bluuebunny/crossref_metadata_2025 huggingface dataset:
Ugandan Kaposi’s Sarcoma-Associated Herpesvirus Phylogeny: Evidence for Cross-Ethnic Transmission of Viral Subtypes
Authors: Kajumbula Henry , Wallace Robert G. , Zong Jian-Chao , Hokello Joseph , Sussman Noah , Simms Simon , Rockwell Robert F. , Pozos Robert , Hayward Gary S. , Boto William
Published: January 2006

Objective: The aim of this study was to test the relationship between Kaposi’s sarcoma-associated herpesvirus (KSHV) phylogeny and host ethnicity at the within-country scale. Methods: KSHV genomic DNA samples were isolated from 31 patients across eleven Ugandan ethnic groups. Amino acid sequences of the ORF-K1 gene were used to construct a neighbor-joining phylogenetic tree. Results: A5 and B1 variants predominated with no evidence of distinct ethnic or geographic distribution. A new K1 subtype (F) was identified in a member of the Bantu Gisu tribe and a new subtype B variant (B3) among members of the Bantu Ganda tribe. Conclusions: The phylogeny may yet be structured by host ethnicity if members of Ugandan groups have convoluted biological origins, even as they identify with single tribes. An alternative possibility is that KSHV subtype evolution may have preceded major diversification of sub-Saharan Africans into ethnicities as we know them today, with ethnic groups beginning their histories already hosting multiple subtypes. A third alternative is that horizontal transmission of multiple KSHV subtypes may have broken up vertical lineages of the virus passed down within Ugandan populations.
Growth and Production of the Dengue Virus in C6/36 Cells and Identification of a Laminin-Binding Protein as a Candidate Serotype 3 and 4 Receptor Protein
Authors: Sakoonwatanyoo Prirayapak , Boonsanay Verawan , Smith Duncan R.
Published: January 2006

Objectives: Although dengue is one of the most common mosquito-borne viral diseases, few studies have investigated the relationship between the dengue virus and mosquito cells, and this study sought to describe the binding and propagation of the dengue viruses in C6/36 cells. Methods: The internalization and production of the dengue virus was assayed by standard plaque assay methodologies, while dengue virus receptor proteins were examined by a virus overlay protein-binding assay and candidate gene analysis coupled with virus inhibition studies. Results: All four serotypes were internalized linearly, and de novo virus production occurred 14–19 h postinfection. Virus overlay protein-binding assay identified a band of 50 kDa for dengue serotypes 2, 3 and 4 which comigrated with a protein that reacts with antibodies directed against the human 37/67-kDa high-affinity laminin receptor. Both antibodies directed against the human 37/67-kDa high-affinity laminin receptor protein and soluble laminin inhibited the binding and internalization of serotypes 3 and 4, but not serotypes 1 and 2. Conclusions: The results suggest that multiple receptors may be used by the dengue virus to enter into insect cells, and that one of these proteins may be a laminin-binding protein.
Pregnancy Outcome following a Previous Spontaneous Abortion (Miscarriage)
Authors: Kashanian M. , Akbarian A.R. , Baradaran H. , Shabandoust S.H.
Published: January 2006

Objective: To determine the pregnancy outcome following a previous spontaneous abortion (miscarriage). Method: A prospective cohort study was done on 300 gravida-2 patients: 200 patients (case group) whose previous pregnancy was spontaneously aborted (early abortion), and 100 patients (control group) whose previous pregnancy went to term and a live fetus was delivered. All the patients were followed until delivery, and then the pregnancy outcomes, neonatal complications and delivery routes were determined and compared between the 2 groups. Pregnancy outcomes included: maternal complications (e.g. placenta previa, placental abruption, premature rupture of the membranes, preeclampsia and eclampsia, abortion, breech presentation, preterm labor, intrauterine fetal death); neonatal complications (low birth weight, gross congenital malformations, low Apgar score at 1 min), and delivery routes (cesarean delivery or instrumental delivery, e.g. forceps or vacuum). Statistical analysis was performed using the Statistical Package for Social Science. Results: Statistical analysis showed that the pregnancy complications following a previous spontaneous miscarriage were no different from those of the control group, except for abortion (16.5 vs. 11%, p < 0.003, RR = 1.15, CI 95% = 0.95–1.39), fetal deaths (1.5 vs. 0%, p < 0.004, RR = 1.51, CI 95% = 1.39–1.63), and vaginal bleeding during the first trimester (19 vs. 1%, p < 0.001, RR = 1.57, CI 95% = 1.41–1.75), which were more than those of the control group. Also, the rate of cesarean delivery (28.14 vs. 13.48%) was increased (p = 0.026, RR = 1.25, CI 95% = 1.07–1.47). Neonatal complications were not statistically significantly different in comparison with the control group. Conclusion: A prior spontaneous miscarriage is a risk for the next pregnancy, and the risk of abortion and intrauterine fetal death will increase. Therefore, careful prenatal care is mandatory.
Threshold Estimation in Children Using Auditory Steady-State Responses to Multiple Simultaneous Stimuli
Authors: Han Demin , Mo Lingyan , Liu Hui , Chen Jing , Huang Lihui
Published: January 2006

Objective: It was the aim of this study to explore the use of auditory steady-state response (ASSR) to multiple simultaneous stimuli for threshold estimation in young children. Method: The subjects consisted of 40 children, aged from 6 months to 5 years, with variant degrees of sensorineural hearing loss. Simultaneous tonepips (0.5, 1, 2 and 4 kHz) with an amplitude modulated at different rates from 77 to 103 Hz were presented to both ears by insert phones. All children were tested with ASSR and age-appropriate behavioral tests. Results: We found that (1) ASSR thresholds were usually higher than behavioral thresholds with a difference of 8–15 dB, (2) the behavioral thresholds were significantly correlated with ASSR thresholds (p = 0.000), and (3) there was a great difference between ASSR thresholds and behavioral thresholds found in a child with auditory neuropathy. Conclusion: Being objective, frequency specific and well correlated with behavioral thresholds, ASSR to multiple simultaneous stimuli was proven to be a good tool to predict behavioral hearing thresholds.
Endoscopic Resection of Sinonasal Hemangiomas and Hemangiopericytomas
Authors: Schlosser Rodney J. , Woodworth Bradford A. , Gillespie M. Boyd , Day Terry A.
Published: January 2006

Introduction: Endoscopic resection of benign neoplasms, such as inverted papilloma, has been well described. There are limited case reports of endoscopic resection of benign vascular tumors, including hemangiomas, or those with low-grade malignant potential, such as hemangiopericytomas. Methods: Retrospective review of sinonasal hemangiomas and hemangiopericytomas resected endoscopically at a single tertiary-care facility. Results: Three hemangiomas and 3 hemangiopericytomas were resected endoscopically with no recurrences at a mean follow-up of 22 months. Four tumors involved the skull base; 2 of these underwent preoperative embolization. One patient had a CSF leak that occurred as the tumor was removed from the cribriform plate and that was successfully repaired intraoperatively. The average size of the tumors was 5.8 cm × 2.7 cm with all tumors at least 2.5 cm in greatest dimension by computed tomography or magnetic resonance imaging. The largest tumor was 12 cm in greatest dimension. An average of 8 intraoperative frozen section margins was taken around 5 tumors, with all margins of each tumor clear on final pathology. Patients included 4 males and 2 females with an average age of 47 years. Conclusion: Large vascular neoplasms of the sinonasal cavity, such as hemangiomas and hemangiopericytomas, can be safely removed using endoscopic techniques. Although these patients have a limited follow-up, it is prudent to perform long-term endoscopic follow-up in order to detect recurrences regardless of resection technique.
Contrast-Enhanced Multidetector Computed Tomography Viability Imaging After Myocardial Infarction
Authors: Lardo Albert C. , Cordeiro Marco A.S. , Silva Caterina , Amado Luciano C. , George Richard T. , Saliaris Anastasios P. , Schuleri Karl H. , Fernandes Veronica R. , Zviman Menekhem , Nazarian Saman , Halperin Henry R. , Wu Katherine C. , Hare Joshua M. , Lima Joao A.C.
Published: January 2006

Background—

The ability to distinguish dysfunctional but viable myocardium from nonviable tissue has important prognostic implications after myocardial infarction. The purpose of this study was to validate the accuracy of contrast-enhanced multidetector computed tomography (MDCT) for quantifying myocardial necrosis, microvascular obstruction, and chronic scar after occlusion/reperfusion myocardial infarction.

Methods and Results—

Ten dogs and 7 pigs underwent balloon occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion. Contrast-enhanced (Visipaque, 150 mL, 325 mg/mL) MDCT (0.5 mm × 32 slice) was performed before occlusion and 90 minutes (canine) or 8 weeks (porcine) after reperfusion. MDCT images were analyzed to define infarct size/extent and microvascular obstruction and compared with postmortem myocardial staining (triphenyltetrazolium chloride) and microsphere blood flow measurements. Acute and chronic infarcts by MDCT were characterized by hyperenhancement, whereas regions of microvascular obstruction were characterized by hypoenhancement. MDCT infarct volume compared well with triphenyltetrazolium chloride staining (acute infarcts 21.1±7.2% versus 20.4±7.4%, mean difference 0.7%; chronic infarcts 4.15±1.93% versus 4.92±2.06%, mean difference −0.76%) and accurately reflected morphology and the transmural extent of injury in all animals. Peak hyperenhancement of infarcted regions occurred ≈5 minutes after contrast injection. MDCT-derived regions of microvascular obstruction were also identified accurately in acute studies and correlated with reduced flow regions as measured by microsphere blood flow.

Conclusions—

The spatial extent of acute and healed myocardial infarction can be determined and quantified accurately with contrast-enhanced MDCT. This feature, combined with existing high-resolution MDCT coronary angiography, may have important implications for the comprehensive assessment of cardiovascular disease.
Ventricular Fibrosis Suggested by Cardiovascular Magnetic Resonance in Adults With Repaired Tetralogy of Fallot and Its Relationship to Adverse Markers of Clinical Outcome
Authors: Babu-Narayan Sonya V. , Kilner Philip J. , Li Wei , Moon James C. , Goktekin Omer , Davlouros Periklis A. , Khan Mohammed , Ho Siew Yen , Pennell Dudley J. , Gatzoulis Michael A.
Published: January 2006

Background—

Late morbidity and mortality remain problematic after repair of tetralogy of Fallot (TOF). We hypothesized that fibrosis detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) would be present in adults with repaired TOF and would be related to adverse markers of outcome.

Method and Results—

LGE was scored in the right and left ventricles (RV and LV) of 92 adult patients who had undergone TOF repair. RV LGE was seen in all patients at surgical sites located in the outflow tract (99%) or the site of ventricular septal defect patching (98%) and in the inferior RV insertion point (79%) and trabeculated myocardium (24%). LV LGE (53%) was located at the apex consistent with apical vent insertion (49%), in the inferior or lateral wall consistent with infarction (5%), or in other areas (8%). Patients with supramedian RV LGE score were older (38 versus 27 years,
P
<0.001) and more symptomatic (38% versus 8% in New York Heart Association class II or greater,
P
=0.001), had increased levels of atrial natriuretic peptide (7.3 versus 4.9 pmol/L,
P
=0.041), and had a trend to higher brain natriuretic peptide (12.3 versus 7.2 pmol/L,
P
=0.086), exercise intolerance (maximum V̇
o
2
24 versus 28 mL · min
−1
· kg
−1
,
P
=0.021), RV dysfunction (RV end-systolic volume 61 versus 55 mL/m
2
,
P
=0.018; RV ejection fraction 50% versus 56%,
P
=0.007), and clinical arrhythmia (26% versus 10%,
P
=0.039). Non–apical vent LV LGE also correlated with markers of adverse outcome. In a multivariate model, RV LGE remained a predictor of arrhythmia.

Conclusions—

RV and LV LGE were common after TOF repair and were related to adverse clinical markers, including ventricular dysfunction, exercise intolerance, and neurohormonal activation. Furthermore, RV LGE was significantly associated with clinical arrhythmia.
Potassium Channel Subunit Remodeling in Rabbits Exposed to Long-Term Bradycardia or Tachycardia
Authors: Tsuji Yukiomi , Zicha Stephen , Qi Xiao-Yan , Kodama Itsuo , Nattel Stanley
Published: January 2006

Background—

Sustained heart rate abnormalities produce electrical remodeling and susceptibility to arrhythmia. Uncontrolled tachycardia produces heart failure and ventricular tachyarrhythmia susceptibility, whereas bradycardia promotes spontaneous torsade de pointes (TdP). This study compared arrhythmic phenotypes and molecular electrophysiological remodeling produced by tachycardia versus bradycardia in rabbits.

Methods and Results—

We evaluated mRNA and protein expression of subunits underlying rapid (
I
Kr
) and slow (
I
Ks
) delayed-rectifier and transient-outward K
+
currents in ventricular tissues from sinus rhythm control rabbits and rabbits with AV block submitted to 3-week ventricular pacing either at 60 to 90 bpm (bradypaced) or at 350 to 370 bpm (tachypaced). QT intervals at matched ventricular pacing rates were longer in bradypaced than tachypaced rabbits (eg, by ≈50% at 60 bpm;
P
<0.01). KvLQT1 and minK mRNA and protein levels were downregulated in both bradypaced and tachypaced rabbits, whereas ERG was significantly downregulated in bradypaced rabbits only. Kv4.3 and Kv1.4 were downregulated by tachypacing only. Patch-clamp experiments showed that
I
Ks
was reduced in both but
I
Kr
was decreased in bradypaced rabbits only. Continuous monitoring revealed spontaneous TdP in 75% of bradypaced but only isolated ventricular ectopy in tachypaced rabbits. Administration of dofetilide (0.02 mg/kg) to mimic
I
Kr
downregulation produced ultimately lethal TdP in all tachypaced rabbits.

Conclusions—

Sustained tachycardia and bradycardia downregulate
I
Ks
subunits, but bradycardia also suppresses ERG/
I
Kr
, causing prominent repolarization delays and spontaneous TdP. Susceptibility of tachycardia/heart failure rabbits to malignant tachyarrhythmias is induced by exposure to
I
Kr
blockers. These results point to a crucial role for delayed-rectifier subunit remodeling in TdP susceptibility associated with rate-related cardiac remodeling.
Proliferation of Cardiac Technology in Canada
Authors: Alter David A. , Stukel Therese A. , Newman Alice
Published: January 2006

Background—

Critics remain skeptical about the long-term sustainability of Medicare in Canada because of the proliferation of health technology and escalating expenditures. The objective of this study was to examine the temporal trends in the utilization and costs of cardiovascular technologies for the evaluation and/or management of patients with ischemic heart disease in Canada.

Methods and Results—

This repeated cross-sectional population-based study of Ontario residents examined the temporal trends in the utilization and costs associated with echocardiography, stress (imaging and nonimaging) testing, coronary angiography, percutaneous coronary intervention (PCI), and bypass surgery between 1992 and 2001. Annual costs increased by nearly 2-fold over the 10-year study period and cumulatively accounted for more than $2.8 billion (Canadian) in expenditures. The proliferation in use of cardiac testing/interventions over time outstripped both demographic shifts and changes in the prevalence of coronary artery disease. Annual increases were widespread for all procedures (
P
<0.001) and ranged from 2% per year for nonimaging stress tests to 12% per year for PCI, after adjustment for age and sex. Generally, utilization rates were higher among the elderly, males, and those of low socioeconomic status. With few exceptions, annual increases in the utilization rates of cardiac tests and procedures were disproportionately higher among the elderly and women, but they were similar across socioeconomic subgroups. Increases in utilization appeared to reflect referrals toward higher-risk populations.

Conclusions—

Although definitive conclusions about the appropriateness of temporal patterns cannot be ascertained, the proliferation of cardiac testing challenges the sustainability of Medicare in Canada, especially given uncertainty as to whether the accompanying incremental rise in total expenditures translates into significant outcome benefits in the population.
Physiological Basis of Clinically Used Coronary Hemodynamic Indices
Authors: Spaan Jos A.E. , Piek Jan J. , Hoffman Julien I.E. , Siebes Maria
Published: January 2006

In deriving clinically used hemodynamic indices such as fractional flow reserve and coronary flow velocity reserve, simplified models of the coronary circulation are used. In particular, myocardial resistance is assumed to be independent of factors such as heart contraction and driving pressure. These simplifying assumptions are not always justified. In this review we focus on distensibility of resistance vessels, the shape of coronary pressure-flow lines, and the influence of collateral flow on these lines. We show that (1) the coronary system is intrinsically nonlinear because resistance vessels at maximal vasodilation change diameter with pressure and cardiac function; (2) the assumption of collateral flow is not needed to explain the difference between pressure-derived and flow-derived fractional flow reserve; and (3) collateral flow plays a role only at low distal pressures. We conclude that traditional hemodynamic indices are valuable for clinical decision making but that clinical studies of coronary physiology will benefit greatly from combined measurements of coronary flow or velocity and pressure.
The Effect of Ravuconazole on the Pharmacokinetics of Nelfinavir in Healthy Male Volunteers
Authors: Yan Jing‐He , Marino Maria R. , Smith Robert A. , Kanamaluru Vanaja , O'Mara Edward M. , Grasela Dennis M.
Published: January 2006

An open‐label, nonrandomized study was conducted to assess the effect of ravuconazole on the pharmacokinetics of concomitantly administered nelfinavir. Healthy volunteers received 750 mg nelfinavir on day 1, 750 mg nelfinavir and 400 mg ravuconazole on day 2, 400 mg ravuconazole on days 3 to 28, and 750 mg nelfinavir and 400 mg ravuconazole on day 29. The geometric means of Cmax and area under the curve of nelfinavir coadministered with ravuconazole were 30.7% and 31.9% higher on day 2 and 7.9% and 16.2% lower on day 29, respectively, compared to the corresponding values on day 1. These findings are consistent with the potential for ravuconazole to both inhibit and induce CYP3A isozymes. The alterations in the systemic exposure to nelfinavir were within the range defined by the 90% confidence interval. The study data indicate that coadministration of ravuconazole did not result in a clinically significant change in the plasma levels of nelfinavir.
Medication use to treat memory loss in dementia
Authors: Lindstrom Heather A. , Smyth Kathleen A. , Sami Susie A. , Dawson Neal V. , Patterson Marian B. , Bohinc Jan H. , Post Stephen G. , Barber Melissa J. , Ollerton Sally , Singer Mendel , Whitehouse Peter J.
Published: January 2006

Treatment decisions for symptoms associated with dementia are complex, involving persons with dementia, caregivers and physicians. Our exploratory focus group research examined the views of Caucasian and African-American persons with dementia ( n= 19) and their caregivers ( n= 19) surrounding use of and hopes for existing medications to treat the symptoms of memory loss, willingness to stop medication use at some point in the future, and willingness to try medications that may become available. Participants in our focus groups expressed relatively high hopes for what medications could do to treat memory loss, a general willingness to try hypothetical new treatments, even those with serious side-effects and high costs, and were optimistic that scientists would find new treatments to significantly affect the course of memory loss in their lifetimes. Our results suggest caregivers and persons with dementia need better information about the likely impacts of medications in order to make informed treatment decisions. Efficacy, side-effects, cost, and the need for ‘hope’ embodied in concrete actions (e.g. taking a medication) must be weighed.
Components of coordinated care
Authors: Cockerill Rhonda , Jaglal Susan , Charles Louise Lemieux , Chambers Larry , Brazil Kevin , Cohen Carole
Published: January 2006

This article reports on the development of an instrument to measure dementia patients' and their families' experiences with care provision. Using the responses of 267 care recipient/caregiver dyads, exploratory factor analysis was used to extract an underlying structure of the dyads' assessments of their experiences with dementia networks of care. The results suggested that from the perspective of the care recipient and caregiver, it is the individuals who they interact with in their care journey that define and shape the evaluation of their experiences. In the early stages of dementia, the family physician plays a central role in helping dyads understand the disease and the networks of care that are available to them; in later stages of the disease, it is the activities of the health care worker who is central to the dyad's lived experiences of the care they are receiving. The third important construct linked to the period when a care recipient and caregiver dyad was increasingly aware that dementia services may be needed and the process of assessment and placement was underway. Having information about what resources are available and how they can be accessed, and being able to complete assessments and placements in a timely fashion, was central to their assessment of care networks.
Capturing the Huntington's disease spousal carer experience
Authors: Aubeeluck Aimee , Buchanan Heather
Published: January 2006

The purpose of this exploratory study was to capture and describe the experiences of family carers of Huntington's disease (HD) patients, specifically in relation to their Quality of Life (QoL). Visual representations of QoL were gathered using ‘Photovoice’. Five spousal carers photographed and described elements of their life in which they felt their QoL was being enhanced or compromised. Using content analysis, nine manifest themes were identified and tentative latent inferences were made in relation to these themes. Although some positive issues did emerge, these were minimal compared to the negative impact that HD had on carers' overall QoL. Seven out of the nine themes that emerged were also evident in at least one of the seven QoL domains on the Comprehensive Quality of Life scale – Adult Version (ComQoL-A5); suggesting that QoL is negatively affected for these spousal carers. Findings are discussed in terms of implications for carers and health care professionals.
Mucociliary and long-term particle clearance in airways of patients with immotile cilia
Authors: Möller Winfried , Häußinger Karl , Ziegler-Heitbrock Löms , Heyder Joachim
Published: January 2006

Spherical monodisperse ferromagnetic iron oxide particles of 1.9 μm geometric and 4.2 μm aerodynamic diameter were inhaled by seven patients with primary ciliary dyskinesia (PCD) using the shallow bolus technique, and compared to 13 healthy non-smokers (NS) from a previous study. The bolus penetration front depth was limiting to the phase1 dead space volume. In PCD patients deposition was 58+/-8 % after 8 s breath holding time. Particle retention was measured by the magnetopneumographic method over a period of nine months. Particle clearance from the airways showed a fast and a slow phase. In PCD patients airway clearance was retarded and prolonged, 42+/-12 % followed the fast phase with a mean half time of 16.8+/-8.6 hours. The remaining fraction was cleared slowly with a half time of 121+/-25 days. In healthy NS 49+/-9 % of particles were cleared in the fast phase with a mean half time of 3.0+/-1.6 hours, characteristic of an intact mucociliary clearance. There was no difference in the slow clearance phase between PCD patients and healthy NS. Despite non-functioning cilia the effectiveness of airway clearance in PCD patients is comparable to healthy NS, with a prolonged kinetics of one week, which may primarily reflect the effectiveness of cough clearance. This prolonged airway clearance allows longer residence times of bacteria and viruses in the airways and may be one reason for increased frequency of infections in PCD patients.
Arginase strongly impairs neuronal nitric oxide-mediated airway smooth muscle relaxation in allergic asthma
Authors: Maarsingh Harm , Leusink John , Bos I Sophie T , Zaagsma Johan , Meurs Herman
Published: January 2006

Background

Using guinea pig tracheal preparations, we have recently shown that endogenous arginase activity attenuates inhibitory nonadrenergic noncholinergic (iNANC) nerve-mediated airway smooth muscle relaxation by reducing nitric oxide (NO) production – due to competition with neuronal NO-synthase (nNOS) for the common substrate, L-arginine. Furthermore, in a guinea pig model of allergic asthma, airway arginase activity is markedly increased after the early asthmatic reaction (EAR), leading to deficiency of agonist-induced, epithelium-derived NO and subsequent airway hyperreactivity.

In this study, we investigated whether increased arginase activity after the EAR affects iNANC nerve-derived NO production and airway smooth muscle relaxation.

Methods

Electrical field stimulation (EFS; 150 mA, 4 ms, 4 s, 0.5 – 16 Hz)-induced relaxation was measured in tracheal open-ring preparations precontracted to 30% with histamine in the presence of 1 μM atropine and 3 μM indomethacin. The contribution of NO to EFS-induced relaxation was assessed by the nonselective NOS inhibitor Nω-nitro-L-arginine (L-NNA, 100 μM), while the involvement of arginase activity in the regulation of EFS-induced NO production and relaxation was investigated by the effect of the specific arginase inhibitor Nω-hydroxy-nor-L-arginine (nor-NOHA, 10 μM). Furthermore, the role of substrate availability to nNOS was measured in the presence of exogenous L-arginine (5.0 mM).

Results

At 6 h after ovalbumin-challenge (after the EAR), EFS-induced relaxation (ranging from 3.2 ± 1.1% at 0.5 Hz to 58.5 ± 2.2% at 16 Hz) was significantly decreased compared to unchallenged controls (7.1 ± 0.8% to 75.8 ± 0.7%;P< 0.05 all). In contrast to unchallenged controls, the NOS inhibitor L-NNA did not affect EFS-induced relaxation after allergen challenge, indicating that NO deficiency underlies the impaired relaxation. Remarkably, the specific arginase inhibitor nor-NOHA normalized the impaired relaxation to unchallenged control (P< 0.05 all), which effect was inhibited by L-NNA (P< 0.01 all). Moreover, the effect of nor-NOHA was mimicked by exogenous L-arginine.

Conclusion

The results clearly demonstrate that increased arginase activity after the allergen-induced EAR contributes to a deficiency of iNANC nerve-derived NO and decreased airway smooth muscle relaxation, presumably via increased substrate competition with nNOS.
Tooth loss and obstructive sleep apnoea
Authors: Bucca Caterina , Cicolin Alessandro , Brussino Luisa , Arienti Andrea , Graziano Alessandra , Erovigni Francesco , Pera Paolo , Gai Valerio , Mutani Roberto , Preti Giulio , Rolla Giovanni , Carossa Stefano
Published: January 2006

Background

Complete tooth loss (edentulism) produces anatomical changes that may impair upper airway size and function. The aim of this study was to evaluate whether edentulism favours the occurrence of obstructive sleep apnoea (OSA).

Methods

Polysomnography was performed in 48 edentulous subjects on two consecutive nights, one slept with and the other without dentures. Upper airway size was assessed by cephalometry and by recording forced mid-inspiratory airflow rate (FIF50). Exhaled nitric oxide (eNO) and oral NO (oNO), were measured as markers of airway and oropharyngeal inflammation.

Results

The apnoea/hypopnoea index (AHI) without dentures was significantly higher than with dentures (17·4 ± 3·6 versus 11·0 ± 2·3. p = 0·002), and was inversely related to FIF50 (p = 0·017) and directly related to eNO (p = 0·042). Sleeping with dentures, 23 subjects (48%) had an AHI over 5, consistent with OSA, but sleeping without dentures the number of subjects with abnormal AHI rose to 34 (71%). At cephalometry, removing dentures produced a significant decrease in retropharyngeal space (from 1·522 ± 0·33 cm to 1·27 ± 0·42 cm, p = 0·006). Both morning eNO and oNO were higher after the night slept without dentures (eNO 46·1 ± 8·2 ppb versus 33·7 ± 6·3 ppb, p = 0·035, oNO 84·6 ± 13·7 ppb versus 59·2 ± 17·4 ppb, p = 0·001).

Conclusion

These findings suggest that complete tooth loss favours upper airway obstruction during sleep. This untoward effect seems to be due to decrease in retropharyngeal space and is associated with increased oral and exhaled NO concentration.
Phosphodiesterase type 4 expression and anti-proliferative effects in human pulmonary artery smooth muscle cells
Authors: Growcott Ellena J , Spink Karen G , Ren Xiaohui , Afzal Saliha , Banner Kathy H , Wharton John
Published: January 2006

Background

Pulmonary arterial hypertension is a proliferative vascular disease, characterized by aberrant regulation of smooth muscle cell proliferation and apoptosis in distal pulmonary arteries. Prostacyclin (PGI2) analogues have anti-proliferative effects on distal human pulmonary artery smooth muscle cells (PASMCs), which are dependent on intracellular cAMP stimulation. We therefore sought to investigate the involvement of the main cAMP-specific enzymes, phosphodiesterase type 4 (PDE4), responsible for cAMP hydrolysis.

Methods

Distal human PASMCs were derived from pulmonary arteries by explant culture (n = 14, passage 3–12). Responses to platelet-derived growth factor-BB (5–10 ng/ml), serum, PGI2analogues (cicaprost, iloprost) and PDE4 inhibitors (roflumilast, rolipram, cilomilast) were determined by measuring cAMP phosphodiesterase activity, intracellular cAMP levels, DNA synthesis, apoptosis (as measured by DNA fragmentation and nuclear condensation) and matrix metalloproteinase-2 and -9 (MMP-2, MMP-9) production.

Results

Expression of all fourPDE4A-Dgenes was detected in PASMC isolates. PDE4 contributed to the main proportion (35.9 ± 2.3%, n = 5) of cAMP-specific hydrolytic activity demonstrated in PASMCs, compared to PDE3 (21.5 ± 2.5%), PDE2 (15.8 ± 3.4%) or PDE1 activity (14.5 ± 4.2%). Intracellular cAMP levels were increased by PGI2analogues and further elevated in cells co-treated with roflumilast, rolipram and cilomilast. DNA synthesis was attenuated by 1 μM roflumilast (49 ± 6% inhibition), rolipram (37 ± 6%) and cilomilast (30 ± 4%) and, in the presence of 5 nM cicaprost, these compounds exhibited EC50values of 4.4 (2.6–6.1) nM (Mean and 95% confidence interval), 59 (36–83) nM and 97 (66–130) nM respectively. Roflumilast attenuated cell proliferation and gelatinase (MMP-2 and MMP-9) production and promoted the anti-proliferative effects of PGI2analogues. The cAMP activators iloprost and forskolin also induced apoptosis, whereas roflumilast had no significant effect.

Conclusion

PDE4 enzymes are expressed in distal human PASMCs and the effects of cAMP-stimulating agents on DNA synthesis, proliferation and MMP production is dependent, at least in part, on PDE4 activity. PDE4 inhibition may provide greater control of cAMP-mediated anti-proliferative effects in human PASMCs and therefore could prove useful as an additional therapy for pulmonary arterial hypertension.
An improved procedure for gene selection from microarray experiments using false discovery rate criterion
Authors: Yang James J , Yang Mark CK
Published: January 2006

Background

A large number of genes usually show differential expressions in a microarray experiment with two types of tissues, and thep-values of a proper statistical test are often used to quantify the significance of these differences. The genes with smallp-values are then picked as the genes responsible for the differences in the tissue RNA expressions. One key question is what should be the threshold to consider thep-values small. There is always a trade off between this threshold and the rate of false claims. Recent statistical literature shows that the false discovery rate (FDR) criterion is a powerful and reasonable criterion to pick those genes with differential expression. Moreover, the power of detection can be increased by knowing the number of non-differential expression genes. While this number is unknown in practice, there are methods to estimate it from data. The purpose of this paper is to present a new method of estimating this number and use it for the FDR procedure construction.

Results

A combination of test functions is used to estimate the number of differentially expressed genes. Simulation study shows that the proposed method has a higher power to detect these genes than other existing methods, while still keeping the FDR under control. The improvement can be substantial if the proportion of true differentially expressed genes is large. This procedure has also been tested with good results using a real dataset.

Conclusion

For a given expected FDR, the method proposed in this paper has better power to pick genes that show differentiation in their expression than two other well known methods.
GenoLink: a graph-based querying and browsing system for investigating the function of genes and proteins
Authors: Durand Patrick , Labarre Laurent , Meil Alain , Divol Jean-Louis , Vandenbrouck Yves , Viari Alain , Wojcik Jérôme
Published: January 2006

Background

A large variety of biological data can be represented by graphs. These graphs can be constructed from heterogeneous data coming from genomic and post-genomic technologies, but there is still need for tools aiming at exploring and analysing such graphs. This paper describes GenoLink, a software platform for the graphical querying and exploration of graphs.

Results

GenoLink provides a generic framework for representing and querying data graphs. This framework provides a graph data structure, a graph query engine, allowing to retrieve sub-graphs from the entire data graph, and several graphical interfaces to express such queries and to further explore their results. A query consists in a graph pattern with constraints attached to the vertices and edges. A query result is the set of all sub-graphs of the entire data graph that are isomorphic to the pattern and satisfy the constraints. The graph data structure does not rely upon any particular data model but can dynamically accommodate for any user-supplied data model. However, for genomic and post-genomic applications, we provide a default data model and several parsers for the most popular data sources. GenoLink does not require any programming skill since all operations on graphs and the analysis of the results can be carried out graphically through several dedicated graphical interfaces.

Conclusion

GenoLink is a generic and interactive tool allowing biologists to graphically explore various sources of information. GenoLink is distributed either as a standalone application or as a component of the Genostar/Iogma platform. Both distributions are free for academic research and teaching purposes and can be requested at academy@genostar.com. A commercial licence form can be obtained for profit company at info@genostar.com. See also http://www.genostar.org.
NOXclass: prediction of protein-protein interaction types
Authors: Zhu Hongbo , Domingues Francisco S , Sommer Ingolf , Lengauer Thomas
Published: January 2006

Background

Structural models determined by X-ray crystallography play a central role in understanding protein-protein interactions at the molecular level. Interpretation of these models requires the distinction between non-specific crystal packing contacts and biologically relevant interactions. This has been investigated previously and classification approaches have been proposed. However, less attention has been devoted to distinguishing different types of biological interactions. These interactions are classified as obligate and non-obligate according to the effect of the complex formation on the stability of the protomers. So far no automatic classification methods for distinguishing obligate, non-obligate and crystal packing interactions have been made available.

Results

Six interface properties have been investigated on a dataset of 243 protein interactions. The six properties have been combined using a support vector machine algorithm, resulting in NOXclass, a classifier for distinguishing obligate, non-obligate and crystal packing interactions. We achieve an accuracy of 91.8% for the classification of these three types of interactions using a leave-one-out cross-validation procedure.

Conclusion

NOXclass allows the interpretation and analysis of protein quaternary structures. In particular, it generates testable hypotheses regarding the nature of protein-protein interactions, when experimental results are not available. We expect this server will benefit the users of protein structural models, as well as protein crystallographers and NMR spectroscopists. A web server based on the method and the datasets used in this study are available at http://noxclass.bioinf.mpi-inf.mpg.de/.
A new pooling strategy for high-throughput screening: the Shifted Transversal Design
Authors: Thierry-Mieg Nicolas
Published: January 2006

Background

In binary high-throughput screening projects where the goal is the identification of low-frequency events, beyond the obvious issue of efficiency, false positives and false negatives are a major concern. Pooling constitutes a natural solution: it reduces the number of tests, while providing critical duplication of the individual experiments, thereby correcting for experimental noise. The main difficulty consists in designing the pools in a manner that is both efficient and robust: few pools should be necessary to correct the errors and identify the positives, yet the experiment should not be too vulnerable to biological shakiness. For example, some information should still be obtained even if there are slightly more positives or errors than expected. This is known as the group testing problem, or pooling problem.

Results

In this paper, we present a new non-adaptive combinatorial pooling design: the "shifted transversal design" (STD). It relies on arithmetics, and rests on two intuitive ideas: minimizing the co-occurrence of objects, and constructing pools of constant-sized intersections. We prove that it allows unambiguous decoding of noisy experimental observations. This design is highly flexible, and can be tailored to function robustly in a wide range of experimental settings (i.e., numbers of objects, fractions of positives, and expected error-rates). Furthermore, we show that our design compares favorably, in terms of efficiency, to the previously described non-adaptive combinatorial pooling designs.

Conclusion

This method is currently being validated by field-testing in the context of yeast-two-hybrid interactome mapping, in collaboration with Marc Vidal's lab at the Dana Farber Cancer Institute. Many similar projects could benefit from using the Shifted Transversal Design.
Recrafting the neighbor-joining method
Authors: Mailund Thomas , Brodal Gerth S , Fagerberg Rolf , Pedersen Christian NS , Phillips Derek
Published: January 2006

Background

The neighbor-joining method by Saitou and Nei is a widely used method for constructing phylogenetic trees. The formulation of the method gives rise to a canonical Θ(n3) algorithm upon which all existing implementations are based.

Results

In this paper we present techniques for speeding up the canonical neighbor-joining method. Our algorithms construct the same phylogenetic trees as the canonical neighbor-joining method. The best-case running time of our algorithms areO(n2) but the worst-case remainsO(n3). We empirically evaluate the performance of our algoritms on distance matrices obtained from the Pfam collection of alignments. The experiments indicate that the running time of our algorithms evolve as Θ(n2) on the examined instance collection. We also compare the running time with that of the QuickTree tool, a widely used efficient implementation of the canonical neighbor-joining method.

Conclusion

The experiments show that our algorithms also yield a significant speed-up, already for medium sized instances.
Missing value estimation for DNA microarray gene expression data by Support Vector Regression imputation and orthogonal coding scheme
Authors: Wang Xian , Li Ao , Jiang Zhaohui , Feng Huanqing
Published: January 2006

Background

Gene expression profiling has become a useful biological resource in recent years, and it plays an important role in a broad range of areas in biology. The raw gene expression data, usually in the form of large matrix, may contain missing values. The downstream analysis methods that postulate complete matrix input are thus not applicable. Several methods have been developed to solve this problem, such as K nearest neighbor impute method, Bayesian principal components analysis impute method, etc. In this paper, we introduce a novel imputing approach based on the Support Vector Regression (SVR) method. The proposed approach utilizes an orthogonal coding input scheme, which makes use of multi-missing values in one row of a certain gene expression profile and imputes the missing value into a much higher dimensional space, to obtain better performance.

Results

A comparative study of our method with the previously developed methods has been presented for the estimation of the missing values on six gene expression data sets. Among the three different input-vector coding schemes we tried, the orthogonal input coding scheme obtains the best estimation results with the minimum Normalized Root Mean Squared Error (NRMSE). The results also demonstrate that the SVR method has powerful estimation ability on different kinds of data sets with relatively small NRMSE.

Conclusion

The SVR impute method shows better performance than, or at least comparable with, the previously developed methods in present research. The outstanding estimation ability of this impute method is partly due to the use of the most missing value information by incorporating orthogonal input coding scheme. In addition, the solid theoretical foundation of SVR method also helps in estimation of performance together with orthogonal input coding scheme. The promising estimation ability demonstrated in the results section suggests that the proposed approach provides a proper solution to the missing value estimation problem. The source code of the SVR method is available from http://202.38.78.189/downloads/svrimpute.html for non-commercial use.
The comprehensive updated regulatory network of Escherichia coli K-12
Authors: Salgado Heladia , Santos-Zavaleta Alberto , Gama-Castro Socorro , Peralta-Gil Martín , Peñaloza-Spínola Mónica I , Martínez-Antonio Agustino , Karp Peter D , Collado-Vides Julio
Published: January 2006

Background

Escherichia coli is the model organism for which our knowledge of its regulatory network is the most extensive. Over the last few years, our project has been collecting and curating the literature concerning E. coli transcription initiation and operons, providing in both the RegulonDB and EcoCyc databases the largest electronically encoded network available. A paper published recently by Ma et al. (2004) showed several differences in the versions of the network present in these two databases.

Discrepancies have been corrected, annotations from this and other groups (Shen-Orr et al., 2002) have been added, making the RegulonDB and EcoCyc databases the largest comprehensive and constantly curated regulatory network of E. coli K-12.

Results

Several groups have been using these curated data as part of their bioinformatics and systems biology projects, in combination with external data obtained from other sources, thus enlarging the dataset initially obtained from either RegulonDB or EcoCyc of the E. coli K12 regulatory network. We kindly obtained from the groups of Uri Alon and Hong-Wu Ma the interactions they have added to enrich their public versions of the E. coli regulatory network. These were used to search for original references and curate them with the same standards we use regularly, adding in several cases the original references (instead of reviews or missing references), as well as adding the corresponding experimental evidence codes. We also corrected all discrepancies in the two databases available as explained below.

Conclusion

One hundred and fifty new interactions have been added to our databases as a result of this specific curation effort, in addition to those added as a result of our continuous curation work. RegulonDB gene names are now based on those of EcoCyc to avoid confusion due to gene names and synonyms, and the public releases of RegulonDB and EcoCyc are henceforth synchronized to avoid confusion due to different versions. Public flat files are available providing direct access to the regulatory network interactions thus avoiding errors due to differences in database modelling and representation. The regulatory network available in RegulonDB and EcoCyc is the most comprehensive and regularly updated electronically-encoded regulatory network of E. coli K-12.
ZCURVE_V: a new self-training system for recognizing protein-coding genes in viral and phage genomes
Authors: Guo Feng-Biao , Zhang Chun-Ting
Published: January 2006

Background

It necessary to use highly accurate and statistics-based systems for viral and phage genome annotations. The GeneMark systems for gene-finding in virus and phage genomes suffer from some basic drawbacks. This paper puts forward an alternative approach for viral and phage gene-finding to improve the quality of annotations, particularly for newly sequenced genomes.

Results

The new system ZCURVE_V has been run for 979 viral and 212 phage genomes, respectively, and satisfactory results are obtained. To have a fair comparison with the currently available software of similar function, GeneMark, a total of 30 viral genomes that have not been annotated by GeneMark are selected to be tested. Consequently, the average specificity of both systems is well matched, however the average sensitivity of ZCURVE_V for smaller viral genomes (< 100 kb), which constitute the main parts of viral genomes sequenced so far, is higher than that of GeneMark. Additionally, for the genome of Amsacta moorei entomopoxvirus, probably with the lowest genomic GC content among the sequenced organisms, the accuracy of ZCURVE_V is much better than that of GeneMark, because the later predicts hundreds of false-positive genes. ZCURVE_V is also used to analyze well-studied genomes, such as HIV-1, HBV and SARS-CoV. Accordingly, the performance of ZCURVE_V is generally better than that of GeneMark. Finally, ZCURVE_V may be downloaded and run locally, particularly facilitating its utilization, whereas GeneMark is not downloadable. Based on the above comparison, it is suggested that ZCURVE_V may serve as a preferred gene-finding tool for viral and phage genomes newly sequenced. However, it is also shown that the joint application of both systems, ZCURVE_V and GeneMark, leads to better gene-finding results. The system ZCURVE_V is freely available at: http://tubic.tju.edu.cn/Zcurve_V/.

Conclusion

ZCURVE_V may serve as a preferred gene-finding tool used for viral and phage genomes, especially for anonymous viral and phage genomes newly sequenced.