bluuebunny/crossref_metadata_2025 huggingface dataset:
Autologous cytomegalovirus‐specific T cells as effector cells in immunotherapy of B cell chronic lymphocytic leukaemia
Authors: Kater Arnon P. , Remmerswaal Ester B. M. , Nolte Martijn A. , Eldering Eric , Van Oers Marinus H. J. , Van Lier René A. W.
Published: July 2004

B‐cell chronic lymphocytic leukaemia (B‐CLL) cells express low levels of co‐stimulatory molecules and therefore fail to induce activation and differentiation of tumour‐specific T cells. We have shown that patients with B‐CLL have considerably expanded numbers of cytomegalovirus (CMV) reactive CD8+ T cells. This study demonstrated that B‐CLL cells loaded with CMV peptide not only promoted the ex vivo expansion of autologous, in vivo‐generated virus‐specific T cells, but also constituted excellent target cells for these cytotoxic Tcells, even without ex vivo re‐stimulation. Directing virus‐specific T cells to B‐CLL may overcome the inadequate immunostimulatory capacity of these cells, which could be exploited for T‐cell mediated immunotherapy.
The value of education and self‐monitoring in the management of warfarin therapy in older patients with unstable control of anticoagulation
Authors: Khan Tayyaba Irfan , Kamali Farhad , Kesteven Patrick , Avery Peter , Wynne Hilary
Published: July 2004

Of 125 patients aged 65 years or over, with atrial fibrillation taking warfarin for at least 12 months, with a standard deviation (SD) of prothrombin time, expressed as the International Normalized Ratio (INR) >0·5 over the previous 6 months, 40 were randomized to continue with usual clinic care and 85 to receive education about warfarin. Of these, 44 were randomized to self‐monitor their INR and 41 returned to clinic. Compared with the previous 6 months there was a significant increase in percentage time within the therapeutic range for the 6 months following education [61·1 vs. 70·4; mean difference 8·8; 95% confidence interval (CI): −0·2–17·8; P = 0·054] and following education and self‐monitoring (57 vs. 71·1; mean difference 14·1; 95% CI: 6·7–21·5; P < 0·001), compared with those patients following usual clinic care (60·0 vs. 63·2; mean difference 3·2; 95% CI: −7·3–13·7). Using the same comparative periods, the INR SD fell by 0·24 (P < 0·0001) in the group allocated to education and self‐monitoring, 0·26 (P < 0·0001) in the group receiving education alone and 0·16 (P = 0·003) in the control group. Inter‐group differences were not statistically significant (intervention groups 0·26 ± 0·30 vs. control 0·16 ± 0·3, P = 0·10). Quality‐of‐life measurements and health beliefs about warfarin were unchanged (apart from emotional role limitation) with education or education and self‐monitoring. Patient education regarding anticoagulation therapy could be a cost‐effective initiative and is worthy of further study.
Impaired osteoblastogenesis in myeloma bone disease: role of upregulated apoptosis by cytokines and malignant plasma cells
Authors: Silvestris Franco , Cafforio Paola , Calvani Nicola , Dammacco Franco
Published: July 2004

Bone remodelling is severely affected in myeloma bone disease as a consequence of skeletal metastatization of malignant plasma cells. We investigated whether defective bone replacement is dependent on increased osteoblast apoptosis and/or on deregulated events within the bone microenvironment. Circulating tumour necrosis factor (TNF)‐α, interferon‐γ, interleukin (IL)‐1β, and IL‐6 levels were higher in myeloma patients with overt bone disease, whose osteoblasts constitutively overexpressed Fas, DR4/DR5 complex as receptors to TNF‐related apoptosis inducing ligand, intercellular adhesion molecule‐1 (ICAM‐1), and monocyte chemotactic protein‐1 (MCP‐1). They were functionally exhausted and promptly underwent apoptosis in vitro, in contrast to the minor tendency to death detected in control osteoblasts from patients without bone involvement and normal donors. Osteoblasts dramatically enhanced their apoptosis in co‐cultures with MCC‐2 myeloma cells and upregulated both ICAM‐1 and MCP‐1 in a manner similar to control osteoblasts. Pretreating MCC‐2 cells with soluble ICAM‐1 led to a striking inhibition of their adhesion to osteoblasts, suggesting that the ICAM‐1/lymphocyte function‐associated antigen‐1 system plays a role in the reciprocal membrane contact to trigger apoptogenic signals. Our data suggest that, in the myeloma bone microenvironment, both high cytokine levels and physical interaction of malignant plasma cells with osteoblasts drive the accelerated apoptosis in these cells leading to defective new bone formation.
Genetic diversity of hexaploid wheat cultivars estimated by RAPD markers, morphological traits and coefficients of parentage
Authors: Marić S. , Bolarić S. , Martinčić J. , Pejić I. , Kozumplik V.
Published: July 2004

Estimates of genetic diversity can be based on different types of data. The aim of this research were to study genetic diversity among Croatian wheat cultivars by random amplified polymorphic DNA (RAPD) markers, morphological traits and pedigree records; to analyse differences between wheat cultivars from two breeding centres; and to evaluate usability of RAPD markers for estimation of genetic diversity among wheat cultivars in comparison with morphological traits and pedigree record data. Studies were conducted on 14 wheat cultivars and breeding lines from two breeding centres in Croatia. For the RAPD analysis 36 primers were screened and the 14 most polymorphic ones yielded 341 polymorphic bands. Twelve morphological traits were used for morphological analysis. Pedigrees were composed of seven generations of ancestors. RAPD markers showed a high level of polymorphism among the cultivars examined and the breeding lines. No significant correlations were observed among the methods tested.
Identification of cultivars and accessions of Lolium, Festuca and Festulolium hybrids through the detection of simple sequence repeat polymorphism
Authors: Momotaz A. , Forster J. W. , Yamada T.
Published: July 2004

Molecular diversity and genetic affinity in the Lolium/Festuca grass complex have been assessed using simple sequence repeat (SSR) marker technology. The genotypic set was derived from three accessions of perennial ryegrass, two cultivars of Italian ryegrass, two cultivars of meadow fescue, two cultivars of tall fescue and 10 accessions from different intergeneric hybrid (Festulolium) combinations. The majority of the genomic DNA‐derived SSR primer pairs from perennial ryegrass (LPSSR) and Italian ryegrass (LMSSR) produced clear, simple and distinctive amplification products from the majority of the genotypes. The efficiency of cross‐specific amplification for LPSSR markers varied from 38% in meadow fescue to 93% in two cultivars of Festulolium and from 57% in meadow fescue to 87% in Italian ryegrass for LMSSR markers. Of 40 amplified markers, 14 (35%) produced species‐difference alleles in the relation to cultivars used in the present study. Thirty‐five LPSSR locus‐derived alleles were found to be specific to Lolium species, four to meadow fescue and six to tall fescue. For LMSSR alleles, eight were specific to Lolium species and five were only associated with Italian ryegrass, and null alleles were detected for meadow fescue in all instances. These species‐difference markers could clearly identify different accessions of Festulolium. Cluster analysis separated the individual taxa and showed grouping of intergeneric hybrids based on genomic composition. The data distinguished between the species and reflected the known pedigree of the cultivars and the differences between the species. The dendrogram also distinguished between the Festulolium accessions and clearly demonstrated the relations between Festulolium hybrids and their parent species.
Cytogenetic analysis of two interspecific Citrus allotetraploid somatic hybrids and their diploid fusion parents
Authors: Chen C. L. , Guo W. W. , Yi H. L. , Deng X. X.
Published: July 2004

Microsporogenesis of two interspecific allotetraploid somatic hybrids, i.e.‘Hamlin’ sweet orange +‘Rough Lemon’ (HR) and ‘Key’ lime +‘Valencia’ sweet orange (KV), was examined and compared with their corresponding diploid fusion parents. Meiotic analysis revealed that only 13.2 and 18.0% of the meiocytes exhibited normal tetrad formation in HR and KV somatic hybrid plants, respectively, and irregular chromosome behaviour with univalent or multivalent pairing occurred. Moreover, meiotic abnormalities such as chromosome bridges, chromosomes orientated away from the equatorial plate, especially lagging chromosomes, which resulted in different sizes of pollen grain, were frequently observed in both somatic hybrids. As expected, the percentage of chromosome abnormalities was much lower in their corresponding diploid fusion parents. HR and KV had 15.4 and 7.2% pollen germinability, respectively, intermediate between their corresponding fusion parents. The meiotic behaviour of these somatic hybrids provided valuable information for their practical utilization in a citrus breeding programme.
Detection and genotyping of SNPs tightly linked to two disease resistance loci, Rsv1 and Rsv3, of soybean
Authors: Jeong S. C. , Saghai Maroof M. A.
Published: July 2004

Allele‐specific polymerase chain reaction (AS‐PCR) for assaying single nucleotide polymorphisms (SNPs) would be more widely used with increased availability of AS primers sufficient to distinguish between SNP alleles. AS‐PCR could be a means unambiguously to detect the presence or absence of PCR products. Examples are given here of the detection and genotyping of SNPs in the genomic DNA fragments tightly linked to two soybean mosaic virus resistance genes, Rsv1 and Rsv3, with a modified AS‐PCR procedure in soybean. The modified AS‐PCR that introduces an additional base mismatch closest to the 3′‐end of the AS primers and uses publicly available microsatellite markers as positive controls directly determined SNP alleles from primary PCR of genomic DNAs. It was demonstrated that a set of AS primers designed from two adjacent SNP loci could simultaneously detect the two SNP loci. Using the modified procedure, many SNP loci in eight soybean parental lines and F2 individuals of three mapping populations could be genotyped. The modified AS‐PCR procedure could greatly facilitate small‐to‐medium scale marker‐assisted selection programmes for agronomically important genes.
S‐allele identification by PCR analysis in sweet cherry cultivars
Authors: Wünsch A. , Hormaz J. I.
Published: July 2004

Gametophytic self‐incompatibility, governed by the S‐locus, operates in sweet cherry. The knowledge of the S‐genotype of sweet cherry cultivars is therefore essential to establish productive orchards by defining compatible combinations. The isolation of sweet cherry S‐R Nases has allowed the use of different molecular techniques to characterize the S‐genotypes of sweet cherry cultivars. Previously, incompatibility group assignment could only be carried out on mature trees through pollination tests. In this work, PCR analysis with primers designed on the conserved sequences of sweet cherry S‐R Nases has been used to characterize the S‐genotype of 71 sweet cherry cultivars, including 26 cultivars whose S‐allele constitution had not been previously described. This approach has allowed the detection of alleles that had not been amplified by PCR before, to identify six putative new S‐alleles, to define three new self‐incompatibility groups and to compile the standards for a PCR‐based S‐allele typing method in sweet cherry.
Variation and genetics of tolerance to cull fruit formation in slicing cucumber
Authors: Dhillon N. P. S.
Published: July 2004

Cull fruit formation (CFF) in cucumber is a serious problem in subtropical regions. A world collection of cucumber was evaluated in the field for tolerance to CFF over 2 years. Tolerance was identified in landraces collected from the centre of origin (India). Highly significant genotypic effects for tolerance to CFF were observed. The data revealed the presence of genetic variability among cucumber inbreds for tolerance to CFF, which would be useful to develop CFF‐tolerant varieties or hybrids. Genotype‐by‐environment interaction for tolerance to CFF was not detected. Twenty‐one F1 hybrids evaluated for tolerance to CFF indicated the dominance of a low CFF trait which appears to be controlled by many dominant genes. The in breds ‘JL‐1’, ‘JL‐2’ and ‘JL‐11’ would be good choices as parents for developing CFF‐tolerant cucumber hybrids.
Seedling survivability as a selection criterion for drought tolerance in wheat
Authors: Tomar S. M. S. , Kumar G. T.
Published: July 2004

Ninety genotypes of wheat (Triticum aestivum L.) were screened at the seedling stage in wooden boxes in greenhouse conditions (range of temperature 25‐35°C) for moisture stress. Boxes were filled with a mixture of soil : sand : FYM in a 50 : 45 : 5 ratio. Boxes were given equal quantities of water 12 h before sowing to ensure good germination. Seeds were sown in rows at a uniform depth of 3 cm. No irrigation was provided after sowing. When most of the genotypes started wilting, the boxes were irrigated to study the recovery response (seedling survivability) of the genotypes. Based on the days taken for recovery, wheat genotypes, JWS 98, HD 2329, HW 3081, Halna and MP 1136 withered early and were grouped as susceptible, while the genotypes HI 1494, HW 2044, Kundan, NIAW 588, PBW 514 and NI 5439 resumed growth, showed a better response and were classified as drought‐tolerant. The study on mode of inheritance revealed that seedling survivability is controlled by a single dominant gene.
Segregation patterns of AFLP markers in F1 hybrids of a cross between tetraploid and diploid species in the genus Malus
Authors: Li Y. H. , Han Z. H. , Xu X.
Published: July 2004

Malus xiaojinensis, one of the most important wild genotypes in the genus Malus, is resistant to a variety of stresses such as Fe deficiency chlorosis, drought and cold. However, lack of knowledge of its genetic background prevents using genetic analysis to study those agronomic traits and corresponding gene functions. Here, as the first step towards construction of the linkage map of M. xiaojinensis, genetic analysis of the F1 triploid hybrids (M. xiaojinensis × M. baccata) was performed with amplified fragment length polymorphism (AFLP) markers. Using 15 EcoRI‐ MseI primer combinations, 1110 AFLPs were identified, with 31.3% of M. xiaojinensis‐, 12.7% of M. baccata‐specific markers, 54.9% of common markers, and 1.2% of non‐parental markers; 93.3% of the AFLP markers exhibit the expected segregation ratio. Thirty‐two M. xiaojinensis‐specific markers and 47 common markers display a 5 : 1 and 11:1 segregation ratios, respectively, suggesting that M. xiaojinensis is an autotetraploid, or at least an isosyndetic allotetraploid.
Mapping quantitative trait loci in wheat for resistance against greenbug and Russian wheat aphid
Authors: Castro A. M. , Vasicek A. , Ellerbrook C. , Giménez D. O. , Tocho E. , Tacaliti M. S. , Clúa A. , Snape J. W.
Published: July 2004

Breeding for genetic resistance against greenbug and Russian wheat aphid (RWA) is the most effective way of controlling these widespread pests in wheat. Earlier work had shown that chromosome 7D of a synthetic hexaploid wheat, ‘Synthetic’ (T. dicoccoides × Ae. squarrosa) (AABB × DD) gave resistance when transferred into the genetic background of an aphid‐susceptible cultivar, ‘Chinese Spring’, as the recipient. To map the genes involved, a set of 103 doubled haploid recombinant substitution lines was obtained from crossing the 7D substitution line with the recipient, and used to determine the number and chromosomal location of quantitative trait loci (QTL) controlling antixenosis and antibiosis types of resistance. Antixenosis to RWA was significantly associated with marker loci Xpsr687 on 7DS, and Xgwm437 on 7DL. Antibiosis to greenbug was associated with marker loci Xpsr490, Rc3 (on 7DS), Xgwm44, Xgwm111, Xgwm437, Xgwm121 and D67 (on 7DL). Similarly, antibiosis to RWA was linked to loci Xpsr490, Rc3, Xgwm44, Xgwm437 and Xgwm121. At least two QTL in repulsion phase, one close to the centromere either on the 7DS or 7DL arms, and a second distal on 7DL could explain antibiosis to RWA and, partially, this mechanism against greenbug.
Variance component estimations and allocation of resources for breeding sweetpotato under East African conditions
Authors: Grüneberg W. J. , Abidin E. , Ndolo P. , Pereira C. A. , Hermann M.
Published: July 2004

In Africa, average sweetpotato storage root yields are low and breeding is considered to be an important factor in increasing production. The objectives of this study were to obtain variance component estimations for sweetpotato in this region of the world and then use these to determine the efficiency of variety trials and breeding systems. From an incomplete series of variety trials in Kenya and Uganda (comprising 15 genotypes, three locations, two crop durations and three seasons) variance components were estimated ‐ using the REML method ‐ for the following traits: storage root yield, biomass production, harvest index, storage root dry matter and the Elston index which was used to aggregate all four traits. The storage root yield of clones across all 12 environments ranged from 15.2 to 33.0 t/ha. The variance components were significant for all traits, except the genotype by season interactions for storage root dry matter. The efficiency of selection systems was determined for total test capacities of 450 and 900 plots and using not more than five locations. Two‐stage selection was 17‐81% more efficient than one‐stage selection after two seasons of testing. Two‐stage selection was optimized under the restriction of using at least two locations at step 1. Trials with two locations and one replication at step 1 and five locations and two replications at step 2 were appropriate both for selecting for storage root yield and for simultaneously selecting for storage root yield, biomass production, harvest index and storage root dry matter content by using the Elston index. There are indications that such an allocation of resources for breeding sweetpotato is also appropriate for other regions in Sub‐Saharan Africa.
Mapping quantitative trait loci and expressed sequence tags related to brown planthopper resistance in rice
Authors: Ren X. , Wang X. , Yuan H. , Weng Q. , Zhu L. , He G.
Published: July 2004

To map genes responsible for brown planthopper (BPH) resistance in rice, a rice genetic map was constructed based on a recombinant inbred line population from a cross between a BPH‐resistant line ‘B5’ and a susceptible variety ‘Minghui 63’. Four quantitative trait loci (QTLs) for BPH resistance were detected. ESTs differentially regulated by BPH feeding were isolated by suppressive subtractive hybridization (SSH) and assigned to chromosomes based on RFLP mapping and searches of the rice genome database. The distribution of ESTs showed some clustering, and some ESTs are related to known QTLs and known BPH resistance genes. These findings suggest that the mapping of differentially induced ESTs may be a useful strategy for the identification of candidate plant defence genes, which could be beneficial in the development of a BPH‐resistant rice variety.
Successful treatment for squamous cell carcinoma of the female urethra with combined radio‐ and chemotherapy
Authors: HARA ISAO , HIKOSAKA SATOKO , ETO HIROSHI , MIYAKE HIDEAKI , YAMADA YUJI , SOEJIMA TOSHINORI , SUGIMURA KAZURO , KAMIDONO SADAO
Published: July 2004

Abstract  We report on two cases of women with locally advanced squamous cell carcinoma of the urethra. Patient 1 also displayed regional lymph node metastasis. Treatment comprised combined radiotherapy to 60 Gy and chemotherapy with 5‐fluorouracil and cisplatin. Complete response was obtained in both patients, including the inguinal lymph nodes of Patient 1. Patient 1 experienced recurrent inguinal lymph node metastasis on the contralateral side at 42 months after initial treatment, and the same treatment was performed followed by surgical excision. Both patients remain alive with no evidence of disease, at 12 months after recurrence in Patient 1, and at 27 months after treatment in Patient 2.
Primary extragonadal germ cell tumor of the prostate in a young man
Authors: BASTIAN PATRICK J. , SKOWASCH DIRK , BAURIEDEL GERHARD , BEHRENS PETER , MÜLLER STEFAN C. , ALBERS PETER
Published: July 2004

Abstract  We report on a case of malignant prostatic teratoma treated with radical cystoprostatectomy and cisplatin‐based chemotherapy because of intraoperative tumor rupture. During chemotherapy the patient suffered acute myocardial infarction and was treated with percutanous coronarangiography and stenting.
Comparative study of novel endoluminal ultrasonography and conventional transurethral ultrasonography in staging of bladder cancer
Authors: SAGA YUJI , NUMATA ATSUSHI , TOKUMITSU MASAYUKI , YAMAGUCHI SATOSHI , FUJII HIROMITSU , HASHIMOTO HIROSHI , KANEKO SHIGEO , YACHIKU SUNAO
Published: July 2004

Abstract  Background:  Recent advances in ultrasonic techniques have improved the image quality and diagnostic accuracy for staging of bladder cancer. The aim of this study was to assess the feasibility and usefulness of endoluminal ultrasonography (ELUS) in staging of bladder cancer, and to compare them with those of conventional transurethral ultrasonography (TUUS).

Methods:  From 2000 to 2002, 19 patients with bladder cancer were evaluated by ELUS and TUUS before transurethral resection or biopsy. Clinical staging using ELUS, TUUS, computed tomography (CT) and magnetic resonance imaging (MRI) was compared with the results of pathological staging.

Results:  In 16 of 19 patients, both ELUS and TUUS were able to diagnose tumor stage. In the remaining three patients, both methods were unable to evaluate stage of tumor. In two of these patients, this inability to evaluate tumor state was caused by a difficulty in depicting the tumor base in rectangular scanning. In the remaining patient, the inability to evaluate tumor stage was caused by a difficulty in recognizing the normal muscularis because of edema around the tumor base. Both diagnostic accuracies of ELUS and TUUS were 84%, which were superior to those of CT (44%) and MRI (82%).

Conclusions:  Endoluminal ultrasonography and TUUS were equally useful for staging diagnosis of bladder cancer. Because the ELUS probe is very small in diameter and can be manipulated under direct vision, it is superior to the TUUS in safety and in fine visualization. However, the main limitations of ELUS include an inability to evaluate the depth of invasion of large tumors and an inability to visualize the tumor base in the position of the bladder neck.
BK virus subtype 1 infection associated with tubulointerstitial nephritis in a renal allograft recipient
Authors: TAKAYAMA TATSUYA , MIURA KATSUTOSHI , HAN GUIPING , USHIYAMA TOMOMI , SUZUKI KAZUO , FUJITA KIMIO
Published: July 2004

Abstract  The BK polyomavirus (BKV) infects most of the human population, but clinically relevant infections are usually limited to individuals who are in an immunosuppressed state. The significance of BKV infection was investigated in a 50‐year‐old man who underwent cadaveric kidney transplantation and was treated with tacrolimus, mycophenolate mofetil and prednisolone. By staining renal biopsy specimens with a monoclonal antibody against BK large T antigen, we were able to observe the relationship between the appearance of the BKV antigen and the extent of immunosuppression in this patient. We also determined that BKV belonged to genotype I by analysis of viral DNA from the patient's urine.
Evaluation of adding preoperative or postoperative rectal paracetamol to caudal bupivacaine for postoperative analgesia in children
Authors: Ozyuvaci Emine , Altan Aysel , Yucel Mehmet , Yenmez Kemal
Published: July 2004

Background : Our aim was to investigate whether effects of caudal analgesia could be extended by preoperative or postoperative rectal paracetamol administration in children undergoing surgical repair of hypospadias.

Methods : The group consisted of 60 ASA I boys, aged 3–12 years, who were operated for surgical repair of hypospadias. The patients were randomized into three groups: patients in group I received rectal paracetamol (20–25 mg·kg−1) just before the operation. Group II received only caudal bupivacaine. Group III patients received rectal paracetamol (20–25 mg·kg−1) at the end of the operation. Pain was assessed by Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and the degree of sedation was evaluated. During the first 24 h, time to the patients’ first analgesic requirement and the number of supplementary analgesics needed were recorded.

Results : There was no difference between the demographic and haemodynamic data of the three groups. In addition, the duration of surgery and anaesthesia, pain scores and sedation scores of the groups were not significantly different.

Conclusions : Addition of preoperative or postoperative rectal paracetamol in the doses used did not show an effect on the duration and intensity of postoperative analgesia obtained by caudal bupivacaine.
Anesthesia for proteus syndrome
Authors: Cekmen Nedim , Kordan AyŞegül Zengin , Tuncer Bilge , Gungor Irfan , Akcabay Mehmet
Published: July 2004

Proteus syndrome is a complex disorder comprising malformations and overgrowth of multiple tissues. The disorder is highly variable affecting tissues in a mosaic pattern. A 2‐year‐old boy with Proteus syndrome, with epidermal verrucal naevus, hyperplastic lesions of connective tissue, hyperostosis, overgrowth of tubular bones, bilateral inguinal hernia, and juvenile intestinal polyposis was scheduled for vertebral magnetic resonance imaging (MRI) for further evaluation of malignancies. In addition to the pathological findings of this syndrome, potential complications such as difficult intubation, pulmonary hypertension, and pulmonary thromboembolism necessitate a careful preoperative and anesthetic preparation. MRI was performed under general anesthesia. There were no anesthetic complications. There are few previous reports on anesthesia in a patient with Proteus syndrome.
Symptom management for HIV‐positive persons in Norway
Authors: Bunch E. H.
Published: July 2004

Purpose:  To record symptoms experienced by people with HIV/AIDS, and describe useful self‐care strategies and how symptoms impact on daily life.

Method:  A questionnaire was used with self‐reported answers and descriptions of how symptoms impact on daily activities and suggestions for useful self‐care strategies. Four hundred and twenty‐two (n = 422) HIV‐positive persons from seven sites in the USA and one site in Norway (n = 20) answered the questionnaire.

Results:  In this article subjective symptom descriptions from the Norwegian sample are presented along with self‐care strategies and their effectiveness. Findings revealed the Norwegian sample to be a little older, maybe less anxious and depressed, than participants in the larger study. This difference might be explained by the structure of the national social and health care system in Norway, where treatments, medications and social services are available to all citizens without cost. Respondents described a number of related symptoms as well as their subjective explanations of what triggered the symptoms. Most of the self‐care strategies were learnt by trial and error.

Recommendations:  Community health providers, nurses and physicians should become more knowledgeable about the symptoms that infected persons struggle with, as well as the impact these symptoms have on routine daily self‐care activities and a person's quality of life. There is need for more research about helpful self‐care strategies to assist HIV‐positive persons to manage their symptoms and to disseminate these to community health providers and support groups for HIV infected persons.
Capital Controls, Risk, and Liberalization Cycles
Authors: Alfaro Laura , Kanczuk Fabio
Published: July 2004

The paper presents an overlapping‐generations model where agents vote on whether to open or close the economy to international capital flows. Political decisions are shaped by the risk over capital and labor returns. In an open economy, the capitalists (old) completely hedge their savings income. In contrast, in a closed economy, the workers (young) partially insulate wages from the productivity shocks. There are three possible equilibrium outcomes: economies that eventually remain open; those that eventually remain closed; and those that cycle between open and closed. In line with the stylized facts, cycles are more common in economies with intermediate development levels.
Pricing in International Markets: a “Small‐country” Benchmark
Authors: Parsley David C.
Published: July 2004

The paper studies export pricing to market (PTM) in a “small‐country” context using a panel of disaggregated exports from Hong Kong since 1992. Conventional wisdom is that PTM is commonplace—except for US exports. This study provides a benchmark by which to interpret the puzzling behavior of US export prices. Empirically, Hong Kong's export price behavior is comparable to that of the US. This similarity reinforces the idea that PTM behavior is also a function of home market conditions and the ability to price discriminate across markets. There is little evidence of differences in PTM across Hong Kong's export destinations.
What Are the Chances?
Authors: Helman Danny
Published: July 2004

A lottery coincidence provides the background for discussing the assessment of probabilities and the definition of events.
The Most Compact Subdomain of a Continuous Probability Distribution
Authors: Farnsworth David L.
Published: July 2004

This article describes the most compact 100c% interval for a probability density for 0 < c < 1. An unbiased, distribution‐free estimator when c = 0.5 is presented.
A Further Coin Tossing Experiment
Authors: Bhanu K. S. , Deshpande M. N.
Published: July 2004

In this note, a coin tossing experiment which leads to three discrete distributions is discussed.
Up‐regulation of Na+–Ca2+ exchange activity by interferon‐γ in cultured rat microglia
Authors: Nagano Takayuki , Kawasaki Yasushi , Baba Akemichi , Takemura Motohiko , Matsuda Toshio
Published: July 2004

The Na+–Ca2+ exchanger (NCX) plays a role in regulating intracellular Ca2+ concentration, but little is known about NCX in microglia. We examined mRNA expression of NCX isoforms in cultured rat microglia and the effect of interferon‐γ (IFN‐γ) on NCX activity. RT–PCR showed that all of the known NCX isoforms, NCX1–3, are expressed in cultured microglia. Ouabain and monensin increased 45Ca2+ uptake and intracellular Ca2+ concentration in microglia, suggesting the presence of NCX activity in the reverse mode. Treatment with IFN‐γ (100 U/mL) caused a biphasic increase in NCX activity. The transient increase in NCX activity by IFN‐γ for 1 h was blocked by the protein kinase C (PKC) inhibitors, staurosporine and GF109203X, and the tyrosine kinase inhibitor, herbimycin A. The delayed increase in NCX activity by IFN‐γ for 24 h was blocked by the protein synthesis inhibitor cycloheximide and actinomycin D. Treatment with IFN‐γ for 24 h increased NCX mRNA and protein levels. The increase in NCX activity and NCX protein by IFN‐γ for 24 h was blocked by staurosporine, GF109203X, herbimycin A and the extracellular signal‐regulated kinase inhibitor, PD98059. These findings suggest that NCX is up‐regulated by IFN‐γ in a biphasic manner in microglia. Moreover, PKC and tyrosine kinase are involved in the up‐regulation of NCX and the extracellular signal‐regulated protein kinase is also involved in the delayed increase in NCX activity.
Presenilin‐directed inhibitors of γ‐secretase trigger caspase 3 activation in presenilin‐expressing and presenilin‐deficient cells
Authors: Alves da Costa Cristine , Ayral Erwan , Hernandez Jean‐François , St George‐Hyslop Peter , Checler Frédéric
Published: July 2004

The amyloid β peptide (Aβ) is generated by subsequent cleavages by β‐ and γ‐secretases. Therefore, these two enzymes are putative therapeutic targets to prevent Aβ production, and hopefully to slow down or even stop the Alzheimer's disease (AD) neurodegenerative process. Several studies have revealed that γ‐secretase hydrolyses other important substrates besides β‐amyloid precursor protein (βAPP) thus adding another level of complexity to designing fully AD‐specific interfering drugs. Here we demonstrate that three distinct presenilin‐directed γ‐secretase inhibitors as well as JLK compounds indirectly potentiate caspase 3 activity, the effector caspase of the apoptotic cascade. Thus, inhibitors were shown to drastically stimulate caspase 3 activity in wild‐type mice blastocyst‐derived and fibroblast cells. Interestingly, some of these inhibitors known to interact with presenilins also trigger caspase activation in presenilin‐deficient cells. However, inhibitors do not affect recombinant caspase 3 activity, indicating that the effect on this enzyme was indirect. Furthermore, we established that caspase 3 activation was not due to an effect of γ‐secretase inhibitors on calpains, a family of proteolytic enzymes able to modulate caspase 3 activity. Altogether, our data demonstrate that presenilin‐directed γ‐secretase inhibitors affect caspase 3 activity in a presenilin‐independent manner. Therefore, as presenilin‐dependent γ‐secretase activity is not specific for βAPP and because its inhibitors clearly affect other vital cell functions, care should be taken in considering ‘γ‐secretase’ inhibitors as putative therapeutic tools to interfere with AD pathology.
Atorvastatin‐induced activation of Alzheimer's α secretase is resistant to standard inhibitors of protein phosphorylation‐regulated ectodomain shedding
Authors: Parvathy S. , Ehrlich Michelle , Pedrini Steve , Diaz Nichole , Refolo Lorenzo , Buxbaum Joseph D. , Bogush Alexey , Petanceska Suzana , Gandy Sam
Published: July 2004

Studies of metabolism of the Alzheimer amyloid precursor protein (APP) have focused much recent attention on the biology of juxta‐ and intra‐membranous proteases. Release or ‘shedding’ of the large APP ectodomain can occur via one of two competing pathways, the α‐ and β‐secretase pathways, that are distinguished both by subcellular site of proteolysis and by site of cleavage within APP. The α‐secretase pathway cleaves within the amyloidogenic Aβ domain of APP, precluding the formation of toxic amyloid aggregates. The relative utilization of the α‐ and β‐secretase pathways is controlled by the activation of certain protein phosphorylation signal transduction pathways including protein kinase C (PKC) and extracellular signal regulated protein kinase [ERK/mitogen‐activated protein kinase (MAP kinase)], although the relevant substrates for phosphorylation remain obscure. Because of their apparent ability to decrease the risk for Alzheimer disease, the effects of statins (HMG CoA reductase inhibitors) on APP metabolism were studied. Statin treatment induced an APP processing phenocopy of PKC or ERK activation, raising the possibility that statin effects on APP processing might involve protein phosphorylation. In cultured neuroblastoma cells transfected with human Swedish mutant APP, atorvastatin stimulated the release of α‐secretase‐released, soluble APP (sAPPα). However, statin‐induced stimulation of sAPPα release was not antagonized by inhibitors of either PKC or ERK, or by the co‐expression of a dominant negative isoform of ERK (dnERK), indicating that PKC and ERK do not play key roles in mediating the effect of atorvastatin on sAPPα secretion. These results suggest that statins may regulate α‐secretase activity either by altering the biophysical properties of plasma membranes or by modulating the function of as‐yet unidentified protein kinases that respond to either cholesterol or to some intermediate in the cholesterol metabolic pathway. A ‘phospho‐proteomic’ analysis of N2a cells with and without statin treatment was performed, revealing changes in the phosphorylation state of several protein kinases plausibly related to APP processing. A systematic evaluation of the possible role of these protein kinases in statin‐regulated APP ectodomain shedding is underway.
AMPA protects cultured neurons against glutamate excitotoxicity through a phosphatidylinositol 3‐kinase‐dependent activation in extracellular signal‐regulated kinase to upregulate BDNF gene expression
Authors: Wu Xuan , Zhu Daming , Jiang Xueying , Okagaki Peter , Mearow Karen , Zhu Guanshan , McCall Sherman , Banaudha Krishna , Lipsky Robert H. , Marini Ann M.
Published: July 2004

The signal transduction and molecular mechanisms underlying α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA)‐mediated neuroprotection are unknown. In the present study, we determined a major AMPA receptor‐mediated neuroprotective pathway. Exposure of cerebellar granule cells to AMPA (500 µm) + aniracetam (1 µm), a known blocker of AMPA receptor desensitization, evoked an accumulation of brain‐derived neurotropic factor (BDNF) in the culture medium and enhanced TrkB‐tyrosine phosphorylation following the release of BDNF. AMPA also activated the src‐family tyrosine kinase, Lyn, and the downstream target of the phosphatidylinositol 3‐kinase (PI3‐K) pathway, Akt. Extracellular signal regulated kinase (ERK), a component of the mitogen‐activated protein kinase (MAPK) pathway, was also activated. K252a, a selective inhibitor of neurotrophin signaling, blocked the AMPA‐mediated neuroprotection. The involvement of BDNF release in protecting neurons by AMPA was confirmed using a BDNF‐blocking antibody. AMPA‐mediated neuroprotection is blocked by PP1, an inhibitor of src family kinases, LY294002, a PI3‐K inhibitor, or U0126, a MAPK kinase (MEK) inhibitor. Neuroprotective concentrations of AMPA increased BDNF mRNA levels that was blocked by the AMPA receptor antagonist, 1,2,3,4‐tetrahydro‐6‐nitro‐2,3‐dioxo‐benzo[f]quinoxaline‐7‐sulfonamide (NBQX). The increase in BDNF gene expression appeared to be the downstream target of the PI3‐K‐dependent activation of the MAPK cascade since MEK or the PI3‐K inhibitor blocked the AMPA receptor‐mediated increase in BDNF mRNA. Thus, AMPA receptors protect neurons through a mechanism involving BDNF release, TrkB receptor activation, and a signaling pathway involving a PI3‐K dependent activation of MAPK that increases BDNF expression.
Intracellular lithium and cyclic AMP levels are mutually regulated in neuronal cells
Authors: Montezinho L. P. , B. Duarte C. , Fonseca C. P. , Glinka Y. , Layden B. , Mota de Freitas D. , Geraldes C. F. G. C. , Castro M. M. C. A.
Published: July 2004

In this work, we studied the effect of intracellular 3′,5′‐cyclic adenosine monophosphate (cAMP) on Li+ transport in SH‐SY5Y cells. The cells were stimulated with forskolin, an adenylate cyclase activator, or with the cAMP analogue, dibutyryl‐cAMP. It was observed that under forskolin stimulation both the Li+ influx rate constant and the Li+ accumulation in these cells were increased. Dibutyryl‐cAMP also increased Li+ uptake and identical results were obtained with cortical and hippocampal neurons. The inhibitor of the Na+/Ca2+ exchanger, KB‐R7943, reduced the influx of Li+ under resting conditions, and completely inhibited the effect of forskolin on the accumulation of the cation. Intracellular Ca2+ chelation, or inhibition of N‐type voltage‐sensitive Ca2+ channels, or inhibition of cAMP‐dependent protein kinase (PKA) also abolished the effect of forskolin on Li+ uptake. The involvement of Ca2+ on forskolin‐induced Li+ uptake was confirmed by intracellular free Ca2+ measurements using fluorescence spectroscopy. Exposure of SH‐SY5Y cells to 1 mm Li+ for 24 h increased basal cAMP levels, but preincubation with Li+, at the same concentration, decreased cAMP production in response to forskolin. To summarize, these results demonstrate that intracellular cAMP levels regulate the uptake of Li+ in a Ca2+‐dependent manner, and indicate that Li+ plays an important role in the homeostasis of this second messenger in neuronal cells.
Effects of NGF on acetylcholine, acetyl‐CoA metabolism, and viability of differentiated and non‐differentiated cholinergic neuroblastoma cells
Authors: Szutowicz Andrzej , Madziar Beata , Pawełczyk Tadeusz , Tomaszewicz Maria , Bielarczyk Hanna
Published: July 2004

Nerve growth factor (NGF) is a peptide displaying multiple cholinotropic activities. The aim of this work was to explain mechanisms of the positive and negative effects of NGF on phenotypic properties and viability of cholinergic cells. To discriminate these effects we used two p75NTRreceptor‐positive lines of cholinergic neuroblastoma cells, SN56 and T17 that are devoid of or express high affinity NGF (TrkA) receptors, respectively. cAMP and retinoic acid caused differentiation of both cell lines. In addition to the morphologic maturation, the increase of choline acetyltransferase activity, acetylcholine, Ca and cytoplasmic acetyl‐CoA levels and decrease of mitochondrial acetyl‐CoA and cell viability were observed. NGF caused similar effects in non‐differentiated T17 cells but had no influence on non‐differentiated SN56 cells. On the contrary, in both cAMP/all‐trans‐retinoic acid (RA) differentiated cell lines, NGF resulted in a similar suppression of cholinergic phenotype along with an increase of mitochondrial acetyl‐CoA and cell susceptibility to nitric oxide and amyloid‐β25–35. These effects of NGF were prevented by an antibody against the p75NTRreceptor. Data indicate that: (i) positive cholinotrophic effects of NGF required activation of both TrkA and p75NTRreceptors; (ii) cAMP/RA‐evoked differentiation inhibited NGF effects mediated by TrkA receptors and activated its p75NTR‐dependent suppressing influences and (iii) a differentiation‐evoked decrease of mitochondrial acetyl‐CoA and an elevation of mitochondrial Ca could augment impairment of cholinergic neurons by neurotoxic signals.
Metalloendopeptidase EC3.4.24.15 is constitutively released from the exofacial leaflet of lipid rafts in GT1‐7 cells
Authors: Jeske Nathaniel A. , Glucksman Marc J. , Roberts James L.
Published: July 2004

Metalloendopeptidase EC3.4.24.15 (EP24.15) is a physiologically important neuropeptide‐degrading enzyme involved in the metabolism of multiple neuropeptides. The mechanism of release of EP24.15 from neuronal cells is multimodal, being both constitutive and stimulatable. Previous studies have characterized stimulated EP24.15 secretion, yet little is understood concerning constitutive release of the peptidase. Utilizing the mouse hypothalamic neuronal GT1‐7 cell line, we demonstrate that EP24.15 exists within lipid rafts in the plasma membrane, and that the enzyme is localized to the exofacial leaflet of lipid rafts. Further, we have found that biotinylated EP24.15 on the extracellular surface is released into the cell media in a fashion similar to constitutive release. In addition, classical and non‐classical secretion pathway inhibitors were employed to understand the release of EP24.15 into surrounding cell media. The non‐classical secretion inhibitor glyburide, a blocker of ATP‐sensitive K+ channels, decreased the amount of constitutively released EP24.15 in cell media of GT1‐7 cells. With these data, we conclude that EP24.15 association with lipid rafts on the extracellular surface precedes constitutive release of the peptidase into the extracellular milieu for its action on neuropeptides.
Nomifensine amplifies subsecond dopamine signals in the ventral striatum of freely‐moving rats
Authors: Robinson Donita L. , Wightman R. Mark
Published: July 2004

The present experiment examined the effect of the dopamine transporter blocker nomifensine on subsecond fluctuations in dopamine concentrations, or dopamine transients, in the nucleus accumbens and olfactory tubercle. Extracellular dopamine was measured in real time using fast‐scan cyclic voltammetry at micron‐dimension carbon fibers in freely‐moving rats. Dopamine transients occurred spontaneously throughout the ventral striatum in the absence of apparent sensory input or change in behavioral response. The frequency of dopamine transients increased at the presentation of salient stimuli to the rat (food, novel odors and unexpected noises). Administration of 7 mg/kg nomifensine amplified spontaneous dopamine transients by increasing both amplitude and duration, consistent with its known action at the dopamine transporter and emphasizing the dopaminergic origin of the signals. Moreover, nomifensine increased the frequency of detected dopamine transients, both during baseline conditions and at the presentation of stimuli, but more profoundly in the nucleus accumbens than in the olfactory tubercle. This difference was not explained by nomifensine effects on the kinetics of dopamine release and uptake, as its effects on electrically‐evoked dopamine signals were similar in both regions. These findings demonstrate the heterogeneity of dopamine transients in the ventral striatum and establish that nomifensine elevates the tone of rapid dopamine signals in the brain.
Effects of phosphorylation by protein kinase A on binding of catecholamines to the human tyrosine hydroxylase isoforms
Authors: Sura Giri R. , Daubner S. Colette , Fitzpatrick Paul F.
Published: July 2004

Tyrosine hydroxylase (TyrH), the catalyst for the key regulatory step in catecholamine biosynthesis, is phosphorylated by cAMP‐dependent protein kinase A (PKA) on a serine residue in a regulatory domain. In the case of the rat enzyme, phosphorylation of Ser40 by PKA is critical in regulating the enzyme activity; the effect of phosphorylation is to relieve the enzyme from inhibition by dopamine and dihydroxyphenylalanine (DOPA). There are four isoforms of human tyrosine hydroxylase (hTyrH), differing in the size of an insertion after Met30. The effects of phosphorylation by PKA on the binding of DOPA and dopamine have now been determined for all four human isoforms. There is an increase of about two‐fold in the Kd value for DOPA for isoform 1 upon phosphorylation, from 4.4 to 7.4 µm; this effect decreases with the larger isoforms such that there is no effect of phosphorylation on the Kd value for isoform 4. Dopamine binds more much tightly, with Kd values less than 3 nm for all four unphosphorylated isoforms. Phosphorylation decreases the affinity for dopamine at least two orders of magnitude, resulting in Kd values of about 0.1 µm for the phosphorylated human enzymes, due primarily to increases in the rate constant for dissociation of dopamine. Dopamine binds about two‐fold less tightly to the phosphorylated isoform 1 than to the other three isoforms. The results extend the regulatory model developed for the rat enzyme, in which the activity is regulated by the opposing effects of catecholamine binding and phosphorylation by PKA. The small effects on the relatively high Kd values for DOPA suggest that DOPA levels do not regulate the activity of hTyrH.
Professional stereotyping and interprofessional education
Authors: Mandy Anne , Milton Carl , Mandy Philip
Published: July 2004

Effective interprofessional working is considered to be essential for optimum healthcare delivery. Interprofessional rivalry, tribalism and stereotypes are known to exist within healthcare professions and detract from effective health delivery. Limited literature is available that reports undergraduate healthcare students’ stereotypical perceptions of each other. Stereotypes in relation to interprofessional education are commonly explained through the Contact Hypothesis Theory, the Realistic Conflict Theory, or the Social Identity Theory. The aim of this study was to investigate undergraduate physiotherapy and podiatry students’ stereotypes of each other's professions before and after a semester of interprofessional education. Stereotypes were measured using the Health Team Stereotype Scale. Results indicated that both professional groups had stereotypical perceptions of each other prior to any education, which were reinforced as a result of the education. The results support the Social Identity Theory, which explains intergroup discrimination and describes an interpersonal–intergroup continuum. The timing of the interprofessional education may be critical to reducing such an effect.