bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of cytokine and ICAM-1 gene polymorphisms on susceptibility to chronic pancreatitis
Authors: Howell W M , Pead P J , Shek F W , Rose-Zerilli M J , Armstrong T , Johnson C D , Fine D R , Iredale J P , Bateman A C
Published: May 2005

Aims:To test the hypothesis that single nucleotide polymorphisms (SNPs) within genes (or their promoter regions) encoding cytokines, growth factors, and intercellular adhesion molecules modulate the risk of development of chronic pancreatitis (CP).

Methods:DNA was extracted from peripheral blood leucocytes or formalin fixed, paraffin wax embedded tissue from 53 patients with CP and 266 healthy controls. SNPs within the interleukin 1β (IL-1β), IL-6, IL-8, tumour necrosis factor α (TNFα) and vascular endothelial growth factor (VEGF) gene promoter regions and the transforming growth factor β1 (TGFβ1) and intercellular cell adhesion molecule 1 (ICAM-1) genes were genotyped by the amplification refractory mutation system polymerase chain reaction or 5′ nuclease (Taqman®) techniques. Patient–control comparisons were made using 2 × 2 contingency tables and χ2analyses.

Results:A non-significant decrease in the frequency of the IL-8 −251 AA genotype and a non-significant increase in the frequency of the ICAM-1 +469 GA genotype was seen in patients compared with controls. No associations were identified between SNPs in the promoter regions of the IL-1β, IL-6, or TNFα proinflammatory cytokines genes or the TGFβ1 and VEGF genes and susceptibility to CP.

Conclusions:This preliminary study suggests that genetic polymorphism within several cytokine genes is unlikely to influence susceptibility to CP, but the possible role of IL-8 and ICAM-1 polymorphisms in the development of this disease requires further investigation.
Lymphoma associated chromosomal abnormalities can easily be detected by FISH on tissue imprints. An underused diagnostic alternative
Authors: Buño I , Nava P , Álvarez-Doval A , Álvarez-Rodríguez F , Díez-Martín J L , Menárguez J
Published: May 2005

Background:Fluorescence in situ hybridisation (FISH) is useful for detecting specific chromosomal abnormalities in various tumours. In lymphomas, diagnosis is frequently made using paraffin wax embedded tissue. However, FISH performed under these conditions presents potential technical problems and difficulties in interpretation.

Aims:To show that FISH using tissue imprints and cytopreps or alternatively, bone marrow (BM) smears, constitutes an easy and rapid strategy to overcome these constraints.

Methods:The study comprised 46 patients with lymphoma. Sixty nine tissue imprints, cytopreps, or BM smears were analysed by FISH. Dual colour, dual fusion FISH probes were used to detect the t(8;14), t(11;14), and t(14;18) translocations, whereas a dual colour breakapart FISH probe was used to detect chromosomal translocations involving the BCL6 gene.

Results:Tissue imprints and cytopreps were successfully hybridised in all 52 cases, whereas hybridisation was successful in 16 of 17 archival BM smears. All patients could be analysed to identify either the presence or absence of chromosomal translocations.

Conclusions:The use of tissue imprints, cytopreps, or BM smears to identify chromosomal abnormalities by FISH is a rapid and useful ancillary approach for diagnostic purposes. Therefore, it could be used on a routine basis whenever fresh samples are available.
Differential expression of the eukaryotic release factor 3 (eRF3/GSPT1) according to gastric cancer histological types
Authors: Malta-Vacas J , Aires C , Costa P , Conde A R , Ramos S , Martins A P , Monteiro C , Brito M
Published: May 2005

Background:There are now several lines of evidence to suggest that protein synthesis and translation factors are involved in the regulation of cell proliferation and cancer development.

Aims:To investigate gene expression patterns of eukaryotic releasing factor 3 (eRF3) in gastric cancer.

Methods:RNA was prepared from 25 gastric tumour biopsies and adjacent non-neoplastic mucosa. Real time TaqMan reverse transcription polymerase chain reaction (RT-PCR) was performed to measure the relative gene expression levels. DNA was isolated from tumour and normal tissues and gene dosage was determined by a quantitative real time PCR using SYBR Green dye.

Results:Different histological types of gastric tumours were analysed and nine of the 25 tumours revealed eRF3/GSPT1 overexpression; moreover, eight of the 12 intestinal type carcinomas analysed overexpressed the gene, whereas eRF3/GSPT1 was overexpressed in only one of the 10 diffuse type carcinomas (Kruskal-Wallis Test; p < 0.05). No correlation was found between ploidy and transcript expression levels of eRF3/GSPT1. Overexpression of eRF3/GSPT1 was not associated with increased translation rates because the upregulation of eRF3/GSPT1 did not correlate with increased eRF1 levels.

Conclusions:Overexpression of eRF3/GSPT1 in intestinal type gastric tumours may lead to an increase in the translation efficiency of specific oncogenic transcripts. Alternatively, eRF3/GSPT1 may be involved in tumorigenesis as a result of its non-translational roles, namely (dis)regulating the cell cycle, apoptosis, or transcription.
BRAF and NRAS mutations are uncommon in melanomas arising in diverse internal organs
Authors: Wong C W , Fan Y S , Chan T L , Chan A S W , Ho L C , Ma T K F , Yuen S T , Leung S Y
Published: May 2005

Background:Malignant melanoma arising from different body compartments may be associated with differing aetiological factors and clinical behaviour, and may manifest diverse molecular genetic profiles. Although many studies have focused on cutaneous melanoma, little is known of mucosal and other types of melanoma. In particular, malignant melanoma of soft parts is different from other melanomas in many respects, yet manifests a common melanocytic differentiation. Mutation of BRAF is now known to be common in cutaneous melanomas, and raises possible new therapeutic options of anti-RAF treatment for these patients. Few data are available for non-cutaneous melanomas.

Aims:To study the incidence of BRAF and NRAS mutations in melanomas arising in diverse internal organs.

Methods:Fifty one melanomas from various internal organs were investigated for BRAF and NRAS mutation by direct DNA sequencing.

Results:BRAF and NRAS mutations were found in two and five mucosal melanomas arising from the aerodigestive and female genital tracts (n = 36). Their occurrence is mutually exclusive, giving a combined mutation incidence rate of 19.4% in mucosal melanomas. Both BRAF and NRAS mutations were absent in malignant melanoma of soft parts (n = 7). BRAF mutation was also absent in uveal melanoma (n = 6), but was seen in two of five cutaneous melanomas. The incidence of BRAF or combined BRAF/NRAS mutations in all non-cutaneous groups was significantly lower than published rates for cutaneous melanomas.

Conclusion:Each melanoma subtype may have a unique oncogenetic pathway of tumour development, and only a small fraction of non-cutaneous melanomas may benefit from anti-RAF treatment.
Thymidine phosphorylase expression in tumour cells and tumour response to capecitabine plus docetaxel chemotherapy in non-small cell lung cancer
Authors: Han J-Y , Hong E K , Lee S Y , Yoon S M , Lee D H , Lee J S
Published: May 2005

Background:Thymidine phosphorylase (TP) is the key enzyme for capecitabine activation in tumour cells.

Aims:To examine whether TP expression in tumour cells and stroma is predictive of the tumour response to capecitabine plus docetaxel chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).

Methods:Tumour samples were available from 30 of 39 patients enrolled in a previous phase II study of capecitabine/docetaxel chemotherapy in patients with advanced NSCLC. Stromal and tumour cell TP expression was evaluated by immunohistochemistry using monoclonal antibody PD-ECGF.

Results:High tumour cell TP expression was found in 13 of 30 cases and was negatively associated with stromal TP expression (p = 0.000). High stromal TP expression was found in 16 of 28 cases and was strongly associated with intense macrophage infiltration (p = 0.002), suggesting that macrophages are the major component of TP expression in the stroma. Tumour response to capecitabine/docetaxel was significantly associated with high tumour cell TP expression (p = 0.004) and low stromal TP expression (p = 0.009). Moreover, high tumour cell TP expression was significantly associated with severe hand–foot syndrome, a toxic side effect of capecitabine (p = 0.01). Improved survival was seen for high tumour cell and low stromal TP expression, although results were not significant (p = 0.6 and 0.3, respectively).

Conclusions:In advanced NSCLC, TP expression in tumour cells and stroma is associated with tumour response to capecitabine/docetaxel chemotherapy, and might be a useful predictor of tumour response to capecitabine based chemotherapy. A large scale prospective study is needed to confirm the prognostic significance of TP expression in NSCLC.
Association between tumour characteristics and HER-2/neu by immunohistochemistry in 1362 women with primary operable breast cancer
Authors: Huang H J , Neven P , Drijkoningen M , Paridaens R , Wildiers H , Van Limbergen E , Berteloot P , Amant F , Vergote I , Christiaens M R
Published: May 2005

Aims:To investigate the association between tumour characteristics and HER-2/neu by immunohistochemistry in primary operable breast cancer.

Methods:The association between HER-2/neu and other clinicopathological factors was evaluated in 1362 consecutive patients with primary breast cancer treated between 2000 and July 2003 in one centre. Microscopic tumour size, tumour grade, lymph node status, patient’s age, oestrogen receptor (ER), progesterone receptor (PR), and joint ER/PR status were evaluated, using the χ2test for univariate analysis and logistic regression for multivariate analysis. The hormone receptors and HER-2/neu were studied immunohistochemically. Using the HER-2/neu DAKO scoring system, scores of 0, 1+, or 2+ were defined as negative and 3+ as positive. Data for DAKO scores 2+/3+ versus 0/1+ are also presented.

Results:Hormone receptor negative breast cancers were more often HER-2/neu positive than hormone receptor positive cancers, both for ER (28.7%v6.8%) and PR (19.9%v5.9%). In multivariate analysis, both ER, PR, and tumour grade were independently associated with HER-2/neu. In ER+tumours, HER-2/neu overexpression was significantly lower in PR+than in PR−cases (11.5%v5.4%). HER-2/neu overexpression (2.7%) was lowest in the large subgroup of ER+PR+tumours with low tumour grade (grade 1–2), comprising 46.1% of all patients.

Conclusions:ER, PR, and tumour grade are independent predictors for HER-2/neu overexpression in women with primary operable breast cancer. ER and PR are negatively associated with HER-2/neu, whereas tumour grade is positively associated with HER-2/neu. In women with ER+tumours, PR status also affects the likelihood of HER-2/neu expression.
KSHV/HHV-8 associated Kaposi’s sarcoma in lymph nodes concurrent with Epstein-Barr virus associated Hodgkin lymphoma: Figure 1
Authors: Carbone A
Published: May 2005

Background:The unusual occurrence of a metastatic Kaposi’s sarcoma (KS) in a lymph node affected by Hodgkin lymphoma (HL) was originally reported when knowledge of the specific virological features of these tumours was lacking.

Aim:To re-evaluate this case by assessing whether the simultaneous presence of the two tumours was linked with common aetiopathogenetic factors.

Methods:The presence of EBV was investigated by in situ hybridisation, whereas KS associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) was detected by immunohistochemistry. Both viruses were analysed in the case reported, in 30 lymph nodes from patients with classic HL, and in 22 skin biopsies from patients with KS.

Results:Consistent with the findings in the HL and KS cases analysed, in the case showing features of both HL and KS in the same lymph node, EBV was detectable only in Reed-Sternberg (RS) cells, but not in KS spindle cells, whereas KSHV/HHV-8 was detectable only in KS spindle cells, and not in RS cells.

Conclusion:It is probable that the development of KS and HL was related to two independent aetiological cofactors—KSHV/HHV-8 and EBV, respectively—and that the occurrence of the two malignancies in the same patient was merely fortuitous.
A population based seroepidemiological survey ofChlamydia pneumoniaeinfections in schoolchildren
Authors: Dal Molin G , Longo B , Not T , Poli A , Campello C
Published: May 2005

Aim:A serosurvey was carried out in schoolchildren from a northeastern area of Italy to define the burden ofChlamydia pneumoniaeinfection.

Methods:A sample of 649 schoolchildren underwent a simplified version of the International Study of Asthma and Allergies in Childhood questionnaire and IgG and IgA antibodies were investigated using an enzyme immunoassay, followed by a microimmunofluorescence assay in reactive sera.

Results:Of the children examined, 29% and 19.7% had IgG and IgA antibodies, respectively. The IgG prevalence increased with age. No other sociodemographical variable was related toC pneumoniaeinfection. An association was established between IgA prevalence and previous otitis media.

Conclusions:A mesoendemic (intermediate between high and low endemic level) pattern ofC pneumoniaeinfection is present in schoolchildren from this area and the prevalence rate is related to age. Moreover, this is the first epidemiological evidence of the role ofC pneumoniaein otitis.
Ultrastructural study of the extra-articular Leeds-Keio ligament prosthesis
Authors: Nomura E , Inoue M , Sugiura H
Published: May 2005

Background:There have been several histological studies of the Leeds-Keio ligament in anterior cruciate ligament reconstruction, but there have been few of the Leeds-Keio ligament in the extra-articular portion.

Aims/Methods:To report the histological and ultrastructural findings of two cases of medial patellofemoral ligament reconstruction using the Leeds-Keio ligament, removed 6.1 years and 8.7 years after implantation.

Results:In both cases, the tissue over the Leeds-Keio ligament was a ligament-like tissue. Electron microscopy showed that the diameter of the collagen fibrils in the tissue over the Leeds-Keio ligament was unimodal in the case investigated 6.1 years after implantation but bimodal in the case investigated after 8.7 years.

Conclusions:The tissue over the Leeds-Keio ligament may continue to grow with prolonged periods of mechanical stress.
The impact of the cigarette market opening in Taiwan
Authors: Wen C P , Cheng T Y , Eriksen M P , Tsai S P , Hsu C C
Published: May 2005

Objective:To assess the effect of the opening of the Taiwanese cigarette market on cigarette consumption, changes in market share, and the effects on tobacco control efforts.

Methods:With the use of key word “Taiwan”, the Legacy Tobacco Documents Library of the University of California, San Francisco, was searched for internal documents related to smuggling activities, promotion of light cigarettes, and market share analyses in Taiwan. Age adjusted smoking rates and cigarette and betel quid consumption before and after market opening were compared.

Results:By 2000, the market share of imported cigarettes increased from less than 2% in 1986 to nearly 50%, and per capita cigarette consumption increased 15% following market opening. Because of the sharp increase in smuggling, with contraband cigarettes being as popular as legal imports, and the rapid proliferation of retail outlets, such as betel quid stalls, the market penetration by foreign tobacco companies was greater in Taiwan than among the other Super 301 Asian countries. Aggressive cigarette marketing strategies were associated with a 6% increase in adult male smoking prevalence, and with a 13% increase in the youth rate, within three years after market opening. The market opening also had an incidental effect on increasing the popularity of betel quid. Betel quid chewing has since become a major public health problem in Taiwan.

Conclusion:The opening of the cigarette market in 1987 had a long lasting impact on Taiwan. It increased smoking prevalence and the market has become dominated by foreign companies. The seriousness of smuggling and its associated loss of revenue by the government, the extent of increased youth smoking and its associated future health care costs, and the increased use of betel quid and the associated doubling of oral cancer mortality rates each pose significant problems to Taiwan. However, the market opening galvanised anti-smoking sentiment and forced the government to initiate and intensify a series of tobacco control efforts.
SAMPLING AND OVERSAMPLING IN SHIFT-INVARIANT AND MULTIRESOLUTION SPACES I: VALIDATION OF SAMPLING SCHEMES
Authors: HOGAN J. A. , LAKEY J. D.
Published: May 2005

We ask what conditions can be placed on generators φ of principal shift invariant spaces to ensure the validity of analogues of the classical sampling theorem for bandlimited signals. Critical rate sampling schemes lead to expansion formulas in terms of samples, while oversampling schemes can lead to expansions in which function values depend only on nearby samples. The basic techniques for validating such schemes are built on the Zak transform and the Poisson summation formula. Validation conditions are phrased in terms of orthogonality, smoothness, and self-similarity, as well as bandlimitedness or compact support of the generator. Effective sampling rates which depend on the length of support of the generator or its Fourier transform are derived.
AN ASPECT OF THE SAMPLING THEOREM
Authors: ZHOU XINGWEI , SUN WENCHANG
Published: May 2005

We give a sufficient condition for a function to belong to some sampling space. Also, we prove that a sampling space must be contained in another one which has a Riesz basis consisting of integer translations of a base function. Examples are given.
CONSTRUCTION OF GENERALIZED UNCERTAINTY PRINCIPLES AND WAVELETS IN ANISOTROPIC SOBOLEV SPACES
Authors: TESCHKE GERD
Published: May 2005

This paper deals with the construction of generalized uncertainty relations. Starting with a two-operator parabola ansatz, we derive a new set of uncertainties by extending the parabola ansatz to quadratic forms. This setting can be applied to the computation of uncertainties where more than two operators are involved. For affine Weyl–Heisenberg groups, some examples are explored.
INTELLECTUALS AND NATIONALISM: Anthropological Engagements
Authors: Boyer Dominic , Lomnitz Claudio
Published: May 2005

To what extent are intellectuals artisans of nationalism? In this chapter we review past and present anthropological research that has helped to reveal the agency of intellectuals in the projects and operations of states and nations. If the intellectual has long been defined in the Marxian-Gramscian tradition as a social actor with a special praxical investment in ways and forms of knowing, then what we discuss as “intellectualism,” the social formation of knowledge, should be understood as a central dimension of the (re)production of nations and nationalism both inside and outside of states. We suggest that further drawing anthropological attention to intellectuals and their knowledge practices (ranging from the poetic-literary to the technical-administrative) will help the anthropology of nations and nationalism to (a) locate the role of human agency in the creation, circulation, and contestation of national culture, (b) capture the intellectual work involved in nationalism and bureaucracy in its full diversity, and (c) imagine a new series of ethnographic access points among educated professionals for the study of nationalism in action.
Acute regulation of parathyroid hormone by dietary phosphate
Authors: Martin Daniel R. , Ritter Cynthia S. , Slatopolsky Eduardo , Brown Alex J.
Published: May 2005

Secondary hyperparathyroidism in chronic renal failure is stimulated by dietary phosphate (Pi) loading and ameliorated by dietary Pi restriction. We investigated the rapidity of the response of serum parathyroid hormone (PTH) to changes in dietary Pi. When uremic rats adapted to a high Pi diet (HPD) were fed a single meal of low Pi diet (LPD), plasma PTH fell 80% within 2 h; plasma Pi fell 1 mg/dl with no change in plasma ionized Ca (ICa). When uremic rats on the HPD were gavaged with LPD, PTH fell 60% within 15 min; plasma Pi fell by 3.0 mg/dl with no change in total plasma Ca. However, HPD gavage increased PTH by 80% within 15 min with no change in plasma P or Ca, suggesting that the response may be independent of altered plasma Pi. Duodenal infusion of sodium Pi increased PTH twofold within 10 min, with no change in ICa but an increase in plasma Pi, whereas duodenal infusion of NaCl had no effect on any of these parameters. Intravenous infusion of sodium phosphate also increased PTH within 10 min with no change in plasma ICa; intravenous NaCl had no effect. Additionally, duodenal infusion of phosphonoformate, a nonabsorbable phosphate analog, increased PTH fourfold within 5 min, but did not change plasma P or ICa. These findings indicate that oral Pi increases PTH release in vivo more rapidly than previously reported; this response may be from both plasma phosphate and an additional signal arising from the gastrointestinal tract.
Dietary K+regulates apical membrane expression of maxi-K channels in rabbit cortical collecting duct
Authors: Najjar Fadi , Zhou Hao , Morimoto Tetsuji , Bruns James B. , Li Hai-Sheng , Liu Wen , Kleyman Thomas R. , Satlin Lisa M.
Published: May 2005

The cortical collecting duct (CCD) is a final site for regulation of K+homeostasis. CCD K+secretion is determined by the electrochemical gradient and apical permeability to K+. Conducting secretory K+(SK/ROMK) and maxi-K channels are present in the apical membrane of the CCD, the former in principal cells and the latter in both principal and intercalated cells. Whereas SK channels mediate baseline K+secretion, maxi-K channels appear to participate in flow-stimulated K+secretion. Chronic dietary K+loading enhances the CCD K+secretory capacity due, in part, to an increase in SK channel density (Palmer et al., J Gen Physiol 104: 693–710, 1994). Long-term exposure of Ambystoma tigrinum to elevated K+increases renal K+excretion due to an increase in apical maxi-K channel density in their CDs (Stoner and Viggiano, J Membr Biol 162: 107–116, 1998). The purpose of the present study was to test whether K+adaptation in the mammalian CCD is associated with upregulation of maxi-K channel expression. New Zealand White rabbits were fed a low (LK), control (CK), or high (HK) K+diet for 10–14 days. Real-time PCR quantitation of message encoding maxi-K α- and β2–4-subunits in single CCDs from HK animals was greater than that detected in CK and LK animals ( P < 0.05); β1-subunit was not detected in any CCD sample but was present in whole kidney. Indirect immunofluorescence microscopy revealed a predominantly intracellular distribution of α-subunits in LK kidneys. In contrast, robust apical labeling was detected primarily in α-intercalated cells in HK kidneys. In summary, K+adaptation is associated with an increase in steady-state abundance of maxi-K channel subunit-specific mRNAs and immunodetectable apical α-subunit, the latter observation consistent with redistribution from an intracellular pool to the plasma membrane.
Chronic dDAVP infusion in rats decreases the expression of P2Y2 receptor in inner medulla and P2Y2 receptor-mediated PGE2release by IMCD
Authors: Sun Rujia , Miller R. Lance , Hemmert Andrew C. , Zhang Ping , Shi Huihui , Nelson Raoul D. , Kishore Bellamkonda K.
Published: May 2005

Activation of P2Y2 receptor (P2Y2-R) in inner medullary collecting duct (IMCD) of rat decreases AVP-induced water flow and releases PGE2. We observed that dehydration of rats decreases the expression of P2Y2 receptor in inner medulla (IM) and P2Y2-R-mediated PGE2release by IMCD. Because circulating vasopressin (AVP) levels are increased in dehydrated condition, we examined whether chronic infusion of desmopressin (dDAVP) has a similar effect on the expression and activity of P2Y2-R. Groups of rats were infused with saline or dDAVP (5 or 20 ng/h sc, 5 or 6 days) via osmotic minipumps and euthanized. Urine volume, osmolality, and PGE2metabolite content were determined. AQP2- and P2Y2- and V2-R mRNA and/or protein in IM were quantified by real-time RT-PCR and immunoblotting, respectively. P2Y2-R-mediated PGE2release by freshly prepared IMCD was assayed using ATPγS as a ligand. Chronic dDAVP infusion resulted in low-output of concentrated urine and significantly increased the AQP2 protein abundance in IM. On the contrary, dDAVP infusion at 5 or 20 ng/h significantly decreased P2Y2-R protein abundance (∼40% of saline-treated group). In parallel, the relative expression of P2Y2-R vs. AQP2- or V2-R mRNA was significantly decreased. Furthermore, the P2Y2-R-mediated PGE2release by IMCD was significantly decreased in rats infused 20 ng/h but not 5 ng/h of dDAVP. Urinary PGE2metabolite excretion, however, did not change with dDAVP infusion. In conclusion, chronic dDAVP infusion decreases the expression and activity of P2Y2-R in IM. This may be due to a direct effect of dDAVP or dDAVP-induced increase in medullary tonicity.
Mechanical force-activated phospholipase D is mediated by Gα12/13-Rho and calmodulin-dependent kinase in renal epithelial cells
Authors: Ziembicki Jenny , Tandon Rajnish , Schelling Jeffrey R. , Sedor John R. , Miller R. Tyler , Huang Chunfa
Published: May 2005

The renal glomerulus, the site of plasma ultrafiltration, is exposed to mechanical force in vivo arising from capillary blood pressure and fluid flow. Studies of cultured podocytes demonstrate that they respond to stretch by altering the structure of the actin cytoskeleton, but the mechanisms by which physical force triggers this architectural change and the signaling pathways that lead to generation of second messengers are not defined. In the present study, we found that in renal epithelial cells [podocytes and Madin-Darby canine kidney (MDCK) cells], application of mechanical force to the cell surface through fibronectin-coated ferric beads and exposure of the cells to magnetic force lead to Rho translocation and actin cytoskeleton reorganization. This application of force recruited Rho and filamentous actin (F-actin) to bead loci and subsequently stimulated phospholipase D (PLD), a downstream effector of Rho. Using MDCK cells that stably express regulators of G protein-signaling (RGS) proteins [RGS4 attenuates Gαiand Gαq, and the p115RhoGEF-RGS domain (p115-RGS) attenuates Gα12/13] to define the signaling pathway, we found that mechanical force induced Gα12/13-Rho activation and increased F-actin to stimulate PLD activity. The activation can be partially prevented by the C3exoenzyme. Pretreatment of the cells with chemical inhibitors of several kinases showed that calmodulin-dependent kinase is also involved in stretch-induced PLD activation by a separate pathway. Taken together, our data demonstrate that in cultured podocytes and MDCK cells, mechanical force leads to actin cytoskeleton reorganization and PLD activation. The signaling pathways for PLD activation involve Gα12/13/Rho/F-actin and calmodulin-dependent kinase.
Quantitative trait loci for human muscle strength: linkage analysis of myostatin pathway genes
Authors: Huygens W. , Thomis M. A. I. , Peeters M. W. , Aerssens J. , Vlietinck R. , Beunen G. P.
Published: May 2005

This study reports the results of a multipoint linkage study that aims to unravel the genetic basis of muscle strength and muscle mass in humans. Myostatin ( GDF8) is known to be a strong inhibitor of muscle growth in animals. However, studies examining human myostatin polymorphisms are rare and are limited to the GDF8 gene itself. Here, the contribution to isometric and concentric knee strength of nine key proteins involved in the myostatin pathway is studied in a nonparametric multipoint linkage analysis by means of a variance components and regression method. A sample of 367 healthy young male siblings was phenotyped on an isokinetic dynamometer and genotyped for markers of the myostatin pathway genes. Three of the loci were found significantly linked with a quantitative trait locus (QTL) for knee muscle strength. First, D13S1303 showed replication of an explorative single-point linkage study with a maximum LOD score of 2.7 ( P = 0.0002). Second, maximum LOD scores of 3.4 ( P = 0.00004) and 3.3 ( P = 0.00005) were observed for markers D12S1042 and D12S85, respectively, at 12q12–14. Finally, marker D12S78 showed an LOD score of 2.7 at 12q22–23. We conclude that several genes involved in the myostatin pathway, but not the myostatin gene itself, are important QTLs for human muscle strength. An additional set of valuable candidate genes that were not part of the myostatin pathway was found in the chromosome 12 and 13 genomic regions.
Gene expression profile and aortic vessel distensibility in voluntarily exercised spontaneously hypertensive rats: potential role of heat shock proteins
Authors: Hägg Ulrika , Johansson Maria E. , Grönros Julia , Naylor Andrew S. , Jonsdottir Ingibjörg H. , Bergström Göran , Svensson Per-Arne , Gan Li-ming
Published: May 2005

Physical exercise is considered to be beneficial for cardiovascular health. Nevertheless, the underlying specific molecular mechanisms still remain unexplored. In this study, we aimed to investigate the effects of voluntary exercise on vascular mechanical properties and gene regulation patterns in spontaneously hypertensive rats. By using ultrasound biomicroscopy in an ex vivo perfusion chamber, we studied the distensibility of the thoracic aorta. Furthermore, exercise-induced gene regulation was studied in aortae, using microarray analysis and validated with real-time PCR. We found that distensibility was significantly improved in aortas from exercising compared with control rats ( P < 0.0001). Exercising rats demonstrated a striking pattern of coordinated downregulation of genes belonging to the heat shock protein family. In conclusion, voluntary exercise leads to improved vessel wall distensibility and reduced gene expression of heat shock protein 60 and 70, which may indicate decreased oxidative stress in the aortic vascular wall.
Comprehensive analysis of the ascidian genome reveals novel insights into the molecular evolution of ion channel genes
Authors: Okamura Yasushi , Nishino Atsuo , Murata Yoshimichi , Nakajo Koichi , Iwasaki Hirohide , Ohtsuka Yukio , Tanaka-Kunishima Motoko , Takahashi Nobuyuki , Hara Yuji , Yoshida Takashi , Nishida Motohiro , Okado Haruo , Watari Hirofumi , Meinertzhagen Ian A. , Satoh Nori , Takahashi Kunitaro , Satou Yutaka , Okada Yasunobu , Mori Yasuo
Published: May 2005

Ion fluxes through membrane ion channels play crucial roles both in neuronal signaling and the homeostatic control of body electrolytes. Despite our knowledge about the respective ion channels, just how diversification of ion channel genes underlies adaptation of animals to the physical environment remains unknown. Here we systematically survey up to 160 putative ion channel genes in the genome of Ciona intestinalis and compare them with corresponding gene sets from the genomes of the nematode Chaenorhabditis elegans, the fruit fly Drosophila melanogaster, and the more closely related genomes of vertebrates. Ciona has a set of so-called “prototype” genes for ion channels regulating neuronal excitability, or for neurotransmitter receptors, suggesting that genes responsible for neuronal signaling in mammals appear to have diversified mainly via gene duplications of the more restricted members of ancestral genomes before the ascidian/vertebrate divergence. Most genes responsible for modulation of neuronal excitability and pain sensation are absent from the ascidian genome, suggesting that these genes arose after the divergence of urochordates. In contrast, the divergent genes encoding connexins, transient receptor potential-related channels and chloride channels, channels involved rather in homeostatic control, indicate gene duplication events unique to the ascidian lineage. Because several invertebrate-unique channel genes exist in Ciona genome, the crown group of extant vertebrates not only acquired novel channel genes via gene/genome duplications but also discarded some ancient genes that have persisted in invertebrates. Such genome-wide information of ion channel genes in basal chordates enables us to begin correlating the innovation and remodeling of genes with the adaptation of more recent chordates to their physical environment.
Local inverses of Borel homomorphisms and analytic P‐ideals
Authors: Solecki Sławomir
Published: May 2005

We present a theorem on the existence of local continuous
homomorphic inverses of surjective Borel homomorphisms with
countable kernels from Borel groups onto Polish groups. We also
associate in a canonical way subgroups of ℝ with
certain analytic P‐ideals of subsets of ℕ. These
groups, with appropriate topologies, provide examples of Polish,
nonlocally compact, totally disconnected groups for which global
continuous homomorphic inverses exist in the situation described
above. The method of producing these groups generalizes
constructions of Stevens and Hjorth and, just as those
constructions, yields examples of Polish groups which are totally
disconnected and yet are generated by each neighborhood of the
identity.
Porosity and models with discrete innovations
Authors: Zaslavski Alexander J.
Published: May 2005

In our previous work, we obtained sufficient conditions for the
existence of trajectories with unbounded consumption for a model
of economic dynamics with discrete innovations. In this paper, using the porosity notion, we show that for most models these
conditions hold.
Some typical properties of dimensions of sets and measures
Authors: Myjak Józef
Published: May 2005

This paper contains a review of recent results concerning typical
properties of dimensions of sets and dimensions of measures. In
particular, we are interested in the Hausdorff dimension, box
dimension, and packing dimension of sets and in the Hausdorff
dimension, box dimension, correlation dimension, concentration
dimension, and local dimension of measures.
Extending Stechkin′s theorem and beyond
Authors: Zamfirescu Tudor
Published: May 2005

We generalize Stechkin′s theorem about the single‐valuedness of
the nearest point mapping at most points to any complete length
space without bifurcating geodesics and make further observations.
σ‐porosity in monotonic analysis with applications to optimization
Authors: Rubinov A. M.
Published: May 2005

We introduce and study some metric spaces of increasing positively
homogeneous (IPH) functions, decreasing functions, and conormal
(upward) sets. We prove that the complements of the subset of
strictly increasing IPH functions, of the subset of strictly
decreasing functions, and of the subset of strictly conormal sets
are σ‐porous in corresponding spaces. Some applications to
optimization are given.
Some more recent results concerning weak Asplund spaces
Authors: Moors Warren B.
Published: May 2005

In this paper, we will present some of the latest advances that
have occurred in the study of weak Asplund spaces.
In particular, we will give an example of a Gâteaux
differentiability space that is not weak Asplund.
A porosity result in convex minimization
Authors: Howlett P. G. , Zaslavski A. J.
Published: May 2005

We study the minimization problem f(x) → min, x ∈ C,
where f belongs to a complete metric space ℳ of
convex functions and the set C is a countable intersection of a
decreasing sequence of closed convex sets Ci in a reflexive
Banach space. Let ℱ
be the set of all f ∈ ℳ
for which the solutions of the minimization problem
over the set Ci converge strongly as i → ∞ to the solution over the set C. In our recent work we show that
the set ℱ contains an everywhere dense Gδ subset of ℳ. In this paper, we show that the
complement ℳ\ℱ is not only of the
first Baire category but also a σ‐porous set.
Existence and uniqueness of solutions for a class ofinfinite‐horizon systems derived from optimal control
Authors: Wang Lianwen
Published: May 2005

This paper deals with the existence and uniqueness of
solutions for a class of infinite‐horizon systems derived from
optimal control. An existence and uniqueness theorem is proved
for such Hamiltonian systems under some natural assumptions.
A decomposition method for a semilinear boundary value problemwith a quadratic nonlinearity
Authors: Gordon Michael S.
Published: May 2005

The author adapts the decomposition method of Adomian to find a
series solution of a one‐dimensional boundary value problem for a
semilinear heat equation with a quadratic nonlinearity. Local and
global convergence results are obtained.
A survey of weighted substitution operators and generalizations of Banach‐stone theorem
Authors: Singh R. K.
Published: May 2005

The classical Banach‐Stone theorem characterizes linear
surjective isometries between C(K)‐spaces. The main aim of this paper is to present a survey of
Banach‐Stone‐theorem‐type results between some function
spaces. The weighted substitution operators play an important
role in characterization of isometries, disjointness
preserving operators, and lattice homomorphisms. Some open
problems are given for further investigation.
Generalized (ℱ, b, φ, ρ, θ)‐univex n‐set functions and global semiparametric sufficient efficiencyconditions in multiobjective fractional subset programming
Authors: Zalmai G. J.
Published: May 2005

A fairly large number of global semiparametric sufficient
efficiency results are established under various generalized
(ℱ, b, φ, ρ, θ)‐univexity assumptions for a
multiobjective fractional subset programming problem.
Another Case of Word-Final Disfluencies
Authors: van Borsel John , Geirnaert Elke , van Coster Rudy
Published: May 2005

It has commonly been thought that stuttering and related disfluencies do not occur at the end of words. However, word-final disfluencies have been documented in the literature and may be underreported at present. This study investigated word-final disfluencies as they occurred in a 12-year-old boy. Word-final disfluencies constituted the major type of disfluencies in this individual and most often involved repetition of a linguistic unit larger than a singleton consonant. They occurred more frequently on content words than on function words, more frequently on multisyllabic words than on monosyllabic words, and more frequently at the end of a phrase than in initial or medial position. A direct therapy approach, aimed first at identification and then at suppression of the final repetitions, resulted in complete elimination of these repetitions. The origin of these word-final disfluencies and their resemblance to palilalia are discussed.
Immediate Effects of ‘Voice Massage’ Treatment on the Speaking Voice of Healthy Subjects
Authors: Laukkanen Anne-Maria , Leppänen Kirsti , Tyrmi Jaana , Vilkman Erkki
Published: May 2005

‘Voice massage’ (VM) treatment includes manipulation of muscles related to speech production and voice and breathing exercises. This study investigated the effects of VM in 10 healthy subjects (5 females, 5 males). They recorded repetitions of the word ‘paappa’ at normal loudness and as softly as possible and read a text sample before and after 1-hour (1) VM treatment, (2) fast walking, (3) sitting in a library and (4) lying on a bed. Subglottic pressure was estimated from oral pressure during [p]. Transglottal flow and glottal resistance were measured. Voice production was studied with electroglottography. Fundamental frequency, sound pressure level (SPL) and alpha ratio [(SPL of the range 1–5 kHz) – (SPL of the range 50 Hz–1 kHz)] were calculated from text samples, which were also evaluated by 7 voice experts. A questionnaire was used to record subjects’ sensations. Changes after lying and sitting suggest lowered effort in phonatory muscles, while after fast walking effort seemed to increase. After VM no significant changes were observed in voice parameters or perceptual quality, but ease of phonation and reduced tension in the neck, shoulders and back were reported. The effects of VM may be partly psychological, partly related to a search of phonatory balance.
Differences of Hepatocellular Carcinoma Patients with Hepatitis B Virus Genotypes of Ba, Bj or C in Japan
Authors: Orito Etsuro , Sugauchi Fuminaka , Tanaka Yasuhito , Ichida Takafumi , Sata Michio , Tanaka Eiji , Okanoue Takeshi , Sakugawa Hiroshi , Watanabe Hisatsuyo , Miyakawa Hiroshi , Nishiguchi Shuhei , Kumada Hiromitsu , Ueda Ryuzo , Mizokami Masashi
Published: May 2005

Hepatitis B virus (HBV) genotypes B (HBV/B) and C (HBV/C) are prevalent in Asia. Recently HBV/B has been classified into two subtypes, HBV/Ba which is ubiquitously found in Asia, and HBV/Bj which is specific in Japan. In addition, the frequency of positive HBeAg has been reported to be higher in patients with HBV/Ba than those with HBV/Bj. However, little is known about the differences between patients with various genotypes who developed hepatocellular carcinoma (HCC). In 296 serum samples of HCC patients collected from all over Japan, HBV genotypes were determined with the restriction fragment length polymorphism. HBV/A was detected in 1.0%, HBV/Ba in 4.4%, HBV/Bj in 7.4%, and HBV/C in 86.5%. In the Tohoku district and Okinawa, HBV/Ba, HBV/Bj and HBV/C were found in 6.7, 40.0 and 48.9%, compared to 4.0, 1.6 and 93.2% in the other districts in Japan. HBV/Bj patients were more frequently found in the group older than 65 years while HBV/Ba patients were found in all age groups. The frequency of positive HBeAg in HBV/Bj patients was significantly low compared to that in the other patients. More than 60% of the patients with HCC had cirrhosis as the underlying liver diseases. However, in HBV/Ba patients aged 50 years or younger, 80% of them had chronic hepatitis, while 87.5% of those aged older than 50 years had cirrhosis. These data suggest that great differences exist among patients with HCC infected with different genotypes.
Primary Sclerosing Cholangitis and Hepatitis C Virus Infection
Authors: Kim Soo Ryang , Imoto Susumu , Taniguchi Miyuki , Kim Ke Ih , Sasase Noriko , Matsuoka Toshiyuki , Maekawa Yoko , Ninomiya Toshiaki , Ando Kenji , Mita Keiji , Fuki Shuichi , Koterazawa Toshihiro , Fukuda Katsumi , Kudo Masatoshi , Sakamoto Hiroki , Hayashi Yoshitake
Published: May 2005

Two cases of primary sclerosing cholangitis with hepatic C virus infection in a 62-year-old man and a 60-year-old woman are presented. The infection in the man was eradicated with interferon therapy in 1992. Seven years thereafter, endoscopic retrograde cholangiography revealed a diffuse 2.5-cm-long stenotic lesion in the common bile duct which was consequently resected. Histological examination of the resected specimen revealed proliferation of epithelial cells, plasma cell infiltration, and fibrosis in the submucosal layer of the common bile duct. The human leukocyte antigen DR loci were 2 and 9. In the woman, a 6-month course of interferon therapy in 1992 failed to eradicate the infection. Cholangiography in 1999 revealed multiple narrowings and dilatations of intra- and extrahepatic bile ducts. Ultrasound guided biopsy of the liver in 1992 had revealed onionskin lesions around the bile duct epithelium in the portal tract. The human leukocyte antigen DR locus was 2. From these findings, the 2 cases were diagnosed as primary sclerosing cholangitis. Further studies may provide insights into the relation between the pathogenesis of the disease and the infection.
The Pathophysiology of Portal Hypertension
Authors: Treiber Gerhard , Csepregi Antal , Malfertheiner Peter
Published: May 2005

Portal hypertension is defined by an elevation in blood pressure in the portal system. Different causes are known and include a pre-, intra-, or posthepatic block. Portal hypertension is also classified according to the sinusoidal system. Portal pressure becomes elevated by either an increase in blood flow (Q), an increase in resistance (R), or both. Regulation of the vascular tone in the splanchnic system includes intrinsic and extrinsic aspects. A variety of metabolic end-products (e.g. adenosine), endothelium-derived substances (e.g. nitric oxide), and certain neurotransmitters (e.g. acetylcholine) are known to relax the tone and thus produce vasodilation. Important vasoconstrictor influences on splanchnic arterioles include circulating agents (e.g. angiotensin), endothelium-derived substances (e.g. endothelin), and again neurotransmitters (norepinephrine). Besides vascular tone, structural changes (thrombosis, fibrosis, shear stress, and cell regeneration) add to overall hepatic resistance. Further consequences of portal hypertension include an increase in blood flow which leads to a hyperdynamic state with fluid retention, leading to secondary involvement of other organs, such as cirrhotic cardiomyopathy, hepatopulmonary syndrome and hepatorenal syndrome. Finally, portal hypertension will end up in the formation of collateral vessels. Varices can involve the whole gastrointestinal tract and are a frequent source of bleeding.
The Role of Endoscopy in Portal Hypertension
Authors: Biecker Erwin , Schepke Michael , Sauerbruch Tilman
Published: May 2005

Endoscopy plays a major role in the management of gastrointestinal varices in portal hypertension. It is used for the prophylaxis of the first bleeding episode, therapy of active bleeding and prophylaxis of recurrent bleeding. Today not only nonselective betablockers, but also endoscopic band ligation is an option in the primary prophylaxis of the first bleeding episode in patients with large esophageal varices. Acutely bleeding varices should be treated by ligation, pharmacological and antibiotic therapy. Prophylaxis of recurrent bleeding despite endoscopic and pharmacologic treatment is patient dependent: shunt surgery is an option in young patients in a good medical condition (Child-Pugh class A). In patients with refractory ascites and a bilirubin level below 3 mg/dl, TIPS is a good option. Nevertheless, the first-line treatment in most patients in Germany is endoscopic band ligation. Bleeding from ectopic varices and due to hypertensive gastropathy should be treated individually either by endoscopy, TIPS or drug therapy.
Variceal Bleeding: Pharmacological Therapy
Authors: Bosch Jaime , Abraldes Juan G.
Published: May 2005

The complications of portal hypertension are totally prevented if hepatic venous pressure gradient is decreased below 12 mm Hg. Besides, if this target is not achieved, a 20% decrease in portal pressure from baseline levels offers an almost total protection from variceal bleeding. This sets the rationale for drug therapy to reduce portal pressure in portal hypertension. Pharmacological therapy to decrease portal pressure includes vasoconstrictors to decrease portal blood inflow, vasodilators to decrease hepatic resistance, and combination therapy. Oral agents, such as b-adrenergic blockers and organic nitrates, are used for long-term prevention of variceal bleeding, while parenteral agents, such as somatostatin (and analogues) and terlipressin, are used for the treatment of acute variceal bleeding.