bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic autoregulation of cutaneous circulation: differential control in glabrous versus nonglabrous skin
Authors: Wilson Thad E. , Zhang Rong , Levine Benjamin D. , Crandall Craig G.
Published: March 2005

The purpose of this project was to test the hypothesis that, independent of neural control, glabrous and nonglabrous cutaneous vasculature is capable of autoregulating blood flow. In 10 subjects, spectral and transfer function analyses of arterial pressure and skin blood flow (laser-Doppler flowmetry) from glabrous (palm) and nonglabrous (forearm) regions were performed under three conditions: baseline, ganglionic blockade via intravenous trimethaphan administration, and trimethaphan plus oscillatory lower body negative pressure (LBNP; −5 to −10 mmHg) from 0.05 to 0.07 Hz. Oscillatory LBNP was applied to regenerate mean arterial pressure variability that was abolished by ganglionic blockade. Ganglionic blockade was verified by an absence of a heart rate response to a Valsalva maneuver. Spectral power and transfer function gain between blood pressure and skin blood flow were calculated in this oscillatory frequency range (0.05–0.07 Hz). Within this frequency range, ganglionic blockade significantly decreased spectral power of blood flow in both the forearm and palm, whereas regeneration of arterial blood pressure oscillations significantly increased spectral power of forearm blood flow but not palm blood flow. During oscillatory LBNP, transfer function gain between blood pressure and skin blood flow was significantly elevated at the forearm (0.28 ± 0.03 to 0.53 ± 0.02 flux units/mmHg; P < 0.05) but was reduced at the palm (4.7 ± 0.5 to 1.2 ± 0.1 flux units/mmHg; P < 0.05). These data show that independent of neural control of blood flow, glabrous skin has the ability to buffer blood pressure oscillations and demonstrates a degree of dynamic autoregulation. Conversely, these data suggest that nonglabrous skin has diminished dynamic autoregulatory capabilities.
Influence of size at birth on the endocrine profiles and expression of uncoupling proteins in subcutaneous adipose tissue, lung, and muscle of neonatal pigs
Authors: Mostyn Alison , Litten Jennie C. , Perkins Katharine S. , Euden Philippa J. , Corson Anne M. , Symonds Michael E. , Clarke Lynne
Published: March 2005

Epidemiological studies suggest that infants of low birth weight show poor neonatal growth and increased susceptibility to adult diseases such as diabetes and lung disease. Uncoupling protein 2 and 3 (UCP2 and UCP3) have been implicated in the development of such diseases; pigs provide an ideal model to examine the influence of birth weight due to the natural variance in piglet weight within a litter. This study examined whether birth weight influences the expression of UCP2 and UCP3 in adipose tissue, skeletal muscle, and lung. Piglets from 11 litters were ranked according to birth weight and three from each litter assigned to small (SFD), normal (NFD), or large for dates (LFD) groups. Blood samples and morphometric measurements were taken over the first 14 days of life, and tissue samples were taken on day 7 or 14. Plasma hormone and metabolite concentrations and the expression of UCP2 and UCP3 mRNA in adipose tissue, skeletal muscle, and lung were measured. UCP2 and UCP3 expression in adipose tissue was lower in the SFD compared with the LFD group on day 7. UCP3 expression in skeletal muscle was higher than that of adipose tissue. Lung UCP2 and skeletal muscle UCP3 mRNA expression were unaffected by size at birth. Regression analysis indicated that UCP3 expression was differentially associated with IGF-1, leptin, and insulin. In conclusion, low birth weight is associated with tissue-specific effects on UCP expression. It remains to be established whether these subsequently contribute to pathological conditions such as diabetes.
Nutritional and hormonal control of lipolysis in isolated gilthead seabream (Sparus aurata) adipocytes
Authors: Albalat A. , Gómez-Requeni P. , Rojas P. , Médale F. , Kaushik S. , Vianen G. J. , Van den Thillart G. , Gutiérrez J. , Pérez-Sánchez J. , Navarro I.
Published: March 2005

We examined the effects of diet composition and fasting on lipolysis of freshly isolated adipocytes from gilthead seabream ( Sparus aurata). We also analyzed the effects of insulin, glucagon, and growth hormone (GH) in adipocytes isolated from fish fed with different diets. Basal lipolysis, measured as glycerol release, increased proportionally with cell concentration and time of incubation, which validates the suitability of these cell preparations for the study of hormonal regulation of this metabolic process. Gilthead seabream were fed two different diets, FM (100% of fish meal) and PP (100% of plant protein supplied by plant sources) for 6 wk. After this period, each diet group was divided into two groups: fed and fasted (for 11 days). Lipolysis was significantly higher in adipocytes from PP-fed fish than in adipocytes from FM-fed fish. Fasting provoked a significant increase in the lipolytic rate, about threefold in isolated adipocytes regardless of nutritional history. Hormone effects were similar in the different groups: glucagon increased the lipolytic rate, whereas insulin had almost no effect. GH was clearly lipolytic, although the relative increase in glycerol over control was lower in isolated adipocytes from fasted fish compared with fed fish. Together, we demonstrate for the first time that lipolysis, measured in isolated seabream adipocytes, is affected by the nutritional state of the fish. Furthermore, our data suggest that glucagon and especially GH play a major role in the control of adipocyte lipolysis.
α-Adrenoreceptor blockade with phenoxybenzamine does not affect the ability of the nose to condition air
Authors: Pinto Jayant M. , Assanasen Paraya , Baroody Fuad M. , Naureckas Edward , Naclerio Robert M.
Published: March 2005

The primary function of the nose is to warm and humidify air. We have previously shown that raising nasal mucosal temperature by immersing feet in warm water increases the amount of water evaporated by the nose as air passes through it (nasal conditioning capacity; Abbott D, Baroody F, Naureckas E, and Naclerio R. Am J Rhinol 15: 41–45, 2001). To investigate further the effect of nasal mucosal temperature on nasal conditioning capacity, we raised the temperature through α-adrenoreceptor blockade by intranasally administering phenoxybenzamine. We hypothesized that blocking α-adrenoreceptors during inhalation of cold, dry air would lead to an increase in nasal blood flow, surface temperature, and nasal conditioning capacity, as measured by the water gradient. After appropriate pilot studies, we performed a double-blind, placebo-controlled, two-way crossover study in nine nonatopic, healthy subjects by studying the effect of treatment with intranasal phenoxybenzamine. Nasal mucosal temperature increased significantly after administration of phenoxybenzamine and was associated with a significantly smaller net decrease in nasal mucosal temperature after exposure to cold, dry air ( P < 0.05). However, there were no significant differences in nasal conditioning capacity between treatments ( P > 0.05). Phenoxybenzamine decreased the symptom of rhinorrhea after exposure to cold, dry air ( P < 0.05), but congestion was not different between individuals given phenoxybenzamine and placebo ( P > 0.05). Our data demonstrate that phenoxybenzamine, despite raising mucosal temperature and not affecting nasal volume, did not affect the ability of the nose to warm and humidify air.
Plasma from conscious hypoxic rats stimulates leukocyte-endothelial interactions in normoxic cremaster venules
Authors: Orth Teresa , Allen Julie A. , Wood John G. , Gonzalez Norberto C.
Published: March 2005

Systemic hypoxia results in rapid increases in leukocyte-endothelial adherence (LEA) and emigration, vascular permeability, and mast cell activation in several microcirculations. Observations in cremaster muscle suggest that this response is initiated by a mediator released from a distant site (Dix R, Orth T, Allen JA, Wood JG, and Gonzalez NC. J Appl Physiol 95: 2495–2502, 2003). The present experiments in rat cremaster muscle tested the hypothesis that, if a circulating mediator triggers hypoxia-induced inflammation, then plasma from hypoxic rats should elicit LEA in normoxic cremaster venules. Plasma from conscious donor rats breathing 10% O2-90% N2 for 5 min was applied topically to the cremaster of normoxic anesthetized rats. In this and all other groups described below, the donor plasma had attained normoxic Po2 when applied to the cremaster. LEA (leukocytes/100-μm venule) increased from 2.7 ± 0.8 to 12.3 ± 2.4, and venular shear rate and arteriolar diameter decreased to 79 ± 9% ( P < 0.05, n = 6) and 77 ± 5% of control ( P < 0.05, n = 5), respectively, 10 min after application of plasma from hypoxic donors. The decrease in venular shear rate was exclusively due to a reduction of venular blood flow, secondary to the upstream arteriolar vasoconstriction. Plasma from normoxic donors had no effects. Plasma from blood equilibrated in vitro for 5 min with 5% CO2-95% N2 did not alter LEA or shear rate of normoxic cremasters, suggesting that the putative mediator does not originate in blood cells. The effects of plasma from hypoxic rats persisted when the donors were pretreated with the mast cell stabilizer cromolyn, which prevents hypoxia-induced LEA. This suggests that the effects of hypoxic plasma are not due to inflammatory mediators released by adherent leukocytes in the donor rat. There was a positive correlation between LEA and mast cell degranulation observed histologically. These results support the idea that systemic hypoxia produces the release of a substance transported by the circulation that initiates the microvascular inflammation.
Gene expression of myogenic factors and phenotype-specific markers in electrically stimulated muscle of paraplegics
Authors: Vissing Kristian , Andersen Jesper L. , Harridge Stephen D. R. , Sandri Claudia , Hartkopp Andreas , Kjaer Michael , Schjerling Peter
Published: March 2005

The transcription factors myogenin and MyoD have been suggested to be involved in maintaining slow and fast muscle-fiber phenotypes, respectively, in rodents. Whether this is also the case in human muscle is unknown. To test this, 4 wk of chronic, low-frequency electrical stimulation training of the tibialis anterior muscle of paraplegic subjects were used to evoke a fast-to-slow transformation in muscle phenotype. It was hypothesized that this would result from an upregulation of myogenin and a downregulation of MyoD. The training evoked the expected mRNA increase for slow fiber-specific markers myosin heavy chain I and 3-hydroxyacyl-CoA dehydrogenase A, whereas an mRNA decrease was seen for fast fiber-specific markers myosin heavy chain IIx and glycerol phosphate dehydrogenase. Although the slow fiber-specific markers citrate synthase and muscle fatty acid binding protein did not display a significant increase in mRNA, they did tend to increase. As hypothesized, myogenin mRNA was upregulated. However, contrary to the hypothesis, MyoD mRNA also increased, although later than myogenin. The mRNA levels of the other myogenic regulatory factor family members, myogenic factor 5 and myogenic regulatory factor 4, and the myocyte enhancer factor (MEF) family members, MEF-2A and MEF-2C, did not change. The results indicate that myogenin is indeed involved in the regulation of the slow oxidative phenotype in human skeletal muscle fibers, whereas MyoD appears to have a more complex regulatory function.
NO Generation From Nitrite and Its Role in Vascular Control
Authors: Lundberg Jon O. , Weitzberg Eddie
Published: March 2005

NO generated froml-arginine by NO synthases (NOSs) in the endothelium and in other cells plays a central role in several aspects of vascular biology. The biological activity of NO is acutely terminated by oxidation to nitrite and nitrate, and these compounds have long been considered only as inert end-products of NO. However, this dogma is now being challenged because recent research convincingly has shown that the nitrite ion can be recycled back to bioactive NO again in blood and tissues. Nitrite reduction to NO can occur via several routes involving enzymes, proteins, vitamins, or even simple protons. This pathway may serve as a backup system for NO generation in conditions such as hypoxia, in which the NOS/l-arginine system is compromised, but detrimental effects can also be foreseen. With this new knowledge, nitrate and nitrite should probably be viewed as storage pools for NO rather than inert waste products. Here we discuss novel aspects of nitrite-dependent NO generation in vivo and its role in vascular control.
Impaired KCNQ1–KCNE1 and Phosphatidylinositol-4,5-Bisphosphate Interaction Underlies the Long QT Syndrome
Authors: Park Kyu-Ho , Piron Julien , Dahimene Shehrazade , Mérot Jean , Baró Isabelle , Escande Denis , Loussouarn Gildas
Published: March 2005

Nearly a hundred different KCNQ1 mutations have been reported as leading to the cardiac long QT syndrome, characterized by prolonged QT interval, syncopes, and sudden death. We have previously shown that phosphatidylinositol-4,5-bisphosphate (PIP
2
) regulates the KCNQ1–KCNE1 complex. In the present study, we show that PIP
2
affinity is reduced in three KCNQ1 mutant channels (R243H, R539W, and R555C) associated with the long QT syndrome. In giant excised patches, direct application of PIP
2
on the cytoplasmic face of the three mutant channels counterbalances the loss of function. Reintroduction of a positive charge by application of methanethiosulfonate ethylammonium on the cytoplasmic face of R555C mutant channels also restores channel activity. The channel affinity for a soluble analog of PIP
2
is decreased in the three mutant channels. By using a model that describes the KCNQ1–KCNE1 channel behavior and by fitting the relationship between the kinetics of deactivation and the current amplitude obtained in whole-cell experiments, we estimated the PIP
2
binding and dissociation rates on wild-type and mutant channels. The dissociation rate of the three mutants was higher than for the wild-type channel, suggesting a decreased affinity for PIP
2
. PIP
2
binding was magnesium-dependent, and the PIP
2
-dependent equilibrium constant in the absence of magnesium was higher with the wild-type than with the mutant channels. Altogether, our data suggest that a reduced PIP
2
affinity of KCNQ1 mutants can lead to the long QT syndrome.
Endovascular Stent-Assisted Angioplasty in the Management of Traumatic Internal Carotid Artery Dissections
Authors: Cohen José E. , Ben-Hur Tamir , Rajz Gustavo , Umansky Felix , Gomori John M.
Published: March 2005

Background and Purpose—

The prognosis of traumatic dissection of the internal carotid artery is worse than for spontaneous dissections. Rapid stenting followed by antiplatelet therapy may prevent complications when anticoagulation therapy is not applicable.

Methods—

Patients with angiographically proven traumatic carotid artery dissection and hemodynamic significant hemispheric hypoperfusion, or in whom anticoagulant therapy was either contraindicated or failed clinically, were regarded as being at high risk for stroke and were selected for stenting.

Results—

Ten patients with traumatic dissection underwent stenting. Endovascular treatment reduced mean dissection stenosis from 69% to 8%. During a mean clinical follow-up time of 16 months, none had additional transient ischemic attacks or stroke. Doppler ultrasound studies did not detect any signs of de novo in-stent stenosis.

Conclusion—

In selected cases of traumatic carotid artery dissections, endovascular stent-assisted angioplasty immediately restored the integrity of the vessel lumen and prevented efficiently the occurrence of new ischemic events, without additional anticoagulation.
Family History of Stroke in Patients With Transient Ischemic Attack in Relation to Hypertension and Other Intermediate Phenotypes
Authors: Flossmann Enrico , Rothwell Peter M.
Published: March 2005

Background and Purpose—

Family history of stroke (FHx
stroke
) is a risk factor for ischemic stroke, but there are insufficient data on the relationship with stroke subtypes and intermediate phenotypes (IPs), such as hypertension. Specifically, there are no reliable data on the associations of FHx
stroke
in patients with transient ischemic attack (TIA) in whom relationships with IPs are likely to be determined most reliably.

Methods—

We studied FHx
stroke
and FHx of myocardial infarction (FHx
MI
) in TIA patients from 2 population-based incidence studies and 2 prospective consecutive hospital-referred series. We related the presence of FHx to baseline characteristics, clinical subtype, and IPs.

Results—

Results were similar in the 4 cohorts, and so data on all 783 patients were pooled. FHx
stroke
was less common than FHx
MI
(189 versus 254;
P
=0.0003). FHx
stroke
and FHx
MI
were strongly related to history of hypertension in the proband (odds ratio [OR], 1.78; 95% CI, 1.28 to 2.48;
P
=0.0008; and OR, 2.10, 95% CI, 1.55 to 2.85;
P
<0.0001, respectively). Highest recorded premorbid systolic and diastolic blood pressures (mm Hg) were significantly higher in cases with FHx
stroke
than those without and increased with the number of affected first-degree relatives (0 181/100; 1 185/104; ≥2 198/109;
P
=0.03). There was no association between FHx
stroke
and age, diabetes, smoking, plasma glucose, cholesterol, or territory of TIA, but FHx
stroke
was less common in patients with ocular TIA than in cases with cerebral TIA (OR, 0.53; 95% CI, 0.34 to 0.82;
P
=0.004), although the association was no longer significant after adjustment for hypertension.

Conclusions—

The strong association between hypertension and FHx
stroke
suggests that familial susceptibility to cerebral ischemia is attributable, at least partly, to familial predisposition to hypertension. This should be taken into account in studies of the genetics of ischemic stroke.
Early Recanalization Rates and Clinical Outcomes in Patients With Tandem Internal Carotid Artery/Middle Cerebral Artery Occlusion and Isolated Middle Cerebral Artery Occlusion
Authors: Kim Yo Sik , Garami Zsolt , Mikulik Robert , Molina Carlos A. , Alexandrov Andrei V.
Published: March 2005

Background—

Patients with isolated middle cerebral artery (MCA) and tandem MCA/internal carotid artery (ICA) obstruction have similar presenting symptoms and stroke severity. We aimed to investigate early recanalization of MCA and clinical outcomes in patients with tandem ICA/MCA obstructions and isolated MCA occlusion.

Methods—

Patients with MCA occlusion on pretreatment transcranial Doppler were treated with intravenous tissue plasminogen activator. ICA lesions were detected with carotid duplex. Early neurological improvement (ENI) was defined by reduction of National Institutes of Health Stroke Scale (NIHSS) ≥10 points or total NIHSS ≤3 points. Good outcome at 3 months was a modified Rankin score of ≤2.

Results—

Among 104 patients, 31% had tandem lesions and 69% had isolated MCA occlusions. Complete recanalization rate was 39% in isolated MCA occlusion group and 9% in tandem group (
P
=0.002). ENI at 24 hours occurred in 46% of the isolated MCA occlusion group and in 25% of the tandem group (
P
=0.045). Good outcome was achieved by 30% and 39% respective patients (NS).

Conclusion—

The tandem lesion group showed lower early recanalization rate and ENI rate than the isolated MCA occlusion group. Despite this, good outcomes were similar in both groups.
An Algorithm for the Retrieval of Droplet Number Concentration and Geometrical Thickness of Stratiform Marine Boundary Layer Clouds Applied to MODIS Radiometric Observations
Authors: Schüller Lothar , Bennartz Ralf , Fischer Jürgen , Brenguier Jean-Louis
Published: March 2005

Algorithms are now currently used for the retrieval of cloud optical thickness and droplet effective radius from multispectral radiance measurements. This paper extends their application to the retrieval of cloud droplet number concentration, cloud geometrical thickness, and liquid water path in shallow convective clouds, using an algorithm that was previously tested with airborne measurements of cloud radiances and validated against in situ measurements of the same clouds. The retrieval is based on a stratified cloud model of liquid water content and droplet spectrum. Radiance measurements in visible and near-infrared channels of the Moderate Resolution Imaging Spectroradiometer (MODIS), which is operated from the NASA platforms Terra and Aqua, are analyzed. Because of uncertainties in the simulation of the continental surface reflectance, the algorithm is presently limited to the monitoring of the microphysical structure of boundary layer clouds over the ocean. Two MODIS scenes of extended cloud fields over the North Atlantic Ocean trade wind region are processed. A transport and dispersion model (the Hybrid Single-Particle Lagrangian Integrated Trajectory Model, HYSPLIT4) is also used to characterize the origin of the air masses and hence their aerosol regimes. One cloud field formed in an air mass that was advected from southern Europe and North Africa. It shows high values of the droplet concentration when compared with the second cloud system, which developed in a more pristine environment. The more pristine case also exhibits a higher geometrical thickness and, thus, liquid water path, which counterbalances the expected cloud albedo increase of the polluted case. Estimates of cloud liquid water path are then compared with retrievals from the Special Sensor Microwave Imager (SSM/I). SSM/I-derived liquid water paths are in good agreement with the MODIS-derived values.
AMSU-B Observations of Mixed-Phase Clouds over Land
Authors: Deeter M. N. , Vivekanandan J.
Published: March 2005

Measurements from passive microwave satellite instruments such as the Advanced Microwave Sounding Unit B (AMSU-B) are sensitive to both liquid and ice cloud particles. Radiative transfer modeling is exploited to simulate the response of the AMSU-B instrument to mixed-phase clouds over land. The plane-parallel radiative transfer model employed for the study accounts for scattering and absorption from cloud ice as well as absorption and emission from trace gases and cloud liquid. The radiative effects of mixed-phase clouds on AMSU-B window channels (i.e., 89 and 150 GHz) and water vapor line channels (i.e., 183 ± 1, 3, and 7 GHz) are studied. Sensitivities to noncloud parameters, including surface temperature, surface emissivity, and atmospheric temperature and water vapor profiles, are also quantified. Modeling results indicate that both cloud phases generally have significant radiative effects and that the 150- and 183 ± 7-GHz channels are typically the most sensitive channels to integrated cloud properties (i.e., liquid water path and ice water path). However, results also indicate that AMSU-B measurements alone are probably insufficient for retrieving all mixed-phase cloud properties of interest. These results are supported by comparisons of AMSU-B observations of a mixed-phase cloud over the Atmospheric Radiation Measurement (ARM) Program’s Southern Great Plains (SGP) site with corresponding calculated clear-sky values.
Temporal Structure of the Solar Radiation Field in Cloudy Conditions: Are Retrievals of Hourly Averages from Space Possible?
Authors: Nunez Manuel , Fienberg Kurt , Kuchinke Christopher
Published: March 2005

The authors examine the temporal variability of measured 415- and 611.7-nm spectral solar irradiance in cloudy stratocumulus conditions. This is accomplished by normalizing measured data by the equivalent irradiance for cloudless conditions and the same solar zenith angle. Spectral and other analyses of the time series exhibit fractal behavior in agreement with the multifractal model of Schertzer and Lovejoy. A three-dimensional cloud model with dimensions of 6 km × 38 km is constructed that has these fractal properties, and a Monte Carlo radiative code is applied to obtain irradiances in 50-m grid elements at the surface. Model output is used to test the ability of satellites to calculate hourly irradiance with one, two, three, four, five, and six observations per hour. Root-mean-square errors are substantial—between 17% and 43% for one single satellite observation per hour. The smallest errors of around 5% are obtained with six scans per hour. These results argue that a higher frequency of satellite observations is needed to estimate hourly surface solar irradiances with acceptable accuracy.
Evaluation of GPS Precipitable Water over Canada and the IGS Network
Authors: Deblonde Godelieve , Macpherson Stephen , Mireault Yves , Héroux Pierre
Published: March 2005

Precipitable water (PW) derived from the GPS zenith tropospheric delay (ZTD) is evaluated (as a first step toward variational data assimilation) through comparison with that of collocated radiosondes (RS_PW), operational analyses, and 6-h forecasts (from the Canadian Global Environmental Multiscale model) of the Canadian Meteorological Centre. Two sources of ZTD data are considered: 1) final ZTD (over Canada), computed by the Geodetic Survey Division (GSD) of Natural Resources Canada, and 2) final ZTD (distributed globally), obtained from the International GPS Service (IGS). The mean GSD GPS–derived PW (GPS_PW) is 14.9 mm (reflecting the relatively cold Canadian climate), whereas that of the IGS dataset is 20.8 mm. Intercomparison statistics [correlation, standard deviation (SD), and bias] between GPS_PW and RS_PW are, respectively, 0.97, 2.04 mm, and 1.35 mm for the GSD data and 0.98, 2.6 mm, and 0.67 mm for the IGS data. Comparisons of GPS_PW with 6-h forecast PW (TRIAL_PW) show slightly lower correlations and a higher SD. The increase in SD is greater for the IGS data, which is not surprising, because in regions such as the Tropics and subtropics, moisture forecasts are of a lower quality and the RS observation network is sparse. From a three-way intercomparison (IGS GPS_PW, RS_PW, and TRIAL_PW) of the SD statistics, it is found that GPS_PW has the lowest estimated PW error (≈1 mm) for PW in the 5–30-mm range. For PW greater than 30 mm, the RS_PW estimated error is ≈2 mm, and that of GPS_PW is ≈2.5 mm. The TRIAL_PW estimated error increases with PW, reaching 5.5 mm in the 40–55-mm PW range. These intercomparison results indicate that GPS_PW should be a useful source of humidity information for NWP applications.
Buoyancy of Convective Vertical Motions in the Inner Core of Intense Hurricanes. Part I: General Statistics
Authors: Eastin Matthew D. , Gray William M. , Black Peter G.
Published: March 2005

The buoyancy of hurricane convective vertical motions is studied using aircraft data from 175 radial legs collected in 14 intense hurricanes at four altitudes ranging from 1.5 to 5.5 km. The data of each leg are initially filtered to separate convective-scale features from background mesoscale structure. Convective vertical motion events, called cores, are identified using the criteria that the convective-scale vertical velocity must exceed 1.0 m s−1 for at least 0.5 km. A total of 620 updraft cores and 570 downdraft cores are included in the dataset. Total buoyancy is calculated from convective-scale virtual potential temperature, pressure, and liquid water content using the mesoscale structure as the reference state.

Core properties are summarized for the eyewall and rainband regions at each altitude. Characteristics of core average convective vertical velocity, maximum convective vertical velocity, and diameter are consistent with previous studies of hurricane convection. Most cores are superimposed upon relatively weak mesoscale ascent. The mean eyewall (rainband) updraft core exhibits small, but statistically significant, positive total buoyancy below 4 km (between 2 and 5 km) and a modest increase in vertical velocity with altitude. The mean downdraft core not superimposed upon stronger mesoscale ascent also exhibits positive total buoyancy and a slight decrease in downward vertical velocity with decreasing altitude. Buoyant updraft cores cover less than 5% of the total area in each region but accomplish ∼40% of the total upward transport.

A one-dimensional updraft model is used to elucidate the relative roles played by buoyancy, vertical perturbation pressure gradient forces, water loading, and entrainment in the vertical acceleration of ordinary updraft cores. Small positive total buoyancy values are found to be more than adequate to explain the vertical accelerations observed in updraft core strength, which implies that ordinary vertical perturbation pressure gradient forces are directed downward, opposing the positive buoyancy forces. Entrainment and water loading are also found to limit updraft magnitudes.

The observations support some aspects of both the hot tower hypothesis and symmetric moist neutral ascent, but neither concept appears dominant. Buoyant convective updrafts, however, are integral components of the hurricane’s transverse circulation.
Activation of Th1 and Tc1 cell adenosine A2A receptors directly inhibits IL-2 secretion in vitro and IL-2-driven expansion in vivo
Authors: Erdmann Andreas A. , Gao Zhan-Guo , Jung Unsu , Foley Jason , Borenstein Todd , Jacobson Kenneth A. , Fowler Daniel H.
Published: March 2005

To evaluate the direct effect of adenosine on cytokine-polarized effector T cells, murine type 1 helper T cells (Th1) and type 1 cytotoxic T lymphocytes (Tc1) and Th2/Tc2 cells were generated using an antigen-presenting cell (APC)-free method. Tc1 and Tc2 cells had similar adenosine signaling, as measured by intracellular cyclic AMP (cAMP) increase upon adenosine A2A receptor agonism by CGS21680 (CGS). CGS greatly reduced Tc1 and Tc2 cell interleukin 2 (IL-2) and tumor necrosis factor α (TNF-α) secretion, with nominal effect on interferon γ (IFN-γ) secretion. Tc2 cell IL-4 and IL-5 secretion was not reduced by CGS, and IL-10 secretion was moderately reduced. Agonist-mediated inhibition of IL-2 and TNF-α secretion occurred via A2A receptors, with no involvement of A1, A2B, or A3 receptors. Adenosine agonist concentrations that abrogated cytokine secretion did not inhibit Tc1 or Tc2 cell cytolytic function. Adenosine modulated effector T cells in vivo, as CGS administration reduced CD4+Th1 and CD8+Tc1 cell expansion to alloantigen and, in a separate model, reduced antigen-specific CD4+ Th1 cell numbers. Remarkably, agonist-mediated T-cell inhibition was abrogated by in vivo IL-2 therapy. Adenosine receptor activation therefore preferentially inhibits type I cytokine secretion, most notably IL-2. Modulation of adenosine receptors may thus represent a suitable target primarily for inflammatory conditions mediated by Th1 and Tc1 cells. (Blood. 2005;105: 4707-4714)
Therapeutic potential of a tumor-specific, MHC-unrestricted T-cell receptor expressed on effector cells of the innate and the adaptive immune system through bone marrow transduction and immune reconstitution
Authors: Alajez Nehad M. , Schmielau Jan , Alter Mark D. , Cascio Michael , Finn Olivera J.
Published: March 2005

T-cell receptor (TCR) with unique major histocompatibility complex (MHC)-unrestricted antigen-binding properties was isolated from a human T-cell clone specific for the tumor antigen MUC1. This TCR binds its epitope on the MUC1 protein without the requirement of processing and presentation. A single-chain Vα/Vβ/Cβ (scTCR) was fused to a CD3 zeta (ζ) chain to allow expression on the surface of cells of the innate (granulocytes, macrophages, natural killer [NK] cells) as well as the adaptive (T and B cells) immune system. To test the ability of the cells of the innate immune system to reject a tumor when provided with a tumor antigen-specific TCR, we reconstituted severe combined immunodeficiency (SCID) mice with bone marrow cells transduced with a retroviral vector encoding this receptor and challenged them with a MUC1-positive human tumor. These mice controlled the growth of the tumor significantly better than the control mice. We performed a similar experiment in immunocompetent mice transgenic for human MUC1. Expression of the TCR on large percentages of cells did not result in infiltration or destruction of tissues expressing MUC1. Reconstituted mice controlled the outgrowth of a MUC1-transfected but not the parental control tumor. scTCR expression appears lifelong, suggesting a successful transduction of the self-renewing stem cells. (Blood. 2005;105:4583-4589)
Analysis of leukocyte membrane protein interactions using protein microarrays
Authors: Letarte Michelle , Voulgaraki Despina , Hatherley Deborah , Foster-Cuevas Mildred , Saunders Nigel J , Barclay A Neil
Published: March 2005

Background

Protein microarrays represent an emerging class of proteomic tools to investigate multiple protein-protein interactions in parallel. A sufficient proportion of immobilized proteins must maintain an active conformation and an orientation that allows for the sensitive and specific detection of antibody and ligand binding. In order to establish protein array technology for the characterization of the weak interactions between leukocyte membrane proteins, we selected the human leukocyte membrane protein CD200 (OX2) and its cell surface receptor (hCD200R) as a model system. As antibody-antigen reactions are generally of higher affinity than receptor-ligand binding, we first analyzed the reactivity of monoclonal antibodies (mAb) to normal and mutant forms of immobilized CD200R.

Results

Fluorescently labelled mAb DX147, DX136 and OX108 were specifically reactive with immobilized recombinant hCD200R extracellular region, over a range of 0.1–40 μg ml-1 corresponding to a limit of sensitivity of 0.01–0.05 femtomol per spot. Orientating hCD200R using capture antibodies, showed that DX147 reacts with an epitope spatially distinct from the more closely related DX136 and OX108 epitopes. A panel of soluble recombinant proteins with mutations in hCD200R domain 1 produced by transiently transfected cells, was arrayed directly without purification and screened for binding to the three mAb. Several showed decreased binding to the blocking mAb DX136 and OX108, suggesting close proximity of these epitopes to the CD200 binding site. Binding of hCD200 to directly immobilized rat, mouse, and hCD200R was achieved with multimeric ligands, in the form of biotinylated-hCD200 coupled to FITC-labelled avidin coated beads.

Conclusion

We have achieved sensitive, specific and reproducible detection of immobilized CD200R with different antibodies and mapped antigenic epitopes for two mAb in the vicinity of the ligand binding site using protein microarrays. We also detected CD200 binding to its receptor, a low affinity interaction, using beads presenting multivalent ligands. Our results demonstrate the quantitative aspects of protein arrays and their potential use in detecting simultaneously multiple protein-protein interactions and in particular the weak interactions found between leukocyte membrane proteins.
A comparative sequence analysis reveals a common GBD/FH3-FH1-FH2-DAD architecture in formins from Dictyostelium, fungi and metazoa
Authors: Rivero Francisco , Muramoto Tetsuya , Meyer Ann-Kathrin , Urushihara Hideko , Uyeda Taro QP , Kitayama Chikako
Published: March 2005

Background

Formins are multidomain proteins defined by a conserved FH2 (formin homology 2) domain with actin nucleation activity preceded by a proline-rich FH1 (formin homology 1) domain. Formins act as profilin-modulated processive actin nucleators conserved throughout a wide range of eukaryotes.

Results

We present a detailed sequence analysis of the 10 formins (ForA to J) identified in the genome of the social amoeba Dictyostelium discoideum. With the exception of ForI and ForC all other formins conform to the domain structure GBD/FH3-FH1-FH2-DAD, where DAD is the Diaphanous autoinhibition domain and GBD/FH3 is the Rho GTPase-binding domain/formin homology 3 domain that we propose to represent a single domain. ForC lacks a FH1 domain, ForI lacks recognizable GBD/FH3 and DAD domains and ForA, E and J have additional unique domains. To establish the relationship between formins of Dictyostelium and other organisms we constructed a phylogenetic tree based on the alignment of FH2 domains. Real-time PCR was used to study the expression pattern of formin genes. Expression of forC, D, I and J increased during transition to multi-cellular stages, while the rest of genes displayed less marked developmental variations. During sexual development, expression of forH and forI displayed a significant increase in fusion competent cells.

Conclusion

Our analysis allows some preliminary insight into the functionality of Dictyostelium formins: all isoforms might display actin nucleation activity and, with the exception of ForI, might also be susceptible to autoinhibition and to regulation by Rho GTPases. The architecture GBD/FH3-FH1-FH2-DAD appears common to almost all Dictyostelium, fungal and metazoan formins, for which we propose the denomination of conventional formins, and implies a common regulatory mechanism.
Antioxidant effects of insulin-like growth factor-I (IGF-I) in rats with advanced liver cirrhosis
Authors: García-Fernández María , Castilla-Cortázar Inma , Díaz-Sanchez Matías , Navarro Iñigo , Puche Juan Enrique , Castilla Alberto , Casares Amelia Díaz , Clavijo Encarna , González-Barón Salvador
Published: March 2005

Background

The exogenous administration of Insulin-like Growth Factor-I (IGF-I) induces hepatoprotective and antifibrogenic actions in experimental liver cirrhosis. To better understand the possible pathways behind the beneficial effect of IGF-I, the aim of this work was to investigate severe parameters involved in oxidative damage in hepatic tissue from cirrhotic animals treated with IGF-I (2 μg. 100 g-1. day-1). Iron and copper play an important role in oxidative mechanisms, producing the deleterious hydroxyl radical (*OH) that peroxides lipid membranes and damages DNA. Myeloperoxidase (MPO) and nitric oxide (NO) are known sources of free radicals and induce reduction of ferritin-Fe3+ into free Fe2+, contributing to oxidative damage.

Methods

Liver cirrhosis was induced by CCl4 inhalation in Wistar male rats for 30 weeks. Healthy controls were studied in parallel (n = 10). Fe and Cu were assessed by atomic absoption spectrometry and iron content was also evaluated by Perls' staining. MPO was measured by ELISA and transferrin and ferritin by immunoturbidimetry. iNOS expression was studied by immuno-histochemistry.

Results

Liver cirrhosis was histologically proven and ascites was observed in all cirrhotic rats. Compared to controls untreated cirrhotic rats showed increased hepatic levels of iron, ferritin, transferrin (p < 0.01), copper, MPO and iNOS expression (p < 0.01). However, IGF-treatment induced a significant reduction of all these parameters (p < 0.05).

Conclusion

the hepatoprotective and antifibrogenic effects of IGF-I in cirrhosis are associated with a diminution of the hepatic contents of several factors all of them involved in oxidative damage.
Socioeconomic factors and low birth weight in Mexico
Authors: Torres-Arreola Laura P , Constantino-Casas Patricia , Flores-Hernández Sergio , Villa-Barragán Juan Pablo , Rendón-Macías Enrique
Published: March 2005

Background

Low birth weight (LBW) is a public health problem linked to lack of equity in populations. Despite efforts to decrease the proportion of newborns with LBW, success has been quite limited. In recent years, studies focused on explaining how social factors influence this problem have shown that populations with greater inequities have a greater proportion of newborns with LBW.

Methods

The objective was to describe socioeconomic factors related to LBW adjusted by demographic, reproductive and health services variables in Mexico City. A case-control study was carried out in three hospitals with gynaecological and obstetrics services in Mexico City during the first half of 1996. During the recruiting period all children with LBW (cases), defined as newborns weighing <2500 grams, were matched with children born on the same day to control for time of birth. Upon arrival at the hospital for delivery, women were interviewed to determine if they met our inclusion criteria. Women with a history of chronic conditions and those with twin or multiple pregnancies were excluded. Variables with clinical and statistical significance were included in a multivariate model (logistic regression).

Results

We found that low socioeconomic level was the most important risk factor for LBW and was independent of other factors, including those related to reproduction and nutrition, smoking, morbidity during pregnancy, accessibility to health services and prenatal care (OR 2.68; 95% CI 1.19, 6.03).

Conclusion

We found that socioeconomic factors are relevant to LBW. However further research should be done in different population groups as well as developing precise ways of measuring socioeconomic factors and their role in reproductive health.
Influence of antioxidant (L- ascorbic acid) on tolbutamide induced hypoglycaemia/antihyperglycaemia in normal and diabetic rats
Authors: Sreemantula Satyanarayana , Kilari Eswar K , Vardhan Vishnu A , Jaladi Rajasekhar
Published: March 2005

Background

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycaemia. Increased oxidative stress and decreased antioxidant levels are the leading cause of diabetes and diabetic complications. So it is felt that supplementation of antioxidants may be useful in controlling the glucose levels and to postpone the occurrence of diabetic complications. The objective of our study is to find the influence of antioxidant supplementation (L-ascorbic acid) on tolbutamide activity in normal and diabetic rats.

Methods

L- ascorbic acid/tolbutamide/L-ascorbic acid + tolbutamide were administered orally to 3 different groups of albino rats of either sex in normal and diabetic condition. Blood samples were collected from retro-orbital puncture at different time intervals and were analyzed for blood glucose by GOD-POD method. Diabetes was induced by alloxan 100 mg/kg body weight administered by I.P route.

Results

L-ascorbic acid/ tolbutamide produced hypoglycaemic activity in a dose dependant manner in normal and diabetic condition. In the presence of L-ascorbic acid, tolbuatmide produced early onset of action and maintained for longer period compared to tolbutamide matching control.

Conclusion

Supplementation of antioxidants like L-ascorbic acid was found to improve tolbutamide response in normal and diabetic rats.
Use of biological based therapy in patients with cardiovascular diseases in a university-hospital in New York City
Authors: Chagan Larisa , Bernstein Diane , Cheng Judy WM , Kirschenbaum Harold L , Rozenfeld Vitalina , Caliendo Gina C , Meyer Joanne , Mehl Bernard
Published: March 2005

Background

The use of complementary and alternative products including Biological Based Therapy (BBT) has increased among patients with various medical illnesses and conditions. The studies assessing the prevalence of BBT use among patients with cardiovascular diseases are limited. Therefore, an evaluation of BBT in this patient population would be beneficial. This was a survey designed to determine the effects of demographics on the use of Biological Based Therapy (BBT) in patients with cardiovascular diseases. The objective of this study was to determine the effect of the education level on the use of BBT in cardiovascular patients. This survey also assessed the perceptions of users regarding the safety/efficacy of BBT, types of BBT used and potential BBT-drug interactions.

Method

The survey instrument was designed to assess the findings. Patients were interviewed from February 2001 to December 2002. 198 inpatients with cardiovascular diseases (94 BBT users and 104 non-users) in a university hospital were included in the study.

Results

Users had a significantly higher level of education than non-users (college graduate: 28 [30%] versus 12 [12%], p = 0.003). Top 10 BBT products used were vitamin E [41(43.6%)], vitamin C [30(31.9%)], multivitamins [24(25.5%)], calcium [19(20.2%)], vitamin B complex [17(18.1%)], fish oil [12(12.8%)], coenzyme Q10 [11(11.7%)], glucosamine [10(10.6%)], magnesium [8(8.5%)] and vitamin D [6(6.4%)]. Sixty percent of users' physicians knew of the BBT use. Compared to non-users, users believed BBT to be safer (p < 0.001) and more effective (p < 0.001) than prescription drugs. Forty-two potential drug-BBT interactions were identified.

Conclusion

Incidence of use of BBT in cardiovascular patients is high (47.5%), as is the risk of potential drug interaction. Health care providers need to monitor BBT use in patients with cardiovascular diseases.
Pharmacokinetics of isoflavones, daidzein and genistein, after ingestion of soy beverage compared with soy extract capsules in postmenopausal Thai women
Authors: Anupongsanugool Ekasin , Teekachunhatean Supanimit , Rojanasthien Noppamas , Pongsatha Saipin , Sangdee Chaichan
Published: March 2005

Background

Isoflavones from soybeans may provide some beneficial impacts on postmenopausal health. The purpose of this study was to compare the pharmacokinetics and bioavailability of plasma isoflavones (daidzein and genistein) after a single dose of orally administered soy beverage and soy extract capsules in postmenopausal Thai women.

Methods

We conducted a randomized two-phase crossover pharmacokinetic study in 12 postmenopausal Thai women. In the first phase, each subject randomly received either 2 soy extract capsules (containing daidzin : genistin = 7.79 : 22.57 mg), or soy beverage prepared from 15 g of soy flour (containing daidzin : genistin = 9.27 : 10.51 mg). In the second phase, the subjects received an alternative preparation in the same manner after a washout period of at least 1 week. Blood samples were collected immediately before and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24 and 32 h after administration of the soy preparation in each phase. Plasma daidzein and genistein concentrations were determined by using high performance liquid chromatography (HPLC). The pharmacokinetic parameters of daidzein and genistein, i.e. maximal plasma concentration (Cmax), time to maximal plasma concentration (Tmax), area under the plasma concentration-time curve (AUC) and half-life (t1/2), were estimated using the TopFit version 2.0 software with noncompartmental model analysis.

Results

There were no significant differences in the mean values of Cmax/dose, AUC0–32/dose, AUC0-∝/dose, Tmax, and t1/2 of genistein between both preparations. For pharmacokinetic parameters of daidzein, the mean values of Cmax/dose, Tmax, and t1/2 did not significantly differ between both preparations. Nonetheless, the mean AUC0–32/dose and AUC0-∝/dose after administration of soy extract capsules were slightly (but significantly, p < 0.05) higher than those of soy beverage.

Conclusion

The bioavailability of daidzein, which was adjusted for the administered dose (AUC/dose), following a single oral administration of soy beverage was slightly (but significantly) less than that of soy extract capsules, whereas, the bioavailability adjusted for administered dose of genistein from both soy preparations were comparable. The other pharmacokinetic parameters of daidzein and genistein, including Cmax adjusted for the dose, Tmax and t1/2, were not different between both soy preparations.