bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual health among young adults in Finland: Assessing risk and protective behaviour through a general health survey
Authors: Nikula Minna , Koponen Päivikki , Haavio-Mannila Elina , Hemminki Elina
Published: May 2007

Objective: To describe the extent of sexual risk and protective behaviours and reproductive health outcomes comparing men and women of 18—29 and assess the demographic correlates of these indicators within genders. Design: A module of questions on sexual behaviour and reproductive health outcomes was integrated into a population-based general health survey in Finland. Methods: A representative sample of people over 17, including 1,894 individuals between 18 and 29 years, was drawn from the population registry in 2001. Individual interviews and self-administered questionnaires were used with a response rate of 79% for the interview and 68% for the questionnaire. Results: It was more common for younger men to stay single and have multiple partners while women of the same age were cohabiting or married and chose a regular sex partner. The mean number of sexual partner for men was 5.0 (SD 5.1) and for women 3.4 (SD 2.1). Besides higher prevalence of multiple partners, men reported also casual sex contacts more often than women, 33% vs. 20%. Both genders reported relatively high and concordant rates of contraception use. However, in casual sex contacts a condom was used consistently only by less than half of both sexes. Marital status was the strongest predictor for behaviour and health outcomes. Conclusions: Casual sex is common among young adults in Finland and often occurs without a condom. This study shows that it is feasible to incorporate sexual behaviour questions as part of a larger health survey offering an option for monitoring sexual behaviour when funding for large-scale HIV surveys is decreasing.
Robotic-Assisted Laparoscopic Radical Prostatectomy: An Objective Assessment and Review of the Literature
Authors: Borden Jr. Lester S. , Kozlowski Paul M.
Published: May 2007

Robotic-assisted laparoscopic radical prostatectomy (RLRP) has become an accepted treatment option for men with prostate cancer. A search of the available literature through January 2006 was performed to analyze the surgical technique, outcomes data, and other unique issues regarding RLRP. While prospective, randomized trials and long-term data are lacking, short-term data from single institution series have demonstrated outcomes for RLRP that appear to be equivalent to those for open radical prostatectomy (ORP). Although not yet proven, some encouraging data suggest that RLRP may be able to achieve improved cancer control, postoperative urinary control, and erectile function compared to open surgery for prostate cancer. Definite advantages of RLRP over ORP are not yet established. Future studies will determine the role of RLRP in the surgical treatment of men with prostate cancer.
Superficial Urothelial Cancer in the Prostatic Urethra
Authors: Kirkali Ziya , Canda A. Erdem
Published: May 2007

Transitional cell carcinoma (TCC) is a multifocal disease of the urinary tract that can also involve the prostatic urethra (PU). The exact incidence of superficial involvement of the PU in patients with bladder TCC is not well known. Bladder TCC may involve the prostate in 12—40% of the patients and the degree of involvement can include urethral mucosa, ducts, acini, and stroma of the gland, which has been shown to affect the outcome. Risk factors for superficial urothelial cancer in the PU are high-grade, multifocal bladder TCC and presence of carcinomain situ(CIS) in the bladder. While visible tumors are easy to detect and resect, controversy still exists regarding the optimal technique to identify prostatic involvement by TCC. Prostatic urethral sampling by a transurethral resection biopsy or a cold-cup biopsy, particularly in the high-risk group of bladder cancer patients, has been recommended for detecting prostatic urethral involvement. Management of superficial prostatic involvement by TCC is also unclear. Currently, there is increasing recognition of the value of conservative treatment options with intravesical agents when there is superficial involvement of the PU. Particularly, intravesical bacillus Calmette-Guèrin (BCG) seems to be an effective treatment alternative in the management of superficial involvement of the PU by TCC. Close follow-up by cystoscopy and PU biopsy at 3-month intervals, particularly in intermediate and high-risk patients who respond to intravesical therapy and in whom cystectomy is appropriate, is recommended in order to detect persistent tumor, recurrences, or progression.
Optimal Treatment for Intermediate- and High-Risk, Nonmuscle-Invasive Bladder Cancer
Authors: van der Meijden A.P.M.
Published: May 2007

According to clinical and pathological factors the prognosis of a patient with non-muscle invasive bladder tumors can be assessed. The prognosis is determined by the likelihood of recurrence(30-70%) and/or progression to muscle invasive bladder cancer(1-15%).Trans urethral resection of bladder tumors remains the initial therapy but adjuvant intravesical instillations are necessary.All patients benefit from a single immediate post operative instillation with a chemotherapeutic agent and for low risk tumors this is the optimal therapy.Patients with intermediate and high risk tumors need more intravesical chemo-or immunotherapy. Chemotherapy reduces recurrences but not progression. Intravesical immunotherapy(BCG) prevents or delays progression. Patients at high risk for progression may need upfront cystectomy.
Natural History, Recurrence, and Progression in Superficial Bladder Cancer
Authors: Sylvester Richard J.
Published: May 2007

Superficial bladder cancer encompasses patients with stage Ta T1 tumors and patients with carcinomain situ(CIS). The natural history or treatment-related prognosis of these patients varies considerably from one patient to the next based on the patients clinical and the tumor's pathological characteristics. Based on a review of the literature, the most important prognostic factors for recurrence are the prior recurrence rate, number of tumors, and tumor size; whereas for progression, the most important prognostic factors are the T category, grade, and presence of CIS. Treatment with intravesical bacillus Calmette-Guerin reduces both the risk of recurrence and the risk of progression, and is the treatment of choice in high-risk papillary tumors and in patients with CIS. Assessment of a patient's prognostic factors and his or her risk of recurrence and progression is a prerequisite for determining the most appropriate treatment and frequency of follow-up for a given patient.
The Role of the Surgeon and Transurethral Resection in the Treatment of Superficial Bladder Cancer
Authors: Nieder Alan M. , Manoharan Murugesan
Published: May 2007

Non-muscle invasive bladder cancers are a heterogeneous group of cancers whose spectrum includes low grade Ta lesions and high-grade T1 lesions. Accurate staging and grading during initial evaluation and TUR ensures appropriate treatment and prevents the risk of understaging. TUR should be ideally performed under spinal anesthesia, with a continuous flow video resectoscope to maintain a stable bladder capacity, and a video monitor. The entire bladder must be visualized, with both 30- and 70-degree lenses, and all abnormal areas must be resected, with separate biopsies from each tumor's base. Repeat TUR is recommended for all high grade tumors and T1 tumors, especially if muscle was not present in the initial specimen. Immediate instillation of single dose chemotherapy agents following TUR is highly recommended to reduce the risk of tumor recurrences.
New Strategies in the Treatment of Ta-T1 Transitional Cell Carcinoma (TCC) of the Bladder
Authors: Brausi Maurizio A.
Published: May 2007

In recent years, there have been many advances in the treatment of superficial bladder cancer. Standard intravesical chemotherapeutic agents can now be delivered more effectively thanks to new technological advances in drug delivery. Local microwave hyperthermia and electromotive drug administration are of particular interest. Research has also shown that different combinations of drugs and sequential drug delivery of two or more different drugs for differing periods of time also increase the effectiveness of possible treatments of superficial bladder cancer. Furthermore, new chemotherapeutic drugs for intravesical use are being investigated in various clinical trials, with gemcitabine showing particularly promising results. Also in the pipeline are new approaches to treatment such as gene therapy, but these will need to be developed much more before they become part of routine practice.
Best Approach for Low-Risk Superficial Bladder Cancer
Authors: Solsona Eduardo
Published: May 2007

In order to create better criteria for different grades of superficial bladder tumor, the WHO and ISUOP develop a new classification in 1998, which was modified in 2004. Although the new classification might be more reproducible, it has not yet been widely accepted. The low risk groups include patients with single Ta, G1, ≤3cm diameter tumors. This group has high recurrence and low progression rates. The standard treatment is the complete resection and postoperative single immediate instillation of whatever chemotherapy agent should be considered.
Light-Dependent Regulation of Cell Division inOstreococcus: Evidence for a Major Transcriptional Input
Authors: Moulager Mickael , Monnier Annabelle , Jesson Béline , Bouvet Régis , Mosser Jean , Schwartz Christian , Garnier Lionel , Corellou Florence , Bouget François-Yves
Published: May 2007

Cell division often occurs at specific times of the day in animal and photosynthetic organisms. Studies in unicellular photosynthetic algae, such as Chlamydomonas or Euglena, have shown that the photoperiodic control of cell division is mediated through the circadian clock. However, the underlying mechanisms remain unknown. We have studied the molecular basis of light-dependent control of cell division in the unicellular green alga Ostreococcus. We found that cell division obeys a circadian oscillator in Ostreococcus. We provide evidence suggesting that the clock may, at least in part, regulate directly cell division independently of the metabolism. Combined microarray and quantitative real-time reverse transcription-polymerase chain reaction analysis of the main core cell cycle gene expression revealed an extensive transcriptional regulation of cell division by the photoperiod in Ostreococcus. Finally, transcription of the main core cell cycle genes, including cyclins and cyclin-dependent kinases, was shown to be under circadian control in Ostreococcus, suggesting that these genes are potential targets of the circadian clock in the control of cell division.
Evolution of Flavone Synthase I from Parsley Flavanone 3β-Hydroxylase by Site-Directed Mutagenesis
Authors: Gebhardt Yvonne Helen , Witte Simone , Steuber Holger , Matern Ulrich , Martens Stefan
Published: May 2007

Flavanone 3β-hydroxylase (FHT) and flavone synthase I (FNS I) are 2-oxoglutarate-dependent dioxygenases with 80% sequence identity, which catalyze distinct reactions in flavonoid biosynthesis. However, FNS I has been reported exclusively from a few Apiaceae species, whereas FHTs are more abundant. Domain-swapping experiments joining the N terminus of parsley (Petroselinum crispum) FHT with the C terminus of parsley FNS I and vice versa revealed that the C-terminal portion is not essential for FNS I activity. Sequence alignments identified 26 amino acid substitutions conserved in FHT versus FNS I genes. Homology modeling, based on the related anthocyanidin synthase structure, assigned seven of these amino acids (FHT/FNS I, M106T, I115T, V116I, I131F, D195E, V200I, L215V, and K216R) to the active site. Accordingly, FHT was modified by site-directed mutagenesis, creating mutants encoding from one to seven substitutions, which were expressed in yeast (Saccharomyces cerevisiae) for FNS I and FHT assays. The exchange I131F in combination with either M106T and D195E or L215V and K216R replacements was sufficient to confer some FNS I side activity. Introduction of all seven FNS I substitutions into the FHT sequence, however, caused a nearly complete change in enzyme activity from FHT to FNS I. Both FHT and FNS I were proposed to initially withdraw the β-face-configured hydrogen from carbon-3 of the naringenin substrate. Our results suggest that the 7-fold substitution affects the orientation of the substrate in the active-site pocket such that this is followed by syn-elimination of hydrogen from carbon-2 (FNS I reaction) rather than the rebound hydroxylation of carbon-3 (FHT reaction).
A Chlorophyll-Deficient Rice Mutant with Impaired Chlorophyllide Esterification in Chlorophyll Biosynthesis
Authors: Wu Ziming , Zhang Xin , He Bing , Diao Liping , Sheng Shenglan , Wang Jiulin , Guo Xiuping , Su Ning , Wang Lifeng , Jiang Ling , Wang Chunming , Zhai Huqu , Wan Jianmin
Published: May 2007

Chlorophyll (Chl) synthase catalyzes esterification of chlorophyllide to complete the last step of Chl biosynthesis. Although the Chl synthases and the corresponding genes from various organisms have been well characterized, Chl synthase mutants have not yet been reported in higher plants. In this study, a rice (Oryza Sativa) Chl-deficient mutant, yellow-green leaf1 (ygl1), was isolated, which showed yellow-green leaves in young plants with decreased Chl synthesis, increased level of tetrapyrrole intermediates, and delayed chloroplast development. Genetic analysis demonstrated that the phenotype of ygl1 was caused by a recessive mutation in a nuclear gene. The ygl1 locus was mapped to chromosome 5 and isolated by map-based cloning. Sequence analysis revealed that it encodes the Chl synthase and its identity was verified by transgenic complementation. A missense mutation was found in a highly conserved residue of YGL1 in the ygl1 mutant, resulting in reduction of the enzymatic activity. YGL1 is constitutively expressed in all tissues, and its expression is not significantly affected in the ygl1 mutant. Interestingly, the mRNA expression of the cab1R gene encoding the Chl a/b-binding protein was severely suppressed in the ygl1 mutant. Moreover, the expression of some nuclear genes associated with Chl biosynthesis or chloroplast development was also affected in ygl1 seedlings. These results indicate that the expression of nuclear genes encoding various chloroplast proteins might be feedback regulated by the level of Chl or Chl precursors.
The Nuclear Pore Protein AtTPR Is Required for RNA Homeostasis, Flowering Time, and Auxin Signaling
Authors: Jacob Yannick , Mongkolsiriwatana Chareerat , Veley Kira M. , Kim Sang Yeol , Michaels Scott D.
Published: May 2007

Nuclear pore complexes (NPCs) mediate the transport of RNA and other cargo between the nucleus and the cytoplasm. In vertebrates, the NPC protein TRANSLOCATED PROMOTER REGION (TPR) is associated with the inner filaments of the nuclear basket and is thought to serve as a scaffold for the assembly of transport machinery. In a screen for mutants that suppress the expression of the floral inhibitor FLOWERING LOCUS C, we identified lesions in the Arabidopsis (Arabidopsis thaliana) homolog of TPR (AtTPR). attpr mutants exhibit early-flowering and other pleiotropic phenotypes. A possible explanation for these developmental defects is that attpr mutants exhibit an approximately 8-fold increase in nuclear polyA RNA. Thus AtTPR is required for the efficient export of RNA from the nucleus. Microarray analysis shows that, in wild type, transcript abundance in the nuclear and total RNA pools are highly correlated; whereas, in attpr mutants, a significantly larger fraction of transcripts is enriched in either the nuclear or total pool. Thus AtTPR is required for homeostasis between nuclear and cytoplasmic RNA. We also show that the effects of AtTPR on small RNA abundance and auxin signaling are similar to that of two other NPC-associated proteins, HASTY (HST) and SUPPRESSOR OF AUXIN RESISTANCE3 (SAR3). This suggests that AtTPR, HST, and SAR3 may play related roles in the function of the nuclear pore.
Physical Association of the NB-LRR Resistance Protein Rx with a Ran GTPase–Activating Protein Is Required for Extreme Resistance toPotato virus X
Authors: Tameling Wladimir I.L. , Baulcombe David C.
Published: May 2007

Nucleotide binding leucine-rich repeat (NB-LRR) proteins play an important role in plant and mammalian innate immunity. In plants, these resistance proteins recognize specific pathogen-derived effector proteins. Recognition subsequently triggers a rapid and efficient defense response often associated with the hypersensitive response and other poorly understood processes that suppress the pathogen. To investigate mechanisms associated with the activation of disease resistance responses, we investigated proteins binding to the potato (Solanum tuberosum) NB-LRR protein Rx that confers extreme resistance to Potato virus X (PVX) in potato and Nicotiana benthamiana. By affinity purification experiments, we identified an endogenous N. benthamiana Ran GTPase–Activating Protein2 (RanGAP2) as an Rx-associated protein in vivo. Further characterization confirmed the specificity of this interaction and showed that the association occurs through their N-terminal domains. By specific virus-induced gene silencing of RanGAP2 in N. benthamiana carrying Rx, we demonstrated that this interaction is required for extreme resistance to PVX and suggest that RanGAP2 is part of the Rx signaling complex. These results implicate RanGAP-mediated cellular mechanisms, including nucleocytoplasmic trafficking, in the activation of disease resistance.
An SNF2 Protein Associated with Nuclear RNA Silencing and the Spread of a Silencing Signal between Cells inArabidopsis
Authors: Smith Lisa M. , Pontes Olga , Searle Iain , Yelina Nataliya , Yousafzai Faridoon K. , Herr Alan J. , Pikaard Craig S. , Baulcombe David C.
Published: May 2007

The silencing phenotype in Arabidopsis thaliana lines with an inverted repeat transgene under the control of a phloem-specific promoter was manifested in regions around veins due to a mobile signal of silencing. Genetic analysis implicates RNA-DEPENDENT RNA POLYMERASE2 (RDR2) and an RNA polymerase IVa subunit gene (NRPD1a) in the signaling mechanism. We also identified an SNF2 domain–containing protein (CLASSY1) that acts together with RDR2 and NRPD1a in the spread of transgene silencing and in the production of endogenous 24-nucleotide short interfering RNAs (siRNAs). Cytochemical analysis indicates that CLASSY1 may act in the nucleus with NRPD1a and RDR2 in the upstream part of RNA silencing pathways that generate a double-stranded RNA substrate for Dicer-like (DCL) nucleases. DCL3 and ARGONAUTE4 act in a downstream part of the pathway, leading to endogenous 24-nucleotide siRNA production, but are not required for intercellular signaling. From genetic analysis, we conclude that another downstream part of the pathway associated with intercellular signaling requires DCL4 and at least one other protein required for 21-nucleotide trans-acting siRNAs. We interpret the effect of polymerase IVa and trans-acting siRNA pathway mutations in terms of a modular property of RNA silencing pathways.
A familial platelet function disorder associated with abnormal signalling through the glycoprotein VI pathway
Authors: Dunkley Scott , Arthur Jane F. , Evans Sue , Gardiner Elizabeth E. , Shen Yang , Andrews Robert K.
Published: May 2007

The platelet collagen receptor, glycoprotein (GP)VI, of the immunoreceptor family forms a complex with the von Willebrand factor (VWF) receptor, GPIb‐IX‐V, critical for initiating thrombus formation. GPVI is co‐associated with Fc receptor γ‐chain (FcRγ), which contains a cytoplasmic immunoreceptor tyrosine‐based activation motif domain, involved in activation of Syk, and a signalling cascade leading to (i) activation of αIIbβ3, which binds VWF and fibrinogen and mediates platelet aggregation, and (ii) metalloproteinase‐mediated shedding of the GPVI ectodomain (blocked by Syk inhibitors), a key mechanism for regulating GPVI surface expression. In this study, we report a familial case of abnormal platelet aggregation with dysfunctional signalling through GPVI that uniquely demonstrates divergent αIIbβ3‐activating and GPVI‐shedding pathways. The patient is a 60‐year‐old female with a history of immune disorders, excessive bleeding from childhood and a life‐threatening haemorrhage post‐trauma. Platelet aggregation to ADP, thrombin receptor‐agonist peptide or ristocetin/VWF was normal (indicating normal expression and function of αIIbβ3), but platelet aggregation to GPVI agonists, collagen, collagen‐related peptide, or convulxin, was defective. Both GPVI/FcRγ expression and ligand‐induced GPVI ectodomain shedding were normal, confirming expression of functional GPVI/FcRγ, but suggesting a signalling defect downstream of Syk. A genetic defect in GPVI/Fcγ signalling compromising platelet function is hypothesised in this family.
Serum concentrations of angiogenic cytokines in Waldenstrom macroglobulinaemia: the ratio of angiopoietin‐1 to angiopoietin‐2 and angiogenin correlate with disease severity
Authors: Anagnostopoulos Athanasios , Eleftherakis‐Papaiakovou Vangelis , Zervas Konstantinos , Kastritis Efstathios , Tsionos Konstantinos , Bamias Aristotelis , Meletis John , Dimopoulos Meletios A. , Terpos Evangelos
Published: May 2007

Angiogenesis represents an essential step of disease progression in several haematological malignancies. Microvessel density is increased in 30% of patients with Waldenstrom macroglobulinaemia (WM), but there is very limited information regarding the role of angiogenic cytokines in this disease. Serum levels of vascular endothelial growth factor (VEGF), VEGF‐A, angiogenin, angiopoietin (Ang)‐1 and ‐2, and basic fibroblast growth factor (bFGF) were evaluated in 56 WM patients at different disease phases (24 untreated, 20 relapsed/refractory and 12 patients at remission) and 11 patients with immunoglobulin M type monoclonal gammopathy of undetermined significance (IgM‐MGUS). All patients had increased levels of angiogenin, VEGF, VEGF‐A, and bFGF compared with controls. The Ang‐1/Ang‐2 ratio was reduced in WM but not in IgM‐MGUS patients. Angiogenin levels correlated with disease status: when compared with healthy subjects, patients with IgM‐MGUS and untreated WM patients had increased angiogenin serum levels, which were higher in untreated WM patients than in MGUS. WM patients at remission had lower angiogenin serum levels compared with untreated patients, but these levels were increased again in active disease post‐therapy. Angiogenin also correlated with albumin levels, while VEGF‐A correlated with β2‐microglobulin (β2M). Ang‐1/Ang‐2 ratio showed a strong, negative correlation with β2M, and positive correlation with albumin, haemoglobin and lymphadenopathy. Our results indicate a potential use of angiogenin levels for follow‐up in WM and angiogenic molecules as targets for the development of novel anti‐WM agents.
Recent advances into the understanding of mesenchymal stem cell trafficking
Authors: Fox James M. , Chamberlain Giselle , Ashton Brian A. , Middleton Jim
Published: May 2007

The use of adult stem cells to regenerate damaged tissue circumvents the moral and technical issues associated with the use of those from an embryonic source. Mesenchymal stem cells (MSC) can be isolated from a variety of tissues, most commonly from the bone marrow, and, although they represent a very small percentage of these cells, are easily expandable. Recently, the use of MSC has provided clinical benefit to patients with osteogenesis imperfecta, graft‐versus‐host disease and myocardial infarction. The cellular cues that enabled the MSC to be directed to the sites of tissue damage and the mechanisms by which MSC then exert their therapeutic effect are becoming clearer. This review discusses the relative therapeutic importance of the ability of MSC to differentiate into multiple cell lineages or stimulate resident or attracted cells via a paracrine mode of action. It also reviews recent findings that MSC home to damaged tissues in a similar, but somewhat distinct, manner to that of leucocytes via the utilisation of adhesion molecules, such as selectins and integrins, and chemokines and their receptors in a manner reminiscent of leucocytes trafficking from the blood stream to inflammatory sites.
MicroRNAs and haematology: small molecules, big function
Authors: Lawrie Charles H.
Published: May 2007

MicroRNAs are a recently discovered class of small (∼22nt) endogenously expressed translational‐repressor RNAs that play key roles in many cellular pathways and whose aberrant expression appears to be a common feature of malignancy. MicroRNAs are expressed in specific haematological cell types and play important regulatory roles in early haematopoietic differentiation, erythropoiesis, granulocytosis, megakaryocytosis and lymphoid development. Additionally, there is an emerging body of research to suggest that microRNAs play an important role in the pathology of haematological malignancies. MicroRNAs have been found to act as both tumour suppressor molecules [e.g. MIRN15A (miR‐15a), MIRN16‐1 (miR‐16‐1)] in leukaemias and have oncogenic properties [e.g. MIRN155 (miR‐155) and MIRN17–92 (miR‐17–miR‐92) cluster] in lymphomas. This review discusses the rapidly accumulating research that points to the major role microRNAs play in both haematopoiesis and haematological malignancy.
Atorvastatin therapy improves exercise oxygen uptake kinetics in post‐myocardial infarction patients
Authors: Guazzi M. , Tumminello G. , Reina G. , Vicenzi M. , Guazzi M. D.
Published: May 2007

Background  Statins represent a modern mainstay of the drug treatment of coronary artery disease and acute coronary syndromes. Reduced aerobic work performance and slowed VO2 kinetics are established features of the clinical picture of post‐myocardial infarction (MI) patients. We tested the hypothesis that statin therapy improves VO2 exercise performance in normocholesterolaemic post‐MI patients.

Materials and methods  According to a double‐blinded, randomized, crossover and placebo‐controlled study design, in 18 patients with uncomplicated recent (3 days) MI we investigated the effects of atorvastatin (20 mg day−1) on gas exchange kinetics by calculating VO2 effective time constant (tau) during a 50‐watt constant workload exercise, brachial artery flow‐mediated dilatation (FMD) as an index of endothelial function, left ventricular function (echocardiography) and C‐reactive protein (CRP, as an index of inflammation). Atorvastatin or placebo was given for 3 months each.

Results  Atorvastatin therapy significantly improved exercise VO2 tau and FMD, and reduced CRP levels. We did not observe changes in cardiac contractile function and relaxation properties during all study periods in either group.

Conclusions  In post‐MI patients exercise performance is a potential additional target of benefits related to statin therapy. Endothelial function improvement is very likely implicated in this newly described therapeutic property.
Associations between VHL genotype and clinical phenotype in familial von Hippel–Lindau disease
Authors: Huang J. S. , Huang C. J. , Chen S. K. , Chien C. C. , Chen C. W. , Lin C. M.
Published: May 2007

Background  Von Hippel–Lindau (VHL) disease is an autosomal dominant hereditary disorder associated with tumours and cysts in the central nervous system (CNS) and other visceral organs. Germline mutations in the VHL gene on chromosome 3p25–26 are considered the cause of this disease.

Materials and methods  We studied six patients with VHL disease and their relatives. Loss of heterozygosity (LOH) was determined by five flanking microsatellite polymorphic markers in the VHL locus. Multiplex ligation‐dependent probe amplification (MLPA) and quantitative real‐time polymerase chain reaction (qPCR) amplification were used to detect the genomic deletions. Single‐strand conformation polymorphism (SSCP) analysis was applied to test for sequence variations.

Results  Three germline deletions in the VHL gene (142·9, 53·3 and 3·3 kb) were found by MLPA. These deletions were defined clearly by qPCR analyses. The142·9 kb germline deletion was significantly associated with patients with CNS haemangioblastomas (P < 0·01 by Fisher's exact test), and one missense mutation (Gln209Arg) was detected from a patient with a pancreatic cyst in the same family. LOH was also detected from a patient with bilateral renal cell carcinomas.

Conclusion  Diverse genetic conditions are associated with the clinical manifestations of VHL disease. Genomic deletions that can be detected by MLPA or qPCR are major causes for this syndrome. Missense mutations and LOH accompanying the disease lead to complex clinical symptoms and genotypic determination can facilitate a clinical diagnosis because of their strong association.
Standards and standardization in mastocytosis: Consensus Statements on Diagnostics, Treatment Recommendations and Response Criteria
Authors: Valent P. , Akin C. , Escribano L. , Födinger M. , Hartmann K. , Brockow K. , Castells M. , Sperr W. R. , Kluin‐Nelemans H. C. , Hamdy N. A. T. , Lortholary O. , Robyn J. , Van Doormaal J. , Sotlar K. , Hauswirth A. W. , Arock M. , Hermine O. , Hellmann A. , Triggiani M. , Niedoszytko M. , Schwartz L. B. , Orfao A. , Horny H.‐P. , Metcalfe D. D.
Published: May 2007

Although a classification for mastocytosis and diagnostic criteria are available, there remains a need to define standards for the application of diagnostic tests, clinical evaluations, and treatment responses. To address these demands, leading experts discussed current issues and standards in mastocytosis in a Working Conference. The present article provides the resulting outcome with consensus statements, which focus on the appropriate application of clinical and laboratory tests, patient selection for interventional therapy, and the selection of appropriate drugs. In addition, treatment response criteria for the various clinical conditions, disease‐specific symptoms, and specific pathologies are provided. Resulting recommendations and algorithms should greatly facilitate the management of patients with mastocytosis in clinical practice, selection of patients for therapies, and the conduct of clinical trials.
Age‐related changes in bile acid synthesis and hepatic nuclear receptor expression
Authors: Bertolotti M. , Gabbi C. , Anzivino C. , Crestani M. , Mitro N. , Del Puppo M. , Godio C. , De Fabiani E. , Macchioni D. , Carulli L. , Rossi A. , Ricchi M. , Loria P. , Carulli N.
Published: May 2007

Background  Recent data highlighted the role of nuclear receptors in the transcriptional regulation of the limiting enzyme of bile acid synthesis, cholesterol 7α‐hydroxylase, in cellular and animal models. This study was designed to analyze the effects of age on cholesterol 7α‐hydroxylase and related nuclear receptor expression in human livers.

Design  Surgical liver biopsies were obtained in 23 patients requiring operation on the gastrointestinal tract. mRNA levels of cholesterol 7α‐hydroxylase and related nuclear receptors and co‐activators were assayed by quantitative real‐time RT‐PCR. Serum levels of 7α‐hydroxy‐4‐cholesten‐3‐one, a marker of bile acid synthesis, were assayed by gas‐liquid chromatography:mass spectrometry.

Results  Ageing was inversely correlated with serum 7α‐hydroxy‐4‐cholesten‐3‐one and with cholesterol 7α‐hydroxylase mRNA levels (r = –0·44 and r = −0·45 on a semi‐log scale, respectively, P < 0·05). Among different nuclear factors, cholesterol 7α‐hydroxylase mRNA best correlated with hepatocyte nuclear factor‐4 (r = 0·55 on a log scale, P < 0·05); hepatocyte nuclear factor‐4 levels were also inversely correlated with age (r = –0·64 on a semi‐log scale, P < 0·05). Age was inversely correlated with serum insulin‐like growth factor‐I levels, which were directly correlated with hepatocyte nuclear factor‐4 and cholesterol 7α‐hydroxylase expression. No suppressive effect of short heterodimer partner expression on cholesterol 7α‐hydroxylase was observed.

Conclusions  Ageing associates with reduced bile acid synthesis, possibly related to decreased hepatic expression of hepatocyte nuclear factor‐4 and consequently of cholesterol 7α‐hydroxylase. Age‐related modifications of the growth hormone/insulin‐like growth factor axis might play a role. These findings may help to elucidate the pathophysiology of age‐related modifications of cholesterol metabolism.
Natriuretic peptides and myocardial oxygen supply‐to‐demand ratio in patients with aortic stenosis
Authors: Wagner J. A. , Störk S. , Weidemann F. , Strotmann J. , Fiedel C. , Ertl G. , Voelker W.
Published: May 2007

Background  In severe aortic stenosis (AS), brain natriuretic peptide (BNP) and its precursor, the amino‐terminal pro‐hormone (NT‐proBNP) are independent predictors of outcome. Deterioration of cardiac function in AS is currently assessed by symptomatology and echocardiography to determine the optimal time point for surgery. We investigated whether BNP or NT‐proBNP may help to estimate the individual risk of patients for subendocardial ischaemia in patients with moderate and severe AS.

Design  In 71 patients with AS and 24 controls, the association of plasma natriuretic peptides with invasively measured haemodynamic parameters, including the myocardial oxygen supply‐to‐demand ratio [diastolic pressure time index/systolic pressure time index (DPTI/SPTI)] was cross‐sectionally assessed.

Results  Levels of natriuretic peptides increased with severity of AS. In patients with moderate AS (n = 30), natriuretic peptides differentiated between symptomatic and asymptomatic status (P = 0·01). BNP and NT‐proBNP values correlated negatively with DPTI/SPTI (r = −0·58 and −0·51, P < 0·001, respectively) and left ventricular (LV) ejection fraction (EF) (r = −0·52 and −0·59, P < 0·001, respectively). DPTI/SPTI correlated with aortic valve area (P < 0·0001) but not with EF. Receiver operating characteristic analysis determined cut‐off values of > 450 pg mL−1 for BNP and of > 1800 pg mL−1 for NT‐proBNP for those AS patients who were at highest risk for subendocardial ischaemia (i.e. DPTI/SPTI < 0·22) in combination with impaired LV systolic function (i.e. EF < 45%).

Conclusions  Elevated natriuretic peptides show cardiac deterioration in AS and may help to identify those patients in need for early valve replacement.
The hepatic lipase gene C‐480T polymorphism in the development of early coronary atherosclerosis: the Helsinki Sudden Death Study
Authors: Fan Y. M. , Lehtimäki T. , Rontu R. , Ilveskoski E. , Goebeler S. , Kajander O. , Mikkelsson J. , Viiri L. E. , Perola M. , Karhunen P. J.
Published: May 2007

Background  The T allele of the hepatic lipase (HL) C‐480T polymorphism was previously found to be associated with lower post‐heparin plasma HL activity, atherosclerosis and risk of coronary artery disease. We studied the association of HL C‐480T polymorphism with the extent of atherosclerosis at vessel‐wall level in an autopsy series of middle‐aged men.

Materials and methods  An autopsy cohort of 700 Caucasian Finnish men aged 33–70 years (mean 53 years), which comprised two autopsy series, collected 10 years apart during 1981–82 and 1991–92, were analysed. Areas of coronary wall covered with fatty streaks and fibrotic and complicated lesions were measured using computer‐assisted planimetry and related to HL C‐480T genotypes (CC, CT, and TT).

Results  There was a significant age–by–genotype interaction on the mean percentage area of fatty streaks (P = 0·01). The HL C‐480T polymorphism was a significant explanatory factor for fatty streak area in men under 53 years of age with or without age, body mass index, hypertension, diabetes, smoking, alcohol consumption, apolipoprotein E genotype, and series number as covariates. Men carrying the TT genotype had two times larger areas of fatty streaks compared to the CC carriers (8·8% vs. 4·3%, P = 0·009). However, this association disappeared in men over 53 years. The areas of more advanced atherosclerotic lesions did not vary significantly among the genotype groups.

Conclusions  Our results suggest that the HL C‐480T polymorphism affects the formation of early coronary atherosclerotic lesions in men in their early middle age.
Angiotensin‐converting enzyme gene polymorphism and stroke in type 2 diabetic patients in Taiwan
Authors: Tseng C. H. , Tseng C. P. , Chong C. K. , Sheu J. J. , Cheng J. C.
Published: May 2007

Background  The effect of traditional risk factors on the association between angiotensin‐converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and stroke was rarely studied previously. We investigated such effect in Taiwanese type 2 diabetic patients.

Materials and methods  A total of 872 (422 men and 450 women) patients aged 63·5 (SD: 11·6) years were recruited. Among them, 92 cases (48 men and 44 women) had stroke. Polymerase chain reaction was used to classify the genotypes as II, ID and DD. Analyses were performed in separate sexes.

Results  The adjusted odds ratios for stroke for ID vs. II and DD vs. II were 0·837 (0·413–1·697) and 1·778 (0·596–5·300), respectively, for men; but were 1·700 (0·824–3·505) and 3·706 (1·375–9·985), respectively, for women. In models assuming recessive (DD vs. II + ID), dominant (DD + ID vs. II) and additive (II = 0, ID = 1 and DD = 2) transmission, none of the odds ratios was significant for men; but were all significant for women: 2·784 (1·137–6·818), 1·996 (1·006–3·962) and 1·877 (1·155–3·050), respectively. In models using patients without risk factors (hypertension, obesity, smoking or dyslipidaemia ) as a referent group and comparing them to patients with the risk factor and with ID/II, and with DD genotypes, all models (except for smoking) favoured an increasing trend of risk with patients having the risk factor and DD genotype at the highest risk in women. Similar trends for hypertension and dyslipidaemia were also observed in men.

Conclusion  Traditional risk factors play an important role in the association between the ACE genotypes and stroke. Patients with DD genotype and having traditional risk factors are at the highest risk.
Coronary artery disease investigated using 99mTc‐tetrofosmin myocardial SPECT
Authors: Toriyama T. , Takase H. , Goto T. , Sugiura T. , Nakazawa A. , Hayashi K. , Ishikawa H. , Hikita Y. , Ueda R. , Dohi Y.
Published: May 2007

Background  Coronary artery disease can be diagnosed from stress and delayed images of myocardial single photon emission computed tomography (SPECT) using technetium‐99 m‐tetrofosmin (TcTF). However, the negative predictive value of stress SPECT images after a single injection of a low tracer dose remains unknown. Thus, the present study investigates whether normal stress SPECT results predict event‐free survival.

Materials and methods  We screened 302 consecutive patients who were randomly assigned to two groups for myocardial ischaemia using either stress SPECT with a low dose of TcTF (296 MBq, TcTF group, n = 150) or stress together with rest SPECT using thallium201 chloride (TlCl, 111 MBq; TlCl group, n = 152) as the tracer. A total of 80 patients with abnormal SPECT findings were excluded and the remaining 222 with normal results (age, 66·5 ± 0·7 years; TcTF/TlCl, 112/110) were enrolled in the present study and followed up for 401 ± 9 days, with the endpoint being ischaemic cardiac events.

Results  The incidence of cardiac events did not differ between the two groups (0·9% and 0·0% in TcTF and TlCl groups, respectively). The cost and duration of TcTF and TlCl SPECT examinations were about 425 and 603 Euros and 50 and 280 min, respectively.

Conclusions  The negative predictive values of stress SPECT using a low dose of TcTF and of combined stress and rest SPECT using TlCl did not differ and both were clinically acceptable. Thus, stress SPECT using low dose TcTF is useful in screening patients for myocardial ischaemia.
TGF‐β1 overexpression in the transversalis fascia of patients with direct inguinal hernia
Authors: Pascual G. , Corrales C. , Gómez‐Gil V. , Buján J. , Bellón J. M.
Published: May 2007

Background  The aetiology of inguinal hernia includes changes in collagen turnover and metalloproteinase (MMP) expression, and direct hernia has been linked to increased MMP‐2 expression. Since transforming growth factor β1 (TGFβ1) plays a role in tissue remodelling, this growth factor could directly affect metalloproteinase secretion and thus the proteolytic activity of these enzymes. We hypothesized that TGFβ1 expression could also be altered in direct inguinal hernias.

Materials and methods  Tissue specimens were obtained from the transversalis fascia (TF) of organ donors (controls; n = 10) and patients with inguinal hernia (indirect; n = 20/direct; n = 20), who were also divided into two groups according to age (20–40/41–60 years). Tissue sections were immunohistochemically labelled using anti‐LAP TGFβ1 (latent form) and anti‐TGFβ1 (active form) antibodies, and fragments of tissue were subjected to Western blot analysis.

Results  No significant differences in LAP‐TGFβ1 expression were detected between specimens from control and hernia patients. However, significantly higher levels of active TGFβ1 were detected in the TF of patients with direct hernia (P < 0·05). Age affected the expression of the growth factor in its active form, and significant differences emerged between direct hernias and controls/indirect hernias only in the younger age groups.

Conclusions  Our findings indicate overexpression of the active form of TGFβ1 in the TF of young patients with direct hernia. This overexpression reflects an attempt to counterbalance the enhanced matrix degradation process observed in these patients, identifying a subset of patients requiring the use of a prosthetic material for primary hernia repair.
Predicting the development of early skin test sensitization in offspring of parents with asthma
Authors: Jin Y. , Xu Y. , Xue S. , Liu H. , Zhao J. , Xu M.
Published: May 2007

Background  The direct causal relationship between skin sensitization and asthma are controversial until now and remains to be further researched. Our aim is to analyse the role of parental asthma in the development of skin sensitization in offspring.

Materials and methods  This study was performed among nuclear families (determined by index of asthma patients), and subjects included parents and offspring. Parents were subdivided into four phenotypes on the basis of skin sensitization (SPT+ or SPT–) and asthma status (AST+ or AST–) and offspring were subdivided into three age groups: 3–8, 9–14 and 15–20 years. The main tests included a standard questionnaire and skin prick tests.

Results  Offspring's skin sensitization differed among parental phenotypes at all ages (P < 0·05). In the SPT+/AST–, SPT–/AST+ and SPT+/AST+ groups, offspring were significantly more likely to be allergic than the ones in SPT–/AST– group at 3–8 years. Offspring with at least one parent with asthma were significantly more likely to have positive skin prick test response than those with non‐asthmatic parents at age 3–8 years and 9–14 years, but not at 15–20 years among offspring with allergic parents. Results were independent of asthma in the children and of the characteristics of atopy in the parents.

Conclusion  Parent asthma history is an independent risk factor for allergic sensitization in their offspring in a Chinese population.
Net ecosystem productivity of boreal jack pine stands regenerating from clearcutting under current and future climates
Authors: GRANT R. F. , BARR A. G. , BLACK T. A. , GAUMONT‐GUAY D. , IWASHITA H. , KIDSON J. , McCAUGHEY H. , MORGENSTERN K. , MURAYAMA S. , NESIC Z. , SAIGUSA N. , SHASHKOV A. , ZHA T.
Published: May 2007

Life cycle analysis of climate and disturbance effects on forest net ecosystem productivity (NEP) is necessary to assess changes in forest carbon (C) stocks under current or future climates. Ecosystem models used in such assessments need to undergo well‐constrained tests of their hypotheses for climate and disturbance effects on the processes that determine CO2 exchange between forests and the atmosphere. We tested the ability of the model ecosys to simulate diurnal changes in CO2 fluxes under changing air temperatures (Ta) and soil water contents during forest regeneration with eddy covariance measurements over boreal jack pine (Pinus banksiana) stands along a postclearcut chronosequence. Model hypotheses for hydraulic and nutrient constraints on CO2 fixation allowed ecosys to simulate the recovery of C cycling during the transition of boreal jack pine stands from C sources following clearcutting (NEP from −150 to −200 g C m−2 yr−1) to C sinks at maturity (NEP from 20 to 80 g C m−2 yr−1) with large interannual variability. Over a 126‐year logging cycle, annualized NEP, C harvest, and net biome productivity (NBP=NEP–harvest removals) of boreal jack pine averaged 47, 33 and 14 g C m−2 yr−1. Under an IPCC SRES climate change scenario, rising Ta exacerbated hydraulic constraints that adversely affected NEP of boreal jack pine after 75 years. These adverse effects were avoided in the model by replacing the boreal jack pine ecotype with one adapted to warmer Ta. This replacement raised annualized NEP, C harvest, and NBP to 81, 56 and 25 g C m−2 yr−1 during a 126‐year logging cycle under the same climate change scenario.
Postfire carbon pools and fluxes in semiarid ponderosa pine in Central Oregon
Authors: IRVINE J. , LAW B. E. , HIBBARD K. A.
Published: May 2007

Forest fire dramatically affects the carbon storage and underlying mechanisms that control the carbon balance of recovering ecosystems. In western North America where fire extent has increased in recent years, we measured carbon pools and fluxes in moderately and severely burned forest stands 2 years after a fire to determine the controls on net ecosystem productivity (NEP) and make comparisons with unburned stands in the same region. Total ecosystem carbon in soil and live and dead pools in the burned stands was on average 66% that of unburned stands (11.0 and 16.5 kg C m−2, respectively, P<0.01). Soil carbon accounted for 56% and 43% of the carbon pools in burned and unburned stands. NEP was significantly lower in severely burned compared with unburned stands (P<0.01) with an increasing trend from −125±44 g C m−2 yr−1 (±1 SD) in severely burned stands (stand replacing fire), to −38±96 and +50±47 g C m−2 yr−1 in moderately burned and unburned stands, respectively. Fire of moderate severity killed 82% of trees <20 cm in diameter (diameter at 1.3 m height, DBH); however, this size class only contributed 22% of prefire estimates of bole wood production. Larger trees (> 20 cm DBH) suffered only 34% mortality under moderate severity fire and contributed to 91% of postfire bole wood production. Growth rates of trees that survived the fire were comparable with their prefire rates. Net primary production NPP (g C m−2 yr−1, ±1 SD) of severely burned stands was 47% of unburned stands (167±76, 346±148, respectively, P<0.05), with forb and grass aboveground NPP accounting for 74% and 4% of total aboveground NPP, respectively. Based on continuous seasonal measurements of soil respiration in a severely burned stand, in areas kept free of ground vegetation, soil heterotrophic respiration accounted for 56% of total soil CO2 efflux, comparable with the values of 54% and 49% previously reported for two of the unburned forest stands. Estimates of total ecosystem heterotrophic respiration (Rh) were not significantly different between stand types 2 years after fire. The ratio NPP/Rh averaged 0.55, 0.85 and 1.21 in the severely burned, moderately burned and unburned stands, respectively. Annual soil CO2 efflux was linearly related to aboveground net primary productivity (ANPP) with an increase in soil CO2 efflux of 1.48 g C yr−1 for every 1 g increase in ANPP (P<0.01, r2= 0.76). There was no significant difference in this relationship between the recently burned and unburned stands. Contrary to expectations that the magnitude of NEP 2 years postfire would be principally driven by the sudden increase in detrital pools and increased rates of Rh, the data suggest NPP was more important in determining postfire NEP.