bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping and quantifying hyperpolarized 3He magnetic resonance imaging apparent diffusion coefficient gradients
Authors: Evans Andrea , McCormack David G. , Santyr Giles , Parraga Grace
Published: June 2008

We measured hyperpolarized 3He magnetic resonance imaging (MRI) apparent diffusion coefficients (ADC) and quantified ADC gradients in each three-by-three voxel region of interest (ROI). Such local ADC gradients can be represented in vector maps showing the magnitude (| G3×3|) and direction of ADC gradients, providing a qualitative visualization tool and quantitative measurement of airway and air space heterogeneity. Twenty-four subjects (15 male, mean age = 67 ± 7 yr) with global initiative for chronic obstructive lung disease (GOLD) stage II ( n = 9, mean age 68 ± 6 yr), GOLD stage III chronic obstructive pulmonary disease (COPD; n = 7, mean age 67 ± 8 yr), and age-matched healthy volunteers ( n = 8, mean age 67 ± 6 yr) were enrolled based on their age and spirometry results. Hyperpolarized 3He MRI was performed on a whole body 3.0 Tesla system. Mean 3He ADC and ADC standard deviation were calculated for the center coronal slice, and the mean magnitude and direction of the ADC gradient vectors were calculated for each three-by-three voxel matrix (| G3×3|). While the 3He ADC standard deviation was not significantly different, mean | G3×3| was significantly different between subjects with stage II (0.14 ± 0.03 cm/s) and stage III COPD (0.19 ± 0.03 cm/s; P < 0.005) and between healthy subjects (0.12 ± 0.03 cm/s) and those with stage II COPD ( P < 0.02). The second order statistic | G3×3| may provide a sensitive measure of ADC heterogeneity for ROI representing 9.4 × 9.4 × 30 mm or 2.6 cm3 of lung tissue.
Atomic force microscope elastography reveals phenotypic differences in alveolar cell stiffness
Authors: Azeloglu Evren U. , Bhattacharya Jahar , Costa Kevin D.
Published: June 2008

To understand the connection between alveolar mechanics and key biochemical events such as surfactant secretion, one first needs to characterize the underlying mechanical properties of the lung parenchyma and its cellular constituents. In this study, the mechanics of three major cell types from the neonatal rat lung were studied; primary alveolar type I (AT1) and type II (AT2) epithelial cells and lung fibroblasts were isolated using enzymatic digestion. Atomic force microscopy indentation was used to map the three-dimensional distribution of apparent depth-dependent pointwise elastic modulus. Histograms of apparent modulus data from all three cell types indicated non-Gaussian distributions that were highly skewed and appeared multimodal for AT2 cells and fibroblasts. Nuclear stiffness in all three cell types was similar (2.5 ± 1.0 kPa in AT1 vs. 3.1 ± 1.5 kPa in AT2 vs. 3.3 ± 0.8 kPa in fibroblasts; n = 10 each), whereas cytoplasmic moduli were significantly higher in fibroblasts and AT2 cells (6.0 ± 2.3 and 4.7 ± 2.9 kPa vs. 2.5 ± 1.2 kPa). In both epithelial cell types, actin was arranged in sparse clusters, whereas prominent actin stress fibers were observed in lung fibroblasts. No systematic difference in actin or microtubule organization was noted between AT1 and AT2 cells. Atomic force microscope elastography, combined with live-cell fluorescence imaging, revealed that the stiffer measurements in AT2 cells often colocalized with lamellar bodies. These findings partially explain reported heterogeneity of alveolar cell deformation during in situ lung inflation and provide needed data for better understanding of how mechanical stretch influences surfactant release.
Single muscle fiber contractile properties of young competitive distance runners
Authors: Harber Matthew , Trappe Scott
Published: June 2008

The purpose of this investigation was to characterize the contractile properties of individual slow- and fast-twitch myofibers from highly trained distance runners. Muscle biopsies were obtained from the gastrocnemius of eight competitive runners (Run) and eight recreationally active individuals (Rec). Slow-twitch [myosin heavy chain (MHC) I] and fast-twitch (MHC IIa) myofibers were isolated and analyzed for diameter (μm), peak force (Po; mN), unloaded contraction velocity ( Vo; fiber lengths/s), and power. Maximum oxygen uptake was higher ( P < 0.05) in Run (71 ± 1 vs. 47 ± 2 ml·kg−1·min−1). Diameter of MHC I and MHC IIa fibers from Run subjects was ∼20% greater ( P < 0.05) than Rec. Peak force of the MHC IIa fibers was 31% higher ( P < 0.05) in Run, whereas Po of MHC I fibers was not different between groups. No differences for specific tension (Po/cross-sectional area) were present between groups for either fiber type. Vo was higher ( P < 0.05) in MHC I (+70%) and MHC IIa (+18%) fibers from Run subjects. In vitro peak absolute power (μN·s−1) of both fiber types was greater ( P < 0.05) in Run (131 and 85% for MHC I and MHC IIa, respectively). Additionally, normalized power (W/l) of the MHC I fibers was 64% higher in Run, whereas no differences were noted for normalized power of MHC IIa fibers. These data indicate that highly trained endurance runners have elevated contraction velocity in both slow- and fast-twitch myofibers. These characteristics of the fast-twitch muscle fibers have not been previously reported in competitive endurance athletes and may contribute to the high level of running performance in these athletes.
Ovalbumin sensitizes vagal pulmonary C-fiber afferents in Brown Norway rats
Authors: Kuo Y. L. , Lai C. J.
Published: June 2008

Sensitization of vagal lung C fibers has been postulated to contribute to the development of asthma, but support for this notion is still lacking. We investigated the characteristics and function of pulmonary C fibers (PCFs) in ovalbumin (OVA)-sensitized Brown Norway rats, an established animal model of asthma. Rats were sensitized with intraperitoneal injection of OVA or were treated with saline (control). In study 1, with the use of open-chest and artificially ventilated rats, inhalation of 5% OVA aerosol evoked an augmented increase in total lung resistance in the OVA-sensitized rats, compared with the control rats. Bilateral vagotomy or subcutaneous pretreatment with a high-dose of capsaicin for blocking of C-fiber function equally attenuated this augmented total lung resistance response, suggesting the involvement of PCFs. In study 2, with the use of anesthetized, spontaneously breathing rats, right atrial injection of capsaicin (1 μg/kg; a PCF stimulant) evoked an augmented apneic response in the OVA-sensitized rats, compared with the control rats. In study 3, with the use of open-chest, paralyzed, and artificially ventilated rats, the afferent PCF responses to right atrial injection of capsaicin (0.5 and 1.0 μg/kg), phenylbiguanide (8 μg/kg; a PCF stimulant), or adenosine (0.2 mg/kg; a PCF stimulant) were enhanced in the OVA-sensitized rats, compared with the control rats. However, the baseline activities of PCFs and their afferent responses to mechanical stimulation by lung hyperinflation in the OVA-sensitized and control rats were comparable. Our results suggested that OVA-sensitized Brown Norway rats possess sensitized vagal PCFs, which may participate in the development of the airway hyperreactivity observed in these animals.
Does recombinant human Epo increase exercise capacity by means other than augmenting oxygen transport?
Authors: Lundby C. , Robach P. , Boushel R. , Thomsen J. J. , Rasmussen P. , Koskolou M. , Calbet J. A. L.
Published: June 2008

This study was performed to test the hypothesis that administration of recombinant human erythropoietin (rHuEpo) in humans increases maximal oxygen consumption by augmenting the maximal oxygen carrying capacity of blood. Systemic and leg oxygen delivery and oxygen uptake were studied during exercise in eight subjects before and after 13 wk of rHuEpo treatment and after isovolemic hemodilution to the same hemoglobin concentration observed before the start of rHuEpo administration. At peak exercise, leg oxygen delivery was increased from 1,777.0 ± 102.0 ml/min before rHuEpo treatment to 2,079.8 ± 120.7 ml/min after treatment. After hemodilution, oxygen delivery was decreased to the pretreatment value (1,710.3 ± 138.1 ml/min). Fractional leg arterial oxygen extraction was unaffected at maximal exercise; hence, maximal leg oxygen uptake increased from 1,511.0 ± 130.1 ml/min before treatment to 1,793.0 ± 148.7 ml/min with rHuEpo and decreased after hemodilution to 1,428.0 ± 111.6 ml/min. Pulmonary oxygen uptake at peak exercise increased from 3,950.0 ± 160.7 before administration to 4,254.5 ± 178.4 ml/min with rHuEpo and decreased to 4,059.0 ± 161.1 ml/min with hemodilution ( P = 0.22, compared with values before rHuEpo treatment). Blood buffer capacity remained unaffected by rHuEpo treatment and hemodilution. The augmented hematocrit did not compromise peak cardiac output. In summary, in healthy humans, rHuEpo increases maximal oxygen consumption due to augmented systemic and muscular peak oxygen delivery.
Skeletal muscle proteolysis in response to short-term unloading in humans
Authors: Tesch Per A. , von Walden Ferdinand , Gustafsson Thomas , Linnehan Richard M. , Trappe Todd A.
Published: June 2008

Skeletal muscle atrophy is evident after muscle disuse, unloading, or spaceflight and results from decreased protein content as a consequence of decreased protein synthesis, increased protein breakdown or both. At this time, there are essentially no human data describing proteolysis in skeletal muscle undergoing atrophy on Earth or in space, primarily due to lack of valid and accurate methodology. This particular study aimed at assessing the effects of short-term unloading on the muscle contractile proteolysis rate. Eight men were subjected to 72-h unilateral lower limb suspension (ULLS) and intramuscular interstitial levels of the naturally occurring proteolytic tracer 3-methylhistidine (3MH) were measured by means of microdialysis before and on completion of this intervention. The 3MH concentration following 72-h ULLS (2.01 ± 0.22 nmol/ml) was 44% higher ( P < 0.05) than before ULLS (1.56 ± 0.20 nmol/ml). The present experimental model and the employed method determining 3MH in microdialysates present a promising tool for monitoring skeletal muscle proteolysis or metabolism of specific muscles during conditions resulting in atrophy caused by, e.g., disuse and real or simulated microgravity. This study provides evidence that the atrophic processes are evoked rapidly and within 72 h of unloading and suggests that countermeasures should be employed in the early stages of space missions to offset or prevent muscle loss during the period when the rate of muscle atrophy is the highest.
Effect of Propolis on Oxidative Stress and Histomorphology of Liver Tissue in Experimental Obstructive Jaundice
Authors: Kismet K. , Sabuncuoglu M.Z. , Kilicoglu S.S. , Kilicoglu B. , Devrim E. , Erel S. , Sunay A.E. , Erdemli E. , Durak I. , Akkus M.A.
Published: June 2008

Background: Propolis is a natural product collected by honey bees from various plant sources. We aimed to determine the possible effects of propolis on oxidative stress and hepatocyte apoptosis in experimental obstructive jaundice. Methods:Thirty rats were divided into three groups: group I, sham-operated; group II, ligation and division of the common bile duct (BDL); group III, BDL followed by oral supplementation of propolis in a daily dose of 100 mg/kg. Liver samples were examined under the light microscope and transmission electron microscope. Hepatocyte apoptosis was quantitated using the transferase-mediated uridine nick end labeling (TUNEL) assay. Plasma and liver malondialdehyde (MDA) levels and glutathione peroxidase (GSH-Px) activities were measured. Results: The plasma and liver levels of MDA were significantly lower in the propolis group than in the BDL group (p < 0.05 and 0.014, respectively). Although liver GSH-Px activities were significantly higher in the propolis group than in the BDL group (p < 0.001), there was no significant difference between the plasma GSH-Px activities of these groups (p > 0.05). In the propolis group, the enlargement of hepatocytes, dilatation of canaliculi and the edema regressed. The regenerating and normal hepatocytes were demonstrated. In the TUNEL assay, propolis administration reduced hepatocyte apoptosis. Conclusion: Propolis showed a significant hepatoprotective effect in this experimental obstructive jaundice model.
Social Ties and Cognitive Recovery after Stroke: Does Social Integration Promote Cognitive Resilience?
Authors: Glymour M. Maria , Weuve Jennifer , Fay Martha E. , Glass Thomas , Berkman Lisa F.
Published: June 2008

Background/Aims: Little is known about the possible effects of social resources on stroke survivors’ level and change in cognitive outcomes. Understanding this association may help us identify strategies to improve stroke recovery and help elucidate the etiology of dementia. Methods: We examined the relationship of social ties and social support to cognitive function and cognitive change 6 months after stroke. Participants in the Families in Recovery from Stroke Trial (FIRST) (n = 272) were interviewed approximately 17 days (baseline) and 6 months (follow-up) after stroke. Cognition was assessed with the Mini Mental State Examination (MMSE) and a summary battery of 7 neuropsychological tests. Median-based regression was used to model cognitive outcomes by level of baseline intimate, personal and organizational social ties and received emotional and instrumental support. Results: Baseline social ties and emotional sup- port independently predicted 6-month Cognitive Summary Scores. Emotional support also predicted greater improvements in Cognitive Summary Scores from baseline to the 6-month follow-up. No other social exposures predicted improvements in the MMSE or the Cognitive Summary. Conclusions: Our results suggest that emotional support may promote cognitive resilience while social ties provide cognitive reserve that protects against impaired cognition after stroke. Social ties did not predict cognitive recovery however, so reverse causation cannot be ruled out.
Education-Related Differences in Case Fatality among Elderly with Stroke
Authors: Löfmark Ulrika , Hammarström Anne
Published: June 2008

Background and Purpose: There is strong evidence for the existence of a socioeconomic gradient in stroke incidence and mortality, but there seem to be contradictory findings concerning an association between socioeconomic status and case fatality after stroke. Moreover, there is still a lack of studies that include men and women as well as people over 75 years. Our aim was to investigate whether there were education-related differences in 28-day case fatality after stroke in different age groups. Methods: All patients who were diagnosed with a cerebral infarction at the Umeå University Hospital during a 2-year period were included in this study. Results: In total, 610 stroke patients (331 men, 279 women) aged 20–85 were hospitalized, of whom 77% were first-ever strokes. Overall, there were few education-related differences between the patients in different age groups (20–74 and 75–85 years). The 28-day case fatality after stroke was shown to be associated with a low educational level in patients above 75 years, also after controlling for sex, risk factors and acute stroke care measures. Conclusion: In this population-based study on patients with cerebral infarction, we found an education-related difference in 28-day case fatality in patients aged 75–85 years. The socioeconomic gradient persisted when we adjusted for risk factors and acute care variables. There is a need for more community-based stroke studies including all ages, with good case ascertainment.
Can We Discriminate Stroke Mechanisms by Analyzing the Infarct Patterns in the Striatocapsular Region?
Authors: Lee Kyung Bok , Oh Hyung Geun , Roh Hakjae , Ahn Moo Young
Published: June 2008

Background and Aims: The aims of our study were to elucidate the differences in the distribution of acute middle cerebral artery (MCA) infarctions involving the striatocapsular region and to compare those following embolic striatocapsular infarctions with those originating from MCA disease (MCAD). Methods: We prospectively enrolled patients with acute large infarcts located in the lenticulostriate artery territory. Brain coronal diffusion-weighted imaging (DWI) and magnetic resonance angiography were carried out in all patients. The types of infarct distribution were divided into 3 categories: (1) dominant in the distal territory (DD), (2) distributed equally between the distal and proximal territories (DE) and (3) dominant in the proximal territory. Stroke mechanisms were classified into stroke from proximal embolism, MCAD and stroke of undetermined etiology. Results: A total of 71 patients were recruited. Proximal embolic sources were significantly more prevalent in patients with a DE lesion, but symptomatic MCA stenoses were more common in patients with a DD lesion than in those with a DE lesion. Conclusion: These results suggest that the dominant area of striatocapsular infarctions on coronal DWI can be an important clue for stroke etiology.
Ultrasound Turbulence Index during Thromboendarterectomy Predicts Postoperative Cerebral Microembolism
Authors: Brosig Torge , Hoinkes Annika , Seitz Rüdiger J. , Sandmann Wilhelm , Huber Rita , Siebler Mario
Published: June 2008

Background: Cerebral microembolic signals (MES) after carotid endarterectomy (CEA) are associated with an increased risk of postoperative stroke. We investigated the relationship of an intraoperatively recorded ultrasound turbulence index (TI) during CEA and the occurrence of MES. Methods: Short-time MES detection was performed on 164 patients (mean age 64 years, 140 males) in the ipsilateral middle cerebral artery within 2 h after CEA. A specialized continuous-wave ultrasound Doppler probe measured the TI within the reconstructed internal carotid artery during surgery. Results: The occurrence of postoperative MES increased significantly with the TI: a TI >26 predicted MES with a sensitivity of 72% and a specificity of 76%. The MES rate and TI were higher in patients operated with the eversion technique than in patients operated with the patch technique (p = 0.005). There was no relationship with preoperative MES, site of surgery or age of patients. Female patients had a higher risk of postoperative MES than males (p = 0.003). Conclusions: Simplified intraoperative Doppler sonography or short-time MES detection after CEA are feasible, and may be helpful for surgical quality control and decision making (e.g. treatment with platelet antagonists).
Clinical Evaluation of Experimentally Induced Choroidal Neovascularizations in Pigmented Rabbits by Subretinal Injection of Lipid Hydroperoxide and Consecutive Preliminary Photodynamic Treatment with Tookad
Authors: Framme Carsten , Sachs Helmut G. , Kobuch Karin , Flucke Barbara , Birngruber Reginald
Published: June 2008

Purpose: Up to date several approaches have been undertaken to achieve an ‘easy-to-handle’ animal model of choroidal neovascularizations (CNVs) in rabbits; however, so far in none of the studies could healthy retinal tissue be maintained, which is mandatory to further investigate the effects of photodynamic therapy (PDT) or anti-vascular-endothelial-growth-factor treatments. It was our aim to reevaluate and verify the method of inducing experimental CNVs in rabbits using subretinally injected linoleic acid hydroperoxide (LHP) as proposed by Tamai et al. and to use it for experimental PDT. Material and Methods: In 33 eyes of Chinchilla breed rabbits LHP of two different concentrations (25 and 100 µg/50 µl) was injected into the subretinal space via a transvitreal approach under guidance of an operation microscope. Ophthalmoscopic and angiographic examinations were performed on days 3, 7, 14 and 28 after surgery. Preliminary PDT with different experimental parameter sets was performed in 3 eyes using the new photosensitizer Tookad. Results: Using LHP in the higher concentration, an angiographically determined CNV induction was observed in 27% of all injection sites (n = 34) on days 14 and 28 revealing early well-demarcated and progressive leakage. No CNV was detected at the lower LHP concentration (60 injection sites). Subretinal CNV was verified histologically revealing vessel formation above the retinal pigment epithelium level. Herein, a significant damage to the outer retinal layers was always observed; however, the general structure of the choriocapillary layer was maintained. Tookad PDT was clinically able to completely stop leakage in 1 case and reduce leakage in 2 cases. Histologically the choriocapillary layer was occluded. Conclusion: Subretinal injection of LHP induces angiographically well-demarcated classic CNVs in rabbits; however, the CNV rate was low, and histology revealed severe damage of the outer retinal layers but not of the choriocapillary layer, which is important for studying PDT interactions. Preliminary experimental PDT could clinically stop or reduce leakage from angiographic CNV. Due to the small CNV rate and the significant collateral retinal tissue damage, this model seems to be only of partial suitability for investigating new treatment modalities in CNV.
Epidemiology of Chronic Kidney Disease in Central and Eastern Europe
Authors: Rutkowski Bolesław , Król Ewa
Published: June 2008

Background: The world population suffering from end-stage renal disease (ESRD) is growing. The epidemiology of ESRD is relatively well documented, but data on chronic kidney disease (CKD) are missing, especially in Central and Eastern Europe (CEE). Early detection of CKD is important because it allows introduction of the therapy that slows the progression of CKD. The aim of the present study was to estimate the prevalence of CKD and ESRD in CEE. Methods: Our data are based on two independent surveys: one concerns epidemiology of CKD, the other ESRD. Moreover, we present rough results from the pilot study PolNef on early detection of CKD, performed in North Poland. Estimated glomerular filtration rate, albuminuria and ultrasound examination were the main diagnostic tools. Results: Only limited data from South-East Hungary and North Poland were available: the number of CKD patients under nephrological care and on dialysis. According to the PolNef study, using a dipstick test albuminuria was detected in 15.6% of participants but dropped to 11.9% when it was measured using the turbidimetric method. Conclusions: Data concerning epidemiology of CKD in CEE are missing. Epidemiology of ESRD in CEE seems to be similar to that in Western Europe. PolNef is the first study dealing with renal epidemiological problems in CEE. It shows that renal epidemiological problems in CEE are comparable to those of the other parts of the world. Studies concerning CKD epidemiology in different CEE countries are necessary to confirm that the incidence and prevalence of CKD are similar to those in Western Europe and other parts of the globe.
Effect of Regular Sauna on Epidermal Barrier Function and Stratum Corneum Water-Holding Capacity in vivo in Humans: A Controlled Study
Authors: Kowatzki D. , Macholdt C. , Krull K. , Schmidt D. , Deufel T. , Elsner P. , Fluhr J.W.
Published: June 2008

During the last few years, sauna has become the epitome of wellness. Besides studies in general medicine evaluating the health benefit of sauna, e.g. on the cardiovascular system, no systematic study regarding skin physiology has been published. The present exploratory study was intended to analyse the effect of regular Finnish sauna on skin physiology. The effect of regular sauna bathing was assessed with non-invasive instruments: stratum corneum water-holding capacity, skin redness, transepidermal water loss and surface skin pH were analysed in 41 healthy volunteers, aged 20–49 years, in a group with regular sauna exposure compared to a control group with no regular sauna exposure. A more stable epidermal barrier function, an increase in stratum corneum hydration, a faster recovery of both elevated water loss and skin pH after exposure to 2 × 15 min sauna at 80°C could be demonstrated in volunteers with regular sauna. Heart beat rate and ionic concentration in sweat as well as epidermal blood perfusion showed a training effect under regular sauna. A decrease in casual skin sebum content on the skin surface of the forehead was observed in these volunteers. The present data suggest a protective effect of regular sauna on skin physiology, especially surface pH and stratum corneum water-holding capacity.
Molecular Diagnosis and Management of Hereditary Angioedema in a Greek Family
Authors: Papadopoulou-Alataki Efimia , Foerster Tanja , Antari Vasiliki , Pavlitou-Tsiontsi Aikaterini , Varlamis Georgios
Published: June 2008

Background: Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent angioedema episodes caused by a quantitative or functional defect of the plasma protein C1 esterase inhibitor (C1-INH). Relapsing skin swellings, abdominal pain attacks and upper airway obstruction constitute the typical clinical manifestations. The incidence and severity of angioedema attacks are highly variable among HAE patients. Cases: We report on 4 patients with HAE type I, members of the same family, originating from a Greek island. The patients, 2 males and 2 females (aged 8–45 years) suffer from recurrent edema episodes (1–2 attacks/month). Skin swellings at the extremities and the face, abdominal episodes and laryngeal edema are the classical clinical triad, with significant variation in the severity and frequency of symptoms among our patients. The new missense mutation in exon 2 of the C1-INH gene, c.1A>G; p.Met-22Val (p.Met1Val), in a heterozygous form was detected in all our patients. Acute and severe attacks are successfully treated with administration of C1-INH concentrate. Conclusion: Variability of phenotypic expression of HAE was observed among the affected family members, despite carrying identical mutation of the C1-INH gene. Acute exacerbations of the disease are safely and effectively treated with C1-INH concentrate.
Early Bone Mineral Density Loss after Renal Transplantation and Pre-Transplant PTH: A Prospective Study
Authors: Bubenicek Petr , Sotornik Ivo , Vitko Stefan , Teplan Vladimir
Published: June 2008

Background: Post-transplant osteopathy is a known complication of kidney transplantation (KTx). The aim of this study was to assess bone mineral density (BMD) in a large cohort of patients with treatment depending on pre-transplant pa-rathormone (PTH) and baseline BMD. Patients and Methods: 347 consecutive KTx recipients (222 M, 125 F) finished all follow-up measurements of BMD at lumbar spine, femur and radius using DEXA Lunar (at baseline and at 6 and 18 months). Results: Bone loss with a T-score below –2.5 affected 37.2% of patients before KTx. A negative correlation between baseline PTH and BMD was found (p < 0.01). Patients with high levels of PTH had more bone loss than patients with low PTH values (p < 0.01). In the lumbar spine, a decline of BMD was found in the first 6 months, and after 18 months an improvement was found in all subgroups (p < 0.001). In femur, significant changes were found only in low-PTH patients after 6 months (p < 0.001); the others did not reach significant results. There was no improvement after 18 months in low-PTH patients. In radius, bone loss was not found. Conclusion: A relationship between differences in progression of BMD after transplantation and PTH level at baseline was found.
Assessment of Gene Transcription Demonstrates Connection with the Clinical Course of Idiopathic Interstitial Pneumonia
Authors: Golec Marcin , Lambers Christopher , Hofbauer Elisabeth , Geleff Silvana , Bankier Alexander , Czerny Martin , Ziesche Rolf
Published: June 2008

Background: Mediators of preferably mesenchymal repair such as transforming growth factor β1 (TGF-β1) and mediators of polarized cellular immunity such as interleukin (IL)-13 are thought to be of key importance for progression of lung fibrosis. Nonetheless, a correlation between these mediators and the clinical development of fibrosis has not been performed thus far. Objectives: We correlated the transcription of TGF-β1, connective tissue growth factor (CTGF), IL-4, IL-13 and interferon-γ (IFN-γ) with lung function development in progressive fibrosis in idiopathic interstitial pneumonia. Methods: One hundred seventy nine sets of RT-PCR measurements were analyzed in 49 patients with usual interstitial pneumonia, nonspecific interstitial pneumonia or both. Specimens were taken by surgical and transbronchial lung biopsy. Lung function was measured at the time of biopsy and 1 year later. All patients received conventional treatment. Thirteen individuals were used as controls. Results: Transcription of TGF-β1, CTGF and IL-13 was significantly higher in pulmonary fibrosis compared to control, whereas transcription of IFN-γ and IL-4 was virtually absent in both normal and fibrotic lungs. When comparing gene transcription with development of lung function, a significant correlation was observed between the decrease in both vital capacity and total lung capacity and increased transcription levels of TGF-β1 and IL-13. A reduced pulmonary diffusion capacity correlated with increased levels of TGF-β1 and CTGF. Transcription pattern in transbronchial and surgical samples was similar. Conclusions: We found a significant correlation between gene transcription and decrease in lung function that was more pronounced for TGF-β1 than for CTGF or IL-13. Our results suggest that transcription analysis may be used in clinical assessment of pulmonary fibrosis.
Racial Differences in the Influence of the APOE Epsilon 4 Allele on Cognitive Decline in a Sample of Community-Dwelling Older Adults
Authors: Sawyer Kathryn , Sachs-Ericsson Natalie , Preacher Kristopher J. , Blazer Dan G.
Published: June 2008

Background: Most, but not all, past studies have suggested that the APOE genotype is a risk factor for dementia in whites but not African Americans. This paper first describes explanations as to why some studies may have failed to detect the effect of APOE genotype in African American samples. Briefly, studies have been limited by various methodological problems including small sample sizes, dichotomous measures of cognitive functioning (which tend to be less sensitive to change), and racial bias in assessing demented status. Objective: This paper suggests methods for increasing the likelihood that genuine racial differences will be identified when examining genetic risk factors. Further, we test our model of racial differences in the relationship of APOE genotype and cognitive decline (CD) in a large prospective community sample. Methods: Building on the work of Fillenbaum and colleagues [J Am Geriatr Soc 2001;49:1148–1155], we used data from the Duke EPESE study collected in four waves over a 10-year period (n = 2,076) to illustrate methods which may better assess racial differences in the influence of the APOE ε4 allele on CD. We used multilevel models for repeated measures to examine racial differences in participants’ increase in errors on a continuous measure of cognitive functioning as they aged. Results: We found the APOE ε4 allele to predict CD for both African Americans and whites. Having at least one ε4 allele predicted more cognitive errors at wave 1 and a faster rate of decline for both African Americans and whites over time. While African Americans experienced a faster rate of CD than whites, there was no additional increase in CD from being both African American and a carrier of the ε4 allele. Conclusion: The study points to several common methodological issues that arise when examining racial differences in genetic influences on health-related outcomes. Further, the study’s results highlight the importance of including both African Americans and Caucasians in research concerning the contribution of APOE genotype to CD.
Contribution of Stem Cells to Kidney Repair
Authors: Bussolati Benedetta , Tetta Ciro , Camussi Giovanni
Published: June 2008

The potential role of stem cells in the repair of glomerular and tubular injury is under intensive investigation. Several studies have addressed the role of endogenous bone-marrow (BM)-derived stem cells (SC) in the repair of renal injury. Some reports indicate that BM-derived SC are capable of engraftment into damaged nephrons, although the lineage of SC recruited has not been established. However, this issue remains highly controversial, and several studies point to a paracrine/endocrine action of endogenous SC rather than a direct repopulation of the injured nephron. Administration of exogenous mesenchymal SC in experimental acute kidney injury suggests that an SC-based therapy may improve functional and structural recovery of both glomerular and tubular compartments. A contribution of renal resident SC has also been postulated in the recovery after damage. However, several points still need to be clarified regarding the signals regulating homing of SC to injured tissue, the secreted factors underlying the paracrine/endocrine mechanisms, and in particular the long-term in vivo behavior of the administered SC. This review summarizes the current literature on the physiological role of endogenous SC in renal regeneration and on the potential therapeutic strategies based on the administration of exogenous SC.
Factors Associated with Impaired Arterial Adaptation to Chronically High Wall Shear Rate in the Feeding Artery of PTFE Grafts
Authors: Tuka Vladimir , Slavikova Marcela , Kasalova Zdislava , Malik Jan
Published: June 2008

Background/Aims: The feeding artery of dialysis vascular access is subjected to unusually high wall shear stress (WSS), a hemodynamic factor leading to vasodilatation, for at least several months after access creation. Physiologically, high WSS leads to compensatory endothelium-dependent vasodilatation. We supposed that the dilatation of the feeding artery continues to lower WSS during longer time period after access creation and that this process is limited by risk factors of endothelial dysfunction. Methods: We examined the feeding artery of vascular accesses within 3 months, 1 and 2 years after access creation. By ultrasonography, we obtained internal diameter and blood velocity in the feeding arteries. We calculated wall shear rate (WSR). Results: We examined 75 patients. Internal diameter rose from 3.9 ± 0.1 mm (3 months) to 4.3 ± 0.2 mm within the first year and to 4.6 ± 0.2 mm within the second. Similarly, mean WSR decreased from 1,839 ± 117 to 1,629 ± 123 s–1 and to 1,159 ± 109 s–1, respectively. The vasodilatation was limited by diabetes mellitus, hypercholesterolemia and hypertriglyceridemia. Conclusions: The feeding artery continues to dilate 2 years after access creation, with a simultaneous decrease in WSR. This process is dampened in patients with diabetes mellitus and dyslipidemia.
The Promise and Perils of ‘Targeted Therapy’ of Advanced Ovarian Cancer
Authors: Markman Maurie
Published: June 2008

For several reasons, ovarian cancer is an excellent malignancy to consider the use of ‘targeted’ therapeutic strategies. However, to date, despite considerable effort, there remains limited evidence that such approaches are clinically relevant in the malignancy. The one important exception is the delivery of anti-angiogenic anti-neoplastic agents, which actually appear to be more biologically active as single drugs in ovarian cancer than in other solid tumors where they have been examined. It is anticipated that future trials of ‘targeted’ therapy in ovarian cancer will focus on molecular targets of documented relevance in the malignancy.
Sphingosine-1-Phosphate Receptor Subtypes Differentially Regulate Smooth Muscle Cell Phenotype
Authors: Wamhoff Brian R. , Lynch Kevin R. , Macdonald Timothy L. , Owens Gary K.
Published: June 2008

Objective—

The role of sphingosine-1-phosphate (S1P) receptors in acute vascular injury and smooth muscle cell (SMC) phenotypic modulation is not completely resolved.

Methods and Results—

S1P receptor antagonists were used to test the hypothesis that specific S1P receptor subtypes differentially regulate SMC phenotypic modulation. In response to acute balloon injury of the rat carotid artery, S1P1/S1P3 receptor mRNA levels were transiently increased at 48 hours whereas S1P2 receptor expression was decreased. S1P2 expression was reinduced and increased at 7 to 10 days postinjury. Daily intraperitoneal injection of the S1P1/S1P3 antagonist VPC44116 decreased neointimal hyperplasia by ≈50%. In vitro, pharmacological inhibition of S1P1/S1P3 receptors with VPC25239 attenuated S1P-induced proliferation of rat aortic SMCs. Conversely, inhibition of S1P2 with JTE013 potentiated S1P-induced proliferation. Inhibition of S1P1/S1P3 resulted in S1P-induced activation of the SMC differentiation marker genes SMα-actin and SMMHC, whereas inhibition of S1P2 attenuated this response. S1P2-dependent activation of SMα-actin and SMMHC was shown to be mediated by L-type voltage-gated Ca
2+
channels and subsequent RhoA/Rho kinase–dependent SRF enrichment of
CArG
box promoter regions.

Conclusion—

Results provide evidence that S1P1/S1P3 receptors promote, whereas S1P2 receptors antagonize, SMC proliferation and phenotypic modulation in vitro in response to S1P, or in vivo after vascular injury.
Dynamic Tyrosine Kinase-Regulated Signaling and Actin Polymerisation Mediate Aggregate Stability Under Shear
Authors: Auger Jocelyn M. , Watson Steve P.
Published: June 2008

Objective—

Aggregate formation on collagen at arteriolar rates of shear is mediated by coordinated signaling between tyrosine kinase–linked and G protein–coupled receptors. We have investigated the role of these receptors and the actin cytoskeleton in maintaining aggregate stability under shear.

Methods and Results—

Platelet aggregates are rapidly formed when blood is flowed over collagen at 1000 s
−1
and remain stable over 20 minutes. A novel fibrin-independent mechanism of retraction against the direction of flow occurs at the aggregate front and recruits platelets into the main aggregate. Stable aggregates are not observed in the presence of cytochalasin D, which blocks de novo actin polymerization. When exposed to the Src family kinase inhibitor, PD0173952, preformed aggregates spread in the direction of flow and rounded platelets appear within the aggregate body and are lost in the direction of flow. A similar set of observations is observed in the presence of latrunculin A, which disrupts preexisting actin filaments, but not in the combined presence of inhibitors of ADP and thromboxane A
2
formation.

Conclusions—

Maintenance of stable aggregates at high shear is a dynamic process mediated by Src kinases and actin polymerization. These signals maintain aggregates in a compact structure and prevent continuous streaming of platelets.
Soluble P-Selectin,
SELP
Polymorphisms, and Atherosclerotic Risk in European-American and African-African Young Adults
Authors: Reiner Alexander P. , Carlson Christopher S. , Thyagarajan Bharat , Rieder Mark J. , Polak Joseph F. , Siscovick David S. , Nickerson Deborah A. , Jacobs David R. , Gross Myron D.
Published: June 2008

Objective—

To characterize the genetic and clinical correlates of soluble P-selectin, and the relationship of P-selectin to atherosclerotic risk, in young European-American (EA) and African-American (AA) adults.

Methods and Results—

We assessed the interrelationships between 25 common
SELP
polymorphisms, soluble P-selectin, and atherosclerotic risk in 1222 EA and 1072 AA from the longitudinal population-based CARDIA study. Male sex, smoking, blood pressure, and metabolic status were strong cross-sectional correlates of soluble P-selectin among CARDIA subjects aged 33 to 45 years, explaining 13% of the variance. Among EAs, higher soluble P-selectin predicted carotid intima-media thickness (IMT) measured 5 years later, even after accounting for traditional risk factors. Common
SELP
nucleotide sequence variants explained 11% and 5% of the interindividual variation in soluble P-selectin levels in EAs and AAs, respectively. Four distinct variants contributed to P-selectin phenotype in EAs, including a polymorphism of the 5′
SELP
haplotype block associated with carotid IMT. Half of the phenotypic variation attributable to
SELP
in EAs could be explained by the Thr715Pro polymorphism, whereas Val599Leu was more strongly associated with soluble P-selectin among AAs.

Conclusions—

Common
SELP
polymorphisms were associated with soluble P-selectin and carotid IMT in young adults, but the patterns of association differed between EAs and AAs. These results support the role of P-selectin in the preclinical stages of atherosclerosis.
Large Artery Intracranial Occlusive Disease
Authors: Gorelick Philip B. , Wong Ka Sing , Bae Hee-Joon , Pandey Dilip K.
Published: June 2008

Background and Purpose—

Large artery intracranial occlusive disease (LAICOD) is a common and important stroke subtype. In this commentary, we review key epidemiological aspects of LAICOD.

Summary of Review—

LAICOD has emerged as the most common stroke subtype worldwide and is associated with a high risk of recurrent stroke. Hypotheses have been proposed to explain causation, which include such factors as traditional cardiovascular risk factors, high blood volume states, and genetic abnormalities. Approaches to treatment such as antithrombotic therapies, revascularization procedures, and counterpulsation devices hold promise.

Conclusions—

LAICOD poses a major stroke problem worldwide and is likely the most common stroke subtype. The etiology and treatment of this disorder remain poorly defined. International collaborations are needed to pool collective knowledge and develop definitive studies to better understand causation and treatment of LAICOD.
Postpartum Cervicocephalic Artery Dissection
Authors: Arnold Marcel , Camus-Jacqmin Mathilde , Stapf Christian , Ducros Anne , Viswanathan Anand , Berthet Karine , Bousser Marie Germaine
Published: June 2008

Background and Purpose—

Cervicocephalic artery dissection (CAD) after childbirth is rare. The objective of this study was to determine differences between postpartum and nonpostpartum CAD.

Methods—

We compared consecutive patients with postpartum CAD with a control group of women with nonpostpartum CAD.

Results—

Of 245 patients with CAD, 102 women <50 years (6 with postpartum CAD and 96 with nonpostpartum CAD) were identified. Vascular risk factors and presenting characteristics did not differ significantly between postpartum CAD and nonpostpartum CAD women. By contrast, patients with postpartum CAD had more often coexisting conditions such as reversible cerebral vasoconstriction syndrome (2 of 6 versus 2 of 96;
P
=0.017), reversible posterior leukoencephalopathy syndrome (2 of 6 versus one of 96;
P
=0.009), and subarachnoid hemorrhage without signs of intracranial extension of CAD (2 of 6 versus zero of 96;
P
=0.003).

Conclusion—

CAD and associated conditions should be looked for in women with unusual headache after childbirth.
Plasma Levels of Vascular Endothelial Growth Factor After Treatment for Cerebral Arteriovenous Malformations
Authors: Kim Grace H. , Hahn David K. , Kellner Christopher P. , Hickman Zachary L. , Komotar Ricardo J. , Starke Robert M. , Mack William J. , Mocco J. , Solomon Robert A. , Connolly E. Sander
Published: June 2008

Background and Purpose—

The role of abnormal angiogenesis in the formation and progression of cerebral arteriovenous malformations (AVMs) is unclear. Previous studies have demonstrated increased local expression of vascular endothelial growth factor (VEGF) in AVM tissue and increased circulating levels of VEGF in AVM patients. We sought to further investigate the role of VEGF in AVM pathophysiology by examining changes in plasma VEGF levels in patients undergoing treatment for AVMs.

Methods—

Three serial blood samples were obtained from 13 AVM patients undergoing treatment: (1) before any treatment, (2) 24 hours postresection, and (3) 30 days postresection. Plasma VEGF concentrations were measured via commercially available enzyme-linked immunosorbent assay (ELISA). For controls, blood samples were obtained from 29 lumbar laminectomy patients.

Results—

The mean plasma VEGF level in AVM patients at baseline was 36.08±13.02 pg/mL, significantly lower than that of the control group (80.52±14.02 pg/mL,
P
=0.028). Twenty-four hours postresection, plasma VEGF levels dropped to 20.09±4.54 pg/mL, then increased to 66.81±26.45 pg/mL 30 days later (
P
=0.048). The mean plasma VEGF concentration 30 days after resection was no longer significantly different from the control group (
P
=0.33).

Conclusions—

Plasma VEGF levels in 13 AVM patients were unexpectedly lower than controls, dropped early after AVM resection, then significantly increased 30 days later. These results support the key role of abnormal angiogenesis in AVM pathophysiology and suggest that a disruption in systemic VEGF expression may contribute to the natural history of these lesions.
The Political Culture of Kwun Tong: A Chinese Community in Hong Kong
Authors: King Ambrose Yeo-chi
Published: June 2008

This is a study of political culture of Kwun Tong, a fast-developing industrial community of Hong Kong. Employing a set of concepts developed by sociologists and political scientists, it is attempted to give a systematic explanation of data, thereby throwing some lights on the understanding of people's attitudes and orientations towards politics. This study can provide us with a theoretical and empirical base, be preliminary as it may, to probe into the nature of the political system of the Colony. In analyzing the data bearing on the political culture of the Hong Kong community, empirical findings of other societies are utilized in order to give it a comparative perspective. Furthermore, the Chinese traditional political-cultural value systems have been used as a point of reference, thus showing the continuity and discontinuity of the Chinese political culture of Kwun Tong under investigation Before embarking on analyzing the data directly, a brief articulation of the theoretical framework is in order.