bluuebunny/crossref_metadata_2025 huggingface dataset:
A library of gene expression signatures to illuminate normal and pathological lymphoid biology
Authors: Shaffer Arthur L. , Wright George , Yang Liming , Powell John , Ngo Vu , Lamy Laurence , Lam Lloyd T. , Davis R. Eric , Staudt Louis M.
Published: March 2006

Summary:  Genomics has provided a lever to pry open lymphoid cells and examine their regulatory biology. The large body of available gene expression data has also allowed us to define the of coordinately expressed genes, termed gene expression signatures, which characterize the states of cellular physiology that reflect cellular differentiation, activation of signaling pathways, and the action of transcription factors. Gene expression signatures that reflect the action of individual transcription factors can be defined by perturbing transcription factor function using RNA interference (RNAi), small‐molecule inhibition, and dominant‐negative approaches. We have used this methodology to define gene expression signatures of various transcription factors controlling B‐cell differentiation and activation, including BCL‐6, B lymphocyte‐induced maturation protein‐1 (Blimp‐1), X‐box binding protein‐1 (XBP1), nuclear factor‐κB (NF‐κB), and c‐myc. We have also curated a wide variety of gene expression signatures from the literature and assembled these into a signature database. Statistical methods can define whether any signature in this database is differentially expressed in independent biological samples, an approach we have used to gain mechanistic insights into the origin and clinical behavior of B‐cell lymphomas. We also discuss the use of genomic‐scale RNAi libraries to identify genes and pathways that may serve as therapeutic targets in B‐cell malignancies.
The Phenomenal Content of Experience
Authors: Raftopoulos Athanassios , Müller Vincent C.
Published: March 2006

Abstract: We discuss in some length evidence from the cognitive science suggesting that the representations of objects based on spatiotemporal information and featural information retrieved bottom‐up from a visual scene precede representations of objects that include conceptual information. We argue that a distinction can be drawn between representations with conceptual and nonconceptual content. The distinction is based on perceptual mechanisms that retrieve information in conceptually unmediated ways. The representational contents of the states induced by these mechanisms that are available to a type of awareness called phenomenal awareness constitute the phenomenal content of experience. The phenomenal content of perception contains the existence of objects as separate things that persist in time and time, spatiotemporal information, and information regarding relative spatial relations, motion, surface properties, shape, size, orientation, color, and their functional properties.
Atomic force microscopy as an innovative tool for nanoanalysis of native stratum corneum
Authors: Gorzelanny Christian , Goerge Tobias , Schnaeker Eva‐Maria , Thomas Kai , Luger Thomas A. , Schneider Stefan W.
Published: March 2006

Abstract:  This study demonstrates an innovative application of atomic force microscopy (AFM). The combination of high‐resolution AFM technology and tape stripping is presented as a tool for the structure analysis of human stratum corneum (SC) at a nanometer scale. Topographic images with a vertical resolution of about 10 nm of the SC are presented. Topographical and structural differences between aged and young skin can be observed. Aged skin SC is characterized by an increased single‐cell surface area, prominent intercellular gaps and enhanced cell surface roughness. The use of AFM in combination with other already established methods, e.g. tape stripping in the field of dermatological research will give new insights to the structure, function and morphodynamics of SC.
Activation of Akt by mechanical stretching in human epidermal keratinocytes
Authors: Yano Shoichiro , Komine Mayumi , Fujimoto Manabu , Okochi Hitoshi , Tamaki Kunihiko
Published: March 2006

Abstract:  Mechanical stretching represents an important part of the signaling in skin. We have previously demonstrated that mechanical stretching induced proliferative phenotypes in human keratinocytes, as shown in increased 5‐bromo‐2′‐deoxyuridine (BrdU) incorporation, ERK1/2 activation, and keratin K6 induction. Here we have further investigated the antiapoptotic signals in human keratinocytes provoked by mechanical stretching in vitro. Keratinocytes were plated on flexible silicone supports to transmit mechanical stretching to keratinocytes, involving continuous stretching by +20%. Stretching of these cells for 15–30 min caused the phosphorylation and activation of Akt. Inhibition of mitogen and extracellular signal‐regulated kinase (MEK1/2) with U0126 and phosphoinositide 3‐OH kinase (PI 3‐K) with Wortmannin attenuated Akt activation. The epidermal growth factor (EGF) receptor kinase inhibitor, AG1478, and calcium channel inhibitor, gadolinium (Gd3+), also inhibited Akt activation. In summary, our results demonstrate the activation of the Akt signaling pathway by mechanical stretching, generating not only proliferative but also antiapoptotic signals in human keratinocytes.
Wilms’ tumor gene WT1 17AA(–)/KTS(–) isoform induces morphological changes and promotes cell migration and invasion in vitro
Authors: Jomgeow Tanyarat , Oji Yusuke , Tsuji Naoko , Ikeda Yoko , Ito Ken , Tsuda Asako , Nakazawa Tsutomu , Tatsumi Naoya , Sakaguchi Nao , Takashima Satoshi , Shirakata Toshiaki , Nishida Sumiyuki , Hosen Naoki , Kawakami Manabu , Tsuboi Akihiro , Oka Yoshihiro , Itoh Kazuyuki , Sugiyama Haruo
Published: March 2006

The wild‐type Wilms’ tumor gene WT1 is overexpressed in human primary leukemia and in a wide variety of solid cancers. All of the four WT1 isoforms are expressed in primary cancers and each is considered to have a different function. However, the functions of each of the WT1 isoforms in cancer cells remain unclear. The present study demonstrated that constitutive expression of the WT1 17AA(–)/KTS(–) isoform induces morphological changes characterized by a small‐sized cell shape in TYK‐nu.CP‐r (TYK) ovarian cancer cells. In the WT1 17AA(–)/KTS(–) isoform‐transduced TYK cells, cell–substratum adhesion was suppressed, and cell migration and in vitro invasion were enhanced compared to that in mock vector‐transduced TYK cells. Constitutive expression of the WT1 17AA(–)/KTS(–) isoform also induced morphological changes in five (one gastric, one esophageal, two breast and one fibrosarcoma) of eight cancer cell lines examined. No WT1 isoforms other than the WT1 17AA(–)/KTS(–) isoform induced the phenotypic changes. A decrease in α‐actinin 1 and cofilin expression and an increase in gelsolin expression were observed in WT1 17AA(–)/KTS(–) isoform‐transduced TYK cells. In contrast, co‐expression of α‐actinin 1 and cofilin or knockdown of gelsolin expression by small interfering RNA restored WT1 17AA(–)/KTS(–) isoform‐transduced TYK cells to a phenotype that was comparable to that of the parent TYK cells. These results indicated that the WT1 17AA(–)/KTS(–) isoform exerted its oncogenic functions through modulation of cytoskeletal dynamics. The present results may provide a novel insight into the signaling pathway of the WT1 gene for its oncogenic functions. (Cancer Sci 2006; 97: 259–270)
Shock wave induced cytoskeletal and morphological deformations in a human renal carcinoma cell line
Authors: Moosavi‐Nejad S. Fatemeh , Hosseini S. Hamid R. , Satoh Makoto , Takayama Kazuyoshi
Published: March 2006

Effects of shock waves on the morphology and cytoskeleton of a human renal carcinoma cell line (ACHN) were investigated in vitro. ACHN monolayer cultured on a cover slide glass was treated with 10 shots of focused underwater shock waves, with 16 MPa peak pressure at the focal area of a piezoceramic shock wave generator. After exposure to the shock wave, based on the severity of morphological deformations of the treated cells, the monolayer was divided into three morphological areas; focal, marginal and intact. Morphological deformations were found to be associated with disorganization of the intracellular cytoskeletal filaments. Deformation of the cytoskeletal proteins in the treated cells were separately studied with respect to the location of the cells within the three morphological areas. Among three major cytoskeletal proteins, actin and tubulin, but not vimentin, were affected by the shock waves. The deformed cells reorganized their cytoskeletal network within 3 h with a pattern similar to the control, indicating the transient characteristic of the shock wave induced cytoskeletal damage in the surviving cells. The remaining cell fragments on the slide glass, which contained short actin filaments, indicated the important role of shear stress in damaging the cytoskeletal fibers by shock waves. (Cancer Sci 2006; 97: 296–304)
THIS ARTICLE HAS BEEN RETRACTED Curcumin targets Akt cell survival signaling pathway in HTLV‐I‐infected T‐cell lines
Authors: Tomita Mariko , Matsuda Takehiro , Kawakami Hirochika , Uchihara Jun‐nosuke , Okudaira Taeko , Masuda Masato , Ohshiro Kazuiku , Mori Naoki
Published: March 2006

The Akt signaling pathway is important for survival and growth of cancer cells. In the present paper we show that the Akt signaling pathway is constitutively activated in human T‐cell leukemia virus type I (HTLV‐I)‐infected T‐cell lines and in primary adult T‐cell leukemia (ATL) cells. Curcumin, a natural compound present in turmeric, has been studied vigorously as a potent chemopreventive agent for cancer therapy because of its inhibitory effect on proliferation and induction of apoptosis in several tumor cell lines. We investigated the effect of curcumin on Akt activity in HTLV‐I‐infected T‐cell lines and primary ATL cells. Phosphorylated PDK1 is an activator of Akt by phosphorylating Akt. Curcumin reduced phosphorylation of PDK1 and inhibited constitutive activation of Akt. Curcumin activated glycogen synthase kinase (GSK)‐3β, a downstream target of Akt kinase, by inhibiting phosphorylation of this protein. Curcumin reduced the expression of cell cycle regulators, cyclin D1 and c‐Myc proteins, which are both degraded by activated GSK‐3β. Our results suggest that activation of the Akt signaling pathway plays an important role in ATL cell survival, and that curcumin may have anti‐ATL properties mediated, at least in part, by inhibiting Akt activity. We propose that Akt‐targeting agents could be useful for the treatment of ATL. In this regard, curcumin is a potentially promising compound for the treatment of ATL. (Cancer Sci 2006; 97: 322 – 327)
Trends in primary androgen depletion therapy for patients with localized and locally advanced prostate cancer: Japanese perspective
Authors: Akaza Hideyuki
Published: March 2006

It has been conventionally accepted that primary androgen depletion therapy (PADT) is effective only as a palliative treatment against localized prostate cancer (LPC) and locally advanced prostate cancer (LAPC), like its effect against advanced (metastatic) prostate cancer. In Japan, however, PADT has long been the treatment of choice for LPC and LAPC. The frequency of PADT being chosen to treat LPC and LAPC is also on the rise in clinical practice in the USA. Very little evidence to support this trend has so far been available. A study on the outcomes of endocrine therapy is currently being conducted in Japan by the Japanese Prostate Cancer Surveillance Group. Results of several domestic and overseas randomized trials have recently been published, and evidence for the efficacy of PADT in LPC and LAPC has been accumulating. The effectiveness of PADT in LAPC, in particular, is worthy of attention. There is a possibility that therapeutic strategies for LPC and LAPC may change dramatically in the near future. (Cancer Sci 2006; 97: 243 – 247)
Comparison of the effects of fasting morning, fasting evening and fed bedtime administration of tenatoprazole on intragastric pH in healthy volunteers: a randomized three‐way crossover study
Authors: THOMSON A. B. R. , COHEN P. , FICHEUX H. , FIORENTINI P. , DOMAGALA F. , HOMERIN M. , TACCOEN A.
Published: March 2006

Background  The effectiveness of proton pump inhibitors is influenced by meals and administration time.

Aim  To compare the effects on intragastric acidity of times of dosing of tenatoprazole, a novel imidazopyridine‐based proton pump inhibitor with a prolonged plasma half‐life.

Methods  This randomized three‐period crossover study included 12 Helicobacter pylori‐negative healthy subjects, who received tenatoprazole 40 mg either fasting at 7.00 am, fasting at 7.00 pm or fed at 9.30 pm for 7 days, with a 2‐week washout between periods. Twenty‐four hour intragastric pH was monitored on day 7 of each period.

Results  On day 7, median 24‐h pH was 4.7, 5.1 and 4.7 after breakfast, dinner and bedtime dosing, respectively (P = 0.11), whereas night‐time pH was 4.2, 5.0 and 4.4 (P = 0.13). The mean 24‐h percentage of time over pH 4 was 62, 72 and 64 after breakfast, dinner and bedtime dosing, respectively (N.S.), and 54, 68 and 56 during night‐time (P = 0.06). Nocturnal acid breakthrough incidence decreased from 100% at baseline to 83%, 55% and 75% after 7.00 am, 7.00 pm and 9.30 pm dosing, respectively (P = 0.18), and its mean duration dropped from 6.2 to 2.8, 1.0 and 2.2 h, respectively (P < 0.05).

Conclusion  Seven‐day administration of tenatoprazole provides a prolonged duration of acid suppression, especially during the night‐time, with little effect of food or time of dosing.
Meta‐analysis: colorectal and small bowel cancer risk in patients with Crohn's disease
Authors: CANAVAN C. , ABRAMS K. R. , MAYBERRY J.
Published: March 2006

Background  Crohn's disease is associated with small bowel cancer whilst risk of colorectal cancer is less clear.

Aim  To ascertain the combined estimates of relative risk of these cancers in Crohn's disease.

Methods  MEDLINE was searched to identify relevant papers. Exploding references identified additional publications. When two papers reviewed the same cohort, the later study was used.

Results  Meta‐analysis showed overall colorectal cancer relative risk in Crohn's disease as 2.5 (1.3–4.7), 4.5 (1.3–14.9) for patients with colonic disease and 1.1 (0.8–1.5) in ileal disease. Meta‐regression showed reduction in relative risk over the past 30 years. Subgroup analysis showed Scandinavia had significantly lower colorectal cancer relative risk than the UK and North America. Cumulative risk analysis showed 10 years following diagnosis of Crohn's disease relative risk of colorectal cancer is 2.9% (1.5%–5.3%). Meta‐analysis showed small bowel cancer relative risk in Crohn's disease is 33.2 (15.9–60.9). Small bowel cancer relative risk has not significantly reduced over the last 30 years.

Conclusion  Relative risk of colorectal and small bowel cancers are significantly raised in Crohn's disease. Cumulative risk of colorectal cancer of 2.9% at 10 years suggests a potential benefit from routine screening. However, the value of screening requires rigorous appraisal.
Personal view: a potential novel treatment for fatigue complicating chronic liver disease – how should its efficacy be evaluated?
Authors: JONES E. A.
Published: March 2006

Profound fatigue is a clinically significant complication of chronic liver disease. A mechanism of fatigue in experimental animals and male athletes appears to be increased serotoninergic neurotransmission in the brain. Recently, attempts have been made to assess the efficacy of a serotonin antagonist, specifically the 5‐HT3 receptor subtype antagonist, ondansetron, in ameliorating fatigue in patients with chronic liver disease.

However, the results of a randomized controlled trial of ondansetron for fatigue in patients with primary biliary cirrhosis did not indicate that ondansetron was either effective or ineffective. The reasons for the uncertain outcome of the randomized controlled trial are not clear. One contributing factor may have been the use of subjective indices of fatigue as primary efficacy endpoints. There is a need to develop objective quantitative primary efficacy endpoints for use in trials of therapy for fatigue.

Another contributing factor may relate to the conduct of a randomized controlled trial not invariably being the optimal approach to resolve a specific clinical issue, particularly when the application of statistical methods yields equivocal findings. When the results of a randomized controlled trial are indecisive, findings based on clinical judgement, medicine's most important asset, should be carefully evaluated.
Systematic review: the management of pouchitis
Authors: PARDI D. S. , SANDBORN W. J.
Published: March 2006

Pouchitis is the most common complication following proctocolectomy and ileal pouch‐anal anastomosis in patients with ulcerative colitis. We aim at discussing relevant information on epidemiology, clinical features, risk factors, diagnostic testing, differential diagnosis and treatment of this idiopathic inflammatory condition.

A computerized search of PubMed was performed with the search term ‘pouchitis’, limited to English papers on humans. This strategy identified 514 references. Relevant articles were selected from this list. In addition, the reference list for each of the selected articles was reviewed to identify any additional references.

Pouchitis occurs in up to 60% of patients after ileal pouch‐anal anastomosis for ulcerative colitis, and has characteristic clinical, endoscopic and histological features. The most important test for diagnosis is pouch endoscopy with biopsy. Antibiotics remain the mainstay of treatment, and other options are discussed for those patients who are refractory to antibiotic therapy.
Prolonged n‐3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non‐alcoholic fatty liver disease: a pilot study
Authors: CAPANNI M. , CALELLA F. , BIAGINI M. R. , GENISE S. , RAIMONDI L. , BEDOGNI G. , SVEGLIATI‐BARONI G. , SOFI F. , MILANI S. , ABBATE R. , SURRENTI C. , CASINI A.
Published: March 2006

Background  Recent studies suggest a role of n‐3 long‐chain polyunsaturated fatty acids (n‐3 PUFA) as peroxisome proliferator‐activated receptor‐α ligands in improving non‐alcoholic fatty liver disease (NAFLD) in rodents. However, data in humans are still lacking.

Aim  To evaluate the efficacy of prolonged PUFA supplementation in patients with NAFLD.

Methods  Fifty‐six patients with NAFLD were enrolled. Among the overall eligible patients, 42 assumed n‐3 PUFA 1‐g capsule daily for 12 months, whereas 14 refused the treatment and were analysed as controls. All patients underwent haematochemical and ultrasound follow‐up.

Results  Polyunsaturated fatty acid supplementation significantly decreased serum aspartate transaminase (P = 0.003), alanine transaminase (P = 0.002), γ‐glutamyl transpeptidase (P = 0.03), triglycerides (P = 0.02) and fasting glucose (P = 0.02) in comparison with controls. Circulating arachidonate and n‐6/n‐3 fatty acid ratio was reduced (P = 0.0002, and P = 0.0001 respectively) in treated patients. Moreover, ultrasonography demonstrated improvement of liver echotexture after PUFA (P = 0.0001), and increase of Doppler perfusion index (P = 0.001), whereas no significant changes occurred in controls.

Conclusions  Supplementation with n‐3 PUFA improves biochemical, ultrasonographic and haemodynamic features of liver steatosis. Our study supports the efficacy of n‐3 PUFA as a new therapeutic approach in the treatment of NAFLD.
48 weeks pegylated interferon alpha‐2a is superior to 24 weeks of pegylated interferon alpha‐2b in achieving hepatitis B e antigen seroconversion in chronic hepatitis B infection
Authors: HUI C.‐K. , LAI L. S. W. , LAM P. , ZHANG H.‐Y. , FUNG T.‐T. , LAI S.‐T. , WONG W.‐M. , LO C.‐M. , FAN S.‐T. , LEUNG N. , LAU G. K. K. ,   THE HONG KONG LIVER FIBROSIS STUDY GROUP
Published: March 2006

Background/aim  Although 48‐week therapy with pegylated‐interferons has been shown to be effective for the treatment of chronic hepatitis B virus infection, the efficacy of a shorter duration of therapy with pegylated interferons is unknown.

Method  We reviewed 53 hepatitis B e antigen positive Chinese patients treated with 48 weeks of pegylated interferon alpha‐2a or 24 weeks of pegylated interferon alpha‐2b. Sustained virological response was defined as hepatitis B e antigen seroconversion and hepatitis B virus DNA <105 copies/mL at week 72.

Results  Twenty‐nine patients were treated with 48 weeks of pegylated‐interferon‐alpha‐2a and 24 patients with 24 weeks of pegylated‐interferon‐alpha‐2b. At the end‐of‐therapy, hepatitis B e antigen seroconversion and hepatitis B virus DNA <105 copies/mL were similar between the two groups of patients [9/29 (31.0%) vs. 2/24 (8.3%), respectively, P = 0.09]. At week 72, 10 of the 29 patients (34.5%) treated with 48 weeks of pegylated‐interferon‐alpha‐2a compared with two of the 24 patients (8.3%) treated with 24 weeks of pegylated‐interferon‐alpha‐2b had sustained virological response (P = 0.04). By logistic analysis, 48 weeks of pegylated‐interferon‐alpha‐2a was independently associated with sustained virological response (P = 0.04 adjusted hazards‐ratio 9.37).

Conclusion  Further studies are required to determine the optimal duration of therapy with pegylated interferons in chronic hepatitis B.
Review article: thrombocytopenia in chronic liver disease and pharmacologic treatment options
Authors: GIANNINI E. G.
Published: March 2006

In patients with liver disease, thrombocytopenia is a clinical feature that may represent an obstacle to invasive diagnostic or therapeutic procedures, chemotherapy, and anti‐viral treatment. Stimulation of the bone marrow is the most promising therapeutic intervention for thrombocytopenia in patients with chronic liver disease.

The description of thrombopoietin and its (de)regulation in patients with chronic liver disease have disclosed new treatment opportunities. Indeed, pharmacologic treatment options for thrombocytopenia can be divided into treatments targeted at the thrombopoietin receptor (synthetic thrombopoietins and thrombopoietin‐mimetic agents), and use of cytokines with general thrombopoietic potential. Unfortunately, use of synthetic thrombopoietin was hampered by the development of neutralizing antibodies, and thrombopoietin mimetic agents have not yet entered clinical studies. Interleukin‐11 proved to be useful in increasing platelet count in patients with chronic liver disease, although its use is limited by side‐effects.

Erythropoietin has shown promising results in improving thrombocytopenia in cirrhotic patients. In patients with chronic liver disease, safe and well‐tolerated treatments aimed at improving thrombocytopenia are still lacking. Larger studies are needed to evaluate and better characterize the thrombopoietic potential of erythropoietin. Human studies with thrombopoietin‐mimetic agents are eagerly awaited in order to assess both effectiveness and safety of these drugs.
Research Review: Family centres: a review of the literature
Authors: Warren‐Adamson Chris
Published: March 2006

This paper provides a review of the literature about family centres and other examples of centre‐based practice. The literature reflects a period of some 25 years in which practice has sought to integrate protection, support for families and local development in local centres. The literature shows great descriptive activity in the 1980s, and some Children Act (1989) sponsored studies, particularly of the voluntary sector, in the early 1990s, followed by inactivity before a new and more sophisticated literature emerges in the late 1990s and early 2000. While lacking experimental design, the strengths of the contemporary picture show in the appreciative voice of the user, including those at the very margins; studies of support programmes nurtured by centres; lessons about socially inclusive practice and the melding of formality and informality; theorization about centre‐based practice as a containing space; and attempts to understand complexity and synergy and to develop a theory of change. This domain of practice appears to have much to offer the new UK child care strategy and inter‐professional context if the opportunity is taken.
Changes in spawning stock structure strengthen the link between climate and recruitment in a heavily fished cod (Gadus morhua) stock
Authors: OTTERSEN GEIR , HJERMANN DAG Ø. , STENSETH NILS CHR.
Published: March 2006

Atlantic cod (Gadus morhua) is one of the commercially most important fish species in the North Atlantic and plays a central role in several ecosystems. Fishing pressure has been heavy over a prolonged period and the recent decades have shown dramatic decline in abundance of many stocks. The Arcto‐Norwegian (or North‐east Arctic) cod stock in the Barents Sea is now the largest stock of Atlantic cod. Recruitment to this stock has varied extensively during the last 60 yr. There is evidence for fluctuations in climate, particularly sea temperature, being a main cause for this variability, higher temperatures being favourable for survival throughout the critical early life stages. Our studies of time series present compelling evidence for a strengthening of the climate–cod recruitment link during the last decades. We suggest this is an effect of the age and length composition of the spawning stock having changed distinctly. The age of the average spawner has decreased by more than 3 yr from between 10 and 11 in the late 1940s to 7–8 in the 1990s, average length from just above 90 cm to around 80 cm. The number of age classes contributing to the spawning stock has also decreased, while the number of length groups present increased slightly. Significant decrease in age of spawners has frequently been described for other heavily fished stocks worldwide. We therefore find it likely that the proposed mechanism of increased influence of climate on recruitment through changes in the spawning stock age and size composition is of a general nature and might be found in other systems.
Genetic heterogeneity in supratentorial and infratentorial primitive neuroectodermal tumours of the central nervous system
Authors: Inda M M , Perot C , Guillaud‐Bataille M , Danglot G , Rey J A , Bello M J , Fan X , Eberhart C , Zazpe I , Portillo E , Tuñón T , Martínez‐Peñuela J M , Bernheim A , Castresana J S
Published: March 2006

Aims : Medulloblastoma (MB), a kind of infratentorial primitive neuroectodermal tumour (PNET), is the most frequent malignant brain tumour in childhood. In contrast, supratentorial PNET (sPNET) are very infrequent tumours, but they are histologically similar to MB, although they present a worse clinical outcome. We investigated the differences in genetic abnormalities between sPNET and MB.

Methods and results : We analysed 20 central PNET (14 MB and six sPNET) by conventional comparative genomic hybridization (CGH) in order to determine whether a different genetic profile for each tumour exists. Isochromosome 17q was detected in four of the 14 MB cases, but not in any sPNET. Gains at 17q and 7 happened more frequently in MB, and those at 1q in sPNET. Losses at chromosome 10 were detected only in MB, while losses at 16p and 19p happened more frequently in sPNET. A new amplification site, on 4q12, was detected in two MB.

Conclusions : Central PNET are a heterogeneous group of tumours from the genetic point of view. The present and previous data, together with further results from larger series, might contribute to the establishment of specific treatments for supratentorial and infratentorial PNET.
Impacts of sudden winter habitat loss on the body condition and survival of redshank Tringa totanus
Authors: BURTON NIALL H. K. , REHFISCH MARK M. , CLARK NIGEL A. , DODD STEPHEN G.
Published: March 2006

Recent theoretical modelling has provided important insights into how habitat loss may affect local populations through impacts on individual fitness (survival, body condition, fecundity). Despite this, attempts to provide empirical evidence of such impacts on displaced individuals have been limited. Using a before‐after‐control‐impact (BACI) approach, we report how a sudden loss of wintering habitat impacted on the body condition and survival of redshank Tringa totanus.

The intertidal mudflats of Cardiff Bay, UK, were inundated with freshwater in November 1999 following impoundment by a barrage, resulting in the displacement of c. 300 redshank to adjacent habitat on the Severn Estuary. Movements and the survival of these birds were monitored through observations of colour‐marked individuals. Comparative survival rates were calculated for marked populations at the main recipient site, Rhymney, and a control site.

Displaced redshank had difficulty maintaining their mass in the first winter post‐barrage closure: adults previously only recorded at Cardiff Bay were significantly lighter than those previously recorded at Rhymney.

Survival rates of displaced redshank also declined. The estimated annual survival of adult Cardiff Bay redshank fell from 0·846 in the 2 years pre‐barrage closure to 0·778 in the 3 following years because of a significant decline in winter survival (P = 0·0006). In comparison, there was no significant change in the survival of adult Rhymney redshank, and adult survival at the control site was actually greater post‐barrage closure than beforehand. The lack of decline in these rates and the similarity between those of Cardiff Bay adults pre‐barrage closure and Rhymney adults indicate that the increase in winter mortality of Cardiff Bay birds resulted from their displacement.

Synthesis and applications. This study provides the first conclusive empirical evidence that habitat loss can impact individual fitness in a bird population. Adult redshank displaced from Cardiff Bay experienced poor body condition and a 44% increase in mortality rate. Without an increase in the recruitment of first‐winter birds, such a change is likely to reduce substantially local population size. The results reported here should help to inform governments, planners and non‐governmental organizations (NGOs) seeking to understand how developments might impact on animal populations.
Effect of water potential on mycelial growth and perithecial production of Monosporascus cannonballus in vitro
Authors: Ferrin D. M. , Stanghellini M. E.
Published: March 2006

The effects of osmotic water potential (Ψs) on mycelial growth and perithecial production of Monosporascus cannonballus, the cause of root rot and vine decline of melons, were examined at 25°C on potato dextrose agar (PDA) amended with KCl, NaCl or sucrose. Patterns of the growth responses of four isolates to decreasing Ψs were similar for each of the osmotica. Compared with growth on nonamended PDA (−0·3 MPa), growth of all isolates increased as Ψs was reduced to −0·8 MPa. Maximum growth occurred at Ψs values of −0·6 to −0·8 MPa. Growth was not reduced below that on nonamended PDA until Ψs was reduced to −1·8 MPa, and a 50% reduction in growth did not occur until Ψs was reduced to < −2·5 MPa. Reproduction was much more sensitive to reduced Ψs than was mycelial growth, and perithecia were produced only at Ψs ≥ −0·7 or −0·8 MPa on PDA amended with KCl or NaCl, respectively. Three isolates produced perithecia on PDA amended with sucrose only at Ψs ≥ −0·6 MPa, but the fourth isolate produced perithecia at ≥ −1·9 MPa. Colonization of the xylem early in disease development may provide an essential source of water for subsequent reproduction in the root cortex during plant senescence. Postharvest cultivation to expose and desiccate roots may prevent reproduction even when temperatures lethal to hyphae are not attained.
Evidence for folate‐salvage reactions in plants
Authors: Orsomando Giuseppe , Bozzo Gale G. , de la Garza Rocío Díaz , Basset Gilles J. , Quinlivan Eoin P. , Naponelli Valeria , Rébeillé Fabrice , Ravanel Stéphane , Gregory Jesse F. , Hanson Andrew D.
Published: March 2006

Folates in vivo undergo oxidative cleavage, giving pterin and p‐aminobenzoylglutamate (pABAGlu) moieties. These breakdown products are excreted in animals, but their fate is unclear in microorganisms and unknown in plants. As indirect evidence from this and previous studies strongly suggests that plants can have high folate‐breakdown rates (approximately 10% per day), salvage of the cleavage products seems likely. Four sets of observations support this possibility. First, cleavage products do not normally accumulate: pools of pABAGlu (including its polyglutamyl forms) are equivalent to, at most, 4–14% of typical total folate pools in Arabidopsis thaliana, Lycopersicon esculentum and Pisum sativum tissues. Pools of the pterin oxidation end‐product pterin‐6‐carboxylate are, likewise, fairly small (3–37%) relative to total folate pools. Second, little pABAGlu built up in A. thaliana plantlets when net folate breakdown was induced by blocking folate synthesis with sulfanilamide. Third, A. thaliana and L. esculentum tissues readily converted supplied breakdown products to folate synthesis precursors: pABAGlu was hydrolysed to p‐aminobenzoate and glutamate, and dihydropterin‐6‐aldehyde was reduced to 6‐hydroxymethyldihydropterin. Fourth, both these reactions were detected in vitro; the reduction used NADPH as cofactor. An alternative salvage route for pABAGlu, direct reincorporation into dihydrofolate via the action of dihydropteroate synthase, appears implausible from the properties of this enzyme. We conclude that plants are excellent organisms in which to explore the biochemistry of folate salvage.
Comparison of three microtube column agglutination systems for antibody screening: DG Gel, DiaMed‐ID and Ortho BioVue
Authors: Cid J. , Nogués N. , Montero R. , Hurtado M. , Briega A. , Parra R.
Published: March 2006

summary.  The aims of the present study were to evaluate the estimated diagnostic accuracy of a new microtube column agglutination system (DG Gel, Diagnostic Grifols, Barcelona, Spain), to analyse the antibody reactivity and to compare the data with the two well‐established DiaMed‐ID and Ortho BioVue systems.

We collected 3024 consecutive samples from blood donors, transfusion recipients and pregnant women, and 100 samples containing antibodies of known specificity. All these samples were tested in parallel by the three microtube agglutination systems.

The estimated sensitivity was 100% for DG Gel and Ortho BioVue and 97·58% for DiaMed‐ID. The estimated specificity was 99·93% for Ortho BioVue and 100% for DiaMed‐ID and DG Gel. The score mean and range of the antibody titration of DG Gel, DiaMed‐ID and Ortho BioVue were 34·31 (5–119), 30·3 (3–121) and 37·38 (3–112), respectively.

All three column agglutination systems work well showing a high estimated diagnostic accuracy.
Promoter genetic variants of prostanoid DP receptor (PTGDR) gene in patients with asthma
Authors: Sanz C. , Isidoro‐García M. , Dávila I. , Moreno E. , Laffond E. , Ávila C. , Lorente F.
Published: March 2006

Background:  PTGDR gene has been identified as an asthma‐susceptibility gene. Recently, functional genetic variants have been associated with asthma. The objective of this work was to study −549T>C, −441C>T and −197T>C PTGDR promoter polymorphisms in a Spanish population.

Methods:  In this study, 197 Caucasian individuals were included. Asthma was specialist‐physician diagnosed according to the American Thoracic Society (ATS) criteria and classified following the Global Initiative for Asthma (GINA) guidelines. Skin prick tests were performed in all patients. The polymorphisms were analyzed by direct sequencing.

Results:  −197T>C polymorphism was significantly associated with asthma [Fisher's P‐value = 0.007, Monte Carlo P‐value (104 simulations) = 0.004]. Multivariate analysis adjusted for age and sex confirmed this association with an increased risk of asthma (OR, 3.06; 95% CI, 1.28–7.32; P‐value = 0.012). CCT CCC diplotype was associated with asthma (P‐value < 0.0001; OR, 1.15; 95% CI, 1.07–1.23), specifically with allergic asthma (P‐value < 0.0001). CCT CCC diplotype is unambiguous. All individuals carrying this diplotype had asthma.

Conclusion:  We identified a specific promoter variant of PTGDR that could be associated with asthma. This diplotype is a combination of the two highest transcriptional efficiency haplotypes, recently described. Our in vivo results would support for the first time what was demonstrated in vitro about high‐transcriptional efficiency PTGDR haplotypes in asthma.
Trends in prevalence of asthma, allergic rhinitis and atopic dermatitis in 5–7‐year old Swiss children from 1992 to 2001
Authors: Grize L. , Gassner M. , Wüthrich B. , Bringolf‐Isler B. , Takken‐Sahli K. , Sennhauser F. H. , Stricker T. , Eigenmann P. A. , Braun‐Fahrländer C. ,   the Swiss Surveillance Programme on Childhood Allergy and Respiratory symptoms with respect to Air Pollution (SCARPOL) team
Published: March 2006

Background:  Changing occurrence rates of asthma, allergic rhinitis and atopic dermatitis are of public health concern and require surveillance. Changes in prevalence rates of these atopic diseases were monitored during 10 years and their trend with time was determined taking into account the influence of personal and environmental risk factors.

Methods:  Four cross‐sectional surveys in 5–7‐year old children were performed in seven different communities in Switzerland between 1992 and 2001. Prevalence of respiratory and allergic symptoms and of affecting risk factors including parental environmental concern were assessed using a standardized parental questionnaire.

Results:  A total of 988 (74.1%), 1778 (79.0%), 1406 (82.6%) and 1274 (78.9%) children participated, respectively, in the 1992, 1995, 1998 and 2001 surveys. Prevalence rates of asthma and hay fever symptoms remained quite stable over time (wheeze/past year: 8.8%, 7.8%, 6.4% and 7.4%, sneezing attack during pollen season: 5.0%, 5.6%, 5.4% and 4.6%). Rates of reported atopic dermatitis symptoms (specific skin rash/past year: 4.6%, 6.5%,7.4% and 7.6%) showed an increase over time, but those of diagnosis of eczema did not show a clear pattern (18.4%, 15.7%, 14.0% and 15.2%). Stratified analysis by parental environmental concern and by parental atopy showed similar trends. Rates of atopic dermatitis symptoms showed significant increase in girls but stayed stable in boys.

Conclusion:  Results of these four consecutive surveys suggest that the increase in prevalence of asthma and hay fever in 5–7‐year old children living in Switzerland may have ceased. However, symptoms of atopic dermatitis may still be on the rise, especially among girls.
Human airway and peripheral blood eosinophils enhance Th1 and Th2 cytokine secretion
Authors: Liu L.‐Y. , Mathur S. K. , Sedgwick J. B. , Jarjour N. N. , Busse W. W. , Kelly E. A. B.
Published: March 2006

Background:  The effector function of eosinophils involves their release of toxic granule proteins, reactive oxygen species, cytokines, and lipid mediators. Murine studies have demonstrated that eosinophils can also enhance T cell function. Whether human eosinophils, in particular, airway eosinophils, have similar immunoregulatory activity has not been fully investigated. The aim of this study was to determine whether human blood and airway eosinophils can contribute to Th1 and Th2 cytokine generation from CD4+ T cells stimulated with superantigen.

Methods:  Eosinophils were obtained from blood or bronchoalveolar lavage fluid 48 h after segmental allergen bronchoprovocation. Purified eosinophils were co‐cultured with autologous CD4+ blood T cells in the presence of staphylococcal enterotoxin B (SEB). Cytokine levels in the supernatant fluid were determined by enzyme‐linked immunosorbent assay (ELISA). Eosinophil expression of major histocompatibility complex (MHC) class II and co‐stimulatory molecules was assessed by flow cytometry before culture, 24 h after granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) stimulation, and 24 h after co‐culture with CD4+ T cells and SEB.

Results:  Interleukin (IL)‐5, IL‐13, and interferon (IFN)‐γ generation increased when CD4+ T cells were co‐cultured with either blood or airway eosinophils in the presence of SEB. The ability of eosinophils to enhance cytokine generation was independent of their source (blood vs airway), activation by GM‐CSF, or detectable expression of human leukocyte antigen (HLA)‐DR, CD80, or CD86.

Conclusion:  Our data demonstrate that SEB‐induced generation of Th1 and Th2 cytokines is increased in the presence of human blood and airway eosinophils. Thus, eosinophils can have an immunoregulatory function in pathogen‐associated allergic diseases such as atopic dermatitis, chronic sinusitis, and asthma exacerbations.
Low prevalence of the intrinsic form of atopic dermatitis among adult patients
Authors: Fölster‐Holst R. , Pape M. , Buss Y. L. , Christophers E. , Weichenthal M.
Published: March 2006

Background:  Atopic dermatitis (AD) is a chronic inflammatory skin disease commonly associated with respiratory allergies such as rhinitis and asthma, and a high serum level of IgE. In contrast to the ‘classic’ IgE‐mediated allergic (extrinsic) form of AD, approximately 20% of the patients are reported to show normal IgE levels, lack of sensitizations towards environmental allergens, and absence of associated respiratory allergies. Accordingly, these patients are assigned to a nonallergic (intrinsic) form of the disease.

Objectives:  In order to define these two forms of AD more closely, 259 adult patients with AD were investigated.

Results:  After a thorough diagnostic workup there were 18 patients (6.9%), who fulfilled the criteria of intrinsic AD. After follow‐up, four additional patients had developed respiratory allergies or IgE‐mediated sensitizations resulting in an overall proportion for intrinsic AD of 5.4%.

Conclusions:  Based on these figures the nature and relevance of the intrinsic form of AD deserves further evaluation.
Successful umbilical cord blood stem cell transplantation in a patient with Rothmund–Thomson syndrome and combined immunodeficiency
Authors: Broom MA , Wang LL , Otta SK , Knutsen AP , Siegfried E , Batanian JR , Kelly ME , Shah M
Published: March 2006

The ATP‐dependent DNA helicase Q4 (RECQL4) belongs to a family of conserved RECQ helicases that are felt to be important in maintaining chromosomal integrity (Kitao et al.,1998, Genomics: 54 (3): 443–452; (6)). Deletions in the RECQL4 gene located on chromosome 8 region q24.3 have been associated with Rothmund–Thomson syndrome (RTS, OMIM 268400), a condition characterized by poikiloderma, sparse hair, small stature, skeletal abnormalities, cataracts and an increased risk of malignancy (1–2, 5). We present a patient with a molecularly confirmed diagnosis of RTS with two unique genetic alterations in RECQL4 (IVS16‐2A>T and IVS2+27_51del25), who at the age of 7 months nearly succumbed to Pneumocystis carinii pneumonia. Evaluation of his immune system demonstrated a T–B+NK– phenotype with agammaglobulinemia consistent with combined immunodeficiency (CID). Studies to evaluate for known genetic causes of CID were not revealing. The patient received an umbilical cord blood (UCB) transplant with complete immune reconstitution. This report represents the first description of a CID phenotype and UCB transplantation in a patient with RTS.
LADD syndrome is caused byFGF10mutations
Authors: Milunsky JM , Zhao G , Maher TA , Colby R , Everman DB
Published: March 2006

Lacrimo‐auriculo‐dento‐digital syndrome [LADD (MIM 149730)] is an autosomal‐dominant multiple congenital anomaly disorder characterized by aplasia, atresia or hypoplasia of the lacrimal and salivary systems, cup‐shaped ears, hearing loss, and dental and digital anomalies. Loss of function mutations inFGF10were recently described in aplasia of the lacrimal and salivary glands [ALSG (MIM 180920; MIM 103420)] (Entesarian et al.,Nat Genet2005: 37: 125–127, Milunsky et al., American College of Medical Genetics Annual Meeting, Dallas, TX, 2005: A100). Due to the significant phenotypic overlap between LADD syndrome and ALSG and the variable expressivity of both the disorders, we hypothesized thatFGF10mutations could also result in LADD syndrome. Ade novomissense mutation was found in exon 3 ofFGF10in a 3‐year‐old female (Family 1) with LADD syndrome. This missense mutation, resulting in a non‐conservative amino acid change, was confirmed by restriction enzyme digestion and was not found in 500 control chromosomes. A nonsense mutation was also found in exon 2 ofFGF10(Family 2) in a 19‐year‐old mother with ALSG and her 2‐year‐old daughter with LADD syndrome. Previous studies ofFGF10mutant mice have demonstrated abnormalities consistent with ALSG and LADD syndrome. We conclude that ALSG and LADD syndrome may represent variable presentations of the same clinical spectrum caused byFGF10mutations.
Psychological aspects of pre‐symptomatic testing for Machado–Joseph disease and familial amyloid polyneuropathy type I
Authors: Rolim L , Leite Â , Lêdo S , Paneque M , Sequeiros J , Fleming M
Published: March 2006

Machado–Joseph disease [MJD, also spinocerebellar ataxia type 3 (SCA3)] and familial amyloid polyneuropathy type I (FAP‐I or ATTR V30M) are neurodegenerative disorders, inherited in an autosomal dominant fashion, which have a high prevalence in Portugal, probably due to a founder effect. MJD and FAP‐I are late‐onset diseases, with symptoms emerging usually during adulthood. CGPP, which is the national reference centre for these disorders, has a genetic lab that offers diagnostic, pre‐symptomatic and prenatal testing and an outpatient clinic to counsel and follow relatives at risk for hereditary ataxias, FAP‐I and Huntington disease (HD). The present work is a review of our 10‐year experience with psychological counselling of individuals at risk for MJD and FAP‐I. Persons at risk for FAP‐I may show a better response to pre‐symptomatic testing than those who are at risk for MJD and HD because of the availability of liver transplantation, which may improve their health and life expectancy. Psychological well‐being and specific distress of MJD and FAP‐I test applicants, before undergoing genetic testing (baseline level) and 3 to 6 months after disclosure of test results, have shown a low level of change, both in identified carriers and non‐carriers. A major goal of psychological characterization of at‐risk individuals for MJD and FAP‐I is to determine the factors that influence the uptake of genetic testing.