bluuebunny/crossref_metadata_2025 huggingface dataset:
Maturation of rat proximal tubule chloride permeability
Authors: Baum Michel , Quigley Raymond
Published: July 2005

We have previously shown that neonate rabbit tubules have a lower chloride permeability but comparable mannitol permeability compared with adult proximal tubules. The surprising finding of lower chloride permeability in neonate proximals compared with adults impacts net chloride transport in this segment, which reabsorbs 60% of the filtered chloride in adults. However, this maturational difference in chloride permeability may not be applicable to other species. The present in vitro microperfusion study directly examined the chloride and mannitol permeability using in vitro perfused rat proximal tubules during postnatal maturation. Whereas there was no maturational change in mannitol permeability, chloride permeability was 6.3 ± 1.3 × 10−5cm/s in neonate rat proximal convoluted tubule and 16.1 ± 2.3 × 10−5cm/s in adult rat proximal convoluted tubule ( P < 0.01). There was also a maturational increase in chloride permeability in the rat proximal straight tubule (5.1 ± 0.6 × 10−5cm/s vs. 9.3 ± 0.6 × 10−5cm/s, P < 0.01). There was no maturational change in bicarbonate-to-chloride permeabilities ( PHCO3/ PCl) in the rat proximal straight tubules (PST) and proximal convoluted tubules (PCT) or in the sodium-to-chloride permeability ( PNa/ PCl) in the proximal straight tubule; however, there was a significant maturational decrease in proximal convoluted tubule PNa/ PClwith postnatal development (1.31 ± 0.12 in neonates vs. 0.75 ± 0.06 in adults, P < 0.001). There was no difference in the transepithelial resistance measured by current injection and cable analysis in the PCT, but there was a maturational decrease in the PST (7.2 ± 0.8 vs. 4.6 ± 0.1 Ω·cm2, P < 0.05). These studies demonstrate there are maturational changes in the rat paracellular pathway that impact net NaCl transport during development.
Habitat Quality and Range Use of White-Headed Langurs in Fusui, China
Authors: Li Zhaoyuan , Elizabeth Rogers M.
Published: July 2005

The socioecology of white-headed langurs (Trachypithecus leucocephalus) was studied in Fusui Precious Animal Reserve, Guangxi, China, in 1997/1998. Habitat quality was classified according to the level of human disturbance. Plant species diversity increased with habitat quality. Important foods for the langurs occurred more in high-quality habitat. Home range size varied from 28 to 48 ha, and the home range area per individual decreased as habitat quality increased. Small polygynous langur groups had poorly defended ranges, but large groups defended their ranges intensively. Only harem males were involved in group defence, apparently competing for females by defending their habitat. High-quality habitat was more attractive to females; accordingly, group size increased significantly with habitat quality.
Behavioral Development of Captive Male Hybrid Cercopithecine Monkeys
Authors: Erhart Elizabeth M. , Bramblett Claud A. , Overdorff Deborah J.
Published: July 2005

In this study, we compare the behavioral development of captive male vervet monkeys (Chlorocebus pygerythrus) and Sykes’ monkeys (Cercopithecus albogularis) to male hybrids of these species. Focal animal sampling sessions were conducted on the study subjects from birth to 90 months of age. Behavioral categories (affiliative, approach, play, sexual, tension, aggressive) were plotted for each species and the hybrids; curves were fitted using polynomial regression and were evaluated with the Wilcoxon signed ranks test. With the exception of play behaviors, the male C. pygerythrus × C. albogularis hybrids modeled the Sykes’ pattern of behavioral development. We suggest that this result reflects a sex-linked paternal effect.
Leptin and Ghrelin Levels in Patients with Obstructive Sleep Apnea Syndrome
Authors: Ulukavak Ciftci Tansu , Kokturk Oguz , Bukan Neslihan , Bilgihan Ayse
Published: July 2005

Background: Leptin is a hormone with well-investigated functions concerning body composition, energy homeostasis and feeding behavior in humans. The obstructive sleep apnea syndrome (OSAS) is strongly associated with obesity, which is known to be closely associated with hyperleptinemia. More recently, ghrelin, a hormone that also influences appetite and energy homeostasis, has been discovered. Objectives: The aim of this study was to investigate serum leptin and ghrelin levels in obese patients with OSAS in comparison with equally obese controls without OSAS. Methods: Thirty untreated obese patients with moderate-severe OSAS (apnea-hypopnea index: AHI ≧15) and 22 obese controls (AHI <5) were studied. To confirm the diagnosis, all patients underwent standard polysomnography in our sleep disorders center. Serum samples were taken at 08:00 h in the morning after overnight fasting. Results: Significantly higher serum leptin levels were found in OSAS patients compared to controls (p = 0.012), but there was no significant difference in serum ghrelin levels between OSAS patients and controls. Serum leptin levels were significantly correlated with body mass index in both OSAS patients (r = 0.55, p = 0.002) and controls (r = 0.46, p = 0.028), but only in OSAS patients was the leptin level significantly correlated with AHI (r = 0.38, p = 0.036). Conclusion: These data support findings suggesting that leptin is a hormonal factor affected by OSAS and not determined by obesity alone. Further studies are needed to investigate the relationship between serum ghrelin and OSAS.
Role of the Dialyzer Membrane on the Overall Phosphate Kinetics during Hemodialysis
Authors: Katopodis Konstantinos P. , Chala Anna , Koliousi Elli , Takouli Lamprini , Kalaitzidis Rigas , Theodorou Joanna , Siamopoulos Kostas C.
Published: July 2005

Background/Aim: We investigated the potential role of the membrane type on phosphate kinetics. Methods: Six patients on dialysis (HD) were studied using modified cellulose (Hemophan), ethylene-vinyl alcohol (EVAL) and polyacrylonitrile (PAN). Total (TPR), extracellular (EPR) and intracellular (IPR) phosphate removal and effective dialyzer phosphate clearance (Kd) were determined by the DDQ method. The intercompartment transfer coefficient (KC) was calculated using a mathematical model. Erythrocyte phosphate (PERY) and 2,3-biphosphoglycerate (2,3-BPG) concentrations were determined before and after HD. Results: TPR was 1.2 ± 0.4, 1.10 ± 0.4 and 1.09 ± 0.4 g with Hemophan, EVAL and PAN, respectively (p = n.s.). EPR and IPR were independent of membrane type. There was no difference in KC between membranes (321 ± 70, 338 ± 92 and 341 ± 83 ml/min, respectively). The PERY and 2,3-BPG remained statistically insignificant for all membranes. Conclusion: Our results show that the type of membrane does not influence the kinetics of phosphate during dialysis, neither in the transfer from plasma to dialysate nor from the intra- to the extracellular compartment.
Effect of Oral Sodium Bicarbonate Supplementation on Interdialytic Weight Gain, Plasma Sodium Concentrations and Predialysis Blood Pressure in Hemodialysis Patients
Authors: Movilli Ezio , Gaggia Paola , Camerini Corrado , Brunori Giuliano , Vizzardi Valerio , Cancarini Giovanni
Published: July 2005

Background: Correction of metabolic acidosis in dialysis patients should be considered of paramount importance. However, consuming sodium bicarbonate tablets during the interdialytic interval to reach predialysis bicarbonate levels of 23–24 mmol/l is not widespread due to the fear of greater interdialytic weight gain and fluid overload. For this reason we investigated in a cross-sectional and in an interventional study the effect of oral sodium bicarbonate supplementation on body weight gain, plasma sodium concentrations and predialysis blood pressure in a group of stable uremic patients on regular hemodialysis (HD) treatment. Study Design: 110 patients (67 men, 43 women), mean age 67 ± 15 (range 22–89) years, on regular chronic HD treatment for 6–372 (median 48) months were studied. 70 patients were on regular oral bicarbonate supplementation for at least 4 weeks (group A), 40 patients were not on oral bicarbonate supplementation (group B). The following parameters were recorded: dry body weight (DBW), interdialytic weight gain (IWG), body mass index (BMI), plasma sodium (Na), serum pH, serum bicarbonate (sBic), Kt/V, normalized protein catabolic rate (PCRn), predialysis systolic (SBP) and diastolic (DBP) blood pressure, and bicarbonate therapy (g/day). 18 patients not on oral bicarbonate supplementation with sBic levels ≤20 mmol/l were started on oral bicarbonate therapy and were prospectively followed in the context of an interventional study of correction of chronic metabolic acidosis. The same parameters were recorded before (pre) and after (post) 4 months of oral bicarbonate supplementation. Results:Serum pH and sBic concentrations were significantly higher in patients in group A compared to patients in group B (pH 7.37 ± 0.02 group A vs. 7.33 ± 0.02 group B: p <0.001: sBic 23.8 ± 1.4 group A vs. 20.9 ± 1.4 group B: p < 0.0001). Age, DBW, BMI, IWG, SBP, DBP, Na, Kt/V and PCRn did not differ between groups. The mean daily dose of oral sodium bicarbonate administered to patients in group A was 1.9 ± 0.9 (range 1–5, median 2) g/day. Also in the 18 patients who started bicarbonate treatment, a significant increase in serum pH and sBic concentrations and a significant reduction in PCRn were observed. No significant change in DBW, IWG, SBP, DBP and Na concentrations after 4 months of treatment was found. Conclusions: Our data show that in stable uremic patients on regular HD treatment, oral daily administration of sodium bicarbonate is effective in correcting mild-moderate chronic metabolic acidosis, and does not cause increased interdialytic body weight gain, different plasma sodium concentrations and different systolic-diastolic blood pressure levels compared to patients not on oral sodium bicarbonate supplementation.
Matrix Metalloproteinases in Cerebrovascular Diseases
Authors: Fatar Marc , Stroick Mark , Griebe Martin , Hennerici Michael G.
Published: July 2005

Matrix metalloproteinases are important factors for tissue remodelling and are activated during several physiological and pathological conditions, including cerebrovascular diseases. We give an overview of the structure, production and physiological effects of these widely distributed proteases and describe the genetic background and regulation pathways. In particular, we discuss the role of matrix metalloproteinases in vascular remodelling concerning ischaemic stroke, brain haemorrhage, vascular dementia, carotid artery plaques and cerebral aneurysms.
A Systematic Comparison of the Quality and Volume of Published Data Available on Novel Risk Factors for Stroke versus Coronary Heart Disease
Authors: Bhatia Meena , Rothwell Peter M.
Published: July 2005

Background: To identify new treatments to prevent stroke, it is important that we have reliable data on potential novel risk factors. Methods: We studied seven novel vascular risk factors [apo-lipoprotein (b), C-reactive protein, Chlamydia pneumoniae, fibrin-D dimer, fibrinogen, Helicobacter pylori and lipoprotein (a)] and compared the amount of published data on their relations with ischaemic stroke versus acute coronary events by systematic review of all studies published up to 2003. Results: From a total of 22,875 abstracts reviewed, 266 eligible studies were identified (167 case-control studies and 99 cohort studies). Two hundred and eleven (79%) studies included coronary events as an outcome for the purpose of a risk factor analysis. In 186 (70%) studies, coronary events were the only outcome that was analysed. Only 73 (27%) studies included stroke or TIA as an outcome event, and only 45 studies (17%) reported risk factor analyses for ischaemic stroke separately. These results were qualitatively consistent across the risk factors studied and the relative lack of data on risk factors for stroke was even greater in prospective cohort studies. Conclusion: Data on novel risk factors for stroke are lacking compared with the equivalent data for acute coronary events, and there are very few data on specific subtypes of ischaemic stroke.
CYP4V2 Mutations in Two Japanese Patients with Bietti’s Crystalline Dystrophy
Authors: Gekka Tamaki , Hayashi Takaaki , Takeuchi Tomokazu , Goto-Omoto Satoshi , Kitahara Kenji
Published: July 2005

Bietti’s crystalline dystrophy (BCD) is an autosomal-recessive retinal dystrophy characterized by numerous glistening intraretinal dots scattered over the fundus, particularly in the posterior pole. The purpose of this study was to report mutations in the CYP4V2 gene (encoding a ubiquitously-expressed 525-amino acid sequence belonging to the CYP450 family) and to investigate the impact of the mutation on pre-mRNA splicing. DNA and RNA analyses were conducted using blood samples from two unrelated Japanese patients with BCD (a 46-year-old female and a 52-year-old male). In the female patient, a homozygous deletion/insertion mutation (g.IVS6–8_–1delc.802_810del/insGC) including the 3´-acceptor splice site was identified. Reverse transcription-PCR analysis revealed that the complete length of exon 7 (186 bp), is skipped, resulting in the in-frame deletion mutation (p.V268_E329del). Conversely, the male patient was a compound heterozygote for the deletion/insertion and novel nonsense (p.W340X) mutations. Clinically, the female patient had decreased visual acuity, constriction of visual fields, severely reduced amplitudes in both rod and cone electroretinograms (ERGs). Despite being 6 years older, the male patient presented with milder clinical manifestations having good visual acuity and substantial amplitudes in both rod and cone ERGs. Because the CYP4V2 truncated protein with the p.W340X mutation lacks 186 amino acids at the C-terminus, if expressed, it retains 62 amino acids encoded in exon 7, which are important for enzymatic activity. In the male patient, expression of both mutant alleles may compensate for the malfunction of each mutated protein and could explain why a milder form of BCD results from compound heterozygosity.
Validity and Reproducibility of a Precoded Questionnaire to Assess Fruit and Vegetable Intake in European 11- to 12-Year-Old Schoolchildren
Authors: Haraldsdóttir Jóhanna , Thórsdóttir Inga , de Almeida Maria Daniel Vaz , Maes Lea , Pérez Rodrigo Carmen , Elmadfa Ibrahim , Frost Andersen Lene
Published: July 2005

Background/Aims: Validity and reproducibility were evaluated of a new questionnaire to assess fruit and vegetable intakes in 11- to 12-year-old children. Methods: The precoded teacher-assisted self-administered questionnaire included two sections: a 24-hour recall part and a food frequency part. Validity was tested in 4 countries (Denmark, Iceland, Norway, Portugal; n = 43–60 per country) using a 1-day weighed food record and 7-day food records as reference methods. Test-retest (7–12 days apart) reproducibility was assessed in 6 countries (Belgium, Denmark, Iceland, Norway, Portugal, Spain; n = 60–74 per country). Results: Spearman rank correlations for fruit and vegetable intake according to the frequency part and the 7-day food record ranged between r = 0.40–0.53. Between 25–50% were classified into the same quartile and 70–88% into the same or adjacent quartile. Test-retest Spearman rank correlations for the food frequency part were r = 0.47–0.84. Three countries showed no significant difference between fruit intake as assessed with the 24-hour recall part and the 1-day weighed food record, and 2 countries showed no significant difference for vegetables. In the other countries, the 24-hour recall part resulted in substantially higher mean intake levels. Conclusion: Validity and reproducibility as to ranking of subjects were regarded to be satisfactory in all countries. Group mean intake, based on the original 24-hour part, was valid for fruit in 3 countries and for vegetables in 2 countries, and this part was subsequently adjusted to avoid overestimation, before the questionnaire was used in the Pro Children study.
Aldehyde Dehydrogenase 2 Plays a Role in the Bioactivation of Nitroglycerin in Humans
Authors: Mackenzie Isla S. , Maki-Petaja Kaisa M. , McEniery Carmel M. , Bao Yi Ping , Wallace Sharon M. , Cheriyan Joseph , Monteith Sue , Brown Morris J. , Wilkinson Ian B.
Published: July 2005

Objective—

Nitrates are used widely in clinical practice. However, the mechanism underlying the bioactivation of nitrates to release NO remains unclear. Recent animal data suggest that mitochondrial aldehyde dehydrogenase (ALDH2) plays a central role in nitrate bioactivation, but its role in humans is not known. We investigated the role of ALDH2 in the vascular effects of nitroglycerin (NTG) in humans in vivo.

Methods and Results—

Forearm blood flow (FBF) responses to intra-arterial infusions of NTG, sodium nitroprusside (SNP), and verapamil were measured in 12 healthy volunteers before and after ALDH2 inhibition by disulfiram. All drugs caused a dose-dependent vasodilatation. However, only the response to NTG was significantly reduced after disulfiram therapy (33% reduction in area under the curve [AUC];
P
=0.002). Separately, 11 subjects of East Asian origin, with the loss-of-function glu504lys mutation in the ALDH2 gene, received intra-arterial NTG, SNP, and verapamil. Only the FBF response to NTG was lower in the volunteers with the glu504lys mutation compared with East Asian and non-Asian wild-type control subjects (40% reduction in AUC;
P
=0.02).

Conclusions—

The findings suggest that ALDH2 is involved in the bioactivation of NTG in humans in vivo but accounts for less than half of the total bioactivation. This may be of clinical importance in patients with mutations in the ALDH2 gene and in those taking drugs that inhibit ALDH2.
Lack of the Cysteine Protease Inhibitor Cystatin C Promotes Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Bengtsson Eva , To Fong , Håkansson Katarina , Grubb Anders , Brånén Lena , Nilsson Jan , Jovinge Stefan
Published: July 2005

Objective—

Degradation of extracellular matrix plays an important role in growth and destabilization of atherosclerotic plaques. Cystatin C, inhibitor of the collagen- and elastin-degrading cysteine proteases of the cathepsin family, is produced by virtually all cell types. It is present in the normal artery wall but severely reduced in human atherosclerotic lesions.

Methods and Results—

To determine the functional role of cystatin C in atherosclerosis, we crossed cystatin C–deficient (cysC
−/−
) mice with apolipoprotein E–deficient (apoE
−/−
) mice. After 25 weeks of atherogenic diet, mice lacking apoE and cystatin C (cysC
−/−
apoE
−/−
) had larger subvalvular plaques compared with cysC
+/+
apoE
−/−
mice (766 000±20 000 μm
2
per section versus 662 000±19 000 μm
2
per section;
P
=0.001), suggesting an atheroprotective role of cystatin C. The plaques from cysC
−/−
apoE
−/−
mice were characterized by increased total macrophage content. To determine which cellular source is important for the antiatherosclerotic effect of cystatin C, we performed bone marrow transplantations. ApoE
−/−
mice were transplanted with either cysC
−/−
apoE
−/−
or cysC
+/+
apoE
−/−
bone marrow. No significant differences in plaque area, macrophage, collagen, or lipid content of subvalvular lesions between the 2 groups were detected.

Conclusions—

The result suggests that the protective role of cystatin C in atherosclerosis is dependent primarily on its expression in nonhematopoietic cell types.
N488I Mutation of the γ2-Subunit Results in Bidirectional Changes in AMP-Activated Protein Kinase Activity
Authors: Zou Liqun , Shen Mei , Arad Michael , He Huamei , Løfgren Bo , Ingwall Joanne S. , Seidman Christine E. , Seidman Jon G. , Tian Rong
Published: July 2005

Mutations in the human gene encoding the nucleotide-binding region in the γ-subunit of AMP-activated protein kinase (AMPK) cause cardiomyopathy with preexcitation syndrome. Mutant AMPK showed reduced binding affinity to nucleotides in vitro raising the possibility that altered regulation of AMPK activity by AMP/ATP could contribute to the disease phenotype. In this study, we determined the sensitivity of AMPK activity to AMP/ATP in the beating hearts using transgenic mice expressing a mutant (N488I, γ2-mutant) or wild-type γ2-subunit (γ2-TG). The [ATP] and [AMP] were unaltered in all hearts but the AMPK activity was increased by 2.5-fold in γ2-mutant hearts freeze-clamped at normal AMP/ATP compared with nontransgenic (WT) or γ2-TG. The increased basal AMPK activity was caused by increased Thr-172 phosphorylation of the α-subunit (p-AMPK, by 4-fold) at normal [ATP] and was not changed by reducing glycogen content by 60% in the γ2-mutant hearts. A reversal of AMP/ATP, caused by ATP degradation, increased p-AMPK by 7-fold in WT but caused no change in γ2-mutant hearts. These results demonstrate that the mutation renders AMPK insensitive to the inhibitory and stimulatory effects of the regulatory nucleotides ATP and AMP, respectively, suggesting that the pathogenesis of the human disease may not be attributable to a simple loss- or gain-of-function.
Cardiomyocyte-Specific Knockout and Agonist of Peroxisome Proliferator–Activated Receptor-γ Both Induce Cardiac Hypertrophy in Mice
Authors: Duan Sheng Zhong , Ivashchenko Christine Y. , Russell Mark W. , Milstone David S. , Mortensen Richard M.
Published: July 2005

Peroxisome proliferator–activated receptor (PPAR)-γ is required for adipogenesis but is also found in the cardiovascular system, where it has been proposed to oppose inflammatory pathways and act as a growth suppressor. PPAR-γ agonists, thiazolidinediones (TZDs), inhibit cardiomyocyte growth in vitro and in pressure overload models. Paradoxically, TZDs also induce cardiac hypertrophy in animal models. To directly determine the role of cardiomyocyte PPAR-γ, we have developed a cardiomyocyte-specific PPAR-γ–knockout (CM-PGKO) mouse model. CM-PGKO mice developed cardiac hypertrophy with preserved systolic cardiac function. Treatment with a TZD, rosiglitazone, induced cardiac hypertrophy in both littermate control mice and CM-PGKO mice and activated distinctly different hypertrophic pathways from CM-PGKO. CM-PGKO mice were found to have increased expression of cardiac embryonic genes (atrial natriuretic peptide and β-myosin heavy chain) and elevated nuclear factor κB activity in the heart, effects not found by rosiglitazone treatment. Rosiglitazone increased cardiac phosphorylation of p38 mitogen-activated protein kinase independent of PPAR-γ, whereas rosiglitazone induced phosphorylation of extracellular signal–related kinase 1/2 in the heart dependent of PPAR-γ. Phosphorylation of c-Jun N-terminal kinases was not affected by rosiglitazone or CM-PGKO. Surprisingly, despite hypertrophy, Akt phosphorylation was suppressed in CM-PGKO mouse heart. These data show that cardiomyocyte PPAR-γ suppresses cardiac growth and embryonic gene expression and inhibits nuclear factor κB activity in vivo. Further, rosiglitazone causes cardiac hypertrophy at least partially independent of PPAR-γ in cardiomyocytes and through different mechanisms from CM-PGKO.
Kv1.5 Surface Expression Is Modulated by Retrograde Trafficking of Newly Endocytosed Channels by the Dynein Motor
Authors: Choi Woo Sung , Khurana Anu , Mathur Rajesh , Viswanathan Vijay , Steele David F. , Fedida David
Published: July 2005

In this article we have investigated the mechanisms by which retrograde trafficking regulates the surface expression of the voltage-gated potassium channel, Kv1.5. Overexpression of p50/dynamitin, known to disrupt the dynein–dynactin complex responsible for carrying vesicle cargo, substantially increased outward K
+
currents in HEK293 cells stably expressing Kv1.5 (0.57±0.07 nA/pF, n=12; to 1.18±0.2 nA/pF, n=12,
P
<0.01), as did treatment of the cells with a dynamin inhibitory peptide, which blocks endocytosis. Nocodazole pretreatment, which depolymerizes the microtubule cytoskeleton along which dynein tracks, also doubled Kv1.5 currents in HEK cells and sustained K
+
currents in isolated rat atrial myocytes. These increased currents were blocked by 1 mmol/L 4-aminopyridine, and the specific Kv1.5 antagonist, DMM (100 nM). Confocal imaging of both HEK cells and myocytes, as well as experiments testing the sensitivity of the channel in living cells to external Proteinase K, showed that this increase of K
+
current density was caused by a redistribution of channels toward the plasma membrane. Coimmunoprecipitation experiments demonstrated a direct interaction between Kv1.5 and the dynein motor complex in both heterologous cells and rat cardiac myocytes, supporting the role of this complex in Kv1.5 trafficking, which required an intact SH3-binding domain in the Kv1.5 N terminus to occur. These experiments highlight a pathway for Kv1.5 internalization from the cell surface involving early endosomes, followed by later trafficking by the dynein motor along microtubules. This work has significant implications for understanding the way Kv channel surface expression is regulated.
Paradoxical Cellular Ca
2+
Signaling in Severe but Compensated Canine Left Ventricular Hypertrophy
Authors: Song Long-Sheng , Pi YeQing , Kim Song-Jung , Yatani Atsuko , Guatimosim Silvia , Kudej Raymond K. , Zhang Qingxiu , Cheng Heping , Hittinger Luc , Ghaleh Bijan , Vatner Dorothy E. , Lederer W. Jonathan , Vatner Stephen F.
Published: July 2005

In conscious dogs with severe left ventricular (LV) hypertrophy (H) (doubling of LV/body weight), which developed gradually over 1 to 2 years after aortic banding, baseline LV function was well compensated. The LV was able to generate twice the LV systolic pressure without an increase in LV end-diastolic pressure, or decrease in LV dP/dt or LV wall thickening. However, LV myocytes isolated from LVH dogs exhibited impaired contraction at baseline and in response to Ca
2+
. There was no change in L-type Ca
2+
channel current (
I
Ca
) density but the ability of
I
Ca
to trigger Ca
2+
release from the sarcoplasmic reticulum (SR) was reduced. Immunoblot analysis revealed a 68% decrease in SERCA2a, and a 35% decrease in the number of ryanodine receptors (RyR2), with no changes in protein level of calsequestrin, Na
+
/Ca
2+
exchanger or phospholamban (PLB), but with both RyR2 and PLB hyperphosphorylated. Spontaneous Ca
2+
sparks in LVH cells were found to have prolonged duration but similar intensities despite the reduced SR Ca
2+
load. A higher Ca
2+
spark rate was observed in LVH cells, but this is inconsistent with the reduced SR Ca
2+
content. However, Ca
2+
waves were found to be less frequent, slower and were more likely to be aborted in Ca
2+
-challenged LVH cells. These paradoxical observations could be accounted for by a nonuniform SR Ca
2+
distribution, RyR2 hyperphosphorylation in the presence of decreased global SR Ca
2+
load. We conclude that severe LVH with compensation masks cellular and subcellular Ca
2+
defects that remain likely contributors to the limited contractile reserve of LVH.
Antihypertensive Medications Prescribed at Discharge After an Acute Ischemic Cerebrovascular Event
Authors: Ovbiagele Bruce , Hills Nancy K. , Saver Jeffrey L. , Johnston S. Claiborne
Published: July 2005

Background and Purpose—

Hypertension is poorly controlled in stroke survivors, thereby placing them at increased risk for recurrent events. Clinical trial evidence suggests that antihypertensive treatment may be beneficial for stroke prevention in hypertensive and normotensive stroke patients. We aimed to evaluate the discharge antihypertensive prescription patterns in patients hospitalized for an ischemic cerebrovascular event and to determine factors associated with treatment utilization.

Methods—

We analyzed patients diagnosed with ischemic stroke or transient ischemic attack (TIA) in the California Acute Stroke Prototype Registry (CASPR). We used generalized estimating equations to identify factors independently associated with receiving antihypertensives at the time of hospital discharge.

Results—

Data were collected on 764 consecutive patients with ischemic stroke or TIA encountered at 11 hospitals representative of facilities in the state of California. Overall, the rate of discharge with a prescription for any antihypertensive in the CASPR cohort was 69.4%. Hospital-specific rates were heterogeneous (
P
=0.04), varying from 55% to 100%. In multivariate analysis, independent predictors of prescription for antihypertensive medication at discharge were a history of hypertension (
P
<0.0001), diabetes (
P
=0.0009), and older age.

Conclusions—

About two-thirds of patients hospitalized with acute ischemic cerebrovascular events are discharged from the hospital on ≥1 antihypertensive medication. However, there is great variability in prescription rates between hospitals and considerable room for improvement.
Why Look at Elephants?
Authors: Rothfels Nigel
Published: July 2005

Through analysis of the contending ways elephants have been imagined in a mid twentieth-century circus performance and in a mid nineteenth-century hunting narrative, this essay offers a critique of several basic assumptions behind John Berger's "Why Look at Animals?" The paper argues that studying how elephants have been described and used reveals particularly well the often quickly evolving nature of our understanding of animals and their significance in our lives, and concludes that our historical comprehension of the very terms of "animal" and "human" is often surprisingly complex.
John Berger's "Why Look at Animals?": A Close Reading
Authors: Burt Jonathan
Published: July 2005

This article is a close reading of John Berger's highly influential essay "Why look at animals?" and its implications for thinking about animals in modernity. Berger analyses the alienation of human and animal as a consequence of nineteenth-century capitalism, and contrasts it with an earlier period when human-animal relations were more integrated. Despite the power and simplicity of Berger's argument, which has been taken up uncritically by a number of writers, both his historical analysis and his conception of human-animal relations in modernity are highly problematic and need substantial revision. Furthermore, the consequences of his thesis paradoxically reinforce the very processes he is criticising. Inadequate notions of the place of animals in public visual culture, and a more general bias against visual imagery in favour of text-based notions of the animal, create obstacles to theorising human-animal relations and welfare related issues in the contemporary world. The article suggests other perspectives for understanding what it means to look at animals.
Inventing a Beast with No Body: Radio-Telemetry, the Marginalization of Animals, and the Simulation of Ecology
Authors: Bergman Charles
Published: July 2005

Radio-telemetry is a relatively new technology that is having powerful impacts on the way wildlife is studied. With tens of thousands of new radio-telemetry units produced each year, to be placed on animals in the wild, it is a technology that is becoming increasingly pervasive. This paper begins by examining the way radio-telemetry has been adapted for the study of macaws in Latin America. The paper argues that as a form of surveillance and monitoring, radio-telemetry illustrates some ways in which Michel Foucault's concepts of "biopower" and surveillance can be applied to the management of wildlife. Additionally, as the new technology creates a greater sense of distance between the "sign" of a creature and its actual reality, wild animals seem to become what Jean Baudrillard terms "simulations", in which they are increasingly signs of their own disappearance—both as creatures and as species.
Acting Presidential
Authors: Brown Robert E.
Published: July 2005

Dramaturgy, an interactionist perspective, was developed by Erving Goffman, a sociologist working in the theoretical tradition of seminal social theorists including Durkheim and Parsons. This article’s thesis is that although the typical application of dramaturgy has been to interpersonal contexts, dramaturgy’s symbolic orientation and its rich terminological vocabulary make it particularly well suited for the analysis of political communication, widely perceived as a theatrical and symbolic domain. This metatheoretical article attempts to extend dramaturgy to politics, notwithstanding the apparently little interest in politics displayed by Goffman himself. The article’s political focus is the U.S. presidential campaign of 2004, which opposed George Bush and John Kerry. The contest is examined in the dramaturgic terms of performance, expressive control, disidentification, region management, and stigmatization.
Voter Decision Making
Authors: Levine Kenneth J.
Published: July 2005

There are several models of voter decision making; however, three influential factors (personal identity, personal ethics, and personal benefit) in the decision-making process have received little scholarly attention. These factors are examined to underscore their importance to voters when making a selection for a leader. A longitudinal election scenario is used to measure the effects of these variables on the voting decisions of 143 college-aged respondents. As facts and circumstances change within the scenario, respondents are asked to indicate which candidate they support and why. In addition, a series of interval-level items are asked to measure the effect of the various factors. The rationales for voting for each candidate demonstrate how the three factors play a role in the decision-making process. Small but significant correlations are found to exist between the factors and the respondents’ voting behavior. Implications, limitations, and future research based on these findings are presented.
Presidential Election Campaigns and American Democracy
Authors: Pfau Michael , Houston J. Brian , Semmler Shane M.
Published: July 2005

There is very little research about the relative influence of campaign communication forms or venues on normative outcomes concerning the extent to which campaign communication promotes or degrades basic democratic values. This investigation assesses the relative impact of 17 communication forms on three normative outcomes: political expertise, which embodies people’s awareness, knowledge, and interest in politics; attitude about the process used to elect candidates; and likelihood of participating in the political process. Data are based on results of two national surveys conducted in different phases of the 2004 presidential campaign. Hierarchical regression analyses are used to evaluate the relative influence of the 17 communication forms on normative outcomes, controlling for sociodemographic variables.
Detecting the Effects of Deceptive Presidential Advertisements in the Spring of 2004
Authors: Winneg Kenneth , Kenski Kate , Jamieson Kathleen Hall
Published: July 2005

Long before the political conventions of 2004, the Kerry and Bush campaigns and their surrogates were laying the groundwork for the fall campaign with heavy ad buys. Some of the assertions made on each side were misleading. Here we explore three misleading claims made on each side in the weeks following the effective end of the 2004 primary season and ask, Did they work? If so, with whom? Results from the National Annenberg Election Survey show that some of these misleading claims about George W. Bush and John Kerry were believed by a majority of citizens. Democrats were more likely to believe deceptive claims about Bush, whereas Republicans were more likely to embrace deceptive claims about Kerry. The claim that “George W. Bush favors sending American jobs overseas” gained traction in battleground states, even when demographic variables and party identification were taken into consideration.
Self-Affirmation and the Biased Processing of Threatening Health-Risk Information
Authors: Harris Peter R. , Napper Lucy
Published: July 2005

Self-affirming before reading about the link between alcohol and breast cancer promoted increased message acceptance among young women at higher risk. Differences were maintained on variables measured up to 1 month later. Relative to their nonaffirmed counterparts, higher risk, self-affirmed participants had higher ratings of risk, imagination, intention to reduce alcohol consumption, and negative affect, such as fear, while reading the leaflet. In contrast, there were no differences between the groups on measures of broader message acceptance (belief in the link, evidence strength). Thus, self-affirmation promoted acceptance of the personal relevance of the message, a critical step in the precaution adoption process. Overall, the findings support the view that self-affirmation in an unrelated domain can offset defensive processing of a threatening health message, promoting central route persuasion and producing consequential and durable increases in message acceptance.
Estimating the strength of resistance spot welds based on sonic emission
Authors: Podržaj Primož , Polajnar Ivan , Diaci Janez , Kariž Zoran
Published: July 2005

Audible sound signals detected during the resistance spot welding (RSW) of zinc coated steels were investigated in order to assess their suitability for estimating the strength of the weld. A new sonic emission indicator was introduced and compared to a commonly used emission count indicator. A new method of spot weld strength estimation based on the two indicators is presented. The advantage of the method is that it makes it possible to establish the stage when the electrode is worn out. The method enables the development of improved RSW process control algorithms.
Results of a phase 1 clinical trial of thalidomide in combination with fludarabine as initial therapy for patients with treatment-requiring chronic lymphocytic leukemia (CLL)
Authors: Chanan-Khan Asher , Miller Kena C. , Takeshita Kenichi , Koryzna Alexandra , Donohue Kathleen , Bernstein Zale P. , Mohr Alice , Klippenstein Donald , Wallace Paul , Zeldis Jerome B. , Berger Christine , Czuczman Myron S.
Published: July 2005

Tumor necrosis factor α (TNF-α) and vascular endothelial growth factor (VEGF) play an important role in the biology of chronic lymphocytic leukemia (CLL) cells. Thalidomide is a first-generation immuno-modulating agent that down-regulates TNF-α and VEGF. We initiated a phase 1/2 clinical trial to determine the safety and efficacy of combining thalidomide with fludarabine in patients with treatment-naïve CLL. Patients received 6 months of continuous daily thalidomide with standard monthly doses of fludarabine. Three dose levels of thalidomide (100, 200, and 300 mg) were studied. Results from the phase 1 part of this study are reported here. Thirteen patients were enrolled in the phase 1 component of the study. Dose-limiting toxicity was not reached. The most common toxicities noted were fatigue, constipation, and peripheral sensory neuropathy. Overall response rate was 100% with 55% of patients achieving complete remissions. At a median follow-up of 15+ months none of the patients have had a relapse and the median time to disease progression has not yet been reached. Responses were noted at all dose levels. Thalidomide given up to 300 mg/day concurrently with fludarabine in patients with previously untreated CLL shows encouraging clinical efficacy and acceptable toxicity. An ongoing phase 2 part of this study will help validate the clinical efficacy of this regimen.
Aminoglycoside suppression of nonsense mutations in severe hemophilia
Authors: James Paula D. , Raut Sanj , Rivard Georges E. , Poon Man-Chiu , Warner Margaret , McKenna Susan , Leggo Jayne , Lillicrap David
Published: July 2005

Aminoglycoside antibiotics exhibit their bactericidal effect by interfering with normal ribosomal activity. In this pilot study, we have evaluated the effect of the aminoglycoside antibiotic gentamicin on the factor VIII (FVIII) and IX levels of severe hemophiliacs with known nonsense mutations. Five patients were enrolled and each patient was given 3 consecutive days of gentamicin at a dose of 7 mg/kg intravenously every 24 hours. Two patients (patient no. 1: hemophilia A, Ser1395Stop; and patient no. 5: hemophilia B, Arg333Stop) showed a decrease in their activated partial thromboplastin time (aPTT), an increase in their FVIII (0.016 IU/mL, 1.6%) or FIX (0.02 IU/mL, 2%) levels, and an increase in thrombin generation. The remaining 3 patients (patient no. 2: hemophilia B, Arg252Stop; patient no. 3: hemophilia A, Arg2116Stop; and patient no. 4: hemophilia A, Arg427Stop) showed no response in the aPTTs or factor levels, but one (patient no. 2: hemophilia B, Arg252Stop) showed an increase in the factor IX antigen level (2%-5.5%) that persisted throughout the period of the study and was concordant with an increase in thrombin generation. Gentamicin is unlikely to be an effective treatment for severe hemophilia due to its potential toxicities and the minimal response documented in this report. This study, however, does provide a proof of principle, suggesting that ribosomal interference with a less toxic agent may be a potential therapeutic mechanism for severe hemophilia patients with nonsense mutations.
Epidemiological evidence of effects of coarse airborne particles on health
Authors: Brunekreef B. , Forsberg B.
Published: July 2005

Studies on health effects of airborne particulate matter (PM) have traditionally focused on particles <10 μm in diameter (PM10) or particles <2.5 μm in diameter (PM2.5). The coarse fraction of PM10, particles >2.5 μm, has only been studied recently. These particles have different sources and composition compared with PM2.5. This paper is based on a systematic review of studies that have analysed fine and coarse PM jointly and examines the epidemiological evidence for effects of coarse particles on health.

Time series studies relating ambient PM to mortality have in some places provided evidence of an independent effect of coarse PM on daily mortality, but in most urban areas, the evidence is stronger for fine particles. The few long-term studies of effects of coarse PM on survival do not provide any evidence of association.

In studies of chronic obstructive pulmonary disease, asthma and respiratory admissions, coarse PM has a stronger or as strong short-term effect as fine PM, suggesting that coarse PM may lead to adverse responses in the lungs triggering processes leading to hospital admissions. There is also support for an association between coarse PM and cardiovascular admissions.

It is concluded that special consideration should be given to studying and regulating coarse particles separately from fine particles.
Plasma concentrations of dietary and nondietary antioxidants are low in severe asthma
Authors: Misso N. L. A. , Brooks-Wildhaber J. , Ray S. , Vally H. , Thompson P. J.
Published: July 2005

Low antioxidant levels and oxidative stress due to airway inflammation may be important determinants of asthma severity. The objective of the present study was to determine whether lower antioxidant intake and plasma antioxidant concentrations are associated with more severe asthma.

Dietary antioxidant intakes and asthma severity were assessed using questionnaires, and plasma concentrations of ascorbic acid, vitamin E, carotenoids, bilirubin, albumin, uric acid and total antioxidant status were measured in 53 mild-to-moderate and 28 severe asthmatic patients and in 43 nonasthmatic subjects.

Vitamin C and carotene intakes were lower in males than females and were particularly low in males with severe asthma. Plasma ascorbic acid was lower in severe (31.9±3.6 µM) compared with mild-to-moderate asthmatic (52.3±2.6) or control subjects (52.7±2.9). Low plasma ascorbic acid (odds ratio (OR) 0.93; 95% confidence interval (CI) 0.9–0.97), bilirubin (OR 0.69; 95% CI 0.51–0.93) and increased plasma cholesterol (OR 1.98; 95% CI 1.05–3.73) were independently associated with severe asthma. Albumin was positively and cholesterol negatively correlated with lung function.

Low plasma concentrations of specific antioxidants are associated with more severe asthma. Increased antioxidant intake may help reduce the burden of severe asthma, particularly in males.
Are patients with COPD psychologically distressed?
Authors: Wagena E. J. , Arrindell W. A. , Wouters E. F. M. , van Schayck C. P.
Published: July 2005

This study was designed to assess the level of psychological distress in a heterogeneous group of patients with chronic obstructive pulmonary disease (COPD), and compare them with the general population and psychiatric outpatients.

A total of 118 patients with COPD, a random sample of 500 subjects from the general population and 500 psychiatric outpatients participated in this study. The Dutch version of the Symptom Checklist-90-Revised was used to assess general psychological distress.

The sample of patients with COPD experienced significantly more psychological distress than the general population and significantly less than psychiatric outpatients. Furthermore, no significant association was found between the severity of the pulmonary disease and the level of psychological distress, although patients with severe or very severe COPD appeared to be at increased risk of depression. Lastly, the pattern of psychological complaints seems comparable in depressed patients with COPD and psychiatric outpatients. Once patients with COPD report suffering from depressive symptoms, the level of distress seems to increase to that found in psychiatric outpatients.

In conclusion, in clinical settings in which psychological complaints are not routinely assessed, the Beck Depression Inventory and Symptom Checklist-90-Revised are very useful for drawing attention to depression and psychological distress.
Factors affecting survival of hospitalised patients with COPD
Authors: Gunen H. , Hacievliyagil S. S. , Kosar F. , Mutlu L. C. , Gulbas G. , Pehlivan E. , Sahin I. , Kizkin O.
Published: July 2005

Factors determining in-hospital mortality and long-term survival of patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are not precisely understood. The aim of the present study was to assess the parameters related to in-hospital mortality and long-term survival after hospitalisation of patients with AECOPD.

Clinical and epidemiological parameters on admission in 205 consecutive patients hospitalised with AECOPD were prospectively assessed. Patients were followed-up for 3 yrs. Factors determining short- and long-term mortality were analysed.

In total, 17 patients (8.3%) died in hospital. In-hospital mortality was significantly associated with lower arterial oxygen tension (Pa,O2), higher carbon dioxide arterial tension, lower arterial oxygen saturation and longer hospital stay. The overall 6-month mortality rate was 24%, with 1-, 2- and 3-yr mortality rates of 33%, 39% and 49%, respectively. Cox regression analysis revealed that long-term mortality was associated with longer disease duration (relative risk (RR) = 1.158), lower albumin (RR = 0.411), lowerPa,O2(RR = 0.871) and lower body mass index (RR = 0.830). When the model was run for the time elapsed since first hospitalisation, it also appeared as statistically significant (RR = 1.195).

These findings show that patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease have poor short- and long-term survival. Prediction of survival status may be enhanced by considering arterial oxygen tension, albumin, body mass index, disease duration and time elapsed since the first hospitalisation.