bluuebunny/crossref_metadata_2025 huggingface dataset:
Topographical localisation of cagA positive and cagA negativeHelicobacter pyloristrains in the gastric mucosa; an in situ hybridisation study
Authors: Camorlinga-Ponce M , Romo C , González-Valencia G , Muñoz O , Torres J
Published: July 2004

Background:The cagA gene is a marker for the presence of the cag pathogenicity island, and the presence of cagA positive strains ofHelicobacter pylorican identify individuals with a higher risk of developing gastrointestinal diseases.

Aims:To study the interaction betweenH pyloricagA(+) and cagA(−) strains and the gastric mucosa.

Methods:Patients withH pyloriassociated gastritis and peptic ulcers were studied. Biopsies were obtained from the antrum, corpus, fundus, and incisura forH pyloriculture, and for in situ hybridisation studies. From each biopsy, multiple singleH pyloricolonies were isolated and propagated for DNA isolation, and cagA was detected by the polymerase chain reaction (PCR). For in situ detection ofH pylorian oligonucleotide specific for anH pyloricommon antigen and an oligonucleotide specific for cagA were used as probes. Biotinylated probes were incubated with biopsy sections, developed with streptavidin–horseradish peroxidase, and amplified with the tyramide system.

Results:PCR results for cagA in isolated colonies confirmed the in situ hydridisation studies. In situ hybridisation identified cagA(+) bacteria in patients with cagA(+) isolates; cagA(−) bacteria in patients with cagA(−) isolates, and cagA(+) and cagA (−) bacteria in patients with both cagA(+) and cagA(−) isolates. CagA(−) bacteria usually colonised the mucous gel or the apical epithelial surface, whereas cagA(+) bacteria colonised the immediate vicinity of epithelial cells or the intercellular spaces.

Conclusions:These results document a different in vivo interaction betweenH pyloricagA(+) orcagA(−) strains and the gastric mucosa.
DEDICATED INSTRUMENTATION FOR HIGH SENSITIVITY, LOW FREQUENCY NOISE MEASUREMENT SYSTEMS
Authors: CIOFI C. , GIUSI G. , SCANDURRA G. , NERI B.
Published: July 2004

Low Frequency Noise Measurements (LFNM) can be used as very sensitive tool for the characterization of the quality and the reliability of electron devices. However, especially in those cases in which the frequency range of interest extends below 1 Hz, instrumentation with an acceptable low level of background noise is not easily found on the market. In fact, at very low frequencies, the flicker noise introduced by the electronic components which make up the instrumentation becomes predominant and several interesting phenomena which could be detected by means of LFNM may result completely hidden in the background noise. This consideration is not limited to the case of input preamplifiers but does extend to any piece of instrumentation that contributes to the LFNM systems, and in particular to the power supplies used for biasing the Device Under Test. During the last few years, our research groups have been strongly involved in the design of very low noise instrumentation for application in the field of LFNM. In this work we report the main results which we have obtained together with a discussion of the design guidelines that have allowed us, in a few cases, to reach noise levels not to be equalled by any instrumentation available on the market.
A STATISTICAL REASON FOR THE APPEARANCE OF 1/F SPECTRA FROM NOT PERFECTLY CONTINUOUS PROCESSES
Authors: HÄRTLER GISELA
Published: July 2004

The objective of this paper is the derivation of the spectral estimate for data from a stochastic process that does not perfectly match the common supposition of stochastic continuity. The used model is a Randomly Indexed Random Walk that supposes the data of every sampling interval as the sum of a finite random number of random independent increments. This corresponds to the discreteness of the state space of electron devices. Random increments indicate the transitions between the current state and a randomly selected next one. Transitions are pointlike events occurring at random instants in time. Randomness in time influences the stochastic properties of the recorded data in such a way that the fixed variance of single random increments turns into a random one of the equidistantly recorded data. Thus, despite of the independence of increments, the data appear as positively correlated. The standard spectral estimate yields the 1/f pattern if the random variance component approaches the magnitude of the fixed variance component.
Cardiac mitochondrial damage and biogenesis in a chronic model of type 1 diabetes
Authors: Shen Xia , Zheng Shirong , Thongboonkerd Visith , Xu Ming , Pierce William M. , Klein Jon B. , Epstein Paul N.
Published: July 2004

Diabetic cardiomyopathy is a common complication leading to heightened risk of heart failure and death. In the present report, we performed proteomic analysis on total cardiac proteins from the OVE26 mouse model of type 1 diabetes to identify protein changes that may contribute to diabetic cardiomyopathy. This analysis revealed that a surprising high proportion (12 of 20) of the altered proteins that could be identified by mass spectrometry were of mitochondrial origin. All but one of these proteins were upregulated by diabetes. Quantitative RT-PCR, performed for two of these proteins, indicated that part of the upregulation was attributed to increased messenger RNA levels. Morphological study of diabetic hearts showed significantly increased mitochondrial area and number as well as focal regions with severe damage to mitochondria. Diabetic mitochondria also showed reduced respiratory control ratio (9.63 ± 0.20 vs. 6.13 ± 0.41, P < 0.0001), apparently due to reduced state 3 rate, and diminished GSH level (5.5 ± 0.9 vs. 8.2 ± 2.5 μmol/mg protein, P < 0.05), indicating impaired mitochondrial function and increased oxidative stress. Further examination revealed increased mitochondrial DNA (1.03 ± 0.18 vs. 0.69 ± 0.13 relative copy number, P < 0.001) and a tendency to higher protein yield in OVE26 cardiac mitochondria, as well as increased mRNA level for mitochondrial transcription factor A and two mitochondrial encoded proteins. Taken together, these results show that mitochondria are a primary target in the diabetic heart, probably due to oxidative stress, and that this damage coincides with and may stimulate mitochondrial biogenesis.
Impaired plasma fatty acid oxidation in extremely obese women
Authors: Thyfault John P. , Kraus Raymond M. , Hickner Robert C. , Howell Amy W. , Wolfe Robert R. , Dohm G. Lynis
Published: July 2004

Skeletal muscle from extremely obese individuals exhibits decreased lipid oxidation compared with muscle from lean controls. It is unknown whether this effect is observed in vivo or whether the phenotype is preserved after massive weight loss. The objective of this study was to compare free fatty acid (FFA) oxidation during rest and exercise in female subjects who were either lean [ n = 7; body mass index (BMI) = 22.6 ± 2.2 kg/m2] or extremely obese ( n = 10; BMI = 40.8 ± 5.4 kg/m2) or postgastric bypass patients who had lost >45 kg (weight reduced) ( n = 6; BMI = 33.7 ± 9.9 kg/m2) with the use of tracer ([13C]palmitate and [14C]acetate) methodology and indirect calorimetry. The lean group oxidized significantly more plasma FFA, as measured by percent fatty acid uptake oxidized, than the extremely obese or weight-reduced group during rest (66.6 ± 14.9 vs. 41.5 ± 16.4 vs. 39.9 ± 15.3%) and exercise (86.3 ± 11.9 vs. 56.3 ± 22.1 vs. 57.3 ± 20.3%, respectively). BMI significantly correlated with percent uptake oxidized during both rest ( r = −0.455) and exercise ( r = −0.459). In conclusion, extremely obese women and weight-reduced women both possess inherent defects in plasma FFA oxidation, which may play a role in massive weight gain and associated comorbidities.
Increase in Serum Amyloid A Evoked by Dietary Cholesterol Is Associated With Increased Atherosclerosis in Mice
Authors: Lewis Katherine E. , Kirk Elizabeth A. , McDonald Thomas O. , Wang Shari , Wight Thomas N. , O’Brien Kevin D. , Chait Alan
Published: July 2004

Background—

Elevated serum amyloid A (SAA) levels are associated with increased cardiovascular risk. SAA levels can be increased by dietary fat and cholesterol. Moreover, SAA can cause lipoproteins to bind extracellular vascular proteoglycans, a process that is critical in atherogenesis. Therefore, we hypothesized that diet-induced increases in SAA would increase atherosclerosis independent of their effect on plasma cholesterol levels.

Methods and Results—

Female LDL-receptor–null (LDLR
−/−
) mice were fed high–saturated fat diets (21%, wt/wt), with or without added cholesterol (0.15%, wt/wt), for 10 weeks. Compared with chow-fed controls, the high-fat diets increased plasma SAA levels. Addition of cholesterol further increased SAA levels 2-fold (
P
<0.05) without further increasing plasma cholesterol levels. Addition of dietary cholesterol also increased atherosclerosis (
P
<0.05). Four lines of evidence suggest that SAA actually might cause atherosclerosis: (1) SAA levels when mice were euthanized correlated with the extent of atherosclerosis (
r
=0.49;
P
<0.02); (2) SAA levels after 5 weeks of diet correlated with the extent of atherosclerosis at 10 weeks (
r
=0.66;
P
<0.01); (3) binding of HDL from these animals to proteoglycans in vitro was related to the HDL-SAA content (
r
=0.65;
P
<0.01); and (4) immunoreactive SAA was present in lesion areas enriched with both proteoglycans and apolipoprotein A-I, the major HDL apolipoprotein.

Conclusions—

Addition of cholesterol to a high-fat diet increased plasma SAA levels and atherosclerosis independent of an adverse effect on plasma lipoproteins, consistent with the hypothesis that SAA may promote atherosclerosis directly by mediating retention of SAA-enriched HDL to vascular proteoglycans.
Delayed Ischemic Preconditioning Activates Nuclear-Encoded Electron-Transfer-Chain Gene Expression in Parallel With Enhanced Postanoxic Mitochondrial Respiratory Recovery
Authors: McLeod Christopher J. , Jeyabalan Anandhi P. , Minners Jan O. , Clevenger Randall , Hoyt Robert F. , Sack Michael N.
Published: July 2004

Background—

Delayed ischemic preconditioning promotes cardioprotection via genomic reprogramming. We hypothesize that molecular regulation of mitochondrial energetics is integral to this cardioprotective program.

Methods and Results—

Preconditioning was induced by use of 3 episodes of 3-minute coronary artery occlusion separated by 5 minutes of reperfusion. Twenty-four hours later, infarct size was reduced by 58% after preconditioning compared with sham-operated controls (
P
<0.001). Cardiac mitochondria were isolated from sham and preconditioned rat hearts. Mitochondrial respiration and ATP production were similar between the groups; however, preconditioned mitochondria exhibit modest hyperpolarization of the inner mitochondrial membrane potential (≥22% versus control,
P
<0.001). After 35-minute anoxia and reoxygenation, preconditioned mitochondria demonstrated a 191±12% improvement in ADP-sensitive respiration (
P
=0.002) with preservation of electron-transfer-chain (ETC) activity versus controls. This augmented mitochondrial recovery was eradicated when preconditioning was abolished by the antioxidant 2-mercaptopropionyl glycine (2-MPG). These biochemical modulations appear to be regulated at the genomic level in that the expression of genes encoding rate-controlling complexes in the ETC was significantly upregulated in preconditioned myocardium, with a concordant induction of steady-state protein levels of cytochrome oxidase, cytochrome
c
, and adenine nucleotide translocase-1. 2-MPG abolished preconditioning induction of these transcripts. Moreover, transcripts of nuclear regulatory peptides known to orchestrate mitochondrial biogenesis, nuclear respiratory factor-1 and peroxisome-proliferator–activated receptor gamma coactivator 1α, were significantly induced in preconditioned myocardium.

Conclusions—

Delayed preconditioned mitochondria display increased tolerance against anoxia-reoxygenation in association with modifications in mitochondrial bioenergetics, with concordant genomic induction of a mitochondrial energetic gene regulatory program. This program appears to be mediated by reactive oxygen species signaling.
C-Reactive Protein Induces Apoptosis in Human Coronary Vascular Smooth Muscle Cells
Authors: Blaschke Florian , Bruemmer Dennis , Yin Fen , Takata Yasunori , Wang Wei , Fishbein Michael C. , Okura Takafumi , Higaki Jitsuo , Graf Kristof , Fleck Eckart , Hsueh Willa A. , Law Ronald E.
Published: July 2004

Background—

Accumulating evidence suggests that C-reactive protein (CRP), in addition to being a predictor of coronary events, may have direct actions on the vessel wall in the evolution of atherosclerosis. Although accumulation of vascular smooth muscle cells (VSMCs) in the intima is a key event in the development of arterial lesions, apoptosis of VSMCs also plays an important role in progression of atherosclerotic lesions and contributes to increased plaque vulnerability.

Methods and Results—

In the present study we demonstrate that CRP induces caspase-mediated apoptosis of human coronary VSMCs. DNA microarray analysis was used to identify CRP-regulated genes. The growth arrest– and DNA damage–inducible gene 153 (GADD153) mRNA expression was prominently upregulated by CRP. As confirmed by Northern blot analysis, CRP induced a time- and dose-dependent increase of GADD153 mRNA expression. GADD153, a gene involved in growth arrest and apoptosis in vascular and nonvascular cells, is regulated at both transcriptional and posttranscriptional levels. CRP regulation of GADD153 mRNA expression in VSMCs occurs primarily at the posttranscriptional level by mRNA stabilization. Small interfering RNA (siRNA) specifically targeted to GADD153 reduced CRP-induced apoptosis. GADD153 also specifically colocalized to apoptotic VSMCs in human coronary lesions, further supporting a functional role for GADD153 in CRP-induced cell death.

Conclusions—

These results demonstrate that GADD153 is a CRP-regulated gene in human VSMCs and plays a causal role in CRP-induced apoptosis. Pharmacological targeting of CRP expression or action may provide a novel therapy for atherosclerosis.
Morphology of Atrial Myocardial Extensions Into Human Caval Veins
Authors: Kholová Ivana , Kautzner Josef
Published: July 2004

Background—

Atrial fibrillation (AF) may be triggered from arrhythmogenic foci originating from atrial muscular sleeves that extend into the caval veins (CVs). The aim of this anatomic study was to evaluate both the extent and arrangement of atrial myocardial fibers in CVs in subjects with and without a history of AF.

Methods and Results—

Twenty-five human autopsied hearts (15 men; mean age, 65.5±12 years; range, 39 to 80 years) were studied. Seven subjects had a previous history of AF. The presence and morphology of atrial myocardial extensions were studied microscopically in both CVs. Such extensions were found in 38 of 50 CVs (76%). Their average length in the superior vena cava reached 13.7±13.9 mm (maximum, up to 47 mm) and in the inferior vena cava, 14.6±16.7 mm (maximum, up to 61 mm). The thickness of atrial myocardium extending into the CVs was 1.2±1.0 mm (maximum, 4 mm) for the superior vena cava and 1.2±0.9 mm for the inferior vena cava (maximum, 3 mm). The majority of myocardial extensions revealed discontinuous and circular patterns. Degenerative changes were found in approximately half of the subjects. There was no significant difference between patients with and without a history of AF.

Conclusions—

Atrial myocardial extensions into both CVs are present in the majority of human beings, both with and without a history of AF. The extensions are localized on the outer side of venous adventitia. Arrangement, length, and thickness of myocardial sleeves onto the CVs vary individually, and many of them contain degenerative changes.
Different Effects of Antihypertensive Therapies Based on Losartan or Atenolol on Ultrasound and Biochemical Markers of Myocardial Fibrosis
Authors: Ciulla Michele M. , Paliotti Roberta , Esposito Arturo , Dìez Javier , López Begoña , Dahlöf Björn , Nicholls M. Gary , Smith Ronald D. , Gilles Leen , Magrini Fabio , Zanchetti Alberto
Published: July 2004

Background—

In hypertensive left ventricular hypertrophy (LVH), myocardial texture is altered by a disproportionate increase in fibrosis, but there is insufficient clinical evidence whether antihypertensive therapy or individual agents can induce regression of myocardial fibrosis.

Methods and Results—

We compared the effects of an angiotensin II receptor antagonist with a β-blocker on myocardial collagen volume (assessed by echoreflectivity and serum collagen markers) in 219 hypertensive patients with echocardiographically documented LVH. Patients were allocated randomly to receive losartan 50 to 100 mg/d (n=111) or atenolol 50 to 100 mg/d (n=99) with or without hydrochlorothiazide 12.5 to 25 mg/d for 36 weeks. Echoreflectivity analysis was conducted on ultrasound tracings of the midapex septum with specifically designed and validated software. A color histogram of reflecting echoes was obtained, and its spread (broadband [BB], previously shown to correlate directly with collagen volume fraction on endomyocardial biopsies) was used as the primary outcome measure. Mean color scale and serum markers of collagen synthesis (PIP, PIIIP) or degradation (CITP) were secondary outcome variables. Echoreflectivity analysis proved feasible in 106 patients (losartan 52, atenolol 54). Losartan reduced BB over 36 weeks (from 114.5 to 104.3 color levels,
P
<0.02), whereas atenolol treatment was associated with an increase in BB (from 109.0 to 113.6 color levels,
P
=NS), the difference between treatments being −12.8 color levels (95% CI −23.6 to −2.0,
P
=0.02). Secondary end points (mean color scale and collagen markers) also changed in the direction of decreased collagen in patients receiving losartan, but differences between groups were not statistically significant.

Conclusions—

In hypertensive patients with LVH, losartan decreases myocardial collagen content, whereas atenolol does not. The difference between the 2 treatments is statistically significant.
Modern Pacemaker and Implantable Cardioverter/Defibrillator Systems Can Be Magnetic Resonance Imaging Safe
Authors: Roguin Ariel , Zviman Menekhem M. , Meininger Glenn R. , Rodrigues E. Rene , Dickfeld Timm M. , Bluemke David A. , Lardo Albert , Berger Ronald D. , Calkins Hugh , Halperin Henry R.
Published: July 2004

Background—

MRI has unparalleled soft-tissue imaging capabilities. The presence of devices such as pacemakers and implantable cardioverter/defibrillators (ICDs), however, is historically considered a contraindication to MRI. These devices are now smaller, with less magnetic material and improved electromagnetic interference protection. Our aim was to determine whether these modern systems can be used in an MR environment.

Methods and Results—

We tested in vitro and in vivo lead heating, device function, force acting on the device, and image distortion at 1.5 T. Clinical MR protocols and in vivo measurements yielded temperature changes <0.5°C. Older (manufactured before 2000) ICDs were damaged by the MR scans. Newer ICD systems and most pacemakers, however, were not. The maximal force acting on newer devices was <100 g. Modern (manufactured after 2000) ICD systems were implanted in dogs (n=18), and after 4 weeks, 3- to 4-hour MR scans were performed (n=15). No device dysfunction occurred. The images were of high quality with distortion dependent on the scan sequence and plane. Pacing threshold and intracardiac electrogram amplitude were unchanged over the 8 weeks, except in 1 animal that, after MRI, had a transient (<12 hours) capture failure. Pathological data of the scanned animals revealed very limited necrosis or fibrosis at the tip of the lead area, which was not different from controls (n=3) not subjected to MRI.

Conclusions—

These data suggest that certain modern pacemaker and ICD systems may indeed be MRI safe. This may have major clinical implications for current imaging practices.
Distal Protection With a Filter Device During Coronary Stenting in Patients With Stable and Unstable Angina
Authors: Angelini Annalisa , Rubartelli Paolo , Mistrorigo Flavio , Della Barbera Mila , Abbadessa Francesco , Vischi Massimo , Thiene Gaetano , Chierchia Sergio
Published: July 2004

Background—

Filter protection after percutaneous coronary intervention (PCI) is now available to prevent distal embolization. The aims of this study were (1) to evaluate the microembolization phenomenon during procedures of stent implantation in native coronary arteries of patients with stable and unstable angina, (2) to assess the amount and characteristics of the debris captured by the Angioguard, and (3) to investigate the relation between clinical and angiographic variables and pathological data.

Methods and Results—

Elective coronary stenting with the use of a protective filter was attempted in 39 consecutive coronary artery lesions with >60% stenosis (mean, 67.6±8.79%). Debris was present in 75.6% of the filters. Particle size ranged from 47.16 to 2503.48 μm (mean, 518.83±319.61 μm) in the major axis. Particles >300 μm were found in 24 of 28 filters with debris (85.7%), and particles >1000 μm were present in 10 of 28 filters (35.7%). Patients with unstable angina had greater particles (mean maximum longitudinal diameter, 1098.33±714.3 μm) than those with stable angina (412.91±453 μm;
P
<0.001). The presence of unstable angina (OR, 65; CI, 1.2 to 3420;
P
=0.03) and age >67 years (OR, 42; CI, 1 to 1698;
P
=0.04) were found to be the only independent predictors of embolic particle size.

Conclusions—

By limiting embolization, protective devices may prevent a number of potentially unfavorable events, thereby improving outcome. Our data support the use of these devices, especially in lesions with higher embolic potential, such as those occurring in older patients and in those with unstable angina.
Inhibition of Diet-Induced Atherosclerosis and Endothelial Dysfunction in Apolipoprotein E/Angiotensin II Type 1A Receptor Double-Knockout Mice
Authors: Wassmann Sven , Czech Thomas , van Eickels Martin , Fleming Ingrid , Böhm Michael , Nickenig Georg
Published: July 2004

Background—

Angiotensin II type 1 (AT1) receptor activation is potentially involved in the multifactorial pathogenesis of atherosclerosis.

Methods and Results—

Apolipoprotein E–deficient (ApoE
−/−
) mice were crossed with AT1A receptor–deficient (AT1
−/−
) mice to obtain homozygous double-knockout animals (ApoE
−/−
-AT1
−/−
mice). Wild-type (C57BL/6J), ApoE
−/−
, AT1
−/−
, and ApoE
−/−
-AT1
−/−
mice were fed a high-cholesterol diet for 7 weeks. In contrast to wild-type and AT1
−/−
mice, this treatment led to severe atherosclerotic lesion formation in the aortic sinus and the aorta (oil red O staining) and to an impaired endothelium-dependent vasodilation (organ chamber experiments with isolated aortic segments) in ApoE
−/−
mice. In the age-matched ApoE
−/−
-AT1
−/−
littermates, development of diet-induced endothelial dysfunction and atherosclerotic lesion formation was profoundly inhibited. Concomitantly, aortic release of superoxide radicals was increased 2-fold in ApoE
−/−
mice compared with wild-type animals, whereas aortic superoxide production was normalized in ApoE
−/−
-AT1
−/−
mice (L-012 chemiluminescence). There were no significant differences in plasma cholesterol levels between ApoE
−/−
and ApoE
−/−
-AT1
−/−
animals. Systolic blood pressure was significantly lower in ApoE
−/−
-AT1
−/−
animals than in ApoE
−/−
mice (tail-cuff measurements). Oral treatment of ApoE
−/−
mice with either hydralazine or irbesartan reduced systolic blood pressure to the same level; however, only AT1 receptor antagonist treatment reduced atherosclerotic lesion formation and improved endothelial function.

Conclusions—

Genetic disruption of the AT1A receptor leads to inhibition of vascular oxidative stress, endothelial dysfunction, and atherosclerotic lesion formation in ApoE
−/−
mice irrespective of blood pressure and plasma cholesterol levels. These results indicate a fundamental role of AT1 receptor activation in atherogenesis.
Occupational, Commuting, and Leisure-Time Physical Activity in Relation to Total and Cardiovascular Mortality Among Finnish Subjects With Type 2 Diabetes
Authors: Hu Gang , Eriksson Johan , Barengo Noël C. , Lakka Timo A. , Valle Timo T. , Nissinen Aulikki , Jousilahti Pekka , Tuomilehto Jaakko
Published: July 2004

Background—

Some previous studies have assessed the association between leisure-time physical activity and mortality among patients with diabetes, but the potential effect of occupational and commuting physical activity remains uncertain.

Methods and Results—

We prospectively followed up 3316 Finnish participants 25 to 74 years of age with type 2 diabetes. The association of different types of physical activity with mortality was examined with Cox proportional-hazard models. During a mean follow-up of 18.4 years, 1410 deaths were recorded, 903 of which were due to cardiovascular disease (CVD). The multivariate-adjusted (age, sex, study year, body mass index, systolic blood pressure, cholesterol, smoking, and the 2 other types of physical activity) hazard ratios associated with light, moderate, and active work were 1.00, 0.86, and 0.60 (
P
trend
<0.001) for total mortality and 1.00, 0.91, and 0.60 (
P
trend
<0.001) for CVD mortality, respectively. The multivariate-adjusted hazard ratios associated with low, moderate, and high leisure-time physical activity were 1.00, 0.82, and 0.71 (
P
trend
<0.001) for total mortality and 1.00, 0.83, and 0.67 (
P
trend
=0.005) for CVD mortality, respectively. Active commuting had significant inverse associations with total and CVD mortality, but these relations were no longer significant after additional adjustment for occupational and leisure-time physical activity.

Conclusions—

Moderate or high levels of physical activity reduce total and CVD mortality among patients with type 2 diabetes. Not only leisure-time physical activity but also occupational and commuting physical activities are important components of a healthy lifestyle among patients with diabetes.
Carotid Plaque Echolucency Increases the Risk of Stroke in Carotid Stenting
Authors: Biasi Giorgio M. , Froio Alberto , Diethrich Edward B. , Deleo Gaetano , Galimberti Stefania , Mingazzini Paolo , Nicolaides Andrew N. , Griffin Maura , Raithel Dieter , Reid Donald B. , Valsecchi Maria Grazia
Published: July 2004

Background—

Carotid artery stenting (CAS) has recently emerged as a potential alternative to carotid endarterectomy. Cerebral embolization is the most devastating complication of CAS, and the echogenicity of carotid plaque has been indicated as one of the risk factors involved. This is the first study to analyze the role of a computer-assisted highly reproducible index of echogenicity, namely the gray-scale median (GSM), on the risk of stroke during CAS.

Methods and Results—

The Imaging in Carotid Angioplasty and Risk of Stroke (ICAROS) registry included 418 cases of CAS collected from 11 international centers. An echographic evaluation of carotid plaque with GSM measurement was made preprocedurally. The onset of neurological deficits during the procedure and the postprocedural period was recorded. The overall rate of neurological complications was 3.6%: minor strokes, 2.2%, and major stroke, 1.4%. There were 11 of 155 strokes (7.1%) in patients with GSM ≤25 and 4 of 263 (1.5%) in patients with GSM >25 (
P
=0.005). Patients with severe stenosis (≥85%) had a higher rate of stroke (
P
=0.03). The effectiveness of brain protection devices was confirmed in those with GSM >25 (
P
=0.01) but not in those with GSM ≤25. Multivariate analysis revealed that GSM (OR, 7.11;
P
=0.002) and rate of stenosis (OR, 5.76;
P
=0.010) are independent predictors of stroke.

Conclusions—

Carotid plaque echolucency, as measured by GSM ≤25, increases the risk of stroke in CAS. The inclusion of echolucency measured as GSM in the planning of any endovascular procedure of carotid lesions allows stratification of patients at different risks of complications in CAS.
Renal and Hormonal Effects of Water Deprivation in Late-Term Pregnant Rats
Authors: Salas Sofía P. , Giacaman Andrea , Vío Carlos P.
Published: July 2004

Water-retaining hormones are stimulated during pregnancy allowing normal volume expansion. Because pregnant rats actively retain water, we postulate that water deprivation (WD) would cause a greater reduction in plasma volume in pregnant than in nonpregnant rats. To test this hypothesis, Sprague-Dawley pregnant and nonpregnant rats were water-deprived for 48 hours. At day 19 of pregnancy, or in the corresponding day in nonpregnant rats, they were randomly assigned to either a WD or a control (C) pair-fed group (n=10 to 12 per group). WD significantly reduced body weight, food intake, and creatinine clearance, and increased urinary osmolality in nonpregnant and pregnant rats. WD reduced plasma volume in a similar proportion in nonpregnant and pregnant rats (nonpregnant rats C=13.1±0.4, WD=11.0±0.2; pregnant rats C=19.4±0.7, WD=16.8±0.5 mL,
P
<0.001). Both groups of pregnant rats had a similar reduction in blood pressure. Plasma renin activity (nonpregnant rats C=6.1±1.1, WD=20.5±2.0; pregnant rats C=49±9.7, WD=94±12 ng angiotensin I/mL per hour,
P
<0.001) and plasma aldosterone levels were increased by pregnancy and further increased by WD. WD significantly reduced urinary kallikrein. WD caused a significant reduction in fetal but not placental weights. Present data indicate that 48-hour WD reduced renal kallikrein and further stimulated water-retaining hormones. We speculate that these are compensatory changes contributing to the maintenance of pregnancy in response to WD.
Disruption of Ultradian and Circadian Rhythms of Blood Pressure in Nondipper Hypertensive Patients
Authors: Perez-Lloret Santiago , Aguirre Alejandro García , Cardinali Daniel P. , Toblli Jorge E.
Published: July 2004

Ultradian rhythms in blood pressure (BP) are known to exist, but their modification in hypertension is largely unknown. The present study was undertaken to assess the integrity of ultradian and 24-hour BP rhythms in dipper (n=100) and nondipper (n=20) hypertensive patients compared with 44 dipper normotensive individuals. Fourier analysis was used to fit ultradian (12, 8, and 6 hour) and 24-hour rhythms in BP and heart rate (HR). Mesor, amplitude, and acrophase were calculated for individual and overall rhythm curves. All subjects showed significant ultradian or 24-hour BP and HR rhythms. Systolic and diastolic BP mesor was higher in hypertensive patients compared with normotensive patients. The percentage of variability in ambulatory BP that could be explained by fitting ultradian and 24-hour rhythms was reduced in nondippers compared with normotensives or dippers. Amplitude of ultradian and 24-hour rhythms in BP increased in dippers and decreased in nondippers. Ultradian and 24-hour rhythms in HR did not differ among the 3 groups examined. Results indicate that in nondippers, blunted ultradian and 24-hour rhythm amplitude in BP was accompanied by a loss of rhythm integrity.
Lepirudin for prophylaxis of thrombosis in patients with acute isolated heparin-induced thrombocytopenia: an analysis of 3 prospective studies
Authors: Lubenow Norbert , Eichler Petra , Lietz Theresia , Farner Beate , Greinacher Andreas
Published: July 2004

This analysis of 3 prospective multicenter trials in patients with laboratory-confirmed acute heparin-induced thrombocytopenia (HIT) without clinically evident thromboembolic complications (TECs), isolated HIT, assessed the combined individual end points of death, new TECs, and limb amputation. Patients with the same inclusion criteria who did not receive lepirudin or danaparoid served as a contemporaneous control group. Ninety-one patients were treated with lepirudin (intravenous infusion 0.10 mg/kg/h, no bolus, activated partial thromboplastin time [aPTT]–adjusted to 1.5-2.5 times baseline) for a median of 11.0 days (range, 1-68 days). During the observation period (median 24 days), 13 (14.3%) deaths, 4 (4.4%) new TECs, 3 (3.3%) limb amputations (combined 18 [19.8%]), and 13 (14.3%) major bleeding events occurred. In comparison to the control group (N = 47), the combined end point (P = .0281) and new TECs (P = .02) were reduced, and major bleeding was not significantly different between groups (P = .5419). In renal impairment, lepirudin did not reach its steady state within 4 hours, and additional monitoring every 4 hours after start of lepirudin until steady state is reached is recommended. Lepirudin seems to be effective in patients with isolated HIT. Dose reductions in renal impairment are important. Keeping the aPTT in the range corresponding to 600 to 700 μg/L lepirudin during treatment may minimize bleeding complications.
Peripheral blood stem cell transplantation in 16 patients with POEMS syndrome, and a review of the literature
Authors: Dispenzieri Angela , Moreno-Aspitia Alvaro , Suarez Guillermo A. , Lacy Martha Q. , Colon-Otero Gerardo , Tefferi Ayalew , Litzow Mark R. , Roy Vivek , Hogan William J. , Kyle Robert A. , Gertz Morie A.
Published: July 2004

POEMS syndrome is characterized by peripheral neuropathy (PN), a clonal plasma cell disorder (PCD), organomegaly, endocrinopathy, skin changes, edema, sclerotic bone lesions, and thrombocytosis. Based on the improved response rates observed with peripheral blood stem cell transplantation (PBSCT) in patients with other PCDs, autologous PBSCT may be an attractive treatment option for this syndrome. Sixteen patients with POEMS syndrome have undergone PBSCT at Mayo. Of these patients, 15 had a severe rapidly progressive sensorimotor PN (9 were wheelchair dependent) and 14 were male. Median age was 51 years (range, 19-62 years). The median number of prior therapies was 3 (range, 0-7). From first symptoms and from diagnosis of POEMS the times to transplantation were 42 months and 5 months (ranges, 8-185 months and 2-149 months), respectively. There were 15 patients who had significantly abnormal pretransplant pulmonary function tests. There was one transplant-related death. During the peritransplant period, 5 patients required intubation for respiratory compromise, including one who required intubation during his stem cell mobilization period. Another patient required noninvasive biphasic positive airway pressure throughout his course. Of the 14 evaluable patients, all have had neurologic improvement or stabilization. Other features have improved substantially. PBSCT for POEMS syndrome is effective therapy but may also be associated with significant morbidity. (Blood. 2004;104:3400-3407)
In vivo clearance of surfactant lipids during acute pulmonary inflammation.
Authors: Malloy Jaret L , Wright Jo Rae
Published: July 2004

Background

A decrease in pulmonary surfactant has been suggested to contribute to the lung dysfunction associated with pulmonary inflammation. A number of studies have implicated surfactant clearance as a possible mechanism for altered pool sizes. The objective of the current study was to specifically investigate the mechanisms of surfactant clearance in a rodent model of acute pulmonary inflammation.

Methods

Inflammation was induced by intrapulmonary instillation of lipopolysaccharide (LPS: 100 μg/kg). Lipid clearance was assessed at 18 and 72 hours post-LPS instillation by intratracheal administration of radiolabel surfactant-like liposomes 2 hours prior to isolation and analysis of inflammatory cells and type II cells.

Results

At both 18 and 72 hours after LPS instillation there was significantly less radioactivity recovered in the lavage fluid compared to respective control groups (p < 0.05). At both time points, the number of cells recovered by lavage and their associated radioactivity was greater compared to control groups (p < 0.01). There was no difference in recovery of radioactivity by isolated type II cells or other cells obtained from enzymatic digestion of lung tissue.

Conclusion

These results show that increased clearance of surfactant lipids in our model of acute pulmonary inflammation is primarily due to the inflammatory cells recruited to the airspace and not increased uptake by alveolar type II cells.
Graph-based iterative Group Analysis enhances microarray interpretation
Authors: Breitling Rainer , Amtmann Anna , Herzyk Pawel
Published: July 2004

Background

One of the most time-consuming tasks after performing a gene expression experiment is the biological interpretation of the results by identifying physiologically important associations between the differentially expressed genes. A large part of the relevant functional evidence can be represented in the form of graphs, e.g. metabolic and signaling pathways, protein interaction maps, shared GeneOntology annotations, or literature co-citation relations. Such graphs are easily constructed from available genome annotation data. The problem of biological interpretation can then be described as identifying the subgraphs showing the most significant patterns of gene expression. We applied a graph-based extension of our iterative Group Analysis (iGA) approach to obtain a statistically rigorous identification of the subgraphs of interest in any evidence graph.

Results

We validated the Graph-based iterative Group Analysis (GiGA) by applying it to the classic yeast diauxic shift experiment of DeRisi et al., using GeneOntology and metabolic network information. GiGA reliably identified and summarized all the biological processes discussed in the original publication. Visualization of the detected subgraphs allowed the convenient exploration of the results. The method also identified several processes that were not presented in the original paper but are of obvious relevance to the yeast starvation response.

Conclusions

GiGA provides a fast and flexible delimitation of the most interesting areas in a microarray experiment, and leads to a considerable speed-up and improvement of the interpretation process.
Accuracy of cDNA microarray methods to detect small gene expression changes induced by neuregulin on breast epithelial cells
Authors: Yao Bin , Rakhade Sanjay N , Li Qunfang , Ahmed Sharlin , Krauss Raul , Draghici Sorin , Loeb Jeffrey A
Published: July 2004

Background

cDNA microarrays are a powerful means to screen for biologically relevant gene expression changes, but are often limited by their ability to detect small changes accurately due to "noise" from random and systematic errors. While experimental designs and statistical analysis methods have been proposed to reduce these errors, few studies have tested their accuracy and ability to identify small, but biologically important, changes. Here, we have compared two cDNA microarray experimental design methods with northern blot confirmation to reveal changes in gene expression that could contribute to the early antiproliferative effects of neuregulin on MCF10AT human breast epithelial cells.

Results

We performed parallel experiments on identical samples using a dye-swap design with ANOVA and an experimental design that excludes systematic biases by "correcting" experimental/control hybridization ratios with control/control hybridizations on a spot-by-spot basis. We refer to this approach as the "control correction method" (CCM). Using replicate arrays, we identified a decrease in proliferation genes and an increase in differentiation genes. Using an arbitrary cut-off of 1.7-fold and p values <0.05, we identified a total of 32 differentially expressed genes, 9 with the dye-swap method, 18 with the CCM, and 5 genes with both methods. 23 of these 32 genes were subsequently verified by northern blotting. Most of these were <2-fold changes. While the dye-swap method (using either ANOVA or Bayesian analysis) detected a smaller number of genes (14–16) compared to the CCM (46), it was more accurate (89–92% vs. 75%). Compared to the northern blot results, for most genes, the microarray results underestimated the fold change, implicating the importance of detecting these small changes.

Conclusions

We validated two experimental design paradigms for cDNA microarray experiments capable of detecting small (<2-fold) changes in gene expression with excellent fidelity that revealed potentially important genes associated with the anti-proliferative effects of neuregulin on MCF10AT breast epithelial cells.
The six-minute walk test in community dwelling elderly: influence of health status.
Authors: Bautmans Ivan , Lambert Margareta , Mets Tony
Published: July 2004

Background

The 6 minutes walk test (6MWT) is a useful assessment instrument for the exercise capacity of elderly persons. The impact of the health status on the 6MWT-distance in elderly, however, remains unclear, reducing its value in clinical settings. The objective of this study was to investigate to what extent the 6MWT-distance in community dwelling elderly is determined by health conditions.

Methods

One hundred and fifty-six community dwelling elderly people (53 male, 103 female) were assessed for health status and performed the 6MWT. After clinical evaluation, electrocardiography and laboratory examination participants were categorized into a stratified six-level classification system according to their health status, going from A (completely healthy) to D (signs of active disease at the moment of examination).

Results

The mean 6MWT-distance was 603 m (SD = 178). The 6MWT-distance decreased significantly with increasing age (ANOVA p = 0.0001) and with worsening health status (ANCOVA, corrected for age p < 0.001).

A multiple linear regression model with health status, age and gender as independent variables explained 31% of the 6MWT-distance variability. Anthropometrical measures (stature, weight and BMI) did not significantly improve the prediction model. A significant relationship between 6MWT-distance and stature was only present in category A (completely healthy).

Conclusions

Significant differences in 6MWT-distance are observed according to health status in community-dwelling elderly persons. The proposed health categorizing system for elderly people is able to distinguish persons with lower physical exercise capacity and can be useful when advising physical trainers for seniors.
Caveolin-2 associates with intracellular chlamydial inclusions independently of caveolin-1
Authors: Webley Wilmore C , Norkin Leonard C , Stuart Elizabeth S
Published: July 2004

Background

Lipid raft domains form in plasma membranes of eukaryotic cells by the tight packing of glycosphingolipids and cholesterol. Caveolae are invaginated structures that form in lipid raft domains when the protein caveolin-1 is expressed. The Chlamydiaceae are obligate intracellular bacterial pathogens that replicate entirely within inclusions that develop from the phagocytic vacuoles in which they enter. We recently found that host cell caveolin-1 is associated with the intracellular vacuoles and inclusions of some chlamydial strains and species, and that entry of those strains depends on intact lipid raft domains. Caveolin-2 is another member of the caveolin family of proteins that is present in caveolae, but of unknown function.

Methods

We utilized a caveolin-1 negative/caveolin-2 positive FRT cell line and laser confocal immunofluorescence techniques to visualize the colocalization of caveolin-2 with the chlamydial inclusions.

Results

We show here that in infected HeLa cells, caveolin-2, as well as caveolin-1, colocalizes with inclusions of C. pneumoniae (Cp), C. caviae (GPIC), and C. trachomatis serovars E, F and K. In addition, caveolin-2 also associates with C. trachomatis serovars A, B and C, although caveolin-1 did not colocalize with these organisms. Moreover, caveolin-2 appears to be specifically, or indirectly, associated with the pathogens at the inclusion membranes. Using caveolin-1 deficient FRT cells, we show that although caveolin-2 normally is not transported out of the Golgi in the absence of caveolin-1, it nevertheless colocalizes with chlamydial inclusions in these cells. However, our results also show that caveolin-2 did not colocalize with UV-irradiated Chlamydia in FRT cells, suggesting that in these caveolin-1 negative cells, pathogen viability and very likely pathogen gene expression are necessary for the acquisition of caveolin-2 from the Golgi.

Conclusion

Caveolin-2 associates with the chlamydial inclusion independently of caveolin-1. The function of caveolin-2, either in the uninfected cell or in the chlamydial developmental cycle, remains to be elucidated. Nevertheless, this second caveolin protein can now be added to the small number of host proteins that are associated with the inclusions of this obligate intracellular pathogen.
Stimulation of MMP-11 (stromelysin-3) expression in mouse fibroblasts by cytokines, collagen and co-culture with human breast cancer cell lines
Authors: Selvey Saxon , Haupt Larisa M , Thompson Erik W , Matthaei Klaus I , Irving Michael G , Griffiths Lyn R
Published: July 2004

Background

Matrix metalloproteinases (MMPs) are central to degradation of the extracellular matrix and basement membrane during both normal and carcinogenic tissue remodeling. MT1-MMP (MMP-14) and stromelysin-3 (MMP-11) are two members of the MMP family of proteolytic enzymes that have been specifically implicated in breast cancer progression. Expressed in stromal fibroblasts adjacent to epithelial tumour cells, the mechanism of MT1-MMP and MMP-11 induction remains unknown.

Methods

To investigate possible mechanisms of induction, we examined the effects of a number of plausible regulatory agents and treatments that may physiologically influence MMP expression during tumour progression. Thus NIH3T3 and primary mouse embryonic fibroblasts (MEFs) were: a) treated with the cytokines IL-1β, IL-2, IL-6, IL-8 and TGF-β for 3, 6, 12, 24, and 48 hours; b) grown on collagens I, IV and V; c) treated with fibronectin, con-A and matrigel; and d) co-cultured with a range of HBC (human breast cancer) cell lines of varied invasive and metastatic potential.

Results

Competitive quantitative RT-PCR indicated that MMP-11 expression was stimulated to a level greater than 100%, by 48 hour treatments of IL-1β, IL-2, TGF-β, fibronectin and collagen V. No other substantial changes in expression of MMP-11 or MT1-MMP in either tested fibroblast culture, under any treatment conditions, were observed.

Conclusion

We have demonstrated significant MMP-11 stimulation in mouse fibroblasts using cytokines, matrix constituents and HBC cell lines, and also some inhibition of MT1-MMP. Our data suggest that the regulation of these genes in the complex stromal-epithelial interactions that occur in human breast carcinoma, is influenced by several mechanisms.