bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential of telomerase expression and activity in cervical specimens as a diagnostic tool
Authors: Bravaccini S , Sanchini M A , Amadori A , Medri L , Saragoni L , Calistri D , Monti F , Volpi A , Amadori D
Published: August 2005

Aims:To evaluate the potential use of the immunohistochemical expression of telomerase and the measurement of its activity as diagnostic tools in the uterine cervix.

Methods:The fluorescent telomeric repeat amplification protocol (TRAP) assay was used to evaluate telomerase activity in a series of 43 cervical scrapings. Twenty five cases were cytologically classified as inflammatory, and/or metaplastic, and/or acanthotic, and 18 cases presented cell alterations compatible with mild, moderate, or severe cervical intraepithelial neoplasia (CIN). Immunohistochemistry was performed on a retrospective series of 86 archival, paraffin wax embedded blocks using a recently developed anti-hTERT (human telomerase reverse transcriptase) monoclonal antibody.

Results:Telomerase activity was expressed as arbitrary enzymatic units (AEU). Median values were 38.0 AEU for inflammatory non-dysplastic cell specimens, 33.5 AEU for CIN I, 41.0 AEU for CIN II, and 28.0 AEU for CIN III. The median percentage of immunoreactive dysplastic cells, as detected by immunohistochemistry, was significantly (p  =  0.024) lower in CIN I (45%) than in more severe dysplastic (CIN II 70%, CIN III 80%) lesions. In contrast, no differences were seen in the enzymatic activity detected by the TRAP assay among the different dysplastic lesions.

Conclusions:These data indicate that, using a molecular extra situ method, the telomerase activity of inflammatory and non-dysplastic elements masks the expected differences between mild and severe dysplasia. Conversely, an in situ approach permits the accurate identification of telomerase positive dysplastic cells.
The value of c-kit mutational analysis in a cytokeratin positive gastrointestinal stromal tumour
Authors: Rossi G , Sartori G , Valli R , Bertolini F , Bigiani N , Schirosi L , Cavazza A , Luppi G
Published: August 2005

The expression of cytokeratins in gastrointestinal stromal tumours (GISTs) is rare and may lead to diagnostic confusion when it occurs. This report describes a metastatic GIST that stained strongly for cytokeratins, CD117, and CD34 in a patient who was previously diagnosed with gastric epithelioid angiosarcoma. A review of both tumours showed the same histological and immunohistochemical profiles, and c-kit molecular analysis revealed an insertional mutation at codon 558 of exon 11 in both tumours. Thus, pathologists should be aware that GISTs can occasionally express cytokeratins, and that c-kit mutational investigations may have a key diagnostic role and may prevent diagnostic mistakes that could have important clinical implications.
Three dimensional reconstruction of a human breast carcinoma using routine laboratory equipment and immunohistochemistry
Authors: Kurien T , Boyce R W G , Paish E C , Ronan J , Maddison J , Rakha E A , Green A R , Ellis I O
Published: August 2005

Aims:To establish a three dimensional reconstruction of an invasive breast carcinoma using basic laboratory equipment to evaluate and characterise the spatial arrangement of the parenchymal cells of the breast.

Methods:One hundred and twenty eight sequential 4 μm sections (20 μm apart) of the tumour were stained immunohistochemically with an epithelial specific marker (AE1/AE3) or tumour specific marker (c-erbB-2) to reconstruct two different three dimensional images of the normal and malignant parenchymal cells. Sections were digitally imaged using a microscope, scanner, and digital camera linked to a conventional personal computer. Accurate alignment of the digitalised images was carried out using a semiautomatic graphical method of manual interaction, using the cross correlation coefficient as a goodness of fit measure, and an automatic search algorithm using the Fibonacci search algorithm for automatic alignment. The volume was reconstructed using maximum, minimum point projection and “back to front” opacity blending.

Results:The quality of the reconstructed images was distinct and perfect, providing a comprehensive and explicit view of the normal and malignant parenchymal tissues of the breast that is not possible by viewing two dimensional histological sections. Specifically, this approach showed the spatial arrangement of the tumour cells and their relation to the surrounding tissues at a high resolution.

Conclusion:This simple and reproducible approach enables the spread and infiltration of invasive carcinoma to be understood and could also be used to analyse the spatial relation between atypical hyperplastic and malignant in situ lesions of the breast.
A novel frameshift mutation (+G) at codons 15/16 in a β0 thalassaemia gene results in a significant reduction of β globin mRNA values
Authors: Mo Q-H , Li X-R , Li C-F , He Y-L , Xu X-M
Published: August 2005

Aims:To identify a novel β globin gene mutation found in a Chinese family, and also to assess its functional consequences.

Methods:Haematological analysis was performed on all family members. The 23 common mutations of β thalassaemia found in Chinese populations were detected by means of a reverse dot blot method. Direct DNA sequencing of polymerase chain reaction (PCR) amplified complete β globin gene was carried out to identify the novel mutation. A real time, one step reverse transcription PCR assay was used to measure β globin mRNA in the reticulocytes of heterozygous patients.

Results:A novel frameshift mutation—an insertion of G between codons 15 and 16 in a homonucleotide run of four guanines—was determined, which generates a new premature chain terminator at the 22nd codon. Relative quantitative analysis of the β globin mRNA in heterozygous subjects demonstrated a 39.83% reduction compared normal controls.

Conclusions:The significantly lower amounts of β globin mRNA found in mutation carriers is probably caused by the rapid nonsense mediated degradation of the mutant mRNA. These data, combined with haematological analysis, suggest that this novel mutation of CDs15/16 (+G) results in a β0 thalassaemia phenotype.
Interstitial cells of Cajal, enteric nerves, and glial cells in colonic diverticular disease
Authors: Bassotti G , Battaglia E , Bellone G , Dughera L , Fisogni S , Zambelli C , Morelli A , Mioli P , Emanuelli G , Villanacci V
Published: August 2005

Background:Colonic diverticular disease (diverticulosis) is a common disorder in Western countries. Although its pathogenesis is probably multifactorial, motor abnormalities of the large bowel are thought to play an important role. However, little is known about the basic mechanism that may underlie abnormal colon motility in diverticulosis.

Aims:To investigate the interstitial cells of Cajal (the gut pacemaker cells), together with myenteric and submucosal ganglion and glial cells, in patients with diverticulosis.

Patients:Full thickness colonic samples were obtained from 39 patients undergoing surgery for diverticulosis. Specimens from tumour free areas of the colon in 10 age matched subjects undergoing surgery for colorectal cancer served as controls.

Methods:Interstitial cells of Cajal were assessed using anti-Kit antibodies; submucosal and myenteric plexus neurones and glial cells were assessed by means of anti-PGP 9.5 and anti-S-100 monoclonal antibodies, respectively.

Results:Patients with diverticulosis had normal numbers of myenteric and submucosal plexus neurones compared with controls (p  =  0.103 and p  =  0.516, respectively). All subtypes of interstitial cells of Cajal were significantly (p  =  0.0003) reduced compared with controls, as were glial cells (p  =  0.0041).

Conclusions:Interstitial cells of Cajal and glial cells are decreased in colonic diverticular disease, whereas enteric neurones appear to be normally represented. This finding might explain some of the large bowel motor abnormalities reported to occur in this condition.
A DATA MINING APPLICATION: ANALYSIS OF PROBLEMS OCCURRING DURING A SOFTWARE PROJECT DEVELOPMENT PROCESS
Authors: NAYAK RICHI , QIU TIAN
Published: August 2005

Data mining techniques provide people with new power to research and manipulate the existing large volume of data. A data mining process discovers interesting information from the hidden data that can either be used for future prediction and/or intelligently summarising the details of the data. There are many achievements of applying data mining techniques to various areas such as marketing, medical, and financial, although few of them can be currently seen in software engineering domain. In this paper, a proposed data mining application in software engineering domain is explained and experimented. The empirical results demonstrate the capability of data mining techniques in software engineering domain and the potential benefits in applying data mining to this area.
A BAYESIAN NETWORK APPROACH TO RATIONAL ARCHITECTURAL DESIGN
Authors: ZHANG HONGYU , JARZABEK STAN
Published: August 2005

In software architecture design, we explore design alternatives and make decisions about adoption or rejection of a design from a web of complex and often uncertain information. Different architectural design decisions may lead to systems that satisfy the same set of functional requirements but differ in certain quality attributes. In this paper, we propose a Bayesian Network based approach to rational architectural design. Our Bayesian Network helps software architects record and make design decisions. We can perform both qualitative and quantitative analysis over the Bayesian Network to understand how the design decisions influence system quality attributes, and to reason about rational design decisions. We use the KWIC (Key Word In Context) example to illustrate the principles of our approach.
USING CULTURAL ALGORITHMS TO RE-ENGINEER LARGE-SCALE SEMANTIC NETWORKS
Authors: RYCHTYCKYJ NESTOR , REYNOLDS ROBERT G.
Published: August 2005

Evolutionary computation has been successfully applied in a variety of problem domains and applications. In this paper we discuss the use of a specific form of evolutionary computation known as Cultural Algorithms to improve the efficiency of the subsumption algorithm in semantic networks. We identify two complementary methods of using Cultural Algorithms to solve the problem of re-engineering large-scale dynamic semantic networks in order to optimize the efficiency of subsumption: top-down and bottom-up.

The top-down re-engineering approach improves subsumption efficiency by reducing the number of attributes that need to be compared for every node without impacting the results. We demonstrate that a Cultural Algorithm approach can be used to identify these defining attributes that are most significant for node retrieval. These results are then utilized within an existing vehicle assembly process planning application that utilizes a semantic network based knowledge base to improve the performance and reduce complexity of the network. It is shown that the results obtained by Cultural Algorithms are at least as good, and in most cases better, than those obtained by the human developers. The advantage of Cultural Algorithms is especially pronounced for those classes in the network that are more complex.

The goal of bottom-up approach is to classify the input concepts into new clusters that are most efficient for subsumption and classification. While the resultant subsumption efficiency for the bottom-up approach exceeds that for the top-down approach, it does so by removing structural relationships that made the network understandable to human observers. Like a Rete network in expert systems, it is a compilation of only those relationships that impact subsumption. A direct comparison of the two approaches shows that bottom-up semantic network re-engineering creates a semantic network that is approximately 5 times more efficient than the top-down approach in terms of the cost of subsumption. In conclusion, we will discuss these results and show that some knowledge that is useful to the system users is lost during the bottom-up re-engineering process and that the best approach for re-engineering a semantic network requires a combination of both of these approaches.
THE GENETIC BASIS FOR CARDIAC REMODELING
Authors: Ahmad Ferhaan , Seidman J.G. , Seidman Christine E.
Published: August 2005

▪ Abstract  Cardiomyopathies are primary disorders of cardiac muscle associated with abnormalities of cardiac wall thickness, chamber size, contraction, relaxation, conduction, and rhythm. They are a major cause of morbidity and mortality at all ages and, like acquired forms of cardiovascular disease, often result in heart failure. Over the past two decades, molecular genetic studies of humans and analyses of model organisms have made remarkable progress in defining the pathogenesis of cardiomyopathies. Hypertrophic cardiomyopathy can result from mutations in 11 genes that encode sarcomere proteins, and dilated cardiomyopathy is caused by mutations at 25 chromosome loci where genes encoding contractile, cytoskeletal, and calcium regulatory proteins have been identified. Causes of cardiomyopathies associated with clinically important cardiac arrhythmias have also been discovered: Mutations in cardiac metabolic genes cause hypertrophy in association with ventricular pre-excitation and mutations causing arrhythmogenic right ventricular dysplasia were recently discovered in protein constituents of desmosomes. This considerable genetic heterogeneity suggests that there are multiple pathways that lead to changes in heart structure and function. Defects in myocyte force generation, force transmission, and calcium homeostasis have emerged as particularly critical signals driving these pathologies. Delineation of the cell and molecular events triggered by cardiomyopathy gene mutations provide new fundamental knowledge about myocyte biology and organ physiology that accounts for cardiac remodeling and defines mechanistic pathways that lead to heart failure.
SULFATASES AND HUMAN DISEASE
Authors: Diez-Roux Graciana , Ballabio Andrea
Published: August 2005

▪ Abstract  Sulfatases are a highly conserved family of proteins that cleave sulfate esters from a wide range of substrates. The importance of sulfatases in human metabolism is underscored by the presence of at least eight human monogenic diseases caused by the deficiency of individual sulfatases. Sulfatase activity requires a unique posttranslational modification, which is impaired in patients with multiple sulfatase deficiency (MSD) due to a mutation of the sulfatase modifying factor 1 (SUMF1). Here we review current knowledge and future perspectives on the evolution of the sulfatase gene family, on the role of these enzymes in human metabolism, and on new developments in the therapy of sulfatase deficiencies.
Phosphatidylinositol 3-kinase/Akt signaling stimulates colonic mucosal cell survival during aging
Authors: Majumdar Adhip P. N. , Du Jianhua
Published: August 2005

Although aging is shown to be associated with decreased apoptosis and increased survival of cells in the colonic mucosa of Fischer 344 rats, the regulatory mechanisms are poorly understood. The current investigation examines the involvement of phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway in mediating the events of colonic mucosal cell survival during aging. We have observed that aging is associated with activation of PI3K/Akt signaling, as evidenced by the higher levels of phosphorylated forms of p85, the regulatory subunit of PI3K and of Akt in the proximal and distal colonic mucosa, of aged (21–23 mo) than in young (4–7 mo) rats. These increases are accompanied by a concomitant rise in phosphorylation of proapoptotic protein Bad, which is sequestered by the 14-3-3 family of proteins following phosphorylation by Akt, resulting in a reduction in nonphosphorylated Bad. The amount of antiapoptotic Bcl-xL bound to nonphosporylated Bad in the colonic mucosa is found to be substantially lower in aged than in young rats, resulting in a marked rise in the unbound/free form of Bcl-xL in the aging colon. The age-related activation of PI3K and the reduction in caspase-3 activity could be reversed by wortmannin, a specific inhibitor of PI3K. Increased levels of Bcl-xL and phosphorylated forms of Akt and Bad and reduction in caspase-3 activity were observed throughout the entire length of the colonic crypt of aged rats. We conclude that the constitutive activation of the PI3K/Akt-signaling pathway is partly responsible for the age-related increase in colonic mucosal cell survival. This is evident throughout the entire length of the colonic crypt.
Trypsin and splanchnic protein turnover during feeding and fasting in human subjects
Authors: O’Keefe Stephen J. D. , Lee Ronzo B. , Li Jing , Zhou Wen , Stoll Barbara , Dang Qianyu
Published: August 2005

Knowledge of the stimulatory effects of enteral and parenteral (intravenous) feeding on the synthesis and turnover of trypsin would help in the management of acute pancreatitis, because the disease is caused by the premature activation of trypsin. To investigate this, we labeled intravenous infusions with [1-13C]leucine and enterals with [2H]leucine and measured isotope enrichment of plasma, secreted trypsin, and duodenal mucosal proteins over 6 h by duodenal perfusion/aspiration and endoscopic biopsy. Thirty healthy volunteers were studied during fasting ( n = 7), intravenous feeding ( n = 6), or postpyloric enteral feeding [duodenal polymeric ( n = 6), elemental duodenal ( n = 6), and jejunal elemental ( n = 5)]. All diets provided 1.5 g·kg−1·day−1protein and 40 kcal·kg−1·day−1energy. Results demonstrated that compared with fasting, enteral feeding increased the rate of appearance (71 ± 4 vs. 91 ± 5 min, P = 0.01) and secretion (546 ± 80 vs. 219 ± 37 U/h, P = 0.01) of newly labeled trypsin and expanded zymogen stores (1,660 ± 237 vs. 749 ± 133 units, P = 0.03). These differences persisted whether the feedings were polymeric or elemental, duodenal, or jejunal. In contrast, intravenous feeding had no effect on basal rates. Differential labeling of the plasma amino acid pool by enteral and intravenous isotope infusions suggested that 35% of absorbed amino acids were retained within the splanchnic bed during enteral feeding and that mucosal protein turnover increased from a fasting rate of 34 ± 6 to 108 ± 8%/day ( P < 0.05) compared with no change after intravenous feeding. In conclusion, all common forms of enteral feeding stimulate the synthesis and secretion of pancreatic trypsin, and only parenteral nutrition avoids it.
[Ca2+]i-independent contractile force generation by rat hepatic stellate cells in response to endothelin-1
Authors: Melton Andrew C. , Datta Anuj , Yee Hal F.
Published: August 2005

The contractile force generated by hepatic stellate cells in response to endothelin-1 contributes to sinusoidal blood flow regulation and hepatic fibrosis. This study's aim was to directly test the widely held view that changes in cytosolic Ca2+ concentration ([Ca2+]i) mediate stellate cell force generation. Contractile force generation by primary cultures of rat hepatic stellate cells grown in three-dimensional collagen gels was directly and quantitatively measured using a force transducer. Stellate cell [Ca2+]i, myosin activation, and migration were quantified using standard techniques. [Ca2+]i was modulated using ionomycin, BAPTA, KCl, and removal of extracellular Ca2+. Removal of extracellular Ca2+ did not alter endothelin-1-stimulated force development or [Ca2+]i. Ionomycin, a Ca2+ ionophore, triggered an increase in [Ca2+]i that was three times greater than that stimulated by endothelin-1, but only induced 16% of the force and 38% of the myosin regulatory light chain (MLC) phosphorylation induced by endothelin-1. Physiological increases in [Ca2+]i induced by hyperkalemia had no effect on contractile force. Loading BAPTA, a Ca2+ chelator, in stellate cells completely blocked endothelin-1-induced increases in [Ca2+]i but had no effect on endothelin-1-stimulated force generation or MLC phosphorylation. In contrast, Y-27632, a selective rho-associated kinase inhibitor, inhibited endothelin-1-stimulated force generation by at least 70% and MLC phosphorylation by at least 80%. Taken together, these observations indicate that changes in [Ca2+]i are neither necessary nor sufficient for contractile force generation by rat stellate cells. Our results challenge the current model of contractile regulation in hepatic stellate cells and have important implications for our understanding of hepatic pathophysiology.
Liver fatty acid binding protein gene ablation potentiates hepatic cholesterol accumulation in cholesterol-fed female mice
Authors: Martin Gregory G. , Atshaves Barbara P. , McIntosh Avery L. , Mackie John T. , Kier Ann B. , Schroeder Friedhelm
Published: August 2005

Although liver fatty acid binding protein (L-FABP) is postulated to influence cholesterol homeostasis, the physiological significance of this hypothesis remains to be resolved. This issue was addressed by examining the response of young (7 wk) female mice to L-FABP gene ablation and a cholesterol-rich diet. In control-fed mice, L-FABP gene ablation alone induced hepatic cholesterol accumulation (2.6-fold), increased bile acid levels, and increased body weight gain (primarily as fat tissue mass). In cholesterol-fed mice, L-FABP gene ablation further enhanced the hepatic accumulation of cholesterol (especially cholesterol ester, 12-fold) and potentiated the effects of dietary cholesterol on increased body weight gain, again mainly as fat tissue mass. However, in contrast to the effects of L-FABP gene ablation in control-fed mice, biliary levels of bile acids (as well as cholesterol and phospholipids) were reduced. These phenotypic alterations were not associated with differences in food intake. In conclusion, it was shown for the first time that L-FABP altered cholesterol metabolism and the response of female mice to dietary cholesterol. While the biliary and lipid phenotype of female wild-type L-FABP+/+mice was sensitive to dietary cholesterol, L-FABP gene ablation dramatically enhanced many of the effects of dietary cholesterol to greatly induce hepatic cholesterol (primarily cholesterol ester) and triacylglycerol accumulation as well as to potentiate body weight gain (primarily as fat tissue mass). Taken together, these data support the hypothesis that L-FABP is involved in the physiological regulation of cholesterol metabolism, body weight gain, and obesity.
Cardiac mitochondrial preconditioning by Big Ca2+-sensitive K+ channel opening requires superoxide radical generation
Authors: Stowe David F. , Aldakkak Mohammed , Camara Amadou K. S. , Riess Matthias L. , Heinen Andre , Varadarajan Srinivasan G. , Jiang Ming-Tao
Published: August 2005

ATP-sensitive K+ channel opening in inner mitochondrial membranes protects hearts from ischemia-reperfusion (I/R) injury. Opening of the Big conductance Ca2+-sensitive K+ channel (BKCa) is now also known to elicit cardiac preconditioning. We investigated the role of the pharmacological opening of the BKCa channel on inducing mitochondrial preconditioning during I/R and the role of O2-derived free radicals in modulating protection by putative mitochondrial (m)BKCa channel opening. Left ventricular (LV) pressure (LVP) was measured with a balloon and transducer in guinea pig hearts isolated and perfused at constant pressure. NADH, reactive oxygen species (ROS), principally superoxide (O2−·), and m[Ca2+] were measured spectrophotofluorometrically at the LV free wall using autofluorescence and fluorescent dyes dihydroethidium and indo 1, respectively. BKCa channel opener 1-(2′-hydroxy-5′-trifluoromethylphenyl)-5-trifluoromethyl-2(3H)benzimid-axolone (NS; NS-1619) was given for 15 min, ending 25 min before 30 min of global I/R. Either Mn(III)tetrakis(4-benzoic acid)porphyrin (TB; MnTBAP), a synthetic dismutator of O2−·, or an antagonist of the BKCa channel paxilline (PX) was given alone or for 5 min before, during, and 5 min after NS. NS pretreatment resulted in a 2.5-fold increase in developed LVP and a 2.5-fold decrease in infarct size. This was accompanied by less O2−· generation, decreased m[Ca2+], and more normalized NADH during early ischemia and throughout reperfusion. Both TB and PX antagonized each preconditioning effect. This indicates that 1) NS induces a mitochondrial-preconditioned state, evident during early ischemia, presumably on mBKCa channels; 2) NS effects are blocked by BKCa antagonist PX; and 3) NS-induced preconditioning is dependent on the production of ROS. Thus NS may induce mitochondrial ROS release to initiate preconditioning.
High-dose oral vitamin C partially replenishes vitamin C levels in patients with Type 2 diabetes and low vitamin C levels but does not improve endothelial dysfunction or insulin resistance
Authors: Chen Hui , Karne Rajaram J. , Hall Gail , Campia Umberto , Panza Julio A. , Cannon Richard O. , Wang Yaohui , Katz Arie , Levine Mark , Quon Michael J.
Published: August 2005

Endothelial dysfunction is a hallmark of Type 2 diabetes related to hyperglycemia and oxidative stress. Nitric oxide-dependent vasodilator actions of insulin may augment glucose disposal. Thus endothelial dysfunction may worsen insulin resistance. Intra-arterial administration of vitamin C improves endothelial dysfunction in diabetes. In the present study, we investigated effects of high-dose oral vitamin C to alter endothelial dysfunction and insulin resistance in Type 2 diabetes. Plasma vitamin C levels in 109 diabetic subjects were lower than healthy (36 ± 2 μM) levels. Thirty-two diabetic subjects with low plasma vitamin C (<40 μM) were subsequently enrolled in a randomized, double-blind, placebo-controlled study of vitamin C (800 mg/day for 4 wk). Insulin sensitivity (determined by glucose clamp) and forearm blood flow in response to ACh, sodium nitroprusside (SNP), or insulin (determined by plethysmography) were assessed before and after 4 wk of treatment. In the placebo group ( n = 17 subjects), plasma vitamin C (22 ± 3 μM), fasting glucose (159 ± 12 mg/dl), insulin (19 ± 7 μU/ml), and SIClamp [2.06 ± 0.29 × 10−4 dl·kg−1·min−1/(μU/ml)] did not change significantly after placebo treatment. In the vitamin C group ( n = 15 subjects), basal plasma vitamin C (23 ± 2 μM) increased to 48 ± 6 μM ( P < 0.01) after treatment, but this was significantly less than that expected for healthy subjects (>80 μM). No significant changes in fasting glucose (156 ± 11 mg/dl), insulin (14 ± 2 μU/ml), SIClamp [2.71 ± 0.46 × 10−4 dl·kg−1·min−1/(μU/ml)], or forearm blood flow in response to ACh, SNP, or insulin were observed after vitamin C treatment. We conclude that high-dose oral vitamin C therapy, resulting in incomplete replenishment of vitamin C levels, is ineffective at improving endothelial dysfunction and insulin resistance in Type 2 diabetes.
Myocardial vascular and metabolic adaptations in chronically anemic fetal sheep
Authors: Mascio Christopher E. , Olison Aaron K. , Ralphe J. Carter , Tomanek Robert J. , Scholz Thomas D. , Segar Jeffrey L.
Published: August 2005

Little is known about the vascular and metabolic adaptations that take place in the fetal heart to maintain cardiac function in response to increased load. Chronic fetal anemia has previously been shown to result in increased ventricular mass, increased myocardial vascularization, and increased myocardial expression of hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF). We therefore sought to determine whether chronic fetal anemia induces expression of HIF-1-regulated angiogenic factors and glycolytic enzymes in the fetal myocardium. Anemia was produced in chronically instrumented fetal sheep by daily isovolemic hemorrhage (80–100 ml) for either 3 ( n = 4) or 7 days ( n = 11) beginning at 134 days of gestation (term 145 days). Catheterized, nonbled twins served as controls. Isovolemic hemorrhage over 7 days resulted in decreased fetal hematocrit (37 ± 1 to 20 ± 1%) and arterial oxygen content (6.5 ± 0.4 to 2.8 ± 0.2 ml O2/dl). Myocardial blood flow and vascularization were significantly increased after 7 days of anemia. Myocardial HIF-1 protein expression and VEGF (left ventricular), VEGF receptor-1 (right ventricular), and VEGF receptor-2 (right ventricular, left ventricular) mRNA levels were elevated ( P < 0.05) in 7-day anemic compared with control animals. Myocardial expressions of the glycolytic enzymes aldolase, lactate dehydrogenase A, phosphofructokinase (liver), and phosphoglycerol kinase were also significantly elevated after 7 days of anemia. Despite the absence of a significant increase in myocardial HIF-1α protein in 3-day anemic fetuses, expressions of VEGF, VEGF receptor-1, and the glycolytic enzymes were greater in 3-day compared with 7-day anemic animals. These data suggest that HIF-1 likely participates in the fetal myocardial response to anemia by coordinating an increase in gene expressions that promote capillary growth and anaerobic metabolism. However, factors other than HIF-1 also appear important in the regulation of these genes. We speculate that the return of mRNA levels of angiogenic and glycolytic enzymes toward control levels in the 7-day anemic fetus is explained by a significantly increased resting myocardial blood flow, resulting from coronary vascular growth and increased coronary conductance, and a return to a state of adequate oxygen and nutrient delivery, obviating the need for enhanced transcription of genes encoding angiogenic and glycolytic enzymes.
Central endothelin ETBreceptors mediate IL-1-dependent fever induced by preformed pyrogenic factor and corticotropin-releasing factor in the rat
Authors: Fabricio Aline S. C. , Rae Giles A. , Zampronio Aleksander R. , D'Orléans-Juste Pedro , Souza Glória E. P.
Published: August 2005

Blockade of central endothelin ETBreceptors inhibits fever induced by LPS in conscious rats. The contribution of ETBreceptor-mediated mechanisms to fever triggered by intracerebroventricular IL-6, PGE2, PGF2α, corticotropin-releasing factor (CRF), and preformed pyrogenic factor derived from LPS-stimulated macrophages (PFPF) was examined. The influence of natural IL-1 receptor antagonist or soluble TNF receptor I on endothelin (ET)-1-induced fever was also assessed. The selective ETBreceptor antagonist BQ-788 (3 pmol icv) abolished fever induced by intracerebroventricular ET-1 (1 pmol) or PFPF (200 ng) and reduced that caused by ICV CRF (1 nmol) but not by IL-6 (14.6 pmol), PGE2(1.4 nmol), or PGF2α(2 nmol). CRF-induced fever was also attenuated by bosentan (dual ETA/ETBreceptor antagonist; 10 mg/kg iv) but unaffected by BQ-123 (selective ETAreceptor antagonist; 3 pmol icv). α-Helical CRF9–41(dual CRF1/CRF2receptor antagonist; 6.5 nmol icv) attenuated fever induced by CRF but not by ET-1. Human IL-1 receptor antagonist (9.1 pmol) markedly reduced fever to IL-1β (180 fmol) or ET-1 and attenuated that caused by PFPF or CRF. Murine soluble TNF receptor I (23.8 pmol) reduced fever to TNF-α (14.7 pmol) but not to ET-1. The results of the present study suggest that PFPF and CRF recruit the brain ET system to cause ETBreceptor-mediated IL-1-dependent fever.
Differences in the postexercise threshold for cutaneous active vasodilation between men and women
Authors: Kenny Glen P. , Murrin Jane E. , Journeay W. Shane , Reardon Francis D.
Published: August 2005

The purpose of this study was to evaluate the possible differences in the postexercise cutaneous vasodilatory response between men and women. Fourteen subjects (7 men and 7 women) of similar age, body composition, and fitness status remained seated resting for 15 min or cycled for 15 min at 70% of peak oxygen consumption followed by 15 min of seated recovery. Subjects then donned a liquid-conditioned suit. Mean skin temperature was clamped at ∼34°C for 15 min. Mean skin temperature was then increased at a rate of 4.3 ± 0.8°C/h while local skin temperature was clamped at 34°C. Skin blood flow was measured continuously at two forearm skin sites, one with (UT) and without (BT) (treated with bretylium tosylate) intact α-adrenergic vasoconstrictor activity. The exercise threshold for cutaneous vasodilation in women (37.51 ± 0.08°C and 37.58 ± 0.04°C for UT and BT, respectively) was greater than that measured in men (37.33 ± 0.06°C and 37.35 ± 0.06°C for UT and BT, respectively) ( P < 0.05). Core temperatures were similar to baseline before the start of whole body warming for all conditions. Postexercise heart rate (HR) for the men (77 ± 4 beats/min) and women (87 ± 6 beats/min) were elevated above baseline (61 ± 3 and 68 ± 4 beats/min for men and women, respectively), whereas mean arterial pressure (MAP) for the men (84 ± 3 mmHg) and women (79 ± 3 mmHg) was reduced from baseline (93 ± 3 and 93 ± 4 mmHg for men and women, respectively) ( P < 0.05). A greater increase in HR and a greater decrease in the MAP postexercise were noted in women ( P < 0.05). No differences in core temperature, HR, and MAP were measured in the no-exercise trial. The postexercise threshold for cutaneous vasodilation measured at the UT and BT sites for men (37.15 ± 0.03°C and 37.16 ± 0.04°C, respectively) and women (37.36 ± 0.05°C and 37.42 ± 0.03°C, respectively) were elevated above no exercise (36.94 ± 0.07°C and 36.97 ± 0.05°C for men and 36.99 ± 0.09°C and 37.03 ± 0.11°C for women for the UT and BT sites, respectively) ( P < 0.05). A difference in the magnitude of the thresholds was measured between women and men ( P < 0.05). We conclude that women have a greater postexercise onset threshold for cutaneous vasodilation than do men and that the primary mechanism influencing the difference between men and women in postexercise skin blood flow is likely the result of an altered active vasodilatory response and not an increase in adrenergic vasoconstrictor tone.
Sympathetic overactivity in active ulcerative colitis: effects of clonidine
Authors: Furlan Raffaello , Ardizzone Sandro , Palazzolo Laura , Rimoldi Alexandra , Perego Francesca , Barbic Franca , Bevilacqua Maurizio , Vago Luca , Porro Gabriele Bianchi , Malliani Alberto
Published: August 2005

Previous reports suggest that inflammatory bowel diseases may be accompanied by abnormalities in the neural autonomic profile. We tested the hypotheses that 1) an exaggerated sympathetic activity characterizes active ulcerative colitis (UC) and 2) a reduction of sympathetic activity by clonidine would be associated with clinical changes of UC. In 23 patients with UC and 20 controls, muscle sympathetic nerve activity (MSNA), ECG, blood pressure, and respiration were continuously recorded, and plasma catecholamine was evaluated both at rest and during a 75° head-up tilt. Autonomic profile was assessed by MSNA, norepinephrine, epinephrine, spectral markers of low-frequency (LF) cardiac sympathetic (LFRR; normalized units) and high-frequency (HF) parasympathetic (HFRR; normalized units) modulation and sympathetic vasomotor control (LF systolic arterial pressure; LFSAP), obtained by spectrum analysis of the R-R interval and systolic pressure variability. Among UC patients, 16 agreed to be randomly assigned to 8-wk transdermal clonidine (15 mg/wk, 9 subjects), or placebo (7 patients). An autonomic profile, Disease Activity Index (DAI), and endoscopic pattern were compared before and after clonidine/placebo. At rest, MSNA, heart rate (HR), LFRR, LF/HF, and LFSAP were higher and HFRR was lower in patients than in controls. Tilt decreased HFRR and increased MSNA and LFRR less in patients than in controls. Clonidine decreased HR, MSNA, epinephrine, LFRR, and increased HFRR, whereas placebo had no effects. Changes of the autonomic profile after clonidine were associated with reduction of DAI score. An overall increase of sympathetic activity characterized active UC. Normalization of the autonomic profile by clonidine was accompanied by an improvement of the disease.
Compact space‐like hypersurfaces in de Sitter space
Authors: Lv Jinchi
Published: August 2005

We present some integral formulas for compact space‐like
hypersurfaces in de Sitter space and some equivalent
characterizations for totally umbilical compact space‐like
hypersurfaces in de Sitter space in terms of mean curvature and
higher‐order mean curvatures.
L‐fuzzifying topological vector spaces
Authors: Yan Cong-Hua , Wu Cong-Xin
Published: August 2005

The main purpose of this paper is to introduce a concept of L‐fuzzifying topological vector spaces (here L is a completely distributive lattice) and study some of their basic properties. Also, a characterization of such spaces in terms of the corresponding L‐fuzzifying neighborhood structure of the zero element is given. Finally, the conclusion that the category of
L‐fuzzifying topological vector spaces is topological over the category of vector spaces is proved.
Polo-Like Kinase 1 Expression in Medullary Carcinoma of the Thyroid: Its Relationship with Clinicopathological Features
Authors: Ito Yasuhiro , Nakamura Yasushi , Yoshida Hiroshi , Tomoda Chisato , Uruno Takashi , Takamura Yuuki , Miya Akihiro , Kobayashi Kaoru , Matsuzuka Fumio , Kuma Kanji , Kakudo Kennichi , Miyauchi Akira
Published: August 2005

Objective: Polo-like kinase 1 (PLK1) is one of the serine-threonine kinases that contributes to cell mitosis and is regarded as a marker of cellular proliferation. However, its protein expression in human carcinoma has not been studied in depth. In this study, we investigated PLK1 expression in medullary thyroid carcinoma by means of immunohistochemistry. Methods: We immunohistochemically investigated PLK1 expression in 67 cases of medullary thyroid carcinoma. Results: The PLK1 expression level was elevated in 43 of the 67 cases (64.1%). Furthermore, the expression level was directly linked to lymph node metastasis, advanced stage and male sex. All patients who were negative for PLK1 expression are currently alive without tumor recurrence, while 6 of the 43 PLK1-positive patients showed recurrence and 3 have already died of this disease. Conclusions: These findings suggest that PLK1 expression significantly reflects aggressive characteristics of medullary thyroid carcinoma.
Anionic Peptide Factor/Phosphatidylcholine Particles Promote the Inhibition of Vascular Cell Adhesion Molecule-1 in Human Umbilical Vein Endothelial Cells
Authors: Lombard Elise , Marin Valérie , Domingo Nicole , Grès Sandra , Lorec Anne-Marie , Saunier Vincent , Arlotto Emmanuelle , Portugal Henri , Lairon Denis , Farnarier Catherine , Chanussot Françoise
Published: August 2005

Objective: High-density lipoproteins (HDLs) have significant cardiovascular benefits by retarding the progression of atherosclerosis. One of the mechanisms is the inhibition by HDLs of the vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells. Our objective was to test the effect on VCAM-1 expression by the human umbilical vein endothelial cells (HUVEC) of a minor HDL2 and HDL3 apolipoprotein, the anionic peptide factor (APF). The peptide has previously been found to develop some beneficial effects against atherosclerosis, i.e. by promoting the cholesterol efflux from endothelial cells. Methods: We examined the effects of two HDL apolipoproteins A-I and APF, either in presence or absence of phosphatidylcholines (PCs), or free PCs, on the expression of VCAM-1 by HUVEC. The cells were stimulated with either the tumor necrosis factor-α (TNFα, 500 pg/ml) or the calcium bound to heparin (10 µg Ca2+/ml, 50 µg heparin/ml). Results: In the presence of TNFα, only the free PCs (0.25 and 1 mM) developed an inhibitory effect (up to 50%). In the absence of TNFα and in the presence of calcium bound to heparin, either the lipid-free APF (3.5 µM) or the APF/PC complexes (1:57 molar ratio) or the free PCs (0.25 mM) exhibited a substantial inhibitory effect (72, 71 and 42%, respectively). Conclusion: Our present findings suggest for the first time that one of the mechanisms of the antiatherogenic action of APF involves the inhibition of VCAM-1 expression by HUVEC. The peptide, through its phospholipid-binding and its calcium antagonist abilities, appears to confer on the HDLs a protective effect against the early cellular event of the inflammatory process.
Severe Dilatation of Saphenous Vein Grafts: A Late Complication of Coronary Surgery in Which the Diagnosis Is Suggested by Chest X-Ray
Authors: Almanaseer Yassar , Rosman Howard S. , Kazmouz Ghassan , Giraldo Alvaro A. , Martin James
Published: August 2005

Aneurysmal dilatation of saphenous vein graft (SVG), first reported in 1975, is secondary to true aneurysm or pseudoaneurysm. We report 1 case and review 107 cases published since 1975. Severe SVG dilatations are large (6 ± 3 cm), occur remote from surgery (12 ± 4 years) and are life threatening, with 15.7% in-hospital mortality. Symptoms are nonspecific and the abnormality is initially observed by chest X-ray in 57% of cases. The chest X-ray abnormalities have a distinctive appearance that may suggest both diagnosis and which SVG is involved. Diagnosis is made clinically by imaging, i.e. computed tomography, echocardiography, magnetic resonance and/or surgical observation (66 cases), or most accurately by tissue evaluation by the pathologist (42 cases). Aneurysm is more common than pseudoaneurysm by a 6:1 ratio.
Prognostic Value of Vascular Endothelial Growth Factor Tumor Tissue Content of Colorectal Cancer
Authors: Ferroni Patrizia , Spila Antonella , Martini Francesca , D’Alessandro Roberta , Mariotti Sabrina , Del Monte Girolamo , Graziano Paolo , Buonomo Oreste , Guadagni Fiorella , Roselli Mario
Published: August 2005

Objectives: A longitudinal study was designed to quantify tumor tissue content of vascular endothelial growth factor (VEGF) in patients with colorectal cancer (CRC) and to evaluate its prognostic value in respect to the relapse-free and overall survivals. Methods: Sixty-nine patients with CRC were followed from the time of diagnosis of primary tumor for at least 3 years after surgery. Quantitative evaluation of VEGF content in tissue was performed on whole protein extracts obtained from biopsies of histologically confirmed neoplastic tissues and corresponding mucosa, histologically confirmed as ‘normal’. Results: VEGF levels were higher in CRC tissues, median 141 pg/mg of protein (interquartile range 70–375), compared with corresponding normal mucosa, median 45 pg/mg of protein (interquartile range 22–78; p < 0.0001), and were associated with the stage of disease (p = 0.035) by multivariate analysis. Tumor VEGF content was higher in relapsing patients compared with those who remained disease free (p < 0.001) and was independently associated with relapse-free survival (p = 0.044). Cox’s proportional hazard survival analysis demonstrated that VEGF (p = 0.035) had an independent prognostic value in respect to overall survival. Conclusions: Elevated tumor VEGF content may discriminate between early and late stages of CRC and may be used as an independent prognostic parameter in the management of these patients.
Saccadic Eye Velocity after Selective GABAergic Treatment with Tiagabine in Healthy Volunteers
Authors: Zwanzger Peter , Schüle Cornelius , Eser Daniela , Baghai Thomas C. , Padberg Frank , Ella Robin , Möller Hans-Jürgen , Rupprecht Rainer , Kathmann Norbert
Published: August 2005

Background: Saccadic eye velocity (SEV) has been shown to be a reliable neurophysiological tool for the assessment of γ-aminobutyric acid GABAA receptor sensitivity. Administration of benzodiazepines targeting the GABAA receptor decreases SEV in healthy volunteers. Tiagabine is a new antiepileptic drug which acts via selective blockade of GABA reuptake. Therefore, we examined the effects of tiagabine on saccade parameters. Methods: SEV was analyzed in 8 healthy volunteers before and after 7 days of tiagabine treatment. Subjects received tiagabine in a daily dose of 15 mg. Saccades were measured using a noninvasive infrared oculographic device. Amplitude, latency, and SEV were analyzed as a function of treatment and target eccentricity. Results: SEV and saccade latency increased with target amplitude. Treatment with tiagabine had no significant effect on SEV and saccade amplitude. A trend was found for increased latencies after tiagabine. Conclusion: In contrast to findings with benzodiazepines, tiagabine treatment had no impact on SEV in healthy volunteers. The subchronic tolerance effects or the different site of action on the GABAA/BZD receptor complex may account for this deviating profile.
Auditory Stream Segregation in the Songbird Forebrain: Effects of Time Intervals on Responses to Interleaved Tone Sequences
Authors: Bee Mark A. , Klump Georg M.
Published: August 2005

For both humans and other animals, the abilities to integrate separate sound elements over time into coherent perceptual representations, or ‘auditory streams’, and to segregate these auditory streams from other interleaved sounds are critical for hearing and vocal communication. In humans and European starlings (Sturnus vulgaris) the ability to perceptually segregate a simple interleaved tone sequence comprised of two alternating tones differing in frequency (ABA–ABA–ABA–...) into separate auditory streams of A and B tones is promoted at larger frequency separations (ΔF) between the A and B tones. In humans, segregating A and B tones into different streams also appears to be promoted at shorter interstimulus intervals (ISI) between tones within a stream (e.g., between consecutive A tones). Here, we used the ABA experimental paradigm to investigate the influence of different time intervals between A and B tones in repeated ABA triplets on neural responses in the starling forebrain. The main finding from the study is that a ΔF-dependent effect of ISI had a large influence on the relative responses to A and B tones. Responses to B tones were suppressed, relative to A-tone responses, when the A and B tones were more similar in frequency (smaller ΔFs) and occurred at shorter ISIs. We attribute these suppressive effects to physiological forward masking and suggest that forward masking functions as a mechanism for segregating neural responses to interleaved tones in tonotopic space. We discuss the relevance of our physiological data with respect to previous electrophysiological studies of auditory stream segregation in mammals and previous perceptual studies in humans.
Predictors of Death in Patients on Peritoneal Dialysis: The Missouri Peritoneal Dialysis Study
Authors: Trivedi Hariprasad , Tan Seng Hoe , Prowant Barbara , Sherman Ashley , Voinescu C. Gentiana , Atalla Jamal , Khanna Ramesh , Nolph Karl
Published: August 2005

Background: The study was designed to identify predictors of death in subjects on peritoneal dialysis (PD). Methods: The population consisted of patients initiated on PD at the University of Missouri-Columbia and Dialysis Clinic Incorporated from January 1, 1990, through December 31, 1999. Baseline variables included demographics, clinical data, initial measures of nutritional status, adequacy, and transport characteristics. Co-morbidities were scored using a modified version of the Index of Coexistent Disease. Ongoing (during the course of PD) variables consisted of clinical characteristics and weighted time average of a number of laboratory, adequacy, and nutritional variables. The variables were screened using a univariate procedure, and then analyzed using stepwise logistic regression to evaluate their independent relation to death. Results: There were 105 men and 86 women – 180 Caucasians, 10 African-American, 1 Asian, mean age 61 ± 13 (SD) years, and mean duration of follow-up 21 ± 18 months. Eighty-two patients suffered the outcome of death. Lean body mass (LBM) at the initiation of PD was negatively associated with the risk of death (p < 0.01). In addition, the need for a partner to perform PD, total morbidity count, and the summated severity score of all co-morbidities were associated with an increased risk of death. The analysis of ongoing variables revealed that serum phosphate (negative association, p = 0.02) and number of hospitalization days per month on PD (p = 0.0006) were associated with an increased risk of death. Conclusion: Phosphate levels and LBM are strong negative predictors of death in PD subjects. Further, patients who need the assistance of a partner to perform PD have decreased survival.