bluuebunny/crossref_metadata_2025 huggingface dataset:
Flavour sensory qualities and consumer perceptions – a comparison of sensory and brain activity responses to flavour components in different populations
Authors: Patterson John , Owen Caroline M. , Frank Damian , Smith Rebecca , Cadusch Peter
Published: April 2004

This paper explores the relationship between odour responses of naïve consumers to different flavour components, by investigating the ability of sensory ratings and brain recording techniques to reveal differences in responses associated with differences in background and experience. Two groups of naïve consumers (Australian and Overseas students from Asian/South‐east Asian background; all untrained in sensory work) participated in sensory ratings and brain electrical activity [electroencephalogram (EEG)] recordings of responses to the odours of four flavour components. Results indicated no significant differences in rating responses between cultural groups, but did reveal significant brain electrical activity differences between cultural groups in response to para‐cresol, and a similar (nonsignificant) trend in responses to 2‐heptanone and dimethyltrisulphide. These results suggest that the application of EEG techniques to sensory analysis has the potential to provide physiological evidence of cultural differences in odour responsiveness that cannot always be discriminated by subjective reports.
The perception of risks associated with food‐related hazards and the perceived reliability of sources of information
Authors: Rosati Simona , Saba Anna
Published: April 2004

This study aimed to explore, on the one hand, public perception of risks associated with different food‐related hazards and, on the other hand, perception of reliability of various sources providing information on food‐related risks. Some differences were found when consumers compared six food‐related hazards in terms of perceived personal risk and their knowledge of potential food risks. The concern about food risks was found to be statistically significantly dependent on the perception of risk to the individual. As far as the perception of the reliability of information was concerned, a principal component analysis revealed some differences in terms of respondents’ perception when the sources were compared. Furthermore, a regression analysis showed that the perceived amount of information each source contained about food‐related hazards was an important element in perception of reliability, as well as the degree of concern consumers believed the agencies had with protecting their health from food risks.
Detection of irradiated food by immunoassay – development and optimization of an ELISA for dihydrothymidine in irradiated prawns
Authors: Tyreman Anne L. , Bonwick Graham A. , Smith Christopher J. , Coleman Robert C. , Beaumont Paul C. , Williams John H. H.
Published: April 2004

This paper describes the development and use of a competitive enzyme‐linked immunosorbent assay (ELISA) to detect prawns which have been irradiated. The ELISA utilizes a monoclonal antibody against a modified DNA base, dihydrothymidine. A comparison of extraction procedures demonstrated that DNA purification was not required and that crude prawn homogenate could be used in the ELISA. The ELISA was applied successfully to two prawn species, North Atlantic prawn (Pandalus borealis) and Tiger prawn (Penaeus monodon). The ELISA has a working range of 0.5–2 kGy with CVs typically below 10%. Storage of irradiated prawns for up to 12 months at −20 °C had no effect on ELISA performance. As most food contains DNA the assay has potential to be applied in a wide range of foodstuffs.
Romantic involvement and depressive symptoms in early and late adolescence: The role of a preoccupied relational style
Authors: Davila Joanne , Steinberg Sara J. , Kachadourian Lorig , Cobb Rebecca , Fincham Frank
Published: April 2004

Two studies examined the association between depressive symptoms and romantic involvement in adolescence and tested the hypothesis that romantic involvement is associated more strongly with symptoms among adolescents who have a more preoccupied style of relating, compared to adolescents who have a less preoccupied style of relating. Study 1 (N = 96 early adolescent females) examined concurrent associations and Study 2 (N = 80 late adolescent males and females) examined longitudinal associations. In both age groups, romantic involvement was associated with greater depressive symptoms and this was most true among adolescents with a preoccupied style of relating. Implications for models of depression and adolescent romantic functioning are discussed.
Measurement of communal strength
Authors: Mills Judson , Clark Margaret S. , Ford Thomas E. , Johnson Melanie
Published: April 2004

Communal strength refers to a person's degree of motivation to respond to a communal partner's needs. The development and testing of a questionnaire measure of communal strength is described. Study 1 involved item selection. Studies 2 and 3 found that the 10‐item communal strength measure taps a construct distinct from behavioral interdependence as measured by the Relationship Closeness Inventory of Berscheid, Snyder, and Omoto (1989) and distinct from liking for the partner. As expected, the measure correlated highly with Rubin's (1970) Love Scale. Studies 4 and 5 found the measure predicted allocation of benefits to peers and reports of giving help to, and receiving help from, friends. Study 6 found that, when answered in relation to the respondent's spouse, the measure predicted the spouse's marital satisfaction, after controlling for the respondent's communal orientation and own marital satisfaction.
Associations between insecure attachment and sexual experiences
Authors: Gentzler Amy L. , Kerns Kathryn A.
Published: April 2004

Associations between insecure attachment and sexual experiences were tested in a sample of 328 college students. Variations in adult attachment previously have been shown to relate to sexual behaviors, with the current study extending earlier work by examining different sexual outcomes and by testing factors that may account for these relations. Avoidant attachment was expected to relate to engagement in casual sex (i.e., a greater number of sexual partners and lower percentage of partners within committed relationships), with less restrictive sexual beliefs mediating the relations. In contrast, anxious attachment was expected to relate to more unwanted but consensual sexual experiences, and to more negative affect about sexual experiences, with low self‐esteem mediating the relations. Results showed some support for the hypotheses. Avoidant attachment was related to the type (but not number) of sexual partners, with sexual beliefs mediating the relations. A greater number of unwanted but consensual sexual experiences related to anxious and avoidant attachment for women and to avoidant attachment for men. Anxiety related to negative affect for women and men, and self‐esteem served as a partial mediator of these relations.
Treatment of Full‐thickness Skin Defect with Concomitant Grafting of 6‐fold Extended Mesh Auto‐skin and Allogeneic Cultured Dermal Substitute
Authors: Kashiwa Naohiro , Ito Osamu , Ueda Takeshige , Kubo Kentaro , Matsui Hiromichi , Kuroyanagi Yoshimitsu
Published: April 2004

Abstract:  The aim of this clinical study was to evaluate an allogeneic cultured dermal substitute (CDS) as a biological dressing for highly extended mesh auto‐skin grafting. The subjects were five patients with extensive deep burn wounds. Allogeneic CDS was prepared by seeding fibroblasts on a spongy matrix of hyaluronic acid and atelo‐collagen. Six‐fold extended auto‐skin graft was applied to the debrided wound, on which allogeneic CDS was placed. A conventional ointment‐gauze dressing was used to protect the CDS. The CDS was applied repeatedly at intervals of 5–7 days. In all cases, the wounds were closed by successful take of mesh auto‐skin graft and prompt epithelization from the grafted skin. The skin on the grafted area had a cicatrix appearance, but was soft and thin, maintaining good quality. The application of 6‐fold extended auto‐skin graft in conjunction with allogeneic CDS is an effective method for treatment of extensive severe  burn  wounds.
Effect of an Experimental Stenosis in the Porcine Descending Thoracic Aorta
Authors: Tsatsaris Athanasios , Iliopoulos Dimitrios , Baldoukas Antonios , Triantafyllou Dimitrios , Berketis Nikolaos , Kavantzas Nikolaos
Published: April 2004

Abstract:  Objective: To investigate the alterations of mechanical properties in pre‐ (A) and post‐ (B) stenotic aortic regions after an experimentally induced stenosis in the descending thoracic aorta. Methods: Eight healthy, normalipemic and normotensive Landrace pigs were subjected to thoracotomy under sterile conditions. In the upper segment of the descending thoracic aorta a circumferential symmetric constriction 5 mm in length was imposed and stabilized; thus, a 15–20 mm Hg pressure gradient was established. The pressure gradient was verified via catheterization of the vessel with pressure tip catheters. Pre‐ and poststenotic hemodynamic disturbances were recorded by the use of a bidirectional Doppler flowmeter. Pressure and flow measurements were carried out before, 10 min after, and 90 days after the creation of the stenosis. Euthanasia was performed after 90 days, and the descending thoracic aorta removed. In the A and B regions serial sections of aorta (5 mm in length) create appropriate aortic “rings,” to test in a uniaxial tension device, in order to determine the mechanical properties of the vessel. Histological analysis was performed, so as to estimate the content (%) of collagen and elastin fibers within the aortic wall. Eight sham‐operated pigs were used as controls. Results: Reverse blood flow was recorded at both the A and B sites, and was maintained until euthanasia. Reverse flow in the poststenotic region B was greater than that in the prestenotic region. Mechanical analysis showed that the aortic wall in A and B regions became stiffer particularly at high strains (P < 0.05). Histological analysis indicated that the percentage of elastin fibers remained almost the same in both regions while the percentage of collagen fibers increased considerably, especially in the B region (P < 0.05). Conclusions: A nonhemodynamically significant experimental stenosis located at the level of the descending thoracic aorta induced reverse blood flow before and after the stenosis. The higher the reverse flow, the more collagen fibers were produced and the stiffer the aortic wall. Since hypercholesterolemia can be ruled out as a hardening factor in the present study, disturbed flow seems to be an independent factor which activates fibroblasts to overproduce collagen and to eventually reduce the  aorta's compliance.
Testing of Extracorporeal Membrane Oxygenation Circuit Related Hemolysis Using Long‐term Stored Packed Red Cells and Fresh Frozen Plasma
Authors: Burda Gudrun , Trittenwein Hildegard , Carole Hamilton , Trittenwein Gerhard
Published: April 2004

Abstract:  Background:  The resistance of blood used in these studies to hemolysis differs markedly from that used in neonatal extracorporeal circulation under clinical circumstances. In this study, the possibility of using expired packed red cells to determine hemolysis caused by mechanical and/or environmental factors was investigated.

Methods:  Packed red blood cells stored for 42 days were mixed with fresh frozen plasma and the resultant mixture was divided into three groups, two study groups and a control. For the study groups, two different centrifugal pump heads (Medtronic BP 50 and Jostra RF 32) were used in an extracorporeal membrane oxygenation (ECMO) circuit. Free hemoglobin, lactate dehydrogenase, lactic acid, pH, potassium, and glucose were investigated at various time intervals.

Results:  Hemolysis did not differ between the groups. Free hemoglobin increased in all groups after 12 h. Lactic acid increased linearly in all groups up to 12 h. Glucose and pH decreased steadily in all groups. Hemolysis created during mock ECMO did not differ between the circuits using the two different pump heads  noted.

Conclusion:  Human  donor  blood  stored  up to its expiration date is a feasible medium for mock circulation tests of up to 12 h duration under the circumstances described.
Numerical Estimation of Blood Damage in Artificial Organs
Authors: Goubergrits Leonid , Affeld Klaus
Published: April 2004

Abstract:  The aim of this study was to determine a method for the numerical estimation of blood damage. Normally, human or animal blood is used for in vitro evaluation of lysis by artificial organs. However, blood has some disadvantages: large biological variability and different initial test conditions lead to nonreproducible test results. For that reason, it would be an advantage to have a numerical method for blood damage estimation. This proposed method is based on the calculation of an integrated hemolysis and platelet lysis index along the path line in the flow field of the artificial organ. The time‐dependent shear stress related lysis is based on known experimental data. In order to calibrate these data, the method was first applied to blood circulation in the human body. The results showed that the known data overestimate hemolysis by a factor of approximately 25. Next, the method was applied to a standard Björk–Shiley valve. The flow through a valve was simulated with the computational fluid dynamics program FLUENT. The calculation of lysis was added into FLUENT and done automatically. The results showed that the Björk–Shiley valve  increased  the hemolysis index by 7% if implanted in the human body circulation.
Silence as the Foundation of Learning
Authors: Caranfa Angelo
Published: April 2004

Past and present discussions on education all too frequently neglect the role that silence plays in learning. In this article I set out to demonstrate that silence is the very foundation of learning. My claim is that we must find ways of freeing silence in our pedagogical practices so that our discourse does not denigrate into mere empty words, but becomes a means towards self‐knowledge. My position is that no discourse can awaken self‐knowledge; what it can do, at best, is to help create an inner state of silence necessary for mental, moral, and spiritual growth of the human self. The essay is a defense of Socratic learning, complemented with the poetic discourse of Max Picard. Such a marriage alone can render education creative, most especially when it is applied to reading and writing.
Synaptic interactions between pyramidal cells and interneurone subtypes during seizure‐like activity in the rat hippocampus
Authors: Fujiwara‐Tsukamoto Yoko , Isomura Yoshikazu , Kaneda Katsuyuki , Takada Masahiko
Published: April 2004

We have recently reported that excitatory GABAergic and glutamatergic mechanisms may be involved in the generation of seizure‐like (ictal) rhythmic synchronization (afterdischarge), induced by a strong synaptic stimulation of the CA1 pyramidal cells in the mature rat hippocampus in vitro. To clarify the network mechanism of this neuronal synchronization, dual whole‐cell patch‐clamp recordings of the afterdischarge responses were performed simultaneously from a variety of interneurones and their neighbouring pyramidal cells in hippocampal CA1‐isolated slice preparations. According to morphological and electrophysiological criteria, the recorded interneurones were then classified into distinct subtypes. The non‐fast‐spiking interneurones located in the strata lacunosum‐moleculare and radiatum hardly discharged during the afterdischarge, whereas most of the fast‐spiking and non‐fast‐spiking interneurones in the strata oriens and pyramidale, including the basket, chandelier and bistratified cells, exhibited prominent firings that were precisely synchronous with oscillatory responses in the pyramidal cells. Field potential recordings showed that excitatory synaptic transmissions might take place primarily in the strata oriens and pyramidale during the afterdischarge. Restricted lesions in the strata oriens and pyramidale, but not in the other layers, resulted in the complete desynchronization of afterdischarge activity, and also, local application of glutamate receptor antagonists to these layers blocked the expression of afterdischarge. The present findings indicate that the neuronal synchronization of epileptic afterdischarge may be accomplished in a ‘positive feedback circuit’ formed by the excitatory GABAergic interneurones and the glutamatergic pyramidal cells within the strata oriens and/or pyramidale of the hippocampal CA1 region.
S
-Nitrosylation of Parkin Regulates Ubiquitination and Compromises Parkin's Protective Function
Authors: Chung Kenny K. K. , Thomas Bobby , Li Xiaojie , Pletnikova Olga , Troncoso Juan C. , Marsh Laura , Dawson Valina L. , Dawson Ted M.
Published: April 2004

Parkin is an E3 ubiquitin ligase involved in the ubiquitination of proteins that are important in the survival of dopamine neurons in Parkinson's disease (PD). We show that parkin is
S-
nitrosylated in vitro, as well as in vivo in a mouse model of PD and in brains of patients with PD and diffuse Lewy body disease. Moreover,
S-
nitrosylation inhibits parkin's ubiquitin E3 ligase activity and its protective function. The inhibition of parkin's ubiquitin E3 ligase activity by
S-
nitrosylation could contribute to the degenerative process in these disorders by impairing the ubiquitination of parkin substrates.
HPV and histological status of pelvic lymph node metastases in cervical cancer: a prospective study
Authors: Lukaszuk K , Liss J , Wozniak I , Sliwinski W , Emerich J , Wojcikowski C
Published: April 2004

Aims:The purpose of this prospective study was to describe the incidence and distribution pattern of human papillomavirus (HPV) DNA in intraoperative dissected lymph nodes and to relate this to the pathological confirmation of metastasis.

Methods:Samples of primary cervical cancer lesions and dissected lymph nodes were obtained from women undergoing surgical treatment. The presence of HPV DNA was detected by the polymerase chain reaction.

Results:Tissue from 79 tumours and 365 lymph nodes was analysed. Metastasis to the lymph nodes was found in 19 cases. Metastasis correlated with the volume of the primary lesion, the depth of cervical and vaginal invasion, and with invasion of the corpus. HPV DNA was found in 60 of the primary lesions and 31 of the lymph nodes. The presence of HPV DNA in the lymph nodes correlated with the volume of the primary lesion and vaginal invasion.

Conclusions:The incidence of HPV DNA in lymph nodes is twice as high as that of histopathologically confirmed metastases. The risk of the presence of HPV DNA and histopathologically confirmed metastases in lymph nodes is related to certain features of the primary tumour.
Human herpesvirus 8 (HHV8) sequence variations in HHV8 related tumours in Okinawa, a subtropical island in southern Japan
Authors: Kamiyama K , Kinjo T , Chinen K , Iwamasa T , Uezato H , Miyagi J-i , Mori N , Yamane N
Published: April 2004

Background:Although rare in mainland Japan, classic Kaposi’s sarcoma (KS) is frequently reported in Okinawa, a subtropical island in southern Japan. Human herpesvirus 8 (HHV8) has been identified in the tumours and geographical differences occur.

Aim:To sequence HHV8 in classic and AIDS associated KS in Okinawa.

Materials/Methods:Eight classic KS cases, one AIDS associated KS, five granuloma pyogenicum cases, two inflammatory pseudotumours, two Castleman’s disease cases, one angiosarcoma, and one primary effusion lymphoma (PEL) were studied. As a control, HHV8 positive cultured PEL cells (TY-1) were used. The presence of HHV8 sequences was evaluated by PCR and in situ hybridisation. PCR products were sequenced.

Results:There were no histological differences among KS resulting from the different virus genotypes. HHV8 was detected in all cases of KS, in one PEL, and one granuloma pyogenicum. Eight classic KS cases and one granuloma pyogenicum were infected with HHV8 genotype II/C (K1 region) or subtype C (ORF26 region), which had a five amino acid deletion at K1 VR2 region. An AIDS associated KS and a PEL were infected with type I/A virus.

Conclusion:In Okinawa, classic KS cases and one granuloma pyogenicum case were infected with HHV8 genotype II/C, also classified as subtype C. AIDS associated KS and PEL were infected with a different HHV8 (genotype I/A), similar to that found in the USA. In Okinawa, HHV8 infection is more than four times higher than in mainland Japan, resulting in many cases of KS because of HHV8 genotype II/C infection.
The prevalence and spectrum of α and β thalassaemia in Guangdong Province: implications for the future health burden and population screening
Authors: Xu X M , Zhou Y Q , Luo G X , Liao C , Zhou M , Chen P Y , Lu J P , Jia S Q , Xiao G F , Shen X , Li J , Chen H P , Xia Y Y , Wen Y X , Mo Q H , Li W D , Li Y Y , Zhuo L W , Wang Z Q , Chen Y J , Qin C H , Zhong M
Published: April 2004

Aim:Thalassaemia is a good candidate disease for control by preventive genetic programmes in developing countries. Accurate population frequency data are needed for planning the control of thalassaemia in the high risk Guangdong Province of southern China.

Methods:In total, 13 397 consecutive samples from five geographical areas of Guangdong Province were analysed for both haematological and molecular parameters.

Results:There was a high prevalence of carriers of α thalassaemia (8.53%), β thalassaemia (2.54%), and both α and β thalassaemia (0.26%). Overall, 11.07% of the population in this area were heterozygous carriers of α and β thalassaemia. The mutation spectrum of α and β thalassaemia and its constitution were fully described in this area. This study reports the true prevalence of silent α thalassaemia in the southern China population for the first time. In addition, two novel mutations that give rise to α thalassaemia, one deletion resulting in β thalassaemia, and a rare deletion (−−THAIallele) previously unreported in mainland China were detected. The frequency of the most common mutation, the Southeast Asian type of deletion (−−SEA, accounting for 48.54% of all α thalassaemias) was similar to the total of two α+thalassaemia deletions (−α3.7and −α4.2, accounting for 47.49% of α thalassaemia).

Conclusion:Both α and β thalassaemia are widely distributed in Guangdong Province of China. The knowledge gained in this study will enable the projected number of pregnancies at risk to be estimated and a screening strategy for control of thalassaemia to be designed in this area.
ERROR RATE IN CURRENT-CONTROLLED LOGIC PROCESSORS WITH SHOT NOISE
Authors: KIM JONG U. , KISH LASZLO B.
Published: April 2004

The error rate in a current-controlled logic microprocessor dominated by shot noise has been investigated. It is shown that the error rate increases very rapidly with increasing cutoff frequency. The maximum clock frequency of the processor, which works without errors, is obtained as a function of the operational current. The information channel capacity of the system is also studied.
RANDOM WALK THEORY APPLIED TO DAPHNIA MOTION
Authors: KOMIN NIKO , ERDMANN UDO , SCHIMANSKY-GEIER LUTZ
Published: April 2004

The zooplankton Daphnia or "water flea" — one of the most common crustacean to be found in freshwater — is subject to recent studies. It is known to perform vortex motions under certain light conditions as well as more complex navigational tasks. Experimental data show that Daphnia move with a preferred turning angle, what is of main interest in this paper. The above-mentioned experimental fact is taken in order to derive a diffusion law for these types of motion. Deviations from the free diffusive behavior are investigated, based on random walk theory.
A stomatin and a degenerin interact in lipid rafts of the nervous system of Caenorhabditis elegans
Authors: Sedensky M. M. , Siefker J. M. , Koh J. Y. , Miller D. M. , Morgan P. G.
Published: April 2004

In Caenorhabditis elegans, the gene unc-1 controls anesthetic sensitivity and normal locomotion. The protein UNC-1 is a close homolog of the mammalian protein stomatin and is expressed primarily in the nervous system. Genetic studies in C. elegans have shown that the UNC-1 protein interacts with a sodium channel subunit, UNC-8. In humans, absence of stomatin is associated with abnormal sodium and potassium levels in red blood cells. Stomatin also has been postulated to participate in the formation of lipid rafts, which are membrane microdomains associated with protein complexes, cholesterol, and sphingolipids. In this study, we isolated a low-density, detergent-resistant fraction from cell membranes of C. elegans. This fraction contains cholesterol, sphingolipids, and protein consistent with their identification as lipid rafts. We then probed Western blots of protein from the rafts and found that the UNC-1 protein is almost totally restricted to this fraction. The UNC-8 protein is also found in rafts and coimmunoprecipitates UNC-1. A second stomatin-like protein, UNC-24, also affects anesthetic sensitivity, is found in lipid rafts, and regulates UNC-1 distribution. Mutations in the unc-24 gene alter the distribution of UNC-1 in lipid rafts. Each of these mutations alters anesthetic sensitivity in C. elegans. Because lipid rafts contain many of the putative targets of volatile anesthetics, they may represent a novel class of targets for volatile anesthetics.
Importance of antioxidant and antiapoptotic effects of β-receptor blockers in heart failure therapy
Authors: Kawai Keisuke , Qin Fuzhong , Shite Junya , Mao Weike , Fukuoka Shuji , Liang Chang-seng
Published: April 2004

The present study was carried out to determine whether beneficial effects of carvedilol in congestive heart failure (CHF) are mediated via its β-adrenergic blocking, antioxidant, and/or α-adrenergic blocking action. Rabbits with heart failure induced by rapid cardiac pacing were randomized to receive subcutaneous carvedilol, metoprolol, propranolol plus doxazosin, or placebo pellets for 8 wk and compared with sham-operated rabbits without pacing. We found rapid cardiac pacing produced clinical heart failure, left ventricular dilation, and decline of left ventricular fractional shortening. This was associated with an increase in left ventricular end-diastolic pressure, decrease in left ventricular first derivative of left ventricular pressure, and myocyte hypertrophy. Tissue oxidative stress measured by GSH/GSSG was increased in the heart with increased oxidation product of mitochondrial DNA, 8-oxo-7,8-dihydro-2′-deoxyguanosine, increase of Bax, decrease of Bcl-2, and increase of apoptotic myocytes as measured by anti-single-stranded DNA monoclonal antibody. Administration of carvedilol and metoprolol, which had no effect in sham animals, attenuated cardiac ventricular remodeling, cardiac hypertrophy, oxidative stress, and myocyte apoptosis in CHF. In contrast, propranolol plus doxazosin, which has less antioxidant effects, produced smaller effects on left ventricular function and myocyte apoptosis. In all animals, GSH/GSSG correlated significantly with changes of left ventricular end-diastolic dimension ( r = −0.678, P < 0.0001), fractional shortening ( r = 0.706, P < 0.0001), and apoptotic myocytes ( r = −0.473, P = 0.0001). Thus our findings suggest antioxidant and antiapoptotic actions of carvedilol and metoprolol are important determinants of clinical beneficial effects of β-receptors in the treatment of CHF.
Effect of lung-protective ventilation on severePseudomonas aeruginosapneumonia and sepsis in rats
Authors: Kurahashi Kiyoyasu , Ota Shuhei , Nakamura Kyota , Nagashima Yoji , Yazawa Takuya , Satoh Minako , Fujita Asako , Kamiya Ritsuko , Fujita Eri , Baba Yasuko , Uchida Kanji , Morimura Naoto , Andoh Tomio , Yamada Yoshitsugu
Published: April 2004

Pneumonia caused by Pseudomonas aeruginosa carries a high rate of morbidity and mortality. A lung-protective strategy using low tidal volume (VT) ventilation for acute lung injury improves patient outcomes. The goal of this study was to determine whether low VTventilation has similar utility in severe P. aeruginosa infection. A cytotoxic P. aeruginosa strain, PA103, was instilled into the left lung of rats anesthetized with pentobarbital. The lung-protective effect of low VT(6 ml/kg) with or without high positive end-expiratory pressure (PEEP, 10 or 3 cmH2O) was then compared with high VTwith low PEEP ventilation (VT12 ml/kg, PEEP 3 cmH2O). Severe lung injury and septic shock was induced. Although ventilatory mode had little effect on the involved lung or septic physiology, injury to noninvolved regions was attenuated by low VTventilation as indicated by the wet-to-dry weight ratio (W/D; 6.13 ± 0.78 vs. 3.78 ± 0.26, respectively) and confirmed by histopathological examinations. High PEEP did not yield a significant protective effect (W/D, 4.03 ± 0.32) but, rather, caused overdistension of noninvolved lungs. Bronchoalveolar lavage revealed higher concentrations of TNF-α in the fluid of noninvolved lung undergoing high VTventilation compared with those animals receiving low VT. We conclude that low VTventilation is protective in noninvolved regions and that the application of high PEEP attenuated the beneficial effects of low VTventilation, at least short term. Furthermore, low VTventilation cannot protect the involved lung, and high PEEP did not significantly alter lung injury over a short time course.
Phosphatidylinositol 3,4,5-trisphosphate: an early mediator of insulin-stimulated sodium transport in A6 cells
Authors: Markadieu Nicolas , Blero Daniel , Boom Alain , Erneux Christophe , Beauwens Renaud
Published: April 2004

Insulin stimulates sodium transport across A6 epithelial cell monolayers. Activation of phosphatidylinositol 3-kinase (PI 3-kinase) was suggested as an early step in the insulin-stimulated sodium reabsorption (Ref. 35). To establish that the stimulation of the PI 3-kinase signaling cascade is causing stimulation of apical epithelial Na channel, we added permeant forms of phosphatidylinositol (PI) phosphate (P) derivatives complexed with a histone carrier to A6 epithelium. Only PIP3and PI( 3 , 4 )P2but not PI( 4 , 5 )P2stimulated sodium transport, although each of them penetrated into A6 cell monolayers as assessed using fluorescent permeant phosphoinositides derivatives. By Western blot analysis of A6 cell extracts, the inositol 3-phosphatase PTEN and the protein kinase B PKB were both detected. To further establish that the stimulation of sodium transport induced by insulin is related to PIP3levels, we transfected A6 cells with human PTEN cDNA and observed a 30% decrease in the natriferic effect of insulin. Similarly, the increase in sodium transport observed by addition of permeant PIP3was also reduced by 30% in PTEN-overexpressing cells. PKB, a main downstream effector of PI 3-kinase, was phosphorylated at both Thr 308 and Ser 473 residues upon insulin stimulation of the A6 cell monolayer. PKB phosphorylation in response to insulin stimulation was reduced in PTEN-overexpressing cells. Permeant PIP3also increased PKB phosphorylation. Taken together, the present results establish that the d-3-phosphorylated phosphoinositides PIP3and PI( 3 , 4 )P2mediate the effect of insulin on sodium transport across A6 cell monolayers.
Luminal flow induces eNOS activation and translocation in the rat thick ascending limb. II. Role of PI3-kinase and Hsp90
Authors: Ortiz Pablo A. , Hong Nancy J. , Garvin Jeffrey L.
Published: April 2004

Endothelial nitric oxide synthase (eNOS) regulates NaCl absorption by the thick ascending limb of the loop of Henle (THAL). We found that augmenting luminal flow induces eNOS activation and translocation to the apical membrane of THALs (Ortiz PA, Hong NJ, and Garvin JL. Am J Physiol Renal Physiol 287: F274–F280, 2004). In other cells, eNOS activation by shear stress is mediated by phosphatidylinositol 3-OH kinase (PI3)-kinase. We hypothesized that luminal flow induces eNOS activation via PI3-kinase. Pretreatment of THALs with wortmannin, a PI3-kinase inhibitor, significantly reduced flow-induced nitric oxide (NO) release by 75% (from 53.6 ± 6 to 13.2 ± 5.7 pA/mm). Increasing luminal flow from 0 to 20 nl/min induced eNOS translocation to the apical membrane, whereas in the presence of wortmannin eNOS translocation was prevented (basolateral = 32 ± 2%, middle = 38 ± 1%, apical = 30 ± 1%, n = 5, not significant vs. no flow). We next studied which PI3-kinase product mediates eNOS translocation. Addition of PI( 3 , 4 , 5 )P3 (5 μM) in the absence of flow increased NO levels ( P < 0.05) and induced eNOS translocation to the apical membrane (from 40 ± 4 to 60 ± 2% of total eNOS, n = 6, P < 0.05). Incubation with PI( 3 , 4 )P2 or PI( 4 , 5 )P2 did not change eNOS localization. We next tested whether heat shock protein (Hsp)90 is involved in eNOS translocation. The Hsp90 inhibitor geldanamycin blocked flow-induced eNOS translocation to the apical membrane ( n = 6). Flow also induced translocation of Hsp90 to the apical membrane (from 35 ± 2 to 57 ± 2%; P < 0.05) in a PI3-kinase-dependent manner. We conclude that luminal flow induces eNOS translocation and activation in the THAL via PI3-kinase and that Hsp90 is involved in eNOS translocation to the apical membrane.
Exercise-induced intrapulmonary arteriovenous shunting in healthy humans
Authors: Eldridge Marlowe W. , Dempsey Jerome A. , Haverkamp Hans C. , Lovering Andrew T. , Hokanson John S.
Published: April 2004

We hypothesized that increasing exercise intensity recruits dormant arteriovenous intrapulmonary shunts, which may contribute to the widened alveolar-arterial oxygen difference seen with exercise. Twenty-three healthy volunteers (13 men and 10 women, aged 23–48 yr) with normal lung function and a wide range of fitness (mean maximal oxygen uptake = 126% predicted; range = 78–200% predicted) were studied by agitated saline contrast echocardiography (4-chamber apical view). All 23 subjects had normal resting contrast echocardiograms without evidence of intracardiac or intrapulmonary shunting. However, with cycle ergometer exercise, 21 of 23 (91%) of the subjects showed a delayed (>3 cardiac cycles) appearance of contrast bubbles in the left heart. This pattern is consistent with passage of contrast bubbles through the pulmonary circulation. Because the contrast bubbles are known to be significantly larger than pulmonary capillaries, we propose that they are traveling through direct arteriovenous intrapulmonary shunts. In all cases, the intrapulmonary shunting developed at submaximal oxygen uptakes [%maximal oxygen uptake = 59 ± 20 (SD)] and once evident persisted at all subsequent work rates. Within 3 min of exercise termination, the contrast echocardiograms with bubble injection showed no evidence of intrapulmonary shunting. These dynamic shunts will contribute significantly to the widened alveolar-arterial oxygen difference seen with exercise. They may also act as a protective parallel vascular network limiting the rise in regional pulmonary vascular pressure while preserving cardiac output during exercise.
Plasma guanidino compounds are altered by oral creatine supplementation in healthy humans
Authors: Derave Wim , Marescau Bart , Eede Els Vanden , Eijnde Bert O. , De Deyn Peter P. , Hespel Peter
Published: April 2004

Although creatine is one of the most widely used nutritional supplements for athletes as well as for patients with neuromuscular disorders, the effects of oral creatine supplementation on endogenous creatine synthesis in humans remains largely unexplored. The aim of the present study was to investigate the metabolic consequences of a frequently used, long-term creatine ingestion protocol on the circulating creatine synthesis precursor molecules, guanidinoacetate and arginine, and their related guanidino compounds. For this purpose, 16 healthy young volunteers were randomly divided to ingest in a double-blind fashion either creatine monohydrate or placebo (maltodextrine) at a dosage of 20 g/day for the first week (loading phase) and 5 g/day for 19 subsequent wk (maintenance phase). Fasting plasma samples were taken at baseline and at 1, 10, and 20 wk of supplementation, and guanidino compounds were determined. Plasma guanidinoacetate levels were reduced by 50% after creatine loading and remained ∼30% reduced throughout the maintenance phase. Several circulating guanidino compound levels were significantly altered after creatine loading but not during the maintenance phase: homoarginine (+35%), α-keto-δ-guanidinovaleric acid (+45%), and argininic acid (+75%) were increased, whereas guanidinosuccinate was reduced (−25%). The decrease in circulating guanidinoacetate levels suggests that exogenous supply of creatine chronically inhibits endogenous synthesis at the transamidinase step in humans, supporting earlier animal studies showing a powerful repressive effect of creatine on l-arginine:glycine amidinotransferase. Furthermore, these data suggest that this leads to enhanced utilization of arginine as a substrate for secondary pathways.
Adverse effects of myasthenia gravis on rat phrenic diaphragm contractile performance
Authors: van Lunteren Erik , Moyer Michelle , Kaminski Henry J.
Published: April 2004

Myasthenia gravis has variable effects on the respiratory system, ranging from no abnormalities to life-threatening respiratory failure. Studies characterized diaphragm muscle contractile performance in rat autoimmune myasthenia gravis. Rats received monoclonal antibody that recognizes acetylcholine receptor determinants (or inactive antibody); 3 days later, phrenic nerve and diaphragm were studied in vitro. Myasthenic rats segregated into two groups, those with normal vs. impaired limb muscle function when tested in intact animals (“mild” and “severe” myasthenic). Baseline diaphragm twitch force was reduced for both severe ( P < 0.01) and mild ( P < 0.05) myasthenic compared with control animals (twitch force: normal 1,352 ± 140, mild myasthenic 672 ± 99, severe myasthenic 687 ± 74 g/cm2). However, only severe myasthenic diaphragm had impaired diaphragm endurance, based on significantly ( P < 0.05) accelerated rate of peak force decline during the initial period of stimulation (0.02 + 0.02, 0.03 ± 0.01, and 0.09 ± 0.01%/pulse for normal, mild myasthenic, and severe myasthenic, respectively, during continuous stimulation) and intratrain fatigue (up to 30.5 ± 7.4% intratrain force drop in severe myasthenic vs. none in normal and mild myasthenic, P < 0.01). Furthermore, compared with continuous stimulation, intermittent stimulation had a protective effect on force of severe myasthenic diaphragm (force after 2,000 pulses was 31.4 ± 2.0% of initial during intermittent stimulation vs. 13.0 ± 2.1% of initial during continuous stimulation, P < 0.01) but not on normal diaphragm. These data indicate that baseline force and fatigue may be affected to different extents by varying severity of myasthenia gravis and furthermore provide a mechanism by which alterations in breathing pattern may worsen respiratory muscle function in neuromuscular diseases.
Estimation of the Electrical Parameters of Spinal Motoneurons Using Impedance Measurements
Authors: Maltenfort Mitchell G. , Hamm Thomas M.
Published: April 2004

Electrical parameters of spinal motoneurons were estimated by optimizing the parameters of motoneuron models to match experimentally determined impedance functions with those of the models. The model was described by soma area, somatic and dendritic membrane resistivities, and the diameter of an equivalent dendritic cable having a standard profile. The impedance functions of motoneurons and optimized models usually differed (rms error) by <2% of input resistance. Consistent estimates for most parameters were obtained from repeated impedance determinations in individual motoneurons; estimates of dendritic resistivity were most variable. The few cells that could not be fit well had reduced impedance phase lag consistent with dendritic penetrations. Most fits were improved by inclusion of a voltage-dependent conductance GV with time constant τV. A uniformly distributed GV with τV >5 ms provided a better fit for most cells. The magnitude of this conductance decreased with depolarization. Impedance functions of other cells were adequately fit by a passive model or by a model with a somatic GV and τV <5 ms. Most of these neurons (7/8) had resting potentials positive to −60 mV. The electrotonic parameters ρ, τ, and L, estimated from model parameters, were consistent with published distributions. Most motoneuron parameters obtained in somatic shunt and sigmoidal models were well correlated, and parameters were moderately affected by changes in dendritic profile. These results demonstrate the utility and limitations of impedance measurements for estimating motoneuron parameters and suggest that voltage-dependent conductances are a substantial component of resting electrical properties.
Symplectic difference systems: oscillation theory and hyperbolicPrüfer transformation
Authors: Došlý Ondřej
Published: April 2004

We present basic methods of oscillation
theory of symplectic difference systems (SDSs). A particular
attention is devoted to the variational principle and to the
transformation method. Hyperbolic Prüfer transformation for
SDSs is established.
Three‐Dimensional Culture ofHybridoma Cells Secreting Anti‐Human Chorionic Gonadotropin by a New Rolling Culture System
Authors: Wang Yan , Jiao Hong-Li , Zhang Jin-Zhu , He Rong-Qiao
Published: April 2004

Cell growth rate and production of monoclonal antibody (MAb) of
hybridoma cells producing anti‐human chorionic gonadotropin (hCG)
MAb have been used as investigation criteria in double‐mouthed
rolling bottle (DMRB). Compared with T‐flask cell culture, both
of the cell number and MAb production increased by approximately
42.5% when the medium was supplemented with 5% fetal calf serum
(FCS) and DMRB rotated at 2 turns per minute. Yield of MAb was
experimentally related to the number of viable cells.
Interestingly, MAb yield was four times as high as that cultured
in T‐flask in the first 24 hours, and about 75% yield of
total MAb was secreted by 48 hours during the culture. It
appears that the promoted cell growth and MAb yield are resulted
from the three‐dimensional growth of hybridoma cells under a
suitably revolving condition.
Evidence for a Novel, Caspase‐8‐Independent, Fas Death Domain‐Mediated Apoptotic Pathway
Authors: Feng Hanping , Zeng Yi , Graner Michael W. , Whitesell Luke , Katsanis Emmanuel
Published: April 2004

Certain caspase‐8 null cell lines demonstrate resistance to
Fas‐induced apoptosis, indicating that the Fas/FasL apoptotic
pathway may be caspase‐8‐dependent. Some reports, however, have
shown that Fas induces cell death independent of caspase‐8. Here
we provide evidence for an alternative, caspase‐8‐independent,
Fas death domain‐mediated apoptotic pathway. Murine 12B1‐D1 cells
express procaspase‐3, ‐8, and ‐9, which were activated upon the
dimerization of Fas death domain. Bid was cleaved and
mitochondrial transmembrane potential was disrupted in this
apoptotic process. All apoptotic events were completely blocked
by the broad‐spectrum caspase inhibitor Z‐VAD‐FMK, but not by
other peptide caspase inhibitors. Cyclosporin A (CsA), which
inhibits mitochondrial transition pore permeability, blocked
neither pore permeability disruption nor caspase activation.
However, CsA plus caspase‐8 inhibitor blocked all apoptotic
events of 12B1‐D1 induced by Fas death domain dimerization. Our
data therefore suggest that there is a novel,
caspase‐8‐independent, Z‐VAD‐FMK‐inhibitable, apoptotic pathway in
12B1‐D1 cells that targets mitochondria directly.
Natriuretic Peptides Predict Symptom-Free Survival and Postoperative Outcome in Severe Aortic Stenosis
Authors: Bergler-Klein Jutta , Klaar Ursula , Heger Maria , Rosenhek Raphael , Mundigler Gerald , Gabriel Harald , Binder Thomas , Pacher Richard , Maurer Gerald , Baumgartner Helmut
Published: April 2004

Background—

The prognostic value of natriuretic peptides in aortic stenosis (AS) remains unknown.

Methods and Results—

B-type natriuretic peptide (BNP), N-terminal BNP (NtBNP), and N-terminal atrial natriuretic peptide (NtANP) were determined in 130 patients with severe AS (mean age, 70±12 years; mean gradient, 64±21 mm Hg; valve area, 0.64±0.15 cm
2
) who were followed up for 377±150 days. Natriuretic peptides increased with NYHA class and with decreasing ejection fraction (EF). Even asymptomatic patients frequently had elevated neurohormones. Asymptomatic patients who developed symptoms during follow-up had higher BNP and NtBNP levels at entry compared with those remaining asymptomatic (median for NtBNP, 131 pmol/L [interquartile range, 50 to 202 pmol/L] versus 31 pmol/L [range, 19 to 56 pmol/L];
P
<0.001). Symptom-free survival at 3, 6, 9, and 12 months for patients with NtBNP <80 versus ≥80 pmol/L was 100%, 88±7%, 88±7%, and 69±13% compared with 92±8%, 58±14%, 35±15%, and 18±15%, respectively (
P
<0.001). Seventy-nine patients eventually underwent surgery because of symptoms. Considering preoperative neurohormone levels, age, NYHA class, aortic valve area, EF, and presence of coronary artery disease, we found that neurohormones, EF, and NYHA class predicted survival; neurohormones predicted postoperative symptomatic status; and neurohormones and preoperative EF predicted postoperative EF. However, by multivariate analysis, NtBNP was the only independent predictor of outcome.

Conclusions—

In severe AS, natriuretic peptides provide important prognostic information beyond clinical and echocardiographic evaluation. NtBNP independently predicts symptom-free survival, and preoperative NtBNP independently predicts postoperative outcome with regard to survival, symptomatic status, and left ventricular function. Thus, neurohormones may gain particular importance for timing of surgery in asymptomatic severe AS.
Propensity Analysis of Long-Term Survival After Surgical or Percutaneous Revascularization in Patients With Multivessel Coronary Artery Disease and High-Risk Features
Authors: Brener Sorin J. , Lytle Bruce W. , Casserly Ivan P. , Schneider Jakob P. , Topol Eric J. , Lauer Michael S.
Published: April 2004

Background—

Although most randomized clinical trials have suggested that long-term survival rates after percutaneous coronary intervention (PCI) or surgical multivessel coronary revascularization (CABG) are equivalent, some post hoc analyses in high-risk groups and adjustment for severity of coronary disease have suggested higher mortality after PCI.

Methods and Results—

We studied 6033 consecutive patients who underwent revascularization in the late 1990s. PCI was performed in 872 patients; 5161 underwent CABG. Half the patients had significant left ventricular dysfunction or diabetes. Propensity analysis to predict the probability of undergoing PCI according to 22 variables and their interactions was used. The C-statistic for this model was 0.90, indicating excellent discrimination between treatments. There were 931 deaths during 5 years of follow-up. The 1- and 5-year unadjusted mortality rates were 5% and 16% for PCI and 4% and 14% for CABG (unadjusted hazard ratio, 1.13; 95% CI, 1.0 to 1.4;
P
=0.07). PCI was associated with an increased risk of death (propensity-adjusted hazard ratio, 2.3; 95% CI, 1.9 to 2.9;
P
<0.0001). This difference was observed across all categories of propensity for PCI and in patients with diabetes or left ventricular dysfunction. Other independent predictors of mortality (
P
≤0.01 for all) were renal dysfunction, age, diabetes mellitus, chronic lung disease, peripheral vascular disease, left main trunk stenosis, and extent of coronary disease (Duke angiographic score).

Conclusions—

In patients with multivessel coronary artery disease and many high-risk characteristics, CABG was associated with better survival than PCI after adjustment for risk profile.