bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Age and Gender on the Dysphonia Severity Index
Authors: Hakkesteegt Marieke M. , Brocaar Michael P. , Wieringa Marjan H. , Feenstra Louw
Published: July 2006

Attempts have been made to find objective parameters for assessing voice quality for many years. Objective measurements such as the dysphonia severity index (DSI), using four parameters (highest frequency, lowest intensity, maximum phonation time and jitter), appear to correlate well with perceptual evaluation. The aim of this study was to investigate the influence, if any, of age and gender on the DSI. The DSI of 118 non-smoking adults (69 females, 49 males, age range 20–79 years) without voice complaints was measured. Age has a significant effect on the DSI and on its parameters highest frequency and lowest intensity (only in females). Gender has no effect on the DSI, although it has a significant effect on the parameters highest frequency and maximum phonation time. To be able to distinguish between the effects of (normal) ageing and a voice disorder, normative data of a wide age range are essential. As a result of this study normative DSI values for gender and age have been made available.
Chromosome organization and chromatin modification: influence on genome function and evolution
Authors: Holmquist G.P. , Ashley T.
Published: July 2006

Histone modifications of nucleosomes distinguish euchromatic from heterochromatic chromatin states, distinguish gene regulation in eukaryotes from that of prokaryotes, and appear to allow eukaryotes to focus recombination events on regions of highest gene concentrations. Four additional epigenetic mechanisms that regulate commitment of cell lineages to their differentiated states are involved in the inheritance of differentiated states, e.g., DNA methylation, RNA interference, gene repositioning between interphase compartments, and gene replication time. The number of additional mechanisms used increases with the taxon’s somatic complexity. The ability of siRNA transcribed from one locus to target, in trans, RNAi-associated nucleation of heterochromatin in distal, but complementary, loci seems central to orchestration of chromatin states along chromosomes. Most genes are inactive when heterochromatic. However, genes within β-heterochromatin actually require the heterochromatic state for their activity, a property that uniquely positions such genes as sources of siRNA to target heterochromatinization of both the source locus and distal loci. Vertebrate chromosomes are organized into permanent structures that, during S-phase, regulate simultaneous firing of replicon clusters. The late replicating clusters, seen as G-bands during metaphase and as meiotic chromomeres during meiosis, epitomize an ontological utilization of all five self-reinforcing epigenetic mechanisms to regulate the reversible chromatin state called facultative (conditional) heterochromatin. Alternating euchromatin/heterochromatin domains separated by band boundaries, and interphase repositioning of G-band genes during ontological commitment can impose constraints on both meiotic interactions and mammalian karyotype evolution.
Isolation and functional analysis of human HMBOX1, a homeobox containing protein with transcriptional repressor activity
Authors: Chen S. , Saiyin H. , Zeng X. , Xi J. , Liu X. , Li X. , Yu L.
Published: July 2006

We have identified and isolated a novel human gene, HMBOX1 (homeobox containing 1) from a pancreatic cDNA library. Human HMBOX1 is widely expressed in 18 tissues, and it is highly expressed in pancreas. According to the genome database, HMBOX1 is located at the boundary of 8p12.3 and 8p21.1. HMBOX1 proteins are highly conserved in human, mouse, rat, chicken and Xenopus laevis. A phylogenetic tree shows that HMBOX1 may represent a distinct group in HNF (Hepatocyte Nuclear Factor) transcriptional factors. Functional HMBOX1::EGFP (enhanced green fluorescent protein) fusion protein revealed that HMBOX1 accumulated more in cytoplasm than in nucleus. Co-transfection of HEK-293T cells with pM-HMBOX1 plasmid and reporter plasmid pGAL45tkLUC indicates that HMBOX1 is a transcription repressor. In situ hybridization on paraffin sections of mouse tissues demonstrated that Hmbox1 is widely expressed in pancreas and the expression of this gene can also be detected in pallium, hippocampus and hypothalamus.
Physical organization of the 1.709 satellite IV DNA family in Bovini and Tragelaphini tribes of the Bovidae: sequence and chromosomal evolution
Authors: Adega F. , Chaves R. , Guedes-Pinto H. , Heslop-Harrison J.S.
Published: July 2006

Repetitive DNA in the mammalian genome is a valuable record and marker for evolution, providing information about the order and driving forces related to evolutionary events. The evolutionarily young 1.709 satellite IV DNA family is present near the centromeres of many chromosomes in the Bovidae. Here, we isolated 1.709 satellite DNA sequences from five Bovidae species belonging to Bovini: Bos taurus (BTA, cattle), Bos indicus (BIN, zebu), Bubalus bubalis (BBU, water buffalo) and Tragelaphini tribes: Taurotragus oryx (TOR, eland) and Tragelaphus euryceros (TEU, bongo). Its presence in both tribes shows the sequence predates the evolutionary separation of the two tribes (more than 10 million years ago), and primary sequence shows increasing divergence with evolutionary distance. Genome organization (Southern hybridization) and physical distribution (in situ hybridization) revealed differences in the molecular organization of these satellite DNA sequences. The data suggest that the sequences on the sex chromosomes and the autosomes evolve as relatively independent groups, with the repetitive sequences suggesting that Bovini autosomes and the Tragelaphini sex chromosomes represent the more primitive chromosome forms.
Mobile Telephones and Rates of Brain Cancer
Authors: Muscat Joshua E. , Hinsvark Michelle , Malkin Mark
Published: July 2006

The risk of most primary brain cancers including gliomas and acoustic neuromas is unrelated to the use of mobile telephones in several studies. The long-term effects of mobile phones remain to be determined. An increased risk caused by short-term mobile phone use was reported for neuroepithelial tumors, a rare histologic subgroup of brain cancers that are characterized by neuronal features.We analyzed time trends in the age-adjusted incidence rate of adult neuronal cancers in the Surveillance, Epidemiology and End Results program from 1973 to 2002. The rates did not change during this period, despite the exponential increase in mobile phone subscriptions starting in 1984. These results indicate that mobile phone use is unrelated to the risk of neuronal cancers.
State of the Art Percutaneous Intervention for the Treatment of Valvular Heart Disease: A Review of the Current Technologies and Ongoing Research in the Field of Percutaneous Valve Replacement and Repair
Authors: Babaliaros Vasilis , Block Peter
Published: July 2006

Technical developments in valvular intervention culminated in the first percutaneous valve replacement in the pulmonary position (2000) followed by replacement in the aortic position (2002). More recently, with the proven feasibility of percutaneous mitral valve repair, interventional cardiologists and cardiothoracic surgeons have begun to develop a new subspecialty dedicated to the percutaneous treatment of valvular disease. This review describes the clinical status of the current field, the applicability and limitations of new technologies, and the upcoming devices that will soon reach Phase I clinical trials.
Flow-Associated Dilatory Capacity of the Brachial Artery Is Intact in Early Autosomal Dominant Polycystic Kidney Disease
Authors: Clausen Peter , Feldt-Rasmussen Bo , Iversen Jens , Lange Martin , Eidemak Inge , Strandgaard Svend
Published: July 2006

Background/Aims: Autosomal dominant polycystic kidney disease is associated with endothelial dysfunction of resistance arteries. This study tested whether endothelial dysfunction is also present in the conduit arteries in patients with preserved renal function. Methods:Twenty-seven patients (9 females and 18 males, age 36 ± 10 years) with polycystic kidney disease and normal renal function were compared to 27 healthy controls. The dilatory responses of the brachial artery to postischemic increased blood flow [endothelium-dependent flow-associated dilatation (FAD)] and to nitroglycerin [endothelium-independent nitroglycerin-induced dilatation (NID)] were measured by external ultrasound. Plasma concentrations of the stable end products of nitric oxide nitrate/nitrite (NOx) and of the endothelial markers vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1, E-selectin and von Willebrand factor antigen were also measured. Results:No differences in FAD or NID were found between patients and controls (104.6 ± 4.2 vs. 105.3 ± 3.9%, mean ± SD, p = 0.55, and 117.0 ± 8.4 vs. 117.5 ± 7.6%, p = 0.75). However, the plasma concentration of VCAM-1 was elevated and the plasma concentration of NOx was reduced in patients with polycystic kidney disease. Conclusion: Biochemical markers confirm an association between polycystic kidney disease and endothelial dysfunction. However, a normal FAD of the brachial artery suggests that the endothelial dysfunction does not involve the conduit arteries.
Differences in Retinol Metabolism and Proliferative Response between Neointimal and Medial Smooth Muscle Cells
Authors: Gidlöf Andreas C. , Ocaya Pauline , Olofsson Peder S. , Törmä Hans , Sirsjö Allan
Published: July 2006

Vascular disease is multifactorial and smooth muscle cells (SMCs) play a key role. Retinoids have been shown to influence many disease-promoting processes including proliferation and differentiation in the vessel wall. Phenotypic heterogeneity of vascular SMCs is a well-known phenomenon and phenotypic modulation of SMCs precedes intimal hyperplasia. The SMCs that constitute the intimal hyperplasia demonstrate a distinct phenotype and differ in gene expression compared to medial SMCs. Cellular retinol-binding protein-1 (CRBP-I), involved in retinoid metabolism, is highly expressed in intimal SMCs, indicating altered retinoid metabolism in this subset of cells. The aim of this study was to evaluate the metabolism of all-trans ROH (atROH), the circulating prohormone to active retinoids, in vascular SMCs of different phenotypes. The results show an increased uptake of atROH in intimal SMCs compared to medial SMCs as well as increased expression of the retinoid-metabolizing enzymes retinol dehydrogenase-5 and retinal dehydrogenase-1 and, in conjunction with this gene expression, increased production of all-trans retinoic acid (atRA). Furthermore, the retinoic acid-catabolizing enzyme CYP26A1 is expressed at higher levels in medial SMCs compared to intimal SMCs. Thus, both retinoid activation and deactivation processes are in operation. To analyze if the difference in ROH metabolism was also correlated to differences in the biological response to retinol, the effects of ROH on proliferation of SMCs with this phenotypic heterogeneity were studied. We found that intimal SMCs showed a dose- and time-dependent growth inhibition when treated with atROH in contrast to medial SMCs, in which atROH had a mitogenic effect. This study shows, for the first time, that (1) vascular SMCs are able to synthesize biologically active atRA from the prohormone atROH, (2) intimal SMCs have a higher capacity to internalize atROH and metabolize atROH into atRA compared to medial SMCs and (3) atROH inhibits growth of intimal SMCs, but induces medial SMC growth.
Overexpression of Polo-Like Kinase 1 (PLK1) and Chromosomal Instability in Bladder Cancer
Authors: Yamamoto Yoshiaki , Matsuyama Hideyasu , Kawauchi Shigeto , Matsumoto Hiroaki , Nagao Kazuhiro , Ohmi Chietaka , Sakano Shigeru , Furuya Tomoko , Oga Atsunori , Naito Katsusuke , Sasaki Kohsuke
Published: July 2006

Polo-like kinase 1 (PLK1) participates in bipolar spindle formation and entry into mitosis. Chromosomal instability (CIN) is caused by abnormalities in spindle formation and chromosome segregation. In this study, we investigated the relationship of PLK1 overexpression to CIN, and compared the PLK1 status with clinicopathological parameters in 101 human urothelial carcinomas of the urinary bladder. Expression of PLK1 and the number of centrosomes were assessed by immunohistochemistry. Numerical aberrations of chromosomes 7, 9 and 17 spots that allowed estimation of CIN were evaluated by fluorescence in situhybridization, and DNA ploidy was assessed by laser scanning cytometry. Cancers with a large intercellular variation in centromere copy number were defined as CIN cancers.Tumors with PLK1 overexpression were associated more frequently with CIN (p < 0.0001), DNA aneuploidy (p = 0.0007) and centrosome amplification (p = 0.0013) than those without. Overexpression of PLK1 was significantly related to higher pathological grade (p = 0.0024), multiple tumors (p = 0.0241) and positive urine cytology (p = 0.0192). These data suggest that a high level expression of PLK1 confers tumor progression advantages to urothelial cancer cells, although other factors are also involved.
Matrix Metalloproteinase-2 and -9 Expression Correlated with Angiogenesis in Human Adenomyosis
Authors: Li Tian , Li Yun-Guang , Pu De-Min
Published: July 2006

Background: Adenomyosis is an important cause of dysmenorrhea and infertility for women all over the world, however, the pathogenesis has not been completely elucidated. The purpose of the study was to investigate the role of matrix metalloproteinases (MMPs) and their relation to angiogenesis in human adenomyosis. Methods: Adenomyotic endometrial specimens were removed by hysterectomy from 68 women with adenomyosis. The control group consisted of 26 normal endometrial specimens. Immunohistochemistry was used to demonstrate expression of MMP-2, -9, vascular endothelial growth factor (VEGF) and microvessel density (MVD). Staining intensity was analyzed by computerized image analysis system. Results: In both eutopic and ectopic endometrium of adenomyosis, the expression of MMP-2, -9 as well as VEGF was significantly greater than in normal endometrium (p < 0.05). MVD was higher in ectopic endometrium than eutopic endometrium with or without adenomyosis (p < 0.05). In adenomyosis, a positive correlation was observed between VEGF expression and MMP-2 (p < 0.001, r = 0.583) as well as MMP-9 expression (p = 0.002,r = 0.490). A positive correlation was also found between MVD and MMP-2 (p < 0.001,r = 0.589) or MMP-9 expression (p < 0.001,r = 0.589). Conclusion: Our results indicate that the elevation of MMP-2, -9 expression may have an important role in the development of adenomyosis, probably through contributing to invasion of endometrial tissues into the myometrium and angiogenesis in adenomyotic implants.
A Clinical and Laboratory Evaluation of Methionine Cycle-Transsulfuration and Androgen Pathway Markers in Children with Autistic Disorders
Authors: Geier David A. , Geier Mark R.
Published: July 2006

Background/Aims: The prevalence of autism spectrum disorders (ASDs) is 1 in 300 children in the US. ASDs are characterized by impairments in social relatedness and communication, repetitive behaviors, abnormal movement patterns, and sensory dysfunction. Pre-pubertal age children with ASDs were assessed for metabolites in the methionine cycle-transsulfuration and androgen pathways, and for present physical development/behaviors indicative of hyperandrogenicity. Methods: The Institutional Review Board of the Institute for Chronic Illnesses (Office for Human Research Protections, US Department of Health and Human Services IRB number: IRB00005375) approved the present study. Sixteen consecutive pre-pubertal age children (≤11 years old; mean ± SD: 5.9 ± 2.1 years old) with previously diagnosed ASDs that presented to the Genetic Centers of America for outpatient care were evaluated. Results: Significantly (p < 0.01) increased levels of serum/plasma dehydroepiandrosterone and serum total testosterone relative to the age- and sex-specific normal laboratory reference ranges were observed. Conversely, serum follicle-stimulating hormone levels were significantly (p < 0.01) decreased. Plasma-reduced glutathione (p < 0.01), plasma cysteine (p < 0.01), plasma methionine (p < 0.01), serum cystathionine (p < 0.05), and serum homocysteine (p < 0.01) were all significantly decreased. Conclusion: The results suggest a possible cyclical interaction between the methionine cycle-transsulfuration and androgen pathways in some children with ASDs.
Modulation of Adipose Tissue Development by Pharmacological Inhibition of PAI-1
Authors: Crandall David L. , Quinet Elaine M. , El Ayachi Soulaf , Hreha Amy L. , Leik Courtney E. , Savio Dawn A. , Juhan-Vague Irene , Alessi Marie-Christine
Published: July 2006

Objective—

The effect of a novel small molecule plasminogen activator inhibitor (PAI-1) inhibitor on adipose tissue physiology was investigated.

Methods and Results—

In human preadipocyte cultures, PAI-039 inhibited both basal and glucose-stimulated increases in active PAI-1 antigen, yet had no effect on PAI-1 mRNA, suggesting a direct inactivation of PAI-1. Differentiation of human preadipocytes to adipocytes was associated with leptin synthesis, which was significantly reduced in the presence of PAI-039, together with an atypical adipocyte morphology characterized by a reduction in the size and number of lipid containing vesicles. In a model of diet-induced obesity, pair-fed C57 Bl/6 mice administered PAI-039 in a high-fat diet exhibited a dose-dependent reduction in body weight, epididymal adipose tissue weight, adipocyte volume, and circulating plasma active PAI-1. Plasma glucose, triglycerides, and leptin were also significantly reduced in drug-treated mice, and concentrations of PAI-039 associated with these physiological effects were near the in vitro IC
50
for the inhibition of PAI-1.

Conclusions—

Our results indicate that a small molecule inactivator of PAI-1 can neutralize glucose-stimulated increases in PAI-1in human preadipocyte cultures, reduce adipocyte differentiation, and prevent the development of diet-induced obesity. These data suggest the pharmacological inhibition of PAI-1 could be beneficial in diseases associated with expansion of adipose tissue mass.
α-Tocopherol Modulates Phosphatidylserine Externalization in Erythrocytes
Authors: Klein Alexis , Deckert Valérie , Schneider Martina , Dutrillaux Fabienne , Hammann Arlette , Athias Anne , Le Guern Naig , Pais de Barros Jean-Paul , Desrumaux Catherine , Masson David , Jiang Xian-Cheng , Lagrost Laurent
Published: July 2006

Objective—

The aim of the present study was to assess the effect of α-tocopherol, the main vitamin E isomer on phosphatidylserine (PS) exposure at the surface of circulating erythrocytes, and to determine consequences on erythrocyte properties.

Methods and Results—

In vitro α-tocopherol enrichment of isolated erythrocytes significantly decreased PS externalization as assessed by lower Annexin V-fluorescein isothiocyanate labeling. Plasma phospholipid transfer protein (PLTP) transfers vitamin E, and both α-and γ-tocopherol accumulated in circulating erythrocytes from PLTP-deficient homozygous (PLTP
−/−
) mice as compared with wild-type mice. In agreement with in vitro studies, vitamin E–enriched erythrocytes from PLTP
−/−
mice displayed fewer externalized PS molecules than wild-type controls (−64%,
P
<0.05). The perturbation of phospholipid membrane asymmetry from PLTP
−/−
erythrocytes was accompanied by impairment of their procoagulant properties, with a 20% increase in clotting time as compared with wild-type controls (
P
<0.05). Less pronounced, however still significant, changes were observed in α-tocopherol content, procoagulant properties, and PS externalization in erythrocytes of PLTP-deficient heterozygotes. Finally, whole blood coagulation and circulating level of D-dimer, which reflects increased thrombus formation in vivo, were significantly decreased in PLTP
−/−
mice compared with wild-type mice.

Conclusions—

Vitamin E modifies PS externalization in circulating erythrocytes, thus modulating in vivo their PS-dependent procoagulant properties.
HSPA12B Is Predominantly Expressed in Endothelial Cells and Required for Angiogenesis
Authors: Steagall Rebecca J. , Rusiñol Antonio E. , Truong Quynh A. , Han Zhihua
Published: July 2006

Objective—HSPA12B is the newest member of HSP70 family of proteins and is enriched in atherosclerotic lesions. This study focused on HSPA12B expression in mice and its involvement in angiogenesis.

Methods and Results—The expression of HSPA12B in mice and cultured cells was studied by: (1) Northern blot; (2) in situ hybridization; (3) immunostaining with HSPA12B-specific antibodies; and (4) expressing Enhanced-Green-Fluorescent-Protein under the control of the HSPA12B promoter in mice. The function of HSPA12B was probed by an in vitro angiogenesis assay (Matrigel) and a migration assay. Interacting proteins were identified through a yeast two-hybrid screening. HSPA12B is predominantly expressed in vascular endothelium and induced during angiogenesis. In vitro angiogenesis and migration are inhibited in human umbilical vein endothelial cells in the presence of HSPA12B-neutralizing antibodies. HSPA12B interacts with multiple proteins in yeast 2-hybrid system.

Conclusions—We provide the first evidence to our knowledge that the HSPA12B is predominantly expressed in endothelial cells, required for angiogenesis, and interacts with known angiogenesis regulators. We postulate that HSPA12B provides a new mode of angiogenesis regulation and a novel therapeutic target for angiogenesis-related diseases.
Arrhythmogenesis in Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Liu Nian , Colombi Barbara , Memmi Mirella , Zissimopoulos Spyros , Rizzi Nicoletta , Negri Sara , Imbriani Marcello , Napolitano Carlo , Lai F. Anthony , Priori Silvia G.
Published: July 2006

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by life threatening arrhythmias and mutations in the gene encoding the ryanodine receptor (RyR2). Disagreement exists on whether (1) RyR2 mutations induce abnormal calcium transients in the absence of adrenergic stimulation; (2) decreased affinity of mutant RyR2 for FKBP12.6 causes CPVT; (3) K201 prevent arrhythmias by normalizing the FKBP12.6-RyR2 binding. We studied ventricular myocytes isolated from wild-type (WT) and knock-in mice harboring the R4496C mutation (RyR2
R4496C+/−
). Pacing protocols did not elicit delayed afterdepolarizations (DADs) (n=20) in WT but induced DADs in 21 of 33 (63%) RyR2
R4496C+/−
myocytes (
P
=0.001). Superfusion with isoproterenol (30 nmol/L) induced small DADs (45%) and no triggered activity in WT myocytes, whereas it elicited DADs in 87% and triggered activity in 60% of RyR2
R4496C+/−
myocytes (
P
=0.001). DADs and triggered activity were abolished by ryanodine (10 μmol/L) but not by K201 (1 μmol/L or 10 μmol/L). In vivo administration of K201 failed to prevent induction of polymorphic ventricular tachycardia (VT) in RyR2
R4496C+/−
mice. Measurement of the FKBP12.6/RyR2 ratio in the heavy sarcoplasmic reticulum membrane showed normal RyR2–FKBP12.6 interaction both in WT and RyR2
R4496C+/−
either before and after treatment with caffeine and epinephrine. We suggest that (1) triggered activity is the likely arrhythmogenic mechanism of CPVT; (2) K201 fails to prevent DADs in RyR2
R4496C+/−
myocytes and ventricular arrhythmias in RyR2
R4496C+/−
mice; and (3) RyR2–FKBP12.6 interaction in RyR2
R4496C+/−
is identical to that of WT both before and after epinephrine and caffeine, thus suggesting that it is unlikely that the R4496C mutation interferes with the RyR2/FKBP12.6 complex.
Pulsatile Myocardial Tubes Fabricated With Cell Sheet Engineering
Authors: Sekine Hidekazu , Shimizu Tatsuya , Yang Joseph , Kobayashi Eiji , Okano Teruo
Published: July 2006

Background—

Tissue engineering approaches involving the direct transplantation of cardiac patches have received significant attention as alternative methods for the treatment of damaged hearts. In contrast, we used cardiomyocyte sheets harvested from temperature-responsive culture dishes to create pulsatile myocardial tubes and examined their in vivo function and survival.

Methods and Results—

Neonatal rat cardiomyocyte sheets were sequentially wrapped around a resected adult rat thoracic aorta and transplanted in place of the abdominal aorta of athymic rats (n=17). Four weeks after transplantation, the myocardial tubes demonstrated spontaneous and synchronous pulsations independent of the host heartbeat. Independent graft pressures with a magnitude of 5.9±1.7 mm Hg due to their independent pulsations were also observed (n=4). Additionally, histological examination and transmission electron microscopy indicated that the beating tubes were composed of cardiac tissues that resemble the native heart. Finally, when myocardial tubes used for aortic replacement were compared with grafts implanted in the abdominal cavity (n=7), we observed significantly increased tissue thickness, as well as expression of brain natriuretic peptide, myosin heavy chain-α, and myosin heavy chain-β.

Conclusions—

Functional myocardial tubes that have the potential for circulatory support can be created with cell sheet engineering. These results also suggest that pulsation due to host blood flow within the lumen of the myocardial tubes has a profound effect on stimulating cardiomyocyte hypertrophy and growth. These results demonstrate a novel approach for the future development of engineered cardiac tissues with the ability for independent cardiac assistance.
S
2
Connector Versus Suture
Authors: Suyker Willem J.L. , Matonick John P. , Suyker Paul T.W. , Brutel de la Rivière Aart , Buijsrogge Marc P. , Budde Ricardo P.J. , Verlaan Cees W.J. , Pasterkamp Gerard , Gründeman Paul F. , Borst Cornelius
Published: July 2006

Background—

Anastomotic connectors could be the key to less invasive bypass surgery, including endoscopic procedures, but equivalence to conventional suturing needs to be established. A novel distal coronary connector was tested pre-clinically for safety and efficacy in comparison to conventional suturing.

Methods and Results—

Left internal thoracic to left anterior descending coronary artery bypasses were constructed off-pump in 35 pigs (73±8 kg). An intraluminal metal connector (S
2
AS) was used in 21 and conventional suturing in 14 animals. S
2
AS anastomosis construction was easier achieved in one-fourth of the conventional construction time (3.7±0.7 versus 16.5±2.6 minutes;
P
<0.001). Acute patency tended to be better (
P
=0.15). All anastomoses were evaluated intraoperatively, and subgroups at 90 and at 180 days. Patency was 100%. An effective remodeling response was observed in all groups, resulting in unobstructed anastomoses with excellent hemodynamic performance (fractional flow reserve ≥0.93 at 180 days). At 6 months, the noncompliant connector was covered with stabilized neointima that was thinner than found on the suture line (0.10±0.04 versus 0.31±0.13 mm;
P
=0.01). The connector induced less lumen loss (−0.6±6.5 versus 21.6±19%;
P
=0.03). The initial side-to-side configuration had remodeled to an end-to-side shape as intended.

Conclusions—

In the porcine model, the connector rapidly and consistently produced high-quality anastomoses that fully met current standards on patency and function. Unconventional aspects like a noncompliant intraluminal ring and a side-to-side to end-to-side converted configuration did not interfere with favorable anastomosis remodeling. These findings shed a new light on the anatomical prerequisites for anastomosis patency.
Ex Vivo Activated Human Macrophages Improve Healing, Remodeling, and Function of the Infarcted Heart
Authors: Leor Jonathan , Rozen Liat , Zuloff-Shani Adi , Feinberg Micha S. , Amsalem Yoram , Barbash Israel M. , Kachel Erez , Holbova Radka , Mardor Yael , Daniels Dianne , Ocherashvilli Aharon , Orenstein Arie , Danon David
Published: July 2006

Background—

Activated macrophages have a significant role in wound healing and damaged tissue repair. We sought to explore the ability of ex vivo activated macrophages to promote healing and repair of the infarcted myocardium.

Methods and Results—

Human activated macrophage suspension (AMS) was prepared from a whole blood unit obtained from young donors in a closed sterile system and was activated by a novel method of hypo-osmotic shock. The AMS (&4×10
5
cells) included up to 43% CD14-positive cells and was injected into the ischemic myocardium of rats (n=8) immediately after coronary artery ligation. The control group (n=9) was treated with saline injection. The human cells existed in the infarcted heart 4 to 7 days after injection, as indicated by histology, human growth hormone-specific polymerase chain reaction, and magnetic resonance imaging (MRI) tracking of iron oxide–nanoparticle-labeled cells. After 5 weeks, scar vessel density (±SE) (25±4 versus 10±1 per mm
2
;
P
<0.05), myofibroblast accumulation, and recruitment of resident monocytes and macrophages were greater in AMS-treated hearts compared with controls. Serial echocardiography studies, before and 5 weeks after injection, showed that AMS improved scar thickening (0.15±0.01 versus 0.11±0.01 cm;
P
<0.05), reduced left ventricular (LV) diastolic dilatation (0.87±0.02 versus 0.99±0.04 cm;
P
<0.05), and improved LV fractional shortening (31±2 versus 20±4%;
P
<0.05), compared with controls.

Conclusions—

Early after myocardial infarction, injection of AMS accelerates vascularization, tissue repair, and improves cardiac remodeling and function. Our work suggests a novel clinically relevant option to promote the repair of ischemic tissue.
Impact of Internal Mammary Artery Conduit on Long-term Outcomes After Percutaneous Intervention of Saphenous Vein Graft
Authors: Mehta Rajendra H. , Honeycutt Emily , Peterson Eric D. , Granger Christopher B. , Halabi Abdul R. , Shaw Linda K. , Smith Peter K. , Califf Robert M. , Harrington Robert A. , Sketch Michael H.
Published: July 2006

Background—

The influence of an internal mammary artery (IMA) graft on long-term outcomes after percutaneous saphenous vein graft (SVG) intervention is currently unknown.

Methods and Results—

To examine the impact of IMA on outcomes in patients undergoing SVG interventions, we analyzed 2119 patients from the Duke Cardiovascular Disease Database (1986–2003) with prior coronary artery bypass surgery undergoing cardiac catheterization who had at least 1 SVG graft. Patients were categorized into 4 groups: group I, SVG intervention and patent IMA; group II, no SVG intervention and patent IMA; group III, SVG intervention without patent IMA; and group IV, no SVG intervention without patent IMA. At a median follow-up of 4.8 years (interquartile range, 2.1 to 8.8 years), adjusted survival rates in groups I, II, III, and IV were 72.8%, 72.3%, 64.5%, and 58.9%, respectively. Multivariate Cox proportional hazards modeling showed similar survival for groups I and II (
P
=0.63) and for groups III and IV (
P
=0.33). The presence of IMA graft was related to lower long-term mortality (adjusted hazard ratio [HR], 0.69; 95% CI, 0.58 to 0.82), whereas SVG intervention was not associated with long-term mortality (adjusted HR, 0.94; 95% CI, 0.81 to 1.10). In contrast, the adjusted event-free rates for nonfatal myocardial infarction were lower in the SVG intervention groups (groups I and III) than in the non-SVG intervention groups (groups II and IV) (HR for SVG intervention versus no SVG intervention, 3.19; 95% CI, 2.18 to 4.66), with the presence of patent IMA conferring no significant benefit on this outcome (HR, 1.37; 95% CI, 0.91 to 2.08).

Conclusions—

In patients undergoing SVG interventions, survival, but not nonfatal myocardial infarction, is favorably influenced by the presence of patent IMA. In contrast, SVG intervention had no measurable survival benefit but was associated with an increased risk of nonfatal myocardial infarction.
Long-Term Survival in Patients Presenting With Type A Acute Aortic Dissection
Authors: Tsai Thomas T. , Evangelista Arturo , Nienaber Christoph A. , Trimarchi Santi , Sechtem Udo , Fattori Rossella , Myrmel Truls , Pape Linda , Cooper Jeanna V. , Smith Dean E. , Fang Jianming , Isselbacher Eric , Eagle Kim A.
Published: July 2006

Background—

Earlier studies evaluating long-term survival in type A acute aortic dissection (TA-AAD) have been restricted to a small number of patients in single center experiences. We used data from a contemporary, multi-center international registry of TA-AAD patients to better understand factors associated with long-term survival.

Methods and Results—

We examined 303 consecutive patients with TA-AAD enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2003. We included patients who were discharged alive and had documented clinical follow-up data. Kaplan-Meier survival curves were constructed to depict cumulative survival in patients from date of hospital discharge. Stepwise Cox proportional hazards analysis was performed to identify independent predictors of follow-up mortality. We found that 273 (90.1%) patients had been managed surgically and 30 (9.9%) were managed medically. Patients who were dead at follow-up were more likely to be older (63.9 versus 58.4 years,
P
=0.007) and to have had previous cardiac surgery (23.9% versus 10.6%,
P
=0.01). Survival for patients treated with surgery was 96.1%±2.4% and 90.5%±3.9% at 1 and 3 years versus 88.6%±12.2% and 68.7%±19.8% without surgery (mean follow-up overall, 2.8 years, log rank
P
=0.009). Multivariate analysis identified a history of atherosclerosis (relative risk (RR), 2.17; 95% confidence interval [CI], 1.08 to 4.37;
P
=0.03) and previous cardiac surgery (RR, 2.54; 95% CI, 1.16 to 5.57;
P
=0.02) as significant, independent predictors of follow-up mortality.

Conclusions—

Contemporary 1- and 3-year survival in patients with TA-AAD treated surgically are excellent. Independent predictors of survival during the follow-up period do not appear to be influenced by in-hospital risks but rather preexisting comorbidities.
Recovery of Regional but Not Global Contractile Function by the Direct Intramyocardial Autologous Bone Marrow Transplantation
Authors: Hendrikx Marc , Hensen Karen , Clijsters Christel , Jongen Hanne , Koninckx Remco , Bijnens Eric , Ingels Michel , Jacobs Axel , Geukens Robert , Dendale Paul , Vijgen Johan , Dilling Dagmara , Steels Paul , Mees Urbain , Rummens Jean-Luc
Published: July 2006

Background—

Recent trials have shown that intracoronary infusion of bone marrow cells (BMCs) improves functional recovery after acute myocardial infarction. However, whether this treatment is effective in heart failure as a consequence of remodeling after organized infarcts remains unclear. In this randomized trial, we assessed the hypothesis that direct intramyocardial injection of autologous mononuclear bone marrow cells during coronary artery bypass graft (CABG) could improve global and regional left ventricular ejection fraction (LVEF) at 4-month follow-up.

Methods and Results—

Twenty patients (age 64.8±8.7; 17 male, 3 female) with a postinfarction nonviable scar, as assessed by thallium (Tl) scintigraphy and cardiac magnetic resonance imaging (MRI), scheduled for elective CABG, were included. They were randomized to a control group (n =10, CABG only) or a BMC group (CABG and injection of 60.10
6
±31.10
6
BMC). Primary end points were global LVEF change and wall thickening changes in the infarct area from baseline to 4-month follow-up, as measured by MRI. Changes in metabolic activity were measured by Tl scintigraphy and expressed as a score with a range from 0 to 4, corresponding to percent of maximal myocardial Tl uptake (4 indicates <50%, nonviable scar; 3, 50% to 60%; 2, 60% to 70%; 1, 70% to 80%; 0>80%). Global LVEF at baseline was 39.5±5.5% in controls and 42.9±10.3% in the BMC group (
P
=0.38). At 4 months, LVEF had increased to 43.1±10.9% in the control group and to 48.9±9.5% in the BMC group (
P
=0.23). Systolic thickening had improved from −0.6±1.3 mm at baseline to 1.8±2.6 mm at 4 months in the cell-implanted scars, whereas nontreated scars remained largely akinetic (−0.5±2.0 mm at baseline compared with 0.4±1.7 mm at 4 months,
P
=0.007 control versus BMC-treated group at 4 months). Defect score decreased from 4 to 3.3±0.9 in the BMC group and to 3.7±0.4 in the control group (
P
=0.18).

Conclusions—

At 4 months, there was no significant difference in global LVEF between both groups, but a recovery of regional contractile function in previously nonviable scar was observed in the BMC group.
Gene Expression Profiles and B-Type Natriuretic Peptide Elevation in Heart Transplantation
Authors: Mehra Mandeep R. , Uber Patricia A. , Walther Dirk , Vesely Mark , Wohlgemuth Jay G. , Prentice James , Tayama Darren , Billingham Margaret
Published: July 2006

Background—

B-type natriuretic peptide (BNP) is chronically elevated in heart transplantation and reflects diastolic dysfunction, cardiac allograft vasculopathy, and poor late outcome. This investigation studied peripheral gene expression signatures of elevated BNP concentrations in clinically quiescent heart transplant recipients in an effort to elucidate molecular correlates beyond hemodynamic perturbations.

Methods and Results—

We performed gene microarray analysis in peripheral blood mononuclear cells of 28 heart transplant recipients with clinical quiescence (absence of dyspnea or fatigue; normal left ventricular ejection fraction [EF >55%]; ISHLT biopsy score 0 or 1A; and normal hemodynamics [RAP <7 mm Hg, PCWP ≤15 mm Hg, and CI ≥2.5 L/min per m
2
]). BNP levels were performed using the Triage B-type Natriuretic Peptide test (Biosite Diagnostics Inc, San Diego, Calif) and median BNP concentration was 165 pg/mL. Seventy-eight probes (of 7370) mapped to 54 unique genes were significantly correlated with BNP concentrations (
P
<0.001). Of these, the strongest correlated genes (
P
<0.0001) were in the domains of gelsolin (actin cytoskeleton), matrix metallopeptidases (collagen degradation), platelet function, and immune activity (human leukocyte antigen system, heat shock protein, mast cell, and B-cell lineage).

Conclusions—

In the clinically quiescent heart transplant recipient, an elevated BNP concentration is associated with molecular patterns that point to ongoing active cardiac structural remodeling, vascular injury, inflammation, and alloimmune processes. Thus, these findings allude to the notion that BNP elevation is not merely a hemodynamic marker but should be considered reflective of integrated processes that determine the balance between active cardiac allograft injury and repair.
Chordal Cutting Does Not Adversely Affect Left Ventricle Contractile Function
Authors: Messas Emmanuel , Yosefy Chaim , Chaput Miguel , Guerrero J. Luis , Sullivan Suzanne , Menasché Philippe , Carpentier Alain , Desnos Michel , Hagege Albert A. , Vlahakes Gus J. , Levine Robert A.
Published: July 2006

Background—

Severing a limited number of second-order chordae to the anterior leaflet can improve ischemic mitral regurgitation (MR). Some concerns have been raised regarding possible influence on regional and global left ventricle (LV) function. We evaluated changes in cardiac function in 5 normal sheep with cutting of pre-instrumented chords in the beating heart to maintain constant load.

Methods and Results—

Under cardiopulmonary bypass, wires were placed around the 2 central basal chordae and brought outside the heart, which was restarted. Hemodynamic and imaging data were collected before and after chordal cutting by radiofrequency ablation using those wires. Segmental contractility was assessed invasively using sonomicrometers and noninvasively using Doppler tissue velocity and strain rate (with strain rate viewed as less load-dependent than ejection fraction) at 6 sites: base, mid-ventricle, and apex along the anteroseptal and posterolateral walls. We found no changes from before to after chordal cutting in LV end-diastolic volume (47.2±3.3 after cutting versus 48.4±4.6 mL before cutting,
P
=0.66), end-systolic volume (21.5±1.2 versus 22.3±2.8 mL,
P
=0.68), ejection fraction (54.2±1.8 versus 54.2±2.7%,
P
=0.96), systolic ventricular elastance (7.28±1.68 versus 7.66±2.11 mm Hg/mL,
P
=0.64), preload-recruitable stroke work (46.6±7.7 versus 50.2±10.7 mm Hg,
P
=0.76), and LVdP/dt (1480±238 versus 1392±250 mm Hg/s,
P
=0.45). Doppler tissue velocities and longitudinal strain rates surrounding the papillary muscles were unchanged, as were sonomicrometer longitudinal and mediolateral absolute strains. No wall motion abnormalities were visible around the papillary muscles, and no MR developed.

Conclusion—

We find no evidence for acutely decreased global or segmental LV contractility with chordal cutting. This absence of adverse effects is consistent with long-term clinical experience with cutting these chords in valve repair.
Long-Term Outcomes of the Symmetry Vein Graft Anastomosis Device
Authors: Kachhy Radha G. , Kong David F. , Honeycutt Emily , Shaw Linda K. , Davis R. Duane
Published: July 2006

Background—

The Symmetry Bypass Connector (St. Jude Medical) was developed to rapidly anastomose saphenous vein grafts to the aorta during coronary bypass surgery (CABG) without cross-clamping. Previous uncontrolled studies of this device observed vein graft closures at six months, possibly attributable to neointimal hyperplasia.

Methods and Results—

To assess the long-term clinical outcomes of the Symmetry device, we performed a retrospective matched case–control analysis of patients who underwent CABG at Duke Medical Center between January 1, 2002 and December 31, 2003. In 121 patients, at least one proximal anastomosis used a Symmetry device. Traditional suture methods were used in 178 control patients, matched by age group, gender, use of cardiopulmonary bypass, and Hannan perioperative risk score. One-year outcomes were compared using the log-rank test and Cox proportional hazards regression models. Major adverse events were more frequent among cases compared with controls. By unadjusted Kaplan–Meier analysis for the composite end point of death, nonfatal myocardial infarction, repeat cardiac catheterization, or repeat CABG, there was a trend towards increased events in the Symmetry device group (
P
=0.053). No significant differences were detected for stroke, all cause mortality, or the combined end point of death or nonfatal myocardial infarction.

Conclusions—

Use of the Symmetry Bypass Connector was associated with increased risk for major adverse events at 1 year, suggestive of early graft closure. The potential reductions in operative stroke risk (from the elimination of aortic cross-clamping) must be weighed against the potential risk for later adverse events. These findings encourage close follow-up of patients who received this device.
Mechanism of Recurrent/Persistent Ischemic/Functional Mitral Regurgitation in the Chronic Phase After Surgical Annuloplasty
Authors: Kuwahara Eiji , Otsuji Yutaka , Iguro Yoshifumi , Ueno Tetsuya , Zhu Fang , Mizukami Naoko , Kubota Kayoko , Nakashiki Kenichi , Yuasa Toshinori , Yu Bo , Uemura Takeshi , Takasaki Kunitsugu , Miyata Masaaki , Hamasaki Shuichi , Kisanuki Akira , Levine Robert A. , Sakata Ryuzo , Tei Chuwa
Published: July 2006

Background—

Surgical annuloplasty can potentially hoist the posterior annulus anteriorly, exaggerate posterior leaflet (PML) tethering, and lead to recurrent ischemic/functional mitral regurgitation (MR). Characteristics of leaflet configurations in late postoperative MR were investigated.

Methods and Results—

In 30 patients with surgical annuloplasty for ischemic MR and 20 controls, the anterior leaflet (AML) and PML tethering angles relative to the line connecting annuli, posterior and apical displacement of the coaptation and the MR grade were measured by echocardiography before, early after, and late after surgery. Early after surgery, grade of MR and AML tethering generally decreased (
P
<0.01), whereas PML tethering significantly worsened (
P
<0.01). Nine of the 30 patients showed recurrent/persistent MR late after surgery. Compared with patients without late MR, those with the MR showed similar reduction in the annular area, significant re-increase in posterior displacement of the coaptation, and progressive worsening in PML tethering (
P
<0.05) late after surgery in comparison to the early phase. Both preoperative MR and late postoperative MR were significantly correlated with all tethering variables in univariate analysis. Although apical displacement of the coaptation was the primary determinant of preoperative MR (
r
2
=0.60,
P
<0.0001), increased PML tethering was the primary determinant of late MR (
r
2
=0.75,
P
<0.0001).

Conclusions—

Whereas both leaflets tethering is related to preoperative ischemic MR, both leaflets tethering but with predominant contribution from augmented and progressive PML tethering is related to recurrent/persistent ischemic/functional MR late after surgical annuloplasty.
A Novel Strategy for Myocardial Protection by Combined Antibody Therapy Inhibiting Both P-Selectin and Intercellular Adhesion Molecule-1 Via Retrograde Intracoronary Route
Authors: Fukushima Satsuki , Coppen Steven R. , Varela-Carver Anabel , Yamahara Kenichi , Sarathchandra Padmini , Smolenski Ryszard T. , Yacoub Magdi H. , Suzuki Ken
Published: July 2006

Background—

Antibody therapy to inhibit either P-selectin or intercellular adhesion molecule-1 (ICAM-1) has been reported to provide myocardial protection against leukocyte-mediated reperfusion injury. Because these molecules play different roles in the leukocyte-endothelial interaction, co-inhibition of both may achieve further enhanced cardioprotection. In addition, the therapeutic efficacy of such antibody therapy may be affected by the delivery route used. Retrograde intracoronary infusion will offer an effective, direct access to the postcapillary venules, where the target event (leukocyte–endothelial interaction) takes place. We investigated the feasibility and efficiency of the combined antibody therapy targeting both P-selection and ICAM-1 via the retrograde intracoronary route to attenuate myocardial ischemia-reperfusion injury.

Methods and Results—

Lewis rats underwent 30-minute left coronary artery occlusion. Just before reperfusion, anti-P-selectin monoclonal antibody (150 μg/kg), anti-ICAM-1 monoclonal antibody (200 μg/kg), both antibodies together, or control antibody were retrogradely infused into the left cardiac vein. At 24 hours after reperfusion, administration of either anti-P-selectin or anti-ICAM-1 antibody significantly (
P
<0.05) improved left ventricular ejection fraction and attenuated infarct size (40.6±3.2% and 34.8±3.5%, respectively) compared with the control (56.8±3.4%). This was associated with reduced leukocyte accumulation and improved regional blood flow in the ischemic area. Noticeably, co-administration of both antibodies achieved a much greater reduction in infarct size (19.1±3.6%), associated with greater attenuation in leukocyte infiltration, compared with administration of either single antibody.

Conclusions—

Combined antibody therapy inhibiting both P-selectin and ICAM-1 via the retrograde intracoronary route could be a promising new strategy for myocardial protection against ischemia-reperfusion injury.