bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival of Escherichia coli O157:H7 in the processing and post‐processing stages of acidophilus yogurt
Authors: Kasımoğlu Aylin , Akgün Sadi
Published: April 2004

In this study the survival of Escherichia coli O157:H7 in the production process of acidophilus yogurt was examined and compared with traditional yogurt. Milk was inoculated with different doses of E. coli O157:H7 (102, 104 and 106 CFU mL−1) and two kinds of yogurt were produced. Samples were taken for pH measurements and bacterial enumeration at 0, 3, 24, 48, and 72 h after inoculation. Escherichia coli O157:H7 was analysed by using a Most Probable Number technique and yogurt starter culture and Lactobacillus  acidophilus were counted by using classical culture methods. Elimination times of E. coli O157:H7 were determined for 102 CFU mL−1 as 3 h, and for 104 and 106 CFU mL−1 as 48 h in acidophilus yogurt. Elimination times in traditional yogurt were 48 h for 102 and 104 CFU mL−1 and 72 h for 106 CFU mL−1E. coli O157:H7. In conclusion, the elimination time of E. coli O157:H7 in acidophilus yogurt was shorter than in traditional yogurt during the processing and post‐processing stages.
Ownership Structure and Technological Upgrading in International Joint Ventures
Authors: Lin Ping , Saggi Kamal
Published: April 2004

In a model of a joint venture between a local and a foreign firm who provide complementary inputs, this paper derives optimal ownership structures under different sharing rules. The local firm's profits may be maximized by assigning a majority share to the foreign firm. Efficiency (i.e., the minimization of double moral hazard) requires that the firm with the more productive input should get majority ownership. When only the foreign firm can upgrade its input, it should receive a larger share than what it receives in the absence of upgrading. The analysis implies that a blanket policy of prohibiting majority foreign ownership is theoretically unfounded.
Mutations in a Human
ROBO
Gene Disrupt Hindbrain Axon Pathway Crossing and Morphogenesis
Authors: Jen Joanna C. , Chan Wai-Man , Bosley Thomas M. , Wan Jijun , Carr Janai R. , Rüb Udo , Shattuck David , Salamon Georges , Kudo Lili C. , Ou Jing , Lin Doris D. M. , Salih Mustafa A. M. , Kansu Tülay , al Dhalaan Hesham , al Zayed Zayed , MacDonald David B. , Stigsby Bent , Plaitakis Andreas , Dretakis Emmanuel K. , Gottlob Irene , Pieh Christina , Traboulsi Elias I. , Wang Qing , Wang Lejin , Andrews Caroline , Yamada Koki , Demer Joseph L. , Karim Shaheen , Alger Jeffry R. , Geschwind Daniel H. , Deller Thomas , Sicotte Nancy L. , Nelson Stanley F. , Baloh Robert W. , Engle Elizabeth C.
Published: April 2004

The mechanisms controlling axon guidance are of fundamental importance in understanding brain development. Growing corticospinal and somatosensory axons cross the midline in the medulla to reach their targets and thus form the basis of contralateral motor control and sensory input. The motor and sensory projections appeared uncrossed in patients with horizontal gaze palsy with progressive scoliosis (HGPPS). In patients affected with HGPPS, we identified mutations in the
ROBO3
gene, which shares homology with
roundabout
genes important in axon guidance in developing
Drosophila
, zebrafish, and mouse. Like its murine homolog Rig1/Robo3, but unlike other Robo proteins, ROBO3 is required for hindbrain axon midline crossing.
Solitary fibrous tumour of the falciform ligament containing multiple foci of malignant transformation
Authors: Gidwani A L , Mullan F J , Kenny B
Published: April 2004

Solitary fibrous tumour is an uncommon soft tissue tumour initially described in the pleural cavity. In the past decade, it has been described in various extrapleural sites, including the abdomen. Traditionally regarded as benign, cases of histologically or clinically malignant solitary fibrous tumours are rare. This report describes such a case, although the patient is still disease free five years after excisional surgery, without adjuvant treatment. The acute clinical presentation may be related to malignant transformation occurring in a long standing solitary fibrous tumour.
p73α is a candidate effector in the p53 independent apoptosis pathway of cisplatin damaged primary murine colonocytes
Authors: Oniscu A , Sphyris N , Morris R G , Bader S , Harrison D J
Published: April 2004

Aims:Colonocytes were derived from wild-type (wt) and p53 deficient mice to investigate p53 dependent and independent death pathways after cisplatin treatment, and the role of p53 in growth regulation of primary, untransformed epithelial cells.

Methods:Wt and p53 null colonocytes were exposed to cisplatin and DNA synthesis, apoptosis, and p53, p21, and p73 expression were investigated after six, 12, and 24 hours. Major p73 isoforms were identified by reverse transcription polymerase chain reaction (RT-PCR).

Results:Cisplatin treated wt cells exhibited cell cycle arrest, whereas p53 null cells continued to synthesise DNA, although both cell types died. Apoptosis was significantly higher in cisplatin treated wt and p53 null colonocytes than in controls at all timepoints, although apoptosis was lower in cisplatin treated p53 null colonocytes than in wt cells. p53 expression was upregulated in cisplatin treated wt colonocytes. p21 expression was high and remained unchanged in cisplatin treated wt cells, although it was reduced in the absence of p53. p73 was investigated because it could account for p53 independent p21 expression and p53 independent death. RT-PCR detected full length p73α. p73 transcript levels remained unchanged, whereas p73 protein accumulated in the nucleus of cisplatin treated cells, irrespective of genotype.

Conclusions:p53 is essential for cell cycle arrest, but not apoptosis in primary murine colonocytes. Apoptosis is reduced in cisplatin treated p53 null cells. Nuclear accumulation of endogenous p73 after cisplatin treatment suggests a proapoptotic role for p73α in the absence of p53 and collaboration with p53 in wt colonocytes.
COX-2 dependent PGE2downregulates αvintegrin expression via the EP3receptor in cultured mesangial cells
Authors: Waldner C , Schrör K , Heering P
Published: April 2004

Background:In experimental glomerulonephritis, inhibition of cyclooxygenase 2 (COX-2) enhances the renocortical expression of pathogenic αvintegrins.

Aims:To study whether this effect is mediated by prostaglandin E2(PGE2) acting through its EP3receptor in cultured rat mesangial cells (MCs).

Methods:MCs were incubated with lipopolysaccharide (LPS), celecoxib, PGE2, or the selective EP3agonist, MB28767. The expression of COX-2, EP3, and αvintegrin mRNA was measured by reverse transcriptase polymerase chain reaction.

Results:LPS upregulated COX-2 expression 2.8-fold and αvintegrin expression twofold. The COX-2 inhibitor celecoxib increased αvintegrin mRNA expression twofold. Both exogenous PGE2and the specific EP3receptor agonist, MB28767, reduced constitutive αvintegrin mRNA expression to half normal values. COX-2 dependent PGE2suppressed the expression of αvintegrin mRNA mediated by the EP3receptor in MCs.

Conclusions:These results suggest that COX-2 suppresses the expression of αvintegrins by an increased production of PGE2activating its EP3receptor in glomerulonephritis.
MUC1 and MUC2 in pancreatic neoplasia: Figure 1
Authors: Levi E , Klimstra D S , Adsay N V , Andea A , Basturk O
Published: April 2004

MUCs are glycoproteins with various roles in homeostasis and carcinogenesis. Among other actions, MUC1 may inhibit cell–cell and cell–stroma interactions and function as a signal transducer, participating in cancer progression. In contrast, MUC2 is normally found only in goblet cells, where it contributes to the protective barrier function of these cells. Recently, a tumour suppressor role has been demonstrated for MUC2, and both MUC1 and MUC2 appear to have important roles in pancreatic neoplasia. MUC1 appears to be a marker of aggressive phenotype and may facilitate the vascular spread of carcinoma cells. In contrast, MUC2 is rarely detectable in aggressive pancreatic tumours, but is commonly expressed in intraductal papillary mucinous neoplasms (IPMNs), which are rare, indolent tumours, in intestinal IPMNs, and in indolent colloid carcinomas. MUC2 appears to be not only a marker of this indolent pathway, but also partly responsible for its less aggressive nature. Thus, in pancreatic neoplasia, MUC1 and MUC2 have potential diagnostic and prognostic value as markers of aggressive and indolent phenotypes, respectively, and have potential as therapeutic targets.
COULD FRESNEL OPTICS BE QUANTUM MECHANICS IN PHASE SPACE?
Authors: CRASSER O. , MACK H. , SCHLEICH W. P.
Published: April 2004

We formulate and argue in favor of the following conjecture: There exists an intimate connection between Wigner's quantum mechanical phase space distribution function and classical Fresnel optics.
SYNCHRONIZATION APPROACH TO ANALYSIS OF BIOLOGICAL SYSTEMS
Authors: ROSENBLUM MICHAEL G. , PIKOVSKY ARKADY S. , KURTHS JÜRGEN
Published: April 2004

In this article we review the application of the synchronization theory to the analysis of multivariate biological signals. We address the problem of phase estimation from data and detection and quantification of weak interaction, as well as quantification of the direction of coupling. We discuss the potentials as well as limitations and misinterpretations of the approach.
BURST-ENHANCED SYNCHRONIZATION IN AN ARRAY OF NOISY COUPLED NEURONS
Authors: BAHAR SONYA
Published: April 2004

Stochastic phase synchronization is studied in an array of coupled neurons that are capable of exhibiting diverse bursting behaviors as a system parameter is tuned. It is found that synchronization occurs for lower coupling constants when the neurons are initially in a bursting state. Neurons not initially in a bursting state begin to exhibit bursting behavior concurrently with the onset of synchronization. The system passes through various synchronization regimes as the coupling constant is increased, with the number of spikes per burst increasing in each window of synchronization. In addition, spatial organization, measured by the distribution of local phase differences, is observed during the synchronization windows.
ELECTROSENSORY BRAIN STEM NEURONS COMPUTE THE TIME DERIVATIVE OF ELECTRIC FIELDS IN THE PADDLEFISH
Authors: HOFMANN MICHAEL H. , FALK MARIANNE , WILKENS LON A.
Published: April 2004

For many aquatic animals, the electrosense is an important sensory system used to detect prey or conspecifics at short to medium range and for long-range orientation. Passive electroreceptive animals sense the minute electric fields of animate and inanimate sources and it has been thought that they are most sensitive to sources that modulate the field around a few Hertz. Our data on the properties of the electrosensory system in the paddlefish reveal that the firing rate of electrosensory brain stem neurons represents the first derivative of the stimulus, i.e. the rate of change in intensity of an electric field. Furthermore, the responses to several non-periodic stimuli suggest that the electrosensory system monitors changes in field intensity caused by the relative movement between source and receiver and converts spatial field structure into its time derivative form. This new interpretation solves a number of contradictions between behavioural observations and electrophysiological studies on the electrosensory system of vertebrates.
NOISE AND CORRELATED TRANSPORT IN ION CHANNELS
Authors: HAKEN H.
Published: April 2004

The motion of an ion through a channel is described as a classical/quantum mechanical hopping process between the individual sites of a channel. The transition rates are due to the coupling of an ion to suitable reservoirs. If fluctuating forces are added to the rate equations for the occupation numbers, the equations become quantum mechanical operator equations. Using previous results, the fluctuating forces are uniquely determined by the requirement of quantum mechanical consistency. The resulting equations are solved for several cases and the occupation number fluctuations discussed. Particular emphasis is laid on a model of correlated transport.
IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1
Authors: Sacheck Jennifer M. , Ohtsuka Akira , McLary S. Christine , Goldberg Alfred L.
Published: April 2004

Muscle atrophy results primarily from accelerated protein degradation and is associated with increased expression of two muscle-specific ubiquitin ligases (E3s): atrogin-1 and muscle ring finger 1 (MuRF1). Glucocorticoids are essential for many types of muscle atrophy, and their effects are opposite to those of insulin-like growth factor I (IGF-I) and insulin, which promote growth. In myotubes, dexamethasone (Dex) inhibited growth and enhanced breakdown of long-lived cell proteins, especially myofibrillar proteins (as measured by 3-methylhistidine release), while also increasing atrogin-1 and MuRF1 mRNA. Conversely, IGF-I suppressed protein degradation and prevented the Dex-induced increase in proteolysis. IGF-I rapidly reduced atrogin-1 expression within 1 h by blocking mRNA synthesis without affecting mRNA degradation, whereas IGF-I decreased MuRF1 mRNA slowly. IGF-I and insulin also blocked Dex induction of these E3s and several other atrophy-related genes (“atrogenes”). Changes in overall proteolysis with Dex and IGF-I correlated tightly with changes in atrogin-1 mRNA content, but not with changes in MuRF1 mRNA. IGF-I activates the phosphatidylinositol 3-kinase (PI3K)-Akt pathway, and inhibition of this pathway [but not the calcineurin-nuclear factor of activated T cell (NFAT) or the MEK-ERK pathway] increased proteolysis and atrogin-1 mRNA expression. Thus an important component of growth stimulation by IGF-I, through the PI3K-Akt pathway, is its ability to rapidly suppress transcription of the atrophy-related E3 atrogin-1 and other atrogenes and degradation of myofibrillar proteins.
Modulation of carbohydrate response element-binding protein gene expression in 3T3-L1 adipocytes and rat adipose tissue
Authors: He Zhibin , Jiang Tao , Wang Zhuowei , Levi Moshe , Li Jinping
Published: April 2004

Carbohydrate response element-binding protein (ChREBP) is a rat homolog of human Williams-Beuren syndrome region 14 and a member of the basic helix-loop-helix leucine zipper transcription factor family. Its activation was found to be inducible by carbohydrate in the liver nuclear extracts from rats fed a high-sucrose diet. ChREBP is able to bind to the carbohydrate response element on the promoter of L-type pyruvate kinase and initiate the gene transcription. The detailed expression profile and transcriptional regulation of the ChREBP gene in adipocytes have not been characterized. In the present study, we provide evidence showing that 1) the ChREBP gene is expressed in differentiated 3T3-L1 adipocytes and rat adipose tissue; 2) insulin, glucose, and the antidiabetic agent troglitazone can significantly upregulate the gene expression of ChREBP in 3T3-L1 adipocytes, whereas free fatty acids suppress its expression in this cell type; 3) fasting followed by refeeding with a high-carbohydrate diet resulted in a 10-fold increase of ChREBP mRNA level in rat adipose tissue; and 4) ChREBP expression in adipose tissue is not significantly affected by the diabetic state. Taken together, the results we present are consistent with the idea that ChREBP is an important modulator of adipocyte biology and that its expression in adipose tissue is subject to combined regulation by glucose and insulin in vivo. The induction of ChREBP may serve as a novel pharmacological pathway for troglitazone-mediated hypoglycemic effects in vivo.
Adenovirus vectors activate survival pathways in lung epithelial cells
Authors: Flaherty Dawn M. , Hinde Sara L. , Monick Martha M. , Powers Linda S. , Bradford Mary A. , Yarovinsky Timur , Hunninghake Gary W.
Published: April 2004

Airway epithelial cells are often the sites of targeted adenovirus vector delivery. Activation of the host inflammatory response and modulation of signal transduction pathways by adenovirus vectors have been previously documented, including activation of MAP kinases and phosphatidylinositol 3-kinase (PI3-kinase). The effect of activation of these pathways by adenovirus vectors on cell survival has not been examined. Both the PI3-kinase/Akt and ERK/MAP kinase signaling pathways have been linked to cell survival. Akt has been found to play a role in cell survival and apoptosis through its downstream effects on apoptosis-related proteins. Constitutive activation of either PI3-kinase or Akt blocks apoptosis induced by c-Myc, UV radiation, transforming growth factor-β, Fas, and respiratory syncytial virus infection. We examined the effect of adenovirus vector infection on activation of these prosurvival pathways and its downstream consequences. Airway epithelial cells were transduced with replication-deficient adenoviral vectors containing a nonspecific transgene, green fluorescent protein driven by the cytomegalovirus promoter, or an empty vector with no transgene. They were then exposed to the proapoptotic stimulus actinomycin D plus TNF-α, and evidence of apoptosis was evaluated. Compared with the cells treated with actinomycin/TNF alone, the adenovirus vector-infected cells had a 50% reduction in apoptosis. When we examined induction of the prosurvival pathways, ERK and AKT, in the viral vector-infected cells, we found that there was significant activation of both Akt and ERK.
Androgens augment proximal tubule transport
Authors: Quan Albert , Chakravarty Sumana , Chen Jian-Kang , Chen Jian-Chun , Loleh Samer , Saini Neel , Harris Ray C. , Capdevila Jorge , Quigley Raymond
Published: April 2004

The proximal tubule contains an autonomous renin-angiotensin system that regulates transport independently of circulating angiotensin II. Androgens are known to increase expression of angiotensinogen, but the effect of androgens on proximal tubule transport is unknown. In this in vivo microperfusion study, we examined the effect of androgens on proximal tubule transport. The volume reabsorptive rate in Sprague-Dawley rats given dihydrotestosterone (DHT) injections was significantly higher than in control rats given vehicle injections (4.57 ± 0.31 vs. 3.31 ± 0.23 nl·min−1·mm−1, P < 0.01). Luminally perfusing with either enalaprilat (10−4M) to inhibit production of angiotensin II or losartan (10−8M) to block the angiotensin receptor decreased the proximal tubule volume reabsorptive rate in DHT-treated rats to a significantly greater degree than in control vehicle-injected rats. The renal expression of angiotensinogen was shown to be higher in the DHT-treated animals, using Northern blot analysis. The expression of angiotensin receptors, determined by specific binding of angiotensin II, was not different in the two groups of animals. Brush-border membrane protein abundance of the Na/H exchanger, a membrane transport protein under angiotensin II regulation, was also higher in DHT-treated rats vs. control rats. Rats that received DHT had higher blood pressures than the control rats but had no change in their glomerular filtration rate. In addition, serum angiotensin II levels were lower in DHT-treated vs. control rats. These results suggest that androgens may directly upregulate the proximal tubule renin-angiotensin system, increase the volume reabsorptive rate, and thereby increase extracellular volume and blood pressure and secondarily decrease serum angiotensin II levels.
Inflection points of cardiovascular responses and oxygenation are correlated in the distal but not the proximal portions of muscle during incremental exercise
Authors: Mizuno Masaki , Tokizawa Ken , Iwakawa Takashi , Muraoka Isao
Published: April 2004

To test whether there is a regional difference in the exercise pressor reflex within a given muscle, we investigated the relationship between the inflection points of cardiovascular responses and muscle oxygenation during exercise. Seven subjects performed incremental exercise, which consisted of incremental 30-s static knee extensions, each separated by 30 s of recovery. The workload started at 5% maximal voluntary contraction (MVC) and increased by 5% MVC for each increment until exhaustion. Changes (Δ) in the concentrations (denoted by brackets) of oxygenated Hb (O2Hb) and deoxygenated Hb (HHb) were monitored in proximal and distal portions of the vastus lateralis by near-infrared spectroscopy. The inflection points of mean arterial pressure (MAP), calf vascular resistance (CVR), and muscle deoxygenation index (Δ[O2Hb − HHb]) were calculated as the intersection point of two regression equations obtained at lower and higher workloads. The inflection point of Δ[O2Hb − HHb] differed significantly between proximal and distal portions (28.5 ± 3.0 vs. 39.5 ± 3.0%MVC, P < 0.05). Linear regression analysis showed significant correlations between the inflection point of Δ[O2Hb − HHb] in the distal portion and MAP ( r = 0.89; P < 0.01) and CVR ( r = 0.89; P < 0.05), but no significant relationship between the inflection point in the proximal portion and MAP or CVR. These data show that the inflection point of muscle deoxygenation differs between proximal and distal portions within the vastus lateralis during incremental exercise and suggest that the distal portion of the vastus lateralis contributes more to the pressor response than does the proximal portion.
Relationship between skeletal muscle MCT1 and accumulated exercise during voluntary wheel running
Authors: Yoshida Yuko , Hatta Hideo , Kato Mai , Enoki Taisuke , Kato Hiroyuki , Bonen Arend
Published: April 2004

We examined whether the quantity of exercise performed influences the expression of monocarboxylate transporter (MCT) 1 and MCT4 in mouse skeletal muscles (plantaris, tibialis anterior, soleus) and heart. Wheel running exercise (1, 3, and 6 wk) was used, which results in marked variations in self-selected running activity. Differences in muscle MCT1 and MCT4 among animals, before the initiation of running, were not related to the quantity of exercise performed on the first day of wheel running. No changes in MCT4 were observed over the course of the study ( P > 0.05). After 6 wk of running, were there significant increases in heart (50%; P < 0.05) and muscle MCT1 (31–60%; P < 0.05) but not after 1 and 3 wk ( P > 0.05). Because skeletal muscle MCT1 and running distances varied considerably, we examined the relationship between these two parameters. Within the first week of training, MCT1 was negatively correlated with the accumulated running distance ( r = −0.70, P < 0.05). On further analysis, it appears that, in the first week, excessive running (>20 km/wk) represses MCT1 (−16.1%; P < 0.05), whereas more modest amounts of running (<20 km/wk) increase MCT1 (+37%; P < 0.05). After 3 wk of running, a positive relationship was observed between MCT1 and running distance ( r = +0.76), although there is a threshold that must be exceeded before an increase over the control animals occurs. Finally, in week 6, when MCT1 was increased in the tibialis anterior and plantaris muscles, there were no correlations with the accumulated running distances. These studies have shown that mild exercise training fails to increase MCT4 and that changes in MCT1 are complex, depending not only the accumulated exercise but also on the stage of training.
Expression of Distinct α Subunits of GABAAReceptor Regulates Inhibitory Synaptic Strength
Authors: Ortinski Pavel I. , Lu Congyi , Takagaki Kentaroh , Fu Zhanyan , Vicini Stefano
Published: April 2004

Distinct α subunit subtypes in the molecular assembly of GABAAreceptors are a critical determinant of the functional properties of inhibitory synapses and their modulation by a range of pharmacological agents. We investigated the contribution of these subunits to the developmental changes of inhibitory synapses in cerebellar granule neurons in primary cultures from wild-type and α1 subunit −/− mice. The decay time of miniature inhibitory postsynaptic currents (mIPSCs) halved between 6 days in vitro (DIV6) and DIV12. This was paralleled by the decrease of α2 and α3 subunits, the increase of α1 and α6 subunits expression at synapses, and changes in the action of selective α subunit modulators. A small but significant shortening of mIPSCs was observed with development in cells from −/− mice together with a decrease in the expression of α3 subunit. In contrast, the expression of α2 subunit at inhibitory synapses in −/− cells was significantly higher than in +/+ cells at DIV11-12. α5 subunit was not detected, and increased sensitivity to a selective α4/α6 subunit agonist suggests increased expression of extrasynaptic receptors in −/− mice. β2/β3 subunit expression and loreclezole sensitivity increased with development in +/+ but not in −/− cells, supporting the preferential association of the α1 with the β2 subunit. Synaptic charge transfer strongly decreased with development but was not different between cells in the +/+ and −/− groups until DIV11-12. Our results uncover a pattern of sequential expression of α subunits underlying the changes in functional efficacy of GABAergic networks with development.
Genome-wide analysis of the endothelial transcriptome under short-term chronic hypoxia
Authors: Ning W. , Chu T. J. , Li C. J. , Choi A. M. K. , Peters D. G.
Published: April 2004

We have utilized serial analysis of gene expression (SAGE) to analyze the temporal response of human aortic endothelial cells (HAECs) to short-term chronic hypoxia at the level of transcription. Primary cultures of HAECs were exposed to 1% O2hypoxia for 8 and 24 h and compared with identical same passage cells cultured under standard (5% CO2-95% air) conditions. A total of 121,446 tags representing 37,096 unique tags were sequenced and genes whose expression levels were modulated by hypoxia identified by novel statistical analyses. Hierarchical clustering of genes displaying statistically significant hypoxia-responsive alterations in expression revealed temporal modulation of a number of major functional gene families including those encoding heat shock factors, glycolytic enzymes, extracellular matrix factors, cytoskeletal factors, apoptotic factors, cell cycle regulators and angiogenic factors. Within these families we documented the coordinated modulation of both previously known hypoxia-responsive genes, numerous genes whose expressions have not been previously shown to be altered by hypoxia, tags matching uncharacterized UniGene entries and entirely novel tags with no UniGene match. These preliminary data, which indicate a reduction in cell cycle progression, elevated metabolic stress and increased cytoskeletal remodeling under acute hypoxic stress, provide a foundation for further analyses of the molecular mechanisms underlying the endothelial response to short-term chronic hypoxia.
Periodic solutions for some partial functional differentialequations
Authors: Benkhalti Rachid , Ezzinbi Khalil
Published: April 2004

We study the existence of a periodic solution for some partial
functional differential equations. We assume
that the linear part is nondensely defined and satisfies the
Hille‐Yosida condition. In the nonhomogeneous linear case, we
prove the existence of a periodic solution under the existence of
a bounded solution. In the nonlinear case, using a fixed‐point
theorem concerning set‐valued maps, we establish the existence of
a periodic solution.
Linear differential equations with unbounded delays and a forcingterm
Authors: Čermák Jan , Kundrát Petr
Published: April 2004

The paper discusses the asymptotic behaviour of all solutions of
the differential equation , t ∈ I = [t0, ∞),
with a positive continuous function a, continuous functions
bi, f, and n continuously differentiable unbounded lags. We
establish conditions under which any solution y of this equation
can be estimated by means of a solution of an auxiliary functional
equation with one unbounded lag. Moreover, some related questions
concerning functional equations are discussed as well.
On the exterior magnetic field and silent sources inmagnetoencephalography
Authors: Dassios George , Kariotou Fotini
Published: April 2004

Two main results are included in this
paper. The first one
deals with the leading asymptotic term of the magnetic field
outside any conductive medium. In accord with physical reality,
it is proved mathematically that the leading approximation is
a quadrupole term which means that the conductive brain tissue
weakens the intensity of the magnetic field outside the head.
The second one concerns the orientation of the silent sources
when the geometry of the brain model is not a sphere but an
ellipsoid which provides the best possible mathematical
approximation of the human brain. It is shown that what
characterizes a dipole source as “silent” is not the collinearity
of the dipole moment with its position vector, but the fact that
the dipole moment lives in the Gaussian image space at the point
where the position vector meets the surface of the ellipsoid.
The appropriate representation for the spheroidal case is also
included.
Comparison of differential representations for radially symmetricStokes flow
Authors: Dassios George , Vafeas Panayiotis
Published: April 2004

Papkovich and Neuber (PN), and Palaniappan, Nigam, Amaranath, and
Usha (PNAU) proposed two different representations of the
velocity and the pressure fields in Stokes flow, in terms of
harmonic and biharmonic functions, which form a practical tool
for many important physical applications. One is the
particle‐in‐cell model for Stokes flow through a swarm of
particles. Most of the analytical models in this realm consider
spherical particles since for many interior and exterior flow
problems involving small particles, spherical geometry provides a
very good approximation. In the interest of producing
ready‐to‐use basic functions for Stokes flow, we calculate the
PNAU and the PN eigensolutions generated by the appropriate
eigenfunctions, and the full series expansion is provided. We
obtain connection formulae by which we can transform any solution
of the Stokes system from the PN to the PNAU eigenform. This
procedure shows that any PNAU eigenform corresponds to a
combination of PN eigenfunctions, a fact that reflects the
flexibility of the second representation. Hence, the advantage of
the PN representation as it compares to the PNAU solution is
obvious. An application is included, which solves the problem of
the flow in a fluid cell filling the space between two concentric
spherical surfaces with Kuwabara‐type boundary conditions.
New singular solutions of Protter′s problem for the 3D wave equation
Authors: Grammatikopoulos M. K. , Popivanov N. I. , Popov T. P.
Published: April 2004

In 1952, for the wave equation,Protter formulated some boundary
value problems (BVPs), which are multidimensional
analogues of Darboux problems on the plane. He studied these
problems in a 3D domain Ω0, bounded by two
characteristic cones Σ1 and Σ2,0 and a
plane region Σ0. What is the situation around these
BVPs now after 50 years? It is well known that, for the infinite
number of smooth functions in the right‐hand side of the
equation, these problems do not have classical solutions.
Popivanov and Schneider (1995) discovered the reason of this fact
for the cases of Dirichlet′s or Neumann′s conditions on Σ0. In the present paper, we consider the case of third BVP on
Σ0 and obtain the existence of many singular
solutions for the wave equation. Especially, for Protter′s
problems in ℝ3, it is shown here that for any n ∈ ℕ there exists a ‐ right‐hand
side function, for which the corresponding unique generalized
solution belongs to but
has a strong power‐type singularity of order n at the point
O. This singularity is isolated only at the vertex O of the
characteristic cone Σ2,0 and does not propagate along
the cone.
Definition of Soybean Genomic Regions That Control Seed Phytoestrogen Amounts
Authors: Kassem My A. , Meksem K. , Iqbal M. J. , Njiti V. N. , Banz W. J. , Winters T. A. , Wood A. , Lightfoot D. A.
Published: April 2004

Soybean seeds contain large amounts of isoflavones or
phytoestrogens such as genistein, daidzein, and glycitein that
display biological effects when ingested by humans and animals.
In seeds, the total amount, and amount of each type, of
isoflavone varies by 5 fold between cultivars and locations.
Isoflavone content and quality are one key to the biological
effects of soy foods, dietary supplements, and nutraceuticals.
Previously we had identified 6 loci (QTL) controlling isoflavone
content using 150 DNA markers. This study aimed to identify and
delimit loci underlying heritable variation in isoflavone content
with additional DNA markers. We used a recombinant inbred line
(RIL) population (n = 100) derived from the cross of “Essex” by
“Forrest,” two cultivars that contrast for isoflavone content.
Seed isoflavone content of each RIL was determined by HPLC and
compared against 240 polymorphic microsatellite markers by
one‐way analysis of variance. Two QTL that underlie seed
isoflavone content were newly discovered. The additional markers
confirmed and refined the positions of the six QTL already
reported. The first new region anchored by the marker
BARC‐Satt063 was significantly associated with genistein
(P = 0.009, R2 = 29.5%) and daidzein (P = 0.007, R2 = 17.0%).
The region is located on linkage group B2 and derived the
beneficial allele from Essex. The second new region defined by
the marker BARC‐Satt129 was significantly associated with total
glycitein (P = 0.0005, R2 = 32.0%). The region is located on
linkage group D1a+Q and also derived the beneficial allele from
Essex. Jointly the eight loci can explain the heritable variation
in isoflavone content. The loci may be used to stabilize seed
isoflavone content by selection and to isolate the underlying
genes.
Bradykinin Contributes to the Systemic Hemodynamic Effects of Chronic Angiotensin-Converting Enzyme Inhibition in Patients With Heart Failure
Authors: Cruden Nicholas L.M. , Witherow Fraser N. , Webb David J. , Fox Keith A.A. , Newby David E.
Published: April 2004

Background—

Bradykinin is an endogenous vasodilator that may contribute to the systemic effects of angiotensin-converting enzyme (ACE) inhibitor therapy. Using B9340, a bradykinin receptor antagonist, we determined the contribution of bradykinin to the systemic hemodynamic effects of long-term ACE inhibition in patients with chronic heart failure.

Methods and Results—

Fourteen patients with heart failure received enalapril (10 mg twice daily) or losartan (50 mg twice daily) in a randomized double-blind crossover trial. After 6 weeks treatment, patients underwent right heart catheterization and were randomized to an intravenous infusion of B9340 (2 to 20 μg/kg per minute) or saline placebo. After B9340 infusion in patients treated with enalapril, mean arterial pressure (+5.2 mm Hg), systemic vascular resistance (+315 dynes·s/cm
5
), pulmonary arterial wedge pressure (−1.4 mm Hg), and mean pulmonary arterial pressure (−1.3 mm Hg) were greater compared with losartan (
P
<0.005,
P
=0.07,
P
<0.0001, and
P
<0.05 respectively) or placebo infusion (
P
≤0.005 for all). There was a reduction in cardiac output after B9340 with enalapril compared with placebo (
P
<0.001) but not losartan.

Conclusions—

Bradykinin contributes to the systemic hemodynamic effects of long-term ACE inhibition in patients with heart failure. This mechanism may explain the apparent clinical differences between ACE inhibitors and angiotensin receptor blockers in the treatment of heart failure.
Regionalization of Treatment for Subarachnoid Hemorrhage
Authors: Bardach Naomi S. , Olson Scott J. , Elkins Jacob S. , Smith Wade S. , Lawton Michael T. , Johnston S. Claiborne
Published: April 2004

Background—

Previous studies have shown that for the treatment of subarachnoid hemorrhage (SAH), outcomes are improved but costs are higher at hospitals with a high volume of admissions for SAH. Whether regionalization of care for SAH is cost-effective is unknown.

Methods and Results—

In a cost-utility analysis, health outcomes for patients with SAH were modeled for 2 scenarios: 1 representing the current practice in California in which most patients with SAH are treated at the closest hospital and 1 representing the regionalization of care in which patients at hospitals with <20 SAH admissions annually (low volume) would be transferred to hospitals with ≥20 SAH admissions annually (high volume). Using a Markov model, we compared net quality-adjusted life-years (QALYs) and cost per QALY. Inputs were chosen from the literature and derived from a cohort study in California. Transferring a patient with SAH from a low- to a high-volume hospital would result in a gain of 1.60 QALYs at a cost of $10 548/QALY. For transfer to result in only borderline cost-effectiveness ($50 000/QALY), differences in case fatality rates between low- and high-volume hospitals would have to be one fifth as large (2.2%) or risk of death during transfer would have to be 5 times greater (9.8%) than estimated in the base case.

Conclusions—

Transfer of patients with SAH from low- to high-volume hospitals appears to be cost-effective, and regionalization of care may be justified. However, current estimates of the impact of hospital volume on outcome require confirmation in more detailed cohort studies.
Serum Antibodies Against
Chlamydia pneumoniae
Outer Membrane Protein Cross-React With the Heavy Chain of Immunoglobulin in the Wall of Abdominal Aortic Aneurysms
Authors: Lindholt Jes S. , Støvring Jette , Østergaard Lars , Urbonavicius Sigitas , Henneberg Eskild W. , Honoré Bent , Vorum Henrik
Published: April 2004

Background—

Chlamydia pneumoniae
(
Cp
) has been demonstrated in arteries and abdominal aortic aneurysms (AAAs). However, the validity of the methods used is questioned, and antibiotic treatment trials have thus far shown disappointing results. Nevertheless, antibodies against the
Cp
outer membrane proteins (OMPs) have been associated with progression of atherosclerosis and AAAs. The aim of this study was to detect
Cp
OMPs in the wall of AAA patients by use of purified serum antibodies directed against
Cp
OMP and to assess potential cross-reacting proteins in AAA walls.

Methods and Results—

Seventeen patients undergoing infrarenal AAA repair were studied. Full AAA thickness tissue was collected from the anterior wall of the aneurysm. Anti-OMP was extracted from seropositive AAA patients by use of an ELISA kit (Labsystems). Analysis was performed by use of 2D polyacrylamide gel electrophoresis, immunoblotting, and mass spectrometric protein identification. OMP antigens were not detected in 16 of 17 AAA walls. However, 3 major AAA proteins cross-reacted with anti-OMP. The proteins were all identified as heavy chains of human immunoglobulin.

Conclusions—

We could not find evidence of
Cp
OMP in 16 of 17 AAA walls, but instead, all samples showed a strong cross-reaction between
Cp
OMP antibodies and human immunoglobulin. This might indicate that AAA is an autoimmune disease, perhaps triggered by an initial
Cp
infection.
Thrombocytopenia Caused by Abciximab or Tirofiban and Its Association With Clinical Outcome in Patients Undergoing Coronary Stenting
Authors: Merlini Piera Angelica , Rossi Marco , Menozzi Alberto , Buratti Silvia , Brennan Danielle M. , Moliterno David J. , Topol Eric J. , Ardissino Diego
Published: April 2004

Background—

Thrombocytopenia is a possible complication of treatment with glycoprotein (GP) IIb/IIIa antagonists during percutaneous coronary interventions, but it is not clear whether different GP IIb/IIIa inhibitors carry a different risk of thrombocytopenia, and its relation to clinical outcome is unknown.

Methods and Results—

We analyzed data from the Do Tirofiban and Reopro Give Similar Efficacy Outcomes (TARGET) study, which compared the safety and efficacy of abciximab and tirofiban in patients undergoing coronary stenting. Platelets were measured at baseline and 6 and 24 hours after the beginning of treatment. Thrombocytopenia (nadir platelet count <100×10
9
cells/L) developed in 2.4% of patients treated with abciximab and 0.5% of those treated with tirofiban (
P
<0.001). The variables independently associated with thrombocytopenia were treatment with abciximab within the previous 6 months (OR, 4.4; 95% CI, 1.7 to 11.2), baseline creatinine levels of ≥0.8 mg/dL (OR, 3.8; 95% CI, 1.7 to 8.8), previous transient ischemic attack (OR, 3.2; 95% CI, 1.4 to 7.6), female gender (OR, 1.9; 95% CI, 1.2 to 3.1), and history of peripheral vascular disease (OR, 1.78; 95% CI, 1.0 to 3.1). Severe bleeding occurred more frequently in patients with thrombocytopenia (5.1% versus 0.7%,
P
=0.001), who also more frequently received blood transfusions (6.1% versus 1.4%,
P
=0.001). At the 30-day follow-up, 2.0% of patients with thrombocytopenia and 0.4% of those without (
P
=0.022) had died; myocardial infarction occurred in 9.13% versus 6.11% (
P
=NS); and target vessel revascularization occurred in 6.07% versus 0.60% (
P
<0.001).

Conclusions—

During coronary stenting, abciximab and other risk factors are independently associated with thrombocytopenia. Regardless of the cause, thrombocytopenia is associated with more ischemic events, bleedings, and transfusions.
Regulation of Proangiogenic Factor CCN1 in Cardiac Muscle
Authors: Hilfiker-Kleiner Denise , Kaminski Karol , Kaminska Agnieszka , Fuchs Martin , Klein Gunnar , Podewski Edith , Grote Karsten , Kiian Ioulia , Wollert Kai C. , Hilfiker Andres , Drexler Helmut
Published: April 2004

Background—

CCN1, a potent proangiogenic factor, is induced in the vasculature by tissue injury, angiotensin II (Ang II), and growth factor stimulation. Because these conditions occur in myocardial ischemia and pressure overload, we investigated the regulation of CCN1 in cardiomyocytes in vitro and in the heart in vivo.

Methods and Results—

Ang II, signaling via the angiotensin type 1 (AT
1
) receptor, and α
1
-adrenergic stimulation with phenylephrine induced CCN1 expression in ventricular cardiomyocytes isolated from 1- to 3-day-old rats. Cell culture supernatant of Ang II–treated cardiomyocytes induced migration of smooth muscle cells, which was abolished by neutralizing antibody to CCN1. Ang II– and phenylephrine-mediated induction of CCN1 expression in cardiomyocytes was completely abolished by inhibition of MEK/extracellular signal–regulated kinases (ERK) or protein kinase C (PKC). Likewise, mechanical stretch induced CCN1 expression in cardiomyocytes, an effect that was prevented by AT
1
receptor blockade or PKC inhibition. Similarly, pressure overload in vivo upregulated myocardial CCN1 expression levels via AT
1
receptor– and PKC-dependent mechanisms. After myocardial infarction in mice, CCN1 expression was strongly induced in both ischemic and remote left ventricular myocardium. Marked CCN1 protein expression was noted in cardiomyocytes of patients with end-stage ischemic cardiomyopathy but was almost absent in nonfailing human myocardium.

Conclusions—

Pressure overload, ischemia, and neurohormonal factors, such as Ang II or α
1
-adrenergic stimuli, induce myocardial expression of CCN1, a potent proangiogenic factor, supporting the notion that CCN1 may play an important role in the adaptation of the heart to cardiovascular stress.
Intramural Virtual Electrodes in Ventricular Wall
Authors: Sharifov Oleg F. , Fast Vladimir G.
Published: April 2004

Background—

Intramural virtual electrodes (IVEs) are believed to play an important role in defibrillation, but their existence in intact myocardium remains unproven. Here, IVEs were detected by use of optical recordings of shock-induced transmembrane potential (V
m
) changes (ΔV
m
) measured from the intact epicardial heart surface.

Methods and Results—

To detect IVEs, isolated porcine left ventricles were sequentially stained with a V
m
-sensitive dye by 2 methods: (1) surface staining (SS) and (2) global staining (GS) via coronary perfusion. Shocks (2 to 50 V/cm) were applied across the ventricular wall in an epicardial-to-endocardial direction during the action potential plateau via transparent mesh electrodes, and shock-induced ΔV
m
were measured optically from the same epicardial locations after SS and GS. Optical recordings revealed significant differences between ΔV
m
of 2 types that became more prominent with increasing shock strength: (1) for weak shocks, SS-ΔV
m
were larger and faster than GS-ΔV
m
; (2) for intermediate shocks, cathodal GS-ΔV
m
became multiphasic, whereas SS-ΔV
m
remained monophasic; and (3) for strong shocks, cathodal GS-ΔV
m
became uniformly negative, whereas SS-ΔV
m
typically remained positive. The radical differences in the shape and polarity of SS and GS polarizations can be explained by the contribution of subepicardial IVEs to optical signals. Histological examination revealed a dense network of collagen septa in the subepicardium, which could form the IVE substrate.

Conclusions—

Intramural virtual electrodes are reflected in optical measurements of shock-induced ΔV
m
on the intact epicardial surface. These IVEs could be a result of microscopic resistive discontinuities formed by collagen septa.
Increased Reactive Oxygen Species in Rostral Ventrolateral Medulla Contribute to Neural Mechanisms of Hypertension in Stroke-Prone Spontaneously Hypertensive Rats
Authors: Kishi Takuya , Hirooka Yoshitaka , Kimura Yoshikuni , Ito Koji , Shimokawa Hiroaki , Takeshita Akira
Published: April 2004

Background—

Oxidative stress increases in hypertension. The aim of this study was to determine whether reactive oxygen species (ROS) are increased in the rostral ventrolateral medulla (RVLM) in the brainstem, where the vasomotor center is located, in stroke-prone spontaneously hypertensive rats (SHRSP), and, if so, to determine whether the increased ROS contribute to neural mechanisms of hypertension in SHRSP.

Methods and Results—

We measured ROS levels in the RVLM of SHRSP and compared them with those in Wistar-Kyoto rats (WKY). Thiobarbituric acid–reactive substances were increased in SHRSP compared with WKY. ROS were measured by electron spin resonance (ESR) spectroscopy. The ESR signal decay rate in the RVLM of SHRSP was significantly increased compared with that in WKY, and this increase was abolished by dimethylthiourea (a hydroxyl radical scavenger). The increased ESR signal decay rate was reduced to the same extent in the presence of desferrioxamine, catalase, and Tiron, indicating that hydroxyl radicals are derived from superoxide anions and hydrogen peroxide. In addition, total superoxide dismutase (SOD) activity in the RVLM was decreased in SHRSP compared with WKY. Furthermore, bilateral microinjection of tempol into the RVLM decreased blood pressure in SHRSP but not in WKY, and MnSOD overexpression in the RVLM of SHRSP decreased blood pressure and inhibited sympathetic nerve activity.

Conclusions—

These results suggest that superoxide anions in the RVLM, which generate hydroxyl radicals, are increased in SHRSP and contribute to the neural mechanisms of hypertension in SHRSP.