bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors influencing pain outcome in herpes zoster: an observational study with valaciclovir
Authors: Decroix J , Partsch H , Gonzalez R , Mobacken H , Goh Cl , Walsh Jb , Shukla S , Naisbett B ,   on behalf of the Valaciclovir International Zoster Assessment Group (VIZA)
Published: May 2003

Aim of the study An observational study with valaciclovir was conducted to assess clinical outcome in herpes zoster, especially pain and associated neurological signs and symptoms in relation to a series of demographic and disease characteristics discernible at presentation. The safety and acceptability of valaciclovir for treatment of zoster was assessed in a wide variety of primary care and clinic referral settings.

Methods In total, 1897 immunocompetent adults with clinically diagnosed, localized acute herpes zoster were enrolled in this international, open‐label study of valaciclovir. All subjects received treatment with oral valaciclovir (1000 mg three times daily) for 7 days from entry to the study and were asked to record the presence of zoster‐associated pain and abnormal sensations throughout treatment and 6 months’ follow‐up. They were seen frequently in clinic to verify subjective assessments and for evaluation of rash healing. Safety and tolerability were assessed by adverse event monitoring.

Results Overall, 1191 subjects (63%) were aged ≥ 50 years, and 203 (11%) had ophthalmic zoster. Cessation of zoster‐associated pain was significantly faster in the younger age group; median times to loss of zoster‐associated pain were 23 days and 9 days in the ≥ 50 and < 50 years age groups, respectively. Similarly, abnormal sensations resolved significantly more rapidly in the younger subjects; the median duration of abnormal sensations was 31 days in the ≥ 50 year olds and 16 days in those aged < 50 years. In cases of ophthalmic zoster, the rate of pain resolution was not different from those with zoster in other dermatomes (median duration of pain 18 vs. 16 days). However, abnormal sensations persisted significantly longer in subjects with ophthalmic zoster than in those with zoster at other sites (47 vs. 22 days). In addition to advancing age, subjects suffering moderate to severe prodromal pain or acute pain during the rash phase were at significantly greater risk of zoster‐associated pain and abnormal sensations persisting for longer. Subjects with concomitant neurological disorders were also more likely to develop prolonged abnormal sensations. Valaciclovir treatment was well tolerated, and adverse events were rare and generally mild.

Conclusion This study confirmed the prognostic importance of advancing age and the intensity of prodromal or acute pain as risk factors for prolonged zoster‐associated pain and persisting abnormal sensations in the affected dermatome. Ophthalmic zoster and pre‐existing neurological disorders are also identified as highly significant risk factors for prolonged abnormal sensations in herpes zoster.
Women's worries during pregnancy: testing the Cambridge Worry Scale on 200 Swedish women
Authors: Öhman Susanne Georgsson , Grunewald Charlotta , Waldenström Ulla
Published: May 2003

The Cambridge Worry Scale (CWS) is an instrument including 16 items measuring women's major worries during pregnancy. The aim of the study was to test the scale, translated into Swedish, on pregnant women in Stockholm. We also wanted to explore whether these women were worried about any item not included in the scale. An additional aim was to study possible variation in women's worries related to gestational week. Two hundred women were recruited. The average age was 31 years and 56% were primiparas. Gestational age ranged from 8 to 42 weeks, with a median of 28 weeks. The reliability of the scale was satisfactory (Cronbach's alpha coefficient 0.81). The major worries were about the baby's health, giving birth and miscarriage. These items, all related to pregnancy outcomes, were followed by worries about financial matters. An additional concern not included in the scale was about the maternity services in Stockholm, i.e. that the hospital would be overbooked, the staff being too busy or the medical safety not being guaranteed. Few women worried about their relationship with their partner or if he would be present at birth. Some of the items showed a pattern with a period of less worry in midpregnancy.
Supportive and nonsupportive qualities of child health nurses' contacts with strained infant mothers
Authors: Arborelius Elisabeth U. , Bremberg Sven G.
Published: May 2003

Aim. To examine how strained mothers perceive the support they receive from Swedish child health nurse.

Population and methods. Twenty‐four consecutive strained, infant mothers at nine child health centres were invited to participate. The mothers were interviewed when the child was 8 months of age. The mothers also reported their perceptions of their parenting competence by means of a questionnaire.

Results. Five components of the nurses' support were discerned: positive emotional support, positive informational support, support of the parental role which was either positive or negative, and pressure to accept social norms on child care. A third of the mothers reported strong positive support, decreasing depressive symptoms and favourable perceptions of their own parenting ability. Another third of the mothers reported negative contacts with the nurses, persisting depressive symptoms, and unfavourable perceptions of their parenting competence. The nurses' pressure for the mothers to adapt to certain social norms of child care seemed to affect the latter group of mothers negatively.

Conclusion. In order to support strained mothers effectively it is necessary to clarify and resolve conflicts between different programme objectives.
Long–Term Histologic and Virologic Outcomes of Acute Self–Limited Hepatitis B
Authors: Yuki Nobukazu , Nagaoka Takayuki , Yamashiro Masatoshi , Mochizuki Kiyoshi , Kaneko Akira , Yamamoto Keiji , Omura Masao , Hikiji Kazumasa , Kato Michio
Published: May 2003

The long–term impact of acute self–limited hepatitis B on the liver is unknown. Fourteen patients were recalled at a median of 4.2 years (range, 1.8–9.5 years) after the onset of acute hepatitis B. All showed clinical and serologic recovery with circulating hepatitis B surface antigen (HBsAg) clearance. Antibody to HBsAg (anti–HBs) had developed in 12 patients. Nine underwent liver biopsies at a median of 7.2 years, and histologic findings were evaluated using Ishak scores. Serum samples and frozen liver tissue were subjected to real–time detection polymerase chain reaction (PCR) to quantify the surface and X regions of the hepatitis B virus (HBV) genome and qualitative PCR to detect the covalently closed circular (ccc) HBV DNA replicative intermediate. Three patients had low levels of circulating HBV DNA up to 8.9 years after the onset, whereas both HBV DNA surface and X regions were found in the liver of all 9 patients examined, including 7 negative for serum HBV DNA. Liver viral loads assessed by the 2 regions showed a significant correlation (r = 0.946; P = .008), and all patients tested positive for ccc HBV DNA. Liver fibrosis and mild inflammation persisted in 8 patients. The fibrosis stage had relation to peak serum HBV DNA in the acute phase (P = .046) but not to liver viral loads in the late convalescent phase. In conclusion, occult HBV infection persists in the liver and is accompanied by abnormal liver histology for a decade after complete clinical recovery from acute self–limited hepatitis B.
Peripheral Blood Mononuclear Cell Expression of Toll–Like Receptors and Relation to Cytokine Levels in Cirrhosis
Authors: Riordan Stephen M. , Skinner Narelle , Nagree Ammar , McCallum Helen , McIver Christopher J. , Kurtovic Jelica , Hamilton John A. , Bengmark Stig , Williams Roger , Visvanathan Kumar
Published: May 2003

Activation of macrophages by endotoxin is assumed responsible for increased circulating tumor necrosis factor α (TNF–α) and soluble TNF receptor (sTNFR) levels in cirrhosis. Relevant to this is expression of Toll–like receptor (TLR) 4 and TLR2, which is critically involved in production of TNF–α in response to endotoxin and Gram–positive microbial stimuli, respectively. The first studies on this in cirrhosis are reported here. In 36 cirrhotic patients and 32 controls, we measured (1) circulating endotoxin, TNF–α, and sTNFR levels; (2) peripheral blood mononuclear cell (PBMC) expression of TLR4 and TLR2, and (3) in vitro TNF–α production by PBMCs stimulated with endotoxin or Staphylococcus aureus enterotoxin B (SEB). PBMC expression of TLR2, circulating TNF–α levels, and in vitro TNF–α production were reassessed after supplementation with a synbiotic regimen known to increase intestinal levels of Gram–positive bacteria. Endotoxin, TNF–α, and sTNFR levels were significantly increased in cirrhosis. Endotoxin levels did not correlate significantly with other parameters. PBMC expression of TLR2 but not TLR4 was significantly up–regulated in cirrhosis and correlated significantly with serum TNF–α and sTNFR levels. In vitro TNF–α production by PBMCs stimulated by SEB was significantly blunted. Supplementation with the synbiotic regimen resulted in significant up–regulation of PBMC expression of TLR2. Serum TNF–α levels were further increased and in vitro TNF–α production further reduced in most patients. In conclusion, up–regulation of PBMC expression of TLR2 but not TLR4 occurs in cirrhosis, which implies, contrary to previous assumptions, an important stimulatory role for Gram–positive microbial components but not endotoxin. TLR2 likely contributes to increased circulating TNF–α and sTNFR levels in cirrhosis.
Inhibition of Cholangiocarcinoma Growth by Tannic Acid
Authors: Marienfeld Carla , Tadlock Laura , Yamagiwa Yoko , Patel Tushar
Published: May 2003

Cholangiocarcinoma is an aggressive malignancy of the biliary tract for which effective treatment is lacking. Tannic acid (TA) is a naturally occurring polyphenolic compound with antioxidant and radical scavenging properties as well as anticarcinogenic effects. TA inhibited proliferation of malignant human cholangiocytes in vitro. Furthermore, the growth rate of Mz–ChA–1 cholangiocarcinoma xenografts in balb/c athymic mice was reduced from 10.9 ± 1.8 mm3/d in mice fed with normal water to 5.5 ± 1.2 mm3/d in mice fed with water containing 0.05% TA. Pretreatment with 50 μg/mL TA for 24 hours before xenograft implantation increased tumor latency by 2.5–fold compared with untreated controls, and decreased subsequent growth rates compared with controls in the absence of TA feeding. TA was not cytotoxic to Mz–ChA–1 cells in vitro, but enhanced sensitivity to camptothecin cytotoxicity. TA potently inhibited cell cycle progression, and increased expression of the cyclin–dependent kinase inhibitor p27KIP1. In addition, TA (0–50 μg/mL) inhibited proteasomal activity in cholangiocyte cell extracts in a concentration–dependent manner. In conclusion, the growth inhibitory effects of TA may result from dysregulation of cell cycle progression due to altered proteasomal degradation of these cell cycle regulatory proteins. TA warrants evaluation as a candidate for the treatment of human cholangiocarcinoma either by itself or in combination with other chemotherapeutic agents.
Des–Gamma Carboxyprothrombin Can Differentiate Hepatocellular Carcinoma From Nonmalignant Chronic Liver Disease in American Patients
Authors: Marrero Jorge A. , Su Grace L. , Wei Wei , Emick Dawn , Conjeevaram Hari S. , Fontana Robert J. , Lok Anna S.
Published: May 2003

Mortality due to hepatocellular carcinoma (HCC) has not improved over the last 20 years. This is in part due to the poor performance of available tumor markers leading to delays in diagnosis. Des–gamma carboxy–prothrombin (DCP) has been reported to be more sensitive and specific for the diagnosis of HCC in Japanese patients compared with α–fetoprotein (AFP). We conducted a cross–sectional case control study to evaluate whether DCP is more sensitive and specific than AFP for differentiating HCC from nonmalignant liver disease in a cohort of American patients from a single referral center. Four groups were studied: G1, normal healthy subjects; G2, patients with noncirrhotic chronic hepatitis; G3, patients with compensated cirrhosis; and G4, patients with histologically proven HCC. A total of 207 subjects were enrolled. Both DCP and AFP levels increased progressively from G1 to G4, but DCP values had less overlap among the groups than AFP. ROC curve indicated that a DCP value of 125 mAU/mL yielded the best sensitivity (89%; 95% CI, 77%–95%) and specificity (95%; 95% CI, 82%–96%) for differentiating patients with HCC from those with cirrhosis and chronic hepatitis. The optimal AFP cutoff value was 11 ng/mL and was inferior to the DCP value of 125 mAU/mL, the area under the ROC curves being 0.928 versus 0.810, respectively (P = .002). In conclusion, DCP was more sensitive and specific than AFP for differentiating HCC from nonmalignant chronic liver disease. Prospective studies to evaluate the role of DCP in early HCC are underway.
Sonographic Criteria for the Diagnosis of Hepatic Involvement in Hereditary Hemorrhagic Telangiectasia (Hht)
Authors: Caselitz Martin , Bahr Matthias J. , Bleck Jörg S. , Chavan Ajay , Manns Michael P. , Wagner Siegfried , Gebel Michael
Published: May 2003

Hepatic involvement in hereditary hemorrhagic telangiectasia (HHT) is highly variable and may lead to severe clinical symptoms such as heart failure. This controlled, prospective study defined sonographic criteria for hepatic involvement in HHT. Color Doppler sonography and pulsed Doppler sonography were used to study 25 patients with HHT and liver involvement, 20 patients with HHT without liver involvement, 25 patients with cirrhosis, and 25 patients without liver disease. The diagnosis of hepatic manifestation was confirmed by computed tomography and/or angiography. Liver size, parenchymal changes of the liver, vessel diameters, and flow velocities of the portal vein and the hepatic artery were determined. Resistance index (RI) and pulsatility index (PI) were calculated. The diameter of the common hepatic artery was significantly dilated without overlap between HHT patients with liver involvement and the 3 control groups (mean 11.3 ± 2.8 mm [HHT with liver involvement], 4.6 ± 0.9 mm [HHT without liver involvement], 4.8 ± 1.0 mm [cirrhosis], and 4.4 ± 1.0 mm [healthy controls], P < .001). Doppler parameters of the proper hepatic artery differed significantly (all P < .001). In all patients with HHT and liver involvement, areas with intrahepatic hypervascularization caused by dilated intrahepatic arteries were observed in varying intensity. Cardiac output significantly correlated with the diameter of the common hepatic artery (r = 0.53, P = .007) and the portal vein (r = 0.42, P = .05). In conclusion, the diameter of the common hepatic artery (>7 mm) and intrahepatic hypervascularization are suitable sonographic diagnostic parameters of HHT with high sensitivity and specificity. Dilated diameters of the hepatic feeding vessels are indicators for systemic circulatory distress in these patients.
Differentiation of Embryonic Stem Cells Into Hepatocytes: Biological Functions and Therapeutic Application
Authors: Yamamoto Hanako , Quinn Gary , Asari Akira , Yamanokuchi Hiroko , Teratani Takumi , Terada Masaaki , Ochiya Takahiro
Published: May 2003

Embryonic stem (ES) cells provide a unique source for tissue regeneration. We examined whether mouse ES cells can efficiently differentiate into transplantable hepatocytes. ES cells were implanted into mouse livers 24 hours after carbon tetrachloride intoxication; ES–derived cells with several hepatocyte–cell–markers were generated. They were able to grow in vitro and showed morphology consistent with typical mature hepatocytes and expressed hepatocyte–specific genes. After transplantation into the carbon tetrachloride–injured mouse liver, ES–derived green fluorescent protein–positive cells were incorporated into liver tissue and rescued mice from hepatic injury. No teratoma formation was observed in the transplant recipients. In conclusion, ES cells can provide a valuable tool for studying the molecular basis for differentiation of hepatocytes and form the basis for cell therapies.
Targeted deletion of histidine decarboxylase gene in mice increases bone formation and protects against ovariectomy-induced bone loss
Authors: Fitzpatrick L. A. , Buzas E. , Gagne T. J. , Nagy A. , Horvath C. , Ferencz V. , Mester A. , Kari B. , Ruan M. , Falus A. , Barsony J.
Published: May 2003

Targeted disruption of the histidine decarboxylase gene (HDC
−/−
), the only histamine-synthesizing enzyme, led to a histamine-deficient mice characterized by undetectable tissue histamine levels, impaired gastric acid secretion, impaired passive cutaneous anaphylaxis, and decreased mast cell degranulation. We used this model to study the role of histamine in bone physiology. Compared with WT mice, HDC
−/−
mice receiving a histamine-free diet had increased bone mineral density, increased cortical bone thickness, higher rate of bone formation, and a marked decrease in osteoclasts. After ovariectomy, cortical and trabecular bone loss was reduced by 50% in HDC
−/−
mice compared with WT. Histamine deficiency protected the skeleton from osteoporosis directly, by inhibiting osteoclastogenesis, and indirectly, by increasing calcitriol synthesis. Quantitative RT-PCR showed elevated 25-hydroxyvitamin D-1α-hydroxylase and markedly decreased 25-hydroxyvitamin D-24-hydroxylase mRNA levels. Serum parameters confirming this indirect effect included elevated calcitriol, phosphorus, alkaline phosphatase, and receptor activator of NF-κB ligand concentrations, and suppressed parathyroid hormone concentrations in HDC
−/−
mice compared with WT mice. After ovariectomy, histamine-deficient mice were protected from bone loss by the combination of increased bone formation and reduced bone resorption.
NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease
Authors: Wu Du-Chu , Teismann Peter , Tieu Kim , Vila Miquel , Jackson-Lewis Vernice , Ischiropoulos Harry , Przedborski Serge
Published: May 2003

Parkinson's disease (PD) is a neurodegenerative disorder of uncertain pathogenesis characterized by a loss of substantia nigra pars compacta (SNpc) dopaminergic (DA) neurons, and can be modeled by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Both inflammatory processes and oxidative stress may contribute to MPTP- and PD-related neurodegeneration. However, whether inflammation may cause oxidative damage in MPTP and PD is unknown. Here we show that NADPH-oxidase, the main reactive oxygen species (ROS)-producing enzyme during inflammation, is up-regulated in SNpc of human PD and MPTP mice. These changes coincide with the local production of ROS, microglial activation, and DA neuronal loss seen after MPTP injections. Mutant mice defective in NADPH-oxidase exhibit less SNpc DA neuronal loss and protein oxidation than their WT littermates after MPTP injections. We show that extracellular ROS are a main determinant in inflammation-mediated DA neurotoxicity in the MPTP model of PD. This study supports a critical role for NADPH-oxidase in the pathogenesis of PD and suggests that targeting this enzyme or enhancing extracellular antioxidants may provide novel therapies for PD.
Change of conduction velocity by regional myelination yields constant latency irrespective of distance between thalamus and cortex
Authors: Salami Mahmoud , Itami Chiaki , Tsumoto Tadaharu , Kimura Fumitaka
Published: May 2003

The widely spanning sensory cortex receives inputs from the disproportionately smaller nucleus of the thalamus, which results in a wide variety of travelling distance among thalamic afferents. Yet, latency from the thalamus to a cortical cell is remarkably constant across the cortex (typically, ≈2 ms). Here, we found a mechanism that produces invariability of latency among thalamocortical afferents, irrespective of the variability of travelling distances. The conduction velocity (CV) was calculated from excitatory postsynaptic currents recorded from layer IV cells in mouse thalamocortical slices by stimulating the ventrobasal nucleus of the thalamus (VB) and white matter (WM). In adults, the obtained CV for VB to WM (CV
VB-WM
; 3.28 ± 0.11 m/s) was ≈10 times faster than that of WM to layer IV cells (CV
WM-IV
; 0.33 ± 0.05 m/s). The CV
VB-WM
was confirmed by recording antidromic single-unit responses from VB cells by stimulating WM. Exclusion of synaptic delay from CV
WM-IV
did not account for the 10-fold difference of CV. By histochemical staining, it was revealed that VB to WM was heavily myelinated, whereas in the cortex staining became substantially weaker. We also found that such morphological and physiological characteristics developed in parallel and were accomplished around postnatal week 4. Considering that VB to WM is longer and more variable in length among afferents than is the intracortical region, such an enormous difference of CV makes conduction time heavily dependent on the length of intracortical region, which is relatively constant. Our finding may well provide a general strategy of connecting multiple sites irrespective of distances in the brain.
Complex movements evoked by microstimulation of the ventral intraparietal area
Authors: Cooke Dylan F. , Taylor Charlotte S. R. , Moore Tirin , Graziano Michael S. A.
Published: May 2003

Most neurons in the ventral intraparietal area (VIP) of the macaque brain respond to both visual and tactile stimuli. The tactile receptive field is usually on the face, and the visual receptive field usually corresponds spatially to the tactile receptive field. In this study, electrical microstimulation of VIP, but not of surrounding tissue, caused a constellation of movements including eye closure, facial grimacing, head withdrawal, elevation of the shoulder, and movements of the hand to the space beside the head or shoulder. A similar set of movements was evoked by an air puff to the monkey's cheek. One interpretation is that VIP contributes to defensive movements triggered by stimuli on or near the head.
Behavioral, neurochemical, and electrophysiological characterization of a genetic mouse model of depression
Authors: El Yacoubi Malika , Bouali Saoussen , Popa Daniela , Naudon Laurent , Leroux-Nicollet Isabelle , Hamon Michel , Costentin Jean , Adrien Joëlle , Vaugeois Jean-Marie
Published: May 2003

Depression is a multifactorial illness and genetic factors play a role in its etiology. The understanding of its physiopathology relies on the availability of experimental models potentially mimicking the disease. Here we describe a model built up by selective breeding of mice with strikingly different responses in the tail suspension test, a stress paradigm aimed at screening potential antidepressants. Indeed, “helpless” mice are essentially immobile in the tail suspension test, as well as the Porsolt forced-swim test, and they show reduced consumption of a palatable 2% sucrose solution. In addition, helpless mice exhibit sleep–wakefulness alterations resembling those classically observed in depressed patients, notably a lighter and more fragmented sleep, with an increased pressure of rapid eye movement sleep. Compared with “nonhelpless” mice, they display higher basal seric corticosterone levels and lower serotonin metabolism index in the hippocampus. Remarkably, serotonin
1A
autoreceptor stimulation induces larger hypothermia and inhibition of serotoninergic neuronal firing in the nucleus raphe dorsalis in helpless than in nonhelpless mice. Thus, helpless mice exhibit a decrease in serotoninergic tone, which evokes that associated with endogenous depression in humans. Finally, both the behavioral impairments and the serotoninergic dysfunction can be improved by chronic treatment with the antidepressant fluoxetine. The helpless line of mice may provide an opportunity to approach genes influencing susceptibility to depression and to investigate neurophysiological and neurochemical substrates underlying antidepressant effects.
Antigens in tea-beverage prime human Vγ2Vδ2 T cellsin vitroandin vivofor memory and nonmemory antibacterial cytokine responses
Authors: Kamath Arati B. , Wang Lisheng , Das Hiranmoy , Li Lin , Reinhold Vernon N. , Bukowski Jack F.
Published: May 2003

Human γδ T cells mediate innate immunity to microbes via T cell receptor-dependent recognition of unprocessed antigens with conserved molecular patterns. These nonpeptide alkylamine antigens are shared by tumor cells, bacteria, parasites, and fungi but also by edible plant products such as tea, apples, mushrooms, and wine. Here we show that priming of γδ T cells with alkylamine antigensin vitroresults in a memory response to these antigens. Such priming results also in a nonmemory response to whole bacteria and to lipopolysaccharide, characterized by IL-12-dependent secretion of IFN-γ by γδ T cells and by γδ T cell proliferation. Drinking tea, which containsl-theanine, a precursor of the nonpeptide antigen ethylamine, primed peripheral blood γδ T cells to mediate a memory response on reexposure to ethylamine and to secrete IFN-γ in response to bacteria. This unique combination of innate immune response and immunologic memory shows that γδ T cells can function as a bridge between innate and acquired immunity. In addition, these data provide an explanation for the health benefits of tea.
In Silico Identification of Putative Regulatory Sequence Elements in the 5′-Untranslated Region of Genes That Are Expressed during Male Gametogenesis
Authors: Hulzink Raymond Jozef Maurinus , Weerdesteyn Han , Croes Anton Felix , Gerats Tom , van Herpen Marinus Maria Antonius , van Helden Jacques
Published: May 2003

During pollen development, transcription of a large number of genes results in the appearance of distinct sets of transcripts. Similar mRNA sets are present in pollen of both mono- and dicotyledonous plant species, which indicates an evolutionary conservation of genetic programs that determine pollen gene expression. In pollen, regulation of gene expression occurs at the transcriptional and posttranscriptional level. The 5′-untranslated region (UTR) of several pollen transcripts has been shown to be important for regulation of pollen gene expression. The important regulatory role of 5′-UTR sequences and the evolutionary conservation of genetic programs in pollen led to the hypothesis that the 5′-UTRs of pollen-expressed genes share regulatory sequence elements. In an attempt to identify these pollen 5′-UTR elements, a statistical analysis was performed using 5′-UTR sequences of pollen- and sporophytic-expressed genes. The analysis revealed the presence of several pollen-specific 5′-UTR sequence elements. Assembly of the pollen 5′-UTR elements led to the identification of various consensus sequences, including those that previously have been demonstrated to play a role in the regulation of pollen gene expression. Several pollen 5′-UTR elements were found to be preferentially associated to genes from dicots, wet-type stigma plants, or plants containing bicellular pollen. Moreover, three sequence elements exhibited a preferential association to the 5′-UTR of pollen-expressed genes from Arabidopsis andBrassica napus. Functional implications of these observations are discussed.
Using biometrics for sport venue management in a post 9‐11 era
Authors: Whisenant Warren A.
Published: May 2003

The purpose of this paper is to assess technologies, both currently available and under development, which may be used to assist sport facility and other venue operators in preempting a terrorist act or some other form of organized act of violence. The attack on the World Trade Center on September 11 highlighted the vulnerability of large facilities to attack by committed terrorists. Facility managers and venue operators must face the challenge of protecting physical assets as well as participants and spectators. This technology forecast focuses on technologies associated with biometrics. The proposition presented has been based, in part, on information provided from interviews with industry experts from a variety of professions, including facility management, biometric technologies, event security and anti‐terrorism from both the private and government sectors. A review of published and unpublished materials associated with biometrics is also presented as part of the technology forecast.
Occupational burnout: a cross‐cultural Israeli Jewish‐Arab perspective and its implications for career counselling
Authors: Malach Pines Ayala
Published: May 2003

Since the 1970s, occupational burnout has become a popular topic of research and an important concern for career counsellors. The majority of studies on burnout focussed on documenting its existence within certain occupational groups. The assumption underlying these studies is that occupational burnout is a universal phenomenon that can be best explained by the stresses characterising a particular occupation or organisation. Few studies examined burnout cross‐culturally. The present study attempted to demonstrate the importance of such a cross‐cultural perspective using a comparison between Israeli Jews and Arabs, who live in the same country but are culturally different: Arabs traditional and collectivist, Jews modern and individualistic. Interviews with representative samples of the Jewish and Arab populations in Israel show significant differences in occupational burnout and various burnout correlates. Thus, Arabs’ burnout correlated negatively with the quality of relationships with mother and father, Jews’ with superiors and co‐workers. Arabs were significantly less likely than Jews to talk about a work‐related problem or approach a counsellor. These findings have both theoretical and practical implications for career counselling.
Substantial Change and Spatiotemporal Coincidence
Authors: Lowe E. J.
Published: May 2003

Substantial change occurs when a persisting object of some kind either begins or ceases to exist. Typically, this happens when one or more persisting objects of another kind or kinds are subjected to appropriate varieties of qualitative or relational change, as when the particles composing a lump of bronze are rearranged so as to create a statue. However, such transformations also seem to result, very often, in cases of spatiotemporal coincidence, in which two numerically distinct objects of different kinds exist in exactly the same place at the same time, such as a statue and a lump of bronze. Various attempts to resist this way of describing the results of such transformations are examined and found wanting and objections to the possibility of cases of spatiotemporal coincidence are rebutted.
Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Prolongs the Life Span of Primary Human Umbilical Vein Endothelial Cells
Authors: Watanabe Takahiro , Sugaya Makoto , Atkins April M. , Aquilino Elisabeth A. , Yang Aparche , Borris Debra L. , Brady John , Blauvelt Andrew
Published: May 2003

Tumor spindle cells in all clinical types of Kaposi's sarcoma (KS) are infected with Kaposi's sarcoma-associated herpesvirus (KSHV). Although KSHV contains more than 80 genes, only a few are expressed in tumor spindle cells, including latency-associated nuclear antigen (
LANA
) and k-cyclin (
kCYC
). To assess the oncogenic potential of
LANA
and
kCYC
, primary human umbilical vein endothelial cells (HUVEC) and murine NIH 3T3 cells were stably transduced by using recombinant retroviruses expressing these genes or the known viral oncogene simian virus 40 large T antigen (
LTAg
). Interestingly,
LANA
-transduced HUVEC proliferated faster and demonstrated a greatly prolonged life span (mean ± standard deviation, 38.3 ± 11.0 passages) than untransduced cells and vector-transduced cells (<20 passages). By contrast,
kCYC
-transduced HUVEC did not proliferate faster or live longer than control cells.
LANA
- and
kCYC
-transduced HUVEC, but not
LTAg
-transduced HUVEC, retained the ability to form normal vessel-like structures in an in vitro model of angiogenesis. In cellular assays of transformation,
LANA
- and
kCYC
-transduced NIH 3T3 cells demonstrated minimal or no anchorage-independent growth in soft agar and no tumorigenicity when injected into nude mice, unlike
LTAg
-transduced NIH 3T3 cells. Lastly, gene expression profiling revealed down-regulation, or silencing, of a number of genes within
LANA
-transduced HUVEC. Taken together, these results suggest that KSHV
LANA
is capable of inducing prolonged life span, but not transformation, in primary human cells. These findings may explain why
LANA
-expressing spindle cells proliferate within KS tumors, yet most often do not demonstrate biologic characteristics of transformation or true malignant conversion.
Absence of
p53
Complements Defects in Abelson Murine Leukemia Virus Signaling
Authors: Unnikrishnan Indira , Rosenberg Naomi
Published: May 2003

The v-Abl protein encoded by Abelson murine leukemia virus (Ab-MLV) induces transformation of pre-B cells via a two-stage process. An initial proliferative phase during which cells with limited tumorigenic potential expand is followed by a crisis period marked by high levels of apoptosis and erratic growth. Transformants that survive this phase emerge as fully malignant cells and usually contain mutations that disable the p53 tumor suppressor pathway. Consistent with the importance of p53 in this process, pre-B cells from
p53
null animals bypass crisis. Thus, the transformation process reflects a balance between signals from the v-Abl protein that drive transformation and those coming from the cellular response to inappropriate growth. One prediction of this hypothesis is that Ab-MLV mutants that are compromised in their ability to transform cells may be less equipped to overcome the effects of p53. To test this idea, we examined the ability of the P120/R273K mutant to transform pre-B cells from wild-type,
p53
null, and
Ink4a/Arf
null mice. The SH2 domain of the v-Abl protein encoded by this mutant contains a substitution that affects the phosphotyrosine-binding pocket, and this mutant is compromised in its ability to transform NIH 3T3 and pre-B cells, especially at 39.5°C. Our data reveal that loss of
p53
or
Ink4a/Arf
locus products complements the transforming defect of the P120/R273K mutant, but it does not completely restore wild-type function. These results indicate that one important transforming function of v-Abl proteins is overcoming the effects of a functional p53 pathway.
STRAIN ENERGY BAND ENGINEERING APPROACH TO AlN/GaN/InN HETEROJUNCTION DEVICES
Authors: KHAN ASIF , YANG J. W. , SIMIN G. , GASKA R. , SHUR M. S.
Published: May 2003

Our new Strain and Energy Band Engineering approach allows us to control, modulate or eliminate the strain thereby significantly enhancing the performance of electronic and optoelectronic devices on SiC and sapphire substrates using a new-pulsed atomic layer epitaxy procedure. New types of high power high temperature transistors with improved performance were fabricated XRD, PL and AFM spectra are used to establish a high structural and optical quality of die quaternary multiple quantum wells. We have also demonstrated the use of PALE deposited quaternary AlInGaN multiple quantum wells in the active region of a UV LED with emission ranging from 305 nm to 304 nm.
ARCHITECTURE AND DESIGN OF AN 8-BIT FLUX-1 SUPERCONDUCTOR RSFQ MICROPROCESSOR
Authors: DOROJEVETS MIKHAIL
Published: May 2003

The first single-chip superconductor FLUX-1 microprocessor has been designed in the Rapid Single Flux Quantum (RSFQ) logic and fabricated using 4 kA/cm2, 1.75-μm Nb/AlOx/Nb Josephson junction technology as a result of the collaboration between SUNY Stony Brook and TRW, Inc. A FLUX-1 chip represents an 8-bit deeply pipelined microprocessor prototype with a target clock frequency of 17-20 GHz. A new parallel partitioned architecture has been developed in order to tolerate interconnect delays and fill long FLUX-1 processor pipelines with useful instructions. The processor includes the 16 × 32-bit pipelined instruction memory, 8 integer arithmetic-logic units interleaved with 8 registers, the branch unit, and I/O ports for 5-GHz chip-to-chip communication over Nb microstrip lines on a chip carrier. The FLUX-1 instruction set consists of ~25 arithmetic, logical, and control instructions. A FLUX-1 microprocessor chip contains 65,759 Josephson junctions on a 10.6 mm × 13.2 mm die with flip-chip packaging. First FLUX-1 chips fabricated in August 2001 are currently under testing at TRW, Inc.
A SIMULATION-BASED PREVIEW OF EXTREMELY SCALED DOUBLE-GATE CMOS DEVICES AND CIRCUITS
Authors: FOSSUM JERRY G.
Published: May 2003

This paper gives a simulation-based preview of device-design issues and performance of extremely scaled DG CMOS. A suite of simulation tools, including a 2D numerical device simulator, a 1D numerical Poisson-Schrödinger solver, and a generic, physics/process-based DG MOSFET compact model in Spice, is applied to both asymmetrical-and symmetrical-gate DG CMOS devices and circuits to provide physical insight at the device and circuit levels. The results give added motivation as well as preliminary guidance for the development of DG CMOS.
GINZBURG–LANDAU EQUATION FROM SU(2) GAUGE FIELD THEORY
Authors: DZHUNUSHALIEV VLADIMIR , SINGLETON DOUGLAS
Published: May 2003

The dual superconductor picture of the QCD vacuum is thought to describe the various aspects of the strong interaction including confinement. Ordinary superconductivity is described by the Ginzburg–Landau (GL) equation. In the present work we show that it is possible to arrive at a GL-like equation from pure SU(2) gauge theory. This is accomplished by using Abelian projection to split the SU(2) gauge fields into an Abelian subgroup and its coset. The two gauge field components of the coset part act as the effective, complex, scalar field of the GL equation. The Abelian part of the SU(2) gauge field is then analogous to the electromagnetic potential in the GL equation. An important feature of the dual superconducting model is for the GL Lagrangian to have a spontaneous symmetry breaking potential, and the existence of Nielsen–Olesen flux tube solutions. Both of these require a tachyonic mass for the effective scalar field. Such a tachyonic mass term is obtained from the condensation of ghost fields.
Single-Nucleotide Mutations for Plant Functional Genomics
Authors: Henikoff Steven , Comai Luca
Published: May 2003

In the present genomics era, powerful reverse-genetic strategies are needed to elucidate gene and protein function in the context of a whole organism. However, most current techniques lack the generality and high-throughput potential of descriptive genomic approaches, such as those that rely on microarray hybridization. For example, in plant research, effective insertional mutagenesis and transgenic methods are limited to relatively few species or are inefficient. Fortunately, single-nucleotide changes can be induced in any plant by using traditional chemical mutagens, and progress has been made in efficiently detecting changes. Because base substitutions in proteins provide allelic series, and not just knockouts, this strategy can yield refined insights into protein function. Here, we review recent progress that has been made in genome-wide screening for point mutations and natural variation in plants. Its general applicability leads to the expectation that traditional mutagenesis followed by high-throughput detection will become increasingly important for plant functional genomics.
Apomixis: A Developmental Perspective
Authors: Koltunow Anna M. , Grossniklaus Ueli
Published: May 2003

The term apomixis encompasses a suite of processes whereby seeds form asexually in plants. In contrast to sexual reproduction, seedlings arising from apomixis retain the genotype of the maternal parent. The transfer of apomixis and its effective utilization in crop plants (where it is largely absent) has major advantages in agriculture. The hallmark components of apomixis include female gamete formation without meiosis (apomeiosis), fertilization-independent embryo development (parthenogenesis), and developmental adaptations to ensure functional endosperm formation. Understanding the molecular mechanisms underlying apomixis, a developmentally fascinating phenomenon in plants, is critical for the successful induction and utilization of apomixis in crop plants. This review draws together knowledge gained from analyzing ovule, embryo, and endosperm development in sexual and apomictic plants. It consolidates the view that apomixis and sexuality are closely interrelated developmental pathways where apomixis can be viewed as a deregulation of the sexual process in both time and space.
A Rare Case of Retrocaval Ureter Associated with Persistent Left Vena cava
Authors: Gramegna V. , Madaro A. , Pellegrini F. , Capizzi S. , Romano O. , Massari D. , Liessi G.
Published: May 2003

We report a rare case of a retrocaval ureter associated with a left inferior vena cava transposition and with concomitant nephrolithiasis in a young woman already surgically treated during her first years of life for cardiovascular disease. Diagnosis and surgical procedure are described, including the use of a flexible ureterorenoscope to facilitate kidney stone removal.
Reinduction of Atrial Fibrillation Immediately After Termination of the Arrhythmia Is Mediated by Late Phase 3 Early Afterdepolarization–Induced Triggered Activity
Authors: Burashnikov Alexander , Antzelevitch Charles
Published: May 2003

Background—

Atrial fibrillation (AF) at times recurs immediately after termination of the arrhythmia. The mechanism(s) responsible for the extrasystole that reinduces AF is largely unknown. We hypothesized that abbreviation of action potential duration (APD) would permit very rapid rates of excitation, known to induce intracellular calcium loading, which in turn could promote delayed and/or early afterdepolarizations (EADs).

Methods and Results—

Acetylcholine (ACh, 1 μmol/L) was used to abbreviate atrial APD and permit rapid-pacing induction of AF in isolated coronary-perfused canine right atria. Transmembrane action potentials, pseudo-ECG, and tension development were recorded. AF or rapid pacing was associated with an increase in tonic tension. Termination of AF or rapid pacing (cycle length, 150 to 80 ms) resulted in a dramatic rise of phasic tension, prolongation of repolarization of the initial beats at the regular rate (cycle length, 700 ms), and the development of late phase 3 EADs and extrasystoles. These extrasystoles initiated AF in 15 cases (involving 9 right atria) within the first 11 seconds after termination of AF or rapid pacing. This novel EAD mechanism is observed only in association with marked APD abbreviation. The calcium channel blocker nifedipine reduced, and the sarcoplasmic reticulum calcium release blocker ryanodine eliminated, the post–rapid pacing–induced increase in phasic tension, late phase 3 EADs, and extrasystoles that initiate AF.

Conclusions—

These data suggest that calcium overload conditions present after termination of vagally mediated AF contribute to the development of late phase 3 EAD-induced triggered activity and that this mechanism may be responsible for the extrasystolic activity that reinitiates AF.
Vasopressin V
2
-Receptor Blockade With Tolvaptan in Patients With Chronic Heart Failure
Authors: Gheorghiade Mihai , Niazi Imran , Ouyang John , Czerwiec Frank , Kambayashi Jun-ichi , Zampino Manuela , Orlandi Cesare
Published: May 2003

Background—

In this study, we evaluated the effects of tolvaptan (OPC-41061), a novel, oral, nonpeptide vasopressin V
2
-receptor antagonist in patients with chronic heart failure (CHF).

Methods and Results—

This was a double-blind study investigating the effects of three doses of tolvaptan and placebo in patients with CHF. After a run-in period, 254 patients were randomly assigned to placebo (n=63) or tolvaptan [30 mg (n=64), 45 mg (n=64), or 60 mg (n=63)] once daily for 25 days. Patients were not fluid-restricted and were maintained on stable doses of furosemide. At day 1, when compared with baseline, a decrease in body weight of −0.79±0.99, −0.96±0.93, and −0.84±0.02 kg was observed in the 30-, 45-, and 60-mg tolvaptan groups, respectively, and a body weight increase of +0.32±0.46 kg in the placebo group (
P
<0.001 for all treatment groups versus placebo). Although the initial decrease in body weight was maintained during the study, no further reduction was observed beyond the first day. An increase in urine volume was observed with tolvaptan when compared with placebo (3.9±0.6, 4.2±0.9, 4.6±0.4, and 2.3±0.2 L/24 hours at day 1 for 30-, 45-, and 60-mg tolvaptan groups, and placebo, respectively;
P
<0.001). A decrease in edema and a normalization of serum sodium in patients with hyponatremia were observed in the tolvaptan group but not in the placebo group. No significant changes in heart rate, blood pressure, serum potassium, or renal function were observed.

Conclusions—

In patients with CHF, tolvaptan was well tolerated; it reduced body weight and edema and normalized serum sodium in the hyponatremic patients.
Effects of Intravenous Nesiritide on Human Coronary Vasomotor Regulation and Myocardial Oxygen Uptake
Authors: Michaels Andrew D. , Klein Andrew , Madden James A. , Chatterjee Kanu
Published: May 2003

Background—

Nesiritide, recombinant human B-type natriuretic peptide, has been shown to be efficacious in the treatment of decompensated heart failure. The effects of intravenous nesiritide on the human coronary vasculature have not been studied.

Methods and Results—

Ten patients underwent right and left heart catheterization. Baseline coronary blood flow was determined using quantitative coronary angiography (QCA) and an intracoronary Doppler-tipped guidewire. Myocardial oxygen uptake was measured using a coronary sinus catheter. Patients then received an intravenous infusion of nesiritide (2 μg/kg bolus followed by 0.01 μg/kg per min infusion) for 30 minutes. Right atrial pressure decreased 52% (
P
=0.012), pulmonary artery mean pressure decreased 19% (
P
=0.03), pulmonary capillary wedge pressure decreased 46% (
P
=0.002), and mean arterial pressure decreased 11% (
P
=0.007). QCA demonstrated a 15% increase in coronary artery diameter from a baseline of 2.6±0.8 to 3.0±0.8 mm at 30 minutes (
P
=0.007). The coronary velocity measure of average peak velocity increased 14% from 20.8±6.4 at baseline to 23.8±7.2 cm/s at 5 minutes (
P
=0.015) and then returned to baseline for the remainder of the infusion. Coronary blood flow increased 35% (
P
=0.007), whereas coronary resistance decreased 23% at 15 and 30 minutes (
P
=0.036). Myocardial oxygen uptake decreased 8% during the nesiritide infusion (
P
=0.043).

Conclusions—

Nesiritide exerts coronary vasodilator effects on both the coronary conductance and resistance arteries. Despite a decrease in coronary perfusion pressure, coronary artery blood flow is increased, coronary resistance is decreased, and myocardial oxygen uptake is decreased.