2006 Wiley‐Liss, Inc.