bluuebunny/crossref_metadata_2025 huggingface dataset:
IscR‐dependent gene expression links iron‐sulphur cluster assembly to the control of O2‐regulated genes in Escherichia coli
Authors: Giel Jennifer L. , Rodionov Dmitry , Liu Mingzhu , Blattner Frederick R. , Kiley Patricia J.
Published: April 2006

IscR is an iron‐sulphur (Fe‐S) cluster‐containing transcription factor that represses transcription of the operon containing its own gene and the iscSUA‐hscBA‐fdx genes, whose products are involved in Fe‐S cluster biogenesis. In this study, global transcriptional profiling of Escherichia coli IscR+ and IscR– strains grown under aerobic and anaerobic conditions indicated that 40 genes in 20 predicted operons were regulated by IscR. DNase I footprinting and/or in vitro transcription reactions identified seven new promoters under direct IscR control. Among these were genes encoding known or proposed functions in Fe‐S cluster biogenesis (sufABCDSE, yadR and yhgI) and Fe‐S cluster‐containing anaerobic respiratory enzymes (hyaABCDEF, hybOABCDEFG and napFDAGHBC). The finding that IscR repressed expression of the hyaA, hybO and napF promoters specifically under aerobic growth conditions suggests a new mechanism to explain their upregulation under anaerobic growth conditions. Phylogenetic footprinting of the DNase I protected regions of seven promoters implies that there are at least two different classes of IscR binding sites conserved among many bacteria. The findings presented here indicate a more general role of IscR in the regulation of Fe‐S cluster biogenesis and that IscR contributes to the O2 regulation of several promoters controlling the expression of anaerobic Fe‐S proteins.
Transcriptional regulation of the agr locus and the identification of DNA binding residues of the global regulatory protein SarR in Staphylococcus aureus
Authors: Manna Adhar C. , Cheung Ambrose L.
Published: April 2006

Many members of the transcriptional regulator SarA protein family are winged‐helix proteins that are involved in gene regulation essential to Staphylococcus aureus pathogenesis. Investigation of the mechanism by which this family of genes acts at the molecular level will likely contribute to the understanding of the pathogenesis process and enhance the potential for the development of inhibitors capable of controlling S. aureus infections. Our previously published studies demonstrate that SarR is a repressor of sarA expression. Here, we show that SarR (a member of the SarA protein family) in part regulates agr expression by direct binding to the agr intergenic promoter region as determined by gel shift and DNase I footprinting assays. Analysis of the double sarA/sarR mutant in the early phase of growth reveals its significant role in regulating agr expression as compared with single mutants. Based on the previously reported crystal structure of SarR, we conducted site‐specific mutagenesis and demonstrate that K52 residues within helix–turn–helix (HTH), K80, R82 and R88 (in the wing) and L105 (in the α5 helix) are important for DNA binding. Interestingly, SarR and SarA binding sites on the agr promoter are confined within the same region of DNA. Additional gel shift studies with SarR and SarA suggest that these two proteins may bind the same region of the agr promoter.
Biomagnetic characterization of spatiotemporal parameters of the gastric slow wave
Authors: Bradshaw L. A. , Irimia A. , Sims J. A. , Gallucci M. R. , Palmer R. L. , Richards W. O.
Published: April 2006

Abstract  Certain gastric disorders affect spatiotemporal parameters of the gastric slow wave. Whereas the electrogastrogram (EGG) evaluates electric potentials to determine primarily temporal parameters, fundamental physical limitations imposed by the volume conduction properties of the abdomen suggest the evaluation of gastric magnetic fields. We used a multichannel superconducting quantum interference device magnetometer to study the magnetogastrogram (MGG) in 20 normal human subjects before and after a test meal. We computed the frequency and amplitude parameters of the gastric slow wave from MGG. We identified normal gastric slow wave activity with a frequency of 2.6 ± 0.5 cycles per minute (cpm) preprandial and 2.8 ± 0.3 cpm postprandial. In addition to frequency and amplitude, the use of surface current density mapping applied to the multichannel MGG allowed us to visualize the propagating slow wave and compute its propagation velocity (6.6 ± 1.0 mm s−1 preprandial and 7.4 ± 0.4 mm s−1 postprandial). Whereas MGG and EGG signals exhibited strong correlation, there was very little correlation between the MGG and manometry. The MGG not only records frequency dynamics of the gastric slow wave, but also characterizes gastric propagation. The MGG primarily reflects the underlying gastric electrical activity, but not its mechanical activity.
Iron contributes to dopamine‐induced toxicity in oligodendrocyte progenitors
Authors: Hemdan S. , Almazan G.
Published: April 2006

Iron is potentially toxic to oligodendrocyte progenitors due to its high intracellular levels and its ability to catalyse oxidant‐producing reactions. Oxidative stress resulting from a hypoxic–ischaemic insult has been implicated in death of oligodendrocyte progenitors that occurs in the hypomyelinating disorder periventricular leucomalacia. Ischaemic insults induce the release of various neurotransmitters, including dopamine (DA), and we previously showed that DA is toxic to cultured oligodendrocytes, by inducing oxidative stress and apoptosis. Therefore, we investigated the role of iron in DA‐induced cell death in oligodendrocyte progenitors. Intracellular iron levels were altered using an iron chelator, deferoxamine (DFO), and supplementation with ferrous sulphate (FeSO4). Addition of FeSO4 to cultures increased DA‐induced toxicity as assessed by mitochondrial dehydrogenase activity and cellular release of lactate dehydrogenase. Furthermore, FeSO4 increased expression of the stress protein heme oxygenase‐1 (HO‐1), nuclear condensation and caspase‐3 activation. In contrast, preincubation with DFO reduced these events as well as cleavage of α‐spectrin, a caspase‐3 substrate. In addition, FeSO4 reversed the protective effect of DFO on DA‐induced cytotoxicity, HO‐1 expression and caspase‐3 activation. These results indicate that elevated levels of free iron contribute to DA‐induced toxicity in oligodendrocyte progenitors.
High expression in leaves of the zinc hyperaccumulator Arabidopsis halleri of AhMHX, a homolog of an Arabidopsis thaliana vacuolar metal/proton exchanger
Authors: ELBAZ BENAYAHU , SHOSHANI‐KNAANI NOA , DAVID‐ASSAEL ORA , MIZRACHY‐DAGRI TALYA , MIZRAHI KEREN , SAUL HELEN , BROOK EMIL , BEREZIN IRINA , SHAUL ORIT
Published: April 2006

Zn hyperaccumulator plants sequester Zn into their shoot vacuoles. To date, the only transporters implicated in Zn sequestration into the vacuoles of hyperaccumulator plants are cation diffusion facilitators (CDFs). We investigated the expression in Arabidopsis halleri of a homolog of AtMHX, an A. thaliana tonoplast transporter that exchanges protons with Mg, Zn and Fe ions. A. halleri has a single copy of a homologous gene, encoding a protein that shares 98% sequence identity with AtMHX. Western blot analysis with vacuolar‐enriched membrane fractions suggests localization of AhMHX in the tonoplast. The levels of MHX proteins are much higher in leaves of A. halleri than in leaves of the non‐accumulator plant A. thaliana. At the same time, the levels of MHX transcripts are similar in leaves of the two species. This suggests that the difference in MHX levels is regulated at the post‐transcriptional level. In vitro translation studies indicated that the difference between AhMHX and AtMHX expression is not likely to result from the variations in the sequence of their 5′ untranslated regions (5′UTRs). The high expression of AhMHX in A. halleri leaves is constitutive and not significantly affected by the metal status of the plants. In both species, MHX transcript levels are higher in leaves than in roots, but the difference is higher in A. halleri. Metal sequestration into root vacuoles was suggested to inhibit hyperaccumulation in the shoot. Our data implicate AhMHX as a candidate gene in metal accumulation or tolerance in A. halleri.
Molecular characterization of Erwinia amylovora strains from different host plants through RFLP analysis and sequencing of hrpN and dspA/E genes
Authors: Giorgi S. , Scortichini M.
Published: April 2006

A total of 73 Erwinia amylovora strains obtained from 13 Maloideae host species and from Rubus spp., and isolated from different geographic areas, were assessed using RFLP and DNA sequencing analysis of the 3′hrpN gene and/or of a fragment of 1341 bp of the dspA/E region. An Erwinia pyrifoliae strain, used as outgroup, was checked in the same way. For the three strains isolated from Rubus spp. and for one strain from Amelanchier sp., RFLP analysis of the hrpN gene using the RsaI enzyme yielded a PCR product 60 bp smaller than that of all the other strains. Sequence analysis of the gene revealed this was due to the absence of a 60 bp fragment in the noncoding region downstream of the gene. The strain PD 2915, isolated from Amelanchier sp. grown in Canada, showed five same‐sense substitutions and one missense substitution at position 868 of the hrpN gene, converting aspartic acid into asparagine. Also, restriction analysis of a fragment of 613 bp of the dspA/E region with CfoI revealed an RFLP pattern suitable for differentiating the E. amylovora strains isolated from Rubus spp. and Amelanchier sp. from all the others. In the dspA/E coding region, the four strains showed 13–14 missense point mutations, in some cases yielding drastic amino acid substitutions. In addition, partial sequencing of the dspA/E region of PD 2915 from Amelanchier sp. indicated a higher similarity to E. amylovora strains isolated from Rubus spp. than towards strains from other Maloideae hosts. The E. pyrifoliae strain showed 23 single nucleotide substitutions along the hrpN gene and 88% of nucleotide identity with E. amylovora strains in the portion of dspA/E region. Artificial inoculations on immature pear fruits and young shoots of Maloideae and Ruboideae showed a restricted pathogenicity for the strains from Rubus and Amelanchier, with the latter inciting blight symptoms only on Amelanchier.
Genetic diversity of Claviceps africana on sorghum and Hyparrhenia
Authors: Pažoutová S. , Frederickson D. E.
Published: April 2006

RAPD markers were used to survey genetic variability among 140 isolates of Claviceps africana collected from Southern Africa, India, Thailand, Australia and the Americas in 1992–2002. Amplified fragment length polymorphisms were determined for a subset of the isolates. Both markers gave similar results in phenetic analysis of genetic distances between haplotypes of different geographical origin. In the Americas, a single RAPD haplotype was found throughout the various countries. The Eastern lineage consisted of two close haplotypes (one from India, the other from Thailand and Australia). Among five specialized isolates of C. africana from the alternative hosts (Hyparrhenia spp.), three haplotypes were found. Eleven private alleles distinguished the Hyparrhenia population from that on sorghum. rDNA sequences of sorghum and Hyparrhenia isolates differed in three positions. The African sorghum population of C. africana consisted of 10, mostly closely related haplotypes. Low genotypic diversity (HE = 0·0337) and the fact that most of the variation originated from between populations (GST = 0·866) suggested founder effects following recent invasion. In Southern Africa, no significant differentiation was found among six populations. Therefore the data were pooled and tested for prevalence of clonal or sexual reproduction. The presence of the over‐represented, widespread RAPD haplotype A; gametic disequilibrium (37% loci detected by exact tests); index of association (IA) significantly >0; and the high proportion of compatible loci (in the clone‐corrected and total data sets found to be 94 and 99%, respectively) support the hypothesis of clonality as the predominant means of reproduction.
A transglucosidase necessary for starch degradation and maltose metabolism in leaves at night acts on cytosolic heteroglycans (SHG)
Authors: Fettke Joerg , Chia Tansy , Eckermann Nora , Smith Alison , Steup Martin
Published: April 2006

The recently characterized cytosolic transglucosidase DPE2 (EC 2.4.1.25) is essential for the cytosolic metabolism of maltose, an intermediate on the pathway by which starch is converted to sucrose at night. In in vitro assays, the enzyme utilizes glycogen as a glucosyl acceptor but the in vivo acceptor molecules remained unknown. In this communication we present evidence that DPE2 acts on the recently identified cytosolic water‐soluble heteroglycans (SHG) as does the cytosolic phosphorylase (EC 2.4.1.1) isoform. By using in vitro two‐step 14C labeling assays we demonstrate that the two transferases can utilize the same acceptor sites of the SHG. Cytosolic heteroglycans from a DPE2‐deficient Arabidopsis mutant were characterized. Compared with the wild type the glucose content of the heteroglycans was increased. Most of the additional glucosyl residues were found in the outer chains of SHG that are released by an endo‐α‐arabinanase (EC 3.2.1.99). Additional starch‐related mutants were characterized for further analysis of the increased glucosyl content. Based on these data, the cytosolic metabolism of starch‐derived carbohydrates is discussed.
Steady State Analysis and Experimental Validation of a Model for Hepatic High‐Density Lipoprotein Transport
Authors: Wüstner Daniel
Published: April 2006

Transport of high‐density lipoprotein (HDL) in the hepatocyte plays a fundamental role in reverse cholesterol transport and regulation of plasma HDL levels. On the basis of a recently developed kinetic model, the steady state distribution of HDL was analyzed. Fractional fluorescence of labeled HDL in the basolateral membrane, sorting endosomes (SE), the subapical compartment/ apical recycling compartment, the biliary canaliculus and in late endosomes and lysosomes (LE/LYS) including expected standard deviation is predicted. Improved parameter estimation was obtained by including kinetic data of apical endocytosis of fluorescent markers for LE/LYS, asialoorosomucoid and Rhodamine‐dextran, in the regression. Predicted values using the refined kinetic parameters are in good agreement with experimental values of compartmental steady state fluorescence of Alexa488‐HDL in polarized hepatic HepG2 cells. From calculated steady state fluxes, it is suggested that export of HDL from basolateral SE is the key step for determining the transport of HDL through the hepatocyte. The analysis provides testable predictions for high‐throughput fluorescence microscopy screening experiments on potential inhibitors of hepatic HDL processing. By quantitative fluorescence imaging and model analysis, it is shown that the phosphoinositide kinase inhibitor wortmannin prevents apical transport of fluorescent HDL from basolateral SE. The results support that endosomes of polarized hepatic cells have different sorting functions and that apical endocytosis is an integrative trafficking step in hepatocytes.
Differentiating enterocutaneous fistulae from suture abscesses complicating Crohn’s disease using oral administration of indocyanine green
Authors: Sou Suketo , Matsui Toshiyuki , Yao Tsuneyoshi , Naito Miki , Yorioka Makoto , Beppu Takahiro , Nagahama Takashi , Futami Kitaro
Published: April 2006

Background and Aim:  Clinicians encounter difficulties distinguishing enterocutaneous fistulae from postoperative suture abscesses solely by diagnostic imaging in patients with Crohn’s disease. The aim of this study was to examine whether use of intraintestinal administration of indocyanine green (ICG) could differentiate the conditions.

Methods:  Twenty‐four patients with Crohn’s disease and a possible enterocutaneous fistula at the abdominal wall based on manifestations of pus drainage and exudate were enrolled. A positive test was defined by macroscopic confirmation of staining by ICG dye, which had been administered orally, on the gauze dressing applied to the lesion site.

Results:  Positive responses occurred in 16 of the 24 patients. In 13 of the 16 positive patients, a fistulous communication between the lesion and the gastrointestinal tract was documented by either surgery or X‐ray examination. In the remaining three, fistulae were completely closed after administration of infliximab. The positive predictive value of the oral ICG test was 16/16 (100%). Six of the eight negative oral ICG test patients (75%) had subcutaneous (silk‐suture) abscesses that were easily closed following fistulotomy. The other two patients had fistulas confirmed either by surgery or fistulography, indicating a false negative response from the oral ICG test. The negative predictive value of the oral ICG test was 6/8 (75%); thus, the ability of the oral ICG test to correctly diagnose was 22/24 (92%).

Conclusions:  This oral ICG test offers a suitable methodology for those patients possessing an occult fistulous lesion at an early stage, and where a differential diagnosis is difficult using diagnostic imaging.
Intrafamilial prevalence of hepatitis B virus in Western Brazilian Amazon region: Epidemiologic and biomolecular study
Authors: Lobato Cirley , Tavares‐Neto José , Rios‐Leite Márcio , Trepo Christian , Vitvitski Ludmila , Parvaz Parviz , Zoulim Fabien , D’Oliveira Argemiro , Paraná Raymundo
Published: April 2006

Background:  Hepatitis B is endemic in the Amazon region.

Methods:  Serological markers for hepatitis B virus (HBV) were determined in 266 household members for hepatitis B surface antigen (HBsAg)‐positive women (G1) and 395 household members for HBsAg‐negative women (G2), randomly selected in Acre State Women’s Medical Care Program, in order to evaluate the prevalence of HBV in this population. Before blood sample collection an epidemiological questionnaire was applied.

Results:  The overall prevalence of HBV carriers (HBsAg) and exposed individuals (anti‐HBc, IgG) was, respectively, 21.1% and 60.5% in G1 and 2.8% and 27.4% in G2 (P < 0.0000001). The frequency of HBsAg was higher among siblings from group G1 (75%) compared to the absence of any HBsAg‐positive sibling in G2 (P < 0.00006). The HBV markers in other family members was as follows: G1 parents, 27.3% vs 4.5% (P < 0.03), sexual partners, 21.1% vs 2.5% (P < 0.04), and offspring, 10.4% vs 1.5% (P < 0.04). A low prevalence of HBsAg and anti‐HBc (IgG) was observed for the last offspring of G2 mothers compared to the high prevalence among children of G1 mothers (0% vs 18.2%, P < 0.01 and 2.3% vs 59.1%, P < 0.0000005, respectively), with children younger than 1 year being the most affected. The frequency of the habit of sharing toothbrushes and the presence of at least one HBsAg carrier were higher in G1 than in G2 (P < 0.0001 and P < 0.000002), respectively. Genotypes A, D and G were found to be predominant by Innolipa test. There were cases that reacted to more than one genotype.

Conclusion:  Intrafamilial transmission of HBV is evident in the present study and is possibly associated with the presence of more than one HBV carrier in the family and the shared use of toothbrushes among household contacts. Genotype analysis confirms intrafamilial transmission.
Detrimental effects of nitric oxide inhibition on hepatic encephalopathy in rats with thioacetamide‐induced fulminant hepatic failure: Role of nitric oxide synthase isoforms
Authors: Chu Chi‐Jen , Chang Ching‐Chih , Wang Teh‐Fang , Lee Fa‐Yauh , Chang Full‐Young , Chen Yi‐Chou , Chan Che‐Chang , Huang Hui‐Chun , Wang Sun‐Sang , Lee Shou‐Dong
Published: April 2006

Background:  Hepatic encephalopathy is a complex neuropsychiatric syndrome. A previous study showed that chronic nitric oxide (NO) inhibition aggravated the severity of encephalopathy in thioacetamide (TAA)‐treated rats. The present study investigated the relative contribution of NO synthase (NOS) isoforms on the severity of hepatic encephalopathy in TAA‐treated rats.

Method:  Fulminant hepatic failure was induced in male Sprague‐Dawley rats by intraperitoneal injection of TAA (350 mg/kg/day) for 3 days. Rats were divided into three groups to receive Nω‐nitro‐L‐arginine methyl ester (L‐NAME, a non‐selective NOS inhibitor, 25 mg/kg/day in tap water), L‐canavanine (an inducible NOS inhibitor, 100 mg/kg/day via intraperitoneal injection) or normal saline (N/S) from 2 days prior to TAA administration and lasting for 5 days. Severity of encephalopathy was assessed by the counts of motor activity. Plasma levels of tumor necrosis factor‐α (TNF‐ α) were determined by enzyme‐linked immunosorbent assay (ELISA), and total bilirubin, alanine aminotransferase (ALT) and creatinine were determined by colorimetric assay.

Results:  Compared with L‐canavanine or N/S‐treated rats (0% and 4%, respectively), the mortality rate was significantly higher in rats receiving L‐NAME administration (29%, P < 0.005). Inhibition of NO created detrimental effects on the counts of motor activities (P < 0.05). Rats treated with L‐NAME had significantly higher plasma levels of total bilirubin, ALT, creatinine and TNF‐ α as compared with rats treated with L‐canavanine or N/S (P < 0.01).

Conclusion:  Chronic L‐NAME administration, but not L‐canavanine, had detrimental effects on the severity of hepatic damage and motor activities in TAA‐treated rats. These results suggest that constitutive NOS activities play a major protective role in rats with fulminant hepatic failure.
Necrolytic acral erythema in Egyptian patients with hepatitis C virus infection
Authors: El‐Ghandour Tarek M , Sakr Mohammad A , El‐Sebai Hatem , El‐Gammal Tarek F , El‐Sayed Manal H
Published: April 2006

Background:  Necrolytic acral erythema (NAE) is a distinctive skin lesion that was first described in 1996 with only few cases being reported, mostly from Egypt. It is unique in its acral distribution and exclusive association with hepatitis C virus (HCV) infection.

Methods:  Twenty‐three patients (mean age 41.7 ± 11.5 years; M : F 10:13) with clinical features consistent with NAE were enrolled in a 3‐year period. Five of those were known HCV‐infected individuals and 18 were referred by the dermatologist for evaluation and HCV screening. Liver function tests, serum zinc, hepatitis B markers, HCV antibodies and HCV‐RNA were tested. All patients were subjected to skin biopsy examination; five lesional biopsies were selected for electron microscopic examination and capillary endothelium was scanned for hepatitis C viral particles. An additional five patients were subjected to detection of HCV‐RNA in their skin biopsies by polymerase chain reaction. All patients received oral zinc sulfate supplementation while interferon‐α therapy combined with ribavirin was available for four patients.

Results:  Most NAE patients were adults (91.3%) and the skin lesions were predominantly chronic (78.3%), with affection of the dorsa of toes and/or feet in all cases. Skin biopsies showed hyperkeratosis, psoriasiform epidermis and upper epidermal necrosis. Electron microscope examination demonstrated clumped tonofilaments in the keratinocytes, yet HCV‐RNA could not be detected in the skin lesions of examined cases. Interferon‐α combined with ribavirin caused regression of skin lesions in three patients and complete clearance in one patient. Some improvement was induced by oral zinc administration.

Conclusion:  Necrolytic acral erythema is considered to be a cutaneous marker for HCV infection. The majority of patients are diagnosed by dermatologists. Therefore, improved awareness of this cutaneous lesion should prompt early diagnosis and treatment of HCV, which should in turn cure the lesion and prevent progression of liver disease.
Clinical implications of C‐kit gene mutation in patients with large gastrointestinal stromal tumors
Authors: Lin Shee‐Chan , Liu Chien‐Liang , Wang Tzang‐In , Chang Wen‐Shiung , Tzen Chin‐Yuan , Huang Ming‐Jer
Published: April 2006

Background and Aim:  To evaluate the clinical implications of C‐kit gene mutation in patients with gastrointestinal stromal tumors (GIST) greater than 10 cm in size.

Methods:  All cases of pathologically diagnosed GIST with positive CD117 immunostaining from one hospital were retrospectively reviewed. Tissue from the 25 patients with tumors greater than 10 cm in diameter were collected and DNA was extracted. Exons 9, 11, and 13 of the C‐kit gene were analyzed and the mutations compared with the clinical and pathological characteristics of the corresponding tumors.

Results:  Of the 25 tumors studied, 16 had C‐kit gene mutations and nine did not. Of the 16 with mutations, there were four with exon 9 mutations, 12 with exon 11 mutations, and none with exon 13 mutations. Gene mutations were more frequent in male than female patients (12/13, 92%vs 4/12, 33%). There were no significant differences in age, resectability, recurrence rate, tumor characteristics (ulceration, necrosis, hemorrhage and mitotic counts), or survival in patients with or without gene mutations.

Conclusions:  C‐kit gene mutations were frequently found in patients with large GIST, more commonly in men than in women. However, the presence of a mutation was not predictive of prognosis in patients with large GIST.
Relationship between biomarker expression and allelic alteration in esophageal carcinoma
Authors: Vegh Irene , De‐La‐Calle Santiuste Angel , Colina Francisco , Bor Lázsló , Bermejo Clara , Aragón Ana , Morán‐Jiménez María‐José , Gómez‐Cámara Agustín , De Salamanca Rafael Enríquez , Moreno‐González Enrique
Published: April 2006

Background and Aim:  Expression of biomarkers and probable allelic alterations were studied in esophagus tissue samples from patients with esophageal carcinoma.

Methods:  A total of 116 esophagus tissue samples were obtained from 25 patients with esophagus cancer. Histological studies revealed 23 samples were adenocarcinoma and 14 samples were epidermoid carcinoma while 79 samples were non‐tumor. Expression of biomarkers was determined by enzyme immunoassay, and allelic alterations on chromosome 17p were performed by polymerase chain reaction (PCR) using primers D17S513 and D17S514.

Results:  The adenocarcinoma group exhibited an increase of matrix metalloproteinase (MMP)‐1 (P < 0.0001) and sialyl Le (a) (P < 0.001) mean levels when compared with the non‐tumor group. Adenocarcinoma samples from patients with more than three positive lymph nodes had lower levels of tissue‐inhibitor metalloproteinase (TIMP)‐1 than those with negative nodes (P < 0.0005). Positive allelic alteration was associated with high levels of MMP‐1 expression (P = 0.003). Epidermoid carcinoma samples showed higher expression of MMP‐1 (P < 0.0001) and TIMP‐1 (P < 0.02) than non‐tumor samples. Both epidermal growth factor receptor and sialyl Le (a) levels were overexpressed in tumors of patients with more than three positive lymph nodes (P < 0.005). Carcinoembryonic antigen levels were higher in tumors associated with allelic wild type group (P = 0.0001) and patients with negative lymph nodes (P < 0.05). Furthermore, variability in expression of biomarkers was observed according to sample location, and allelic alterations were also found both in tumor and in some non‐tumor samples.

Conclusion:  The data suggest that overexpression of tissue biomarkers associated with allelic alterations may have potential prognostic implications with different behavior in esophagus cancer.
Association between interleukin‐1 gene polymorphisms and Helicobacter pylori infection in gastric carcinogenesis in a Chinese population
Authors: Li Chun , Xia Harry Hua‐Xiang , Xie Wei , Hu Zhengguo , Ye Mei , Li Jin , Cheng Hong , Zhang Xiaolian , Xia Bing
Published: April 2006

Background and Aim:  Helicobacter pylori is a major cause of chronic gastritis and peptic ulcer disease and a definite carcinogen for gastric adenocarcinoma. However, the underlying pathogenic mechanisms are not fully understood. Interleukin‐1 (IL‐1) is a key cytokine involved in H. pylori‐induced gastric inflammation. The present study aimed to determine polymorphisms of IL‐1B and IL‐1 receptor antagonist (IL‐1RN) genes and their association with H. pylori infection and gastroduodenal diseases in Chinese patients.

Methods:  Three hundred and ninety‐nine patients with gastroduodenal diseases (129 chronic gastritis, 127 duodenal ulcer and 143 non‐cardiac gastric cancer) and 264 healthy controls were genotyped for IL‐1B‐511 and IL‐1RN gene polymorphisms by the PCR‐RFLP method. H. pylori infection status was determined by a validated serological test.

Results:  The frequency of IL‐1B‐511 T allele was significantly higher in H. pylori positive patients with non‐cardiac gastric cancer than in both H. pylori negative patients with non‐cardiac gastric cancer (60%vs 46%, P = 0.0342, OR = 1.666, 95% confidence interval [CI]: 1.045–2.656) and in healthy controls (60%vs 48%, P = 0.0071, OR = 1.665, 95%CI: 1.149–2.412). However, the polymorphism was not associated with chronic gastritis and duodenal ulcer. Multivariate logistic regression analyses identified that IL‐1B‐511 T/T carrier status was an independent risk factor for non‐cardiac gastric cancer in the presence of H. pylori infection (adjusted OR = 3.01, 95%CI: 1.27–7.11, P = 0.01), and the frequency of IL‐1B‐511 T allele was an increased risk factor for developing gastric cancer (P = 0.03, adjusted OR = 2.29, 95%CI: 1.08–4.86). There was no association between IL‐1RN gene polymorphisms and H. pylori infection and other gastroduodenal diseases.

Conclusion:  IL‐1B‐511 T allele is associated with H. pylori infection in non‐cardiac gastric cancer in a Chinese population. The IL‐1B‐511 gene polymorphism appears to play an important role in gastric carcinogenesis in Chinese patients with H. pylori infection.
ErbB receptor signalling regulates dendrite formation in mouse cerebellar granule cells in vivo
Authors: Rieff Heather I. , Corfas Gabriel
Published: April 2006

The formation of morphologically and functionally mature dendrites is a key event in neuronal maturation and the establishment of functional neuronal networks, but the signals that regulate mammalian dendritic development remain poorly understood. Here we show that the erbB receptor signalling pathway, which modulates expression of several neurotransmitter receptors, also regulates dendritic development of cerebellar granule cells in the intact cerebellum. These results suggest that neuregulin–erbB signalling may control a program of postsynaptic development, from initiating dendrite morphogenesis to the formation and maturation of the postsynaptic apparatus.
Divergent thinking training is related to frontal electroencephalogram alpha synchronization
Authors: Fink Andreas , Grabner Roland H. , Benedek Mathias , Neubauer Aljoscha C.
Published: April 2006

Cortical activity in the human electroencephalogram alpha band was measured (by means of an event‐related approach) in a pre‐ and a post‐test (with intermediate training) while participants (n = 30) were confronted with divergent thinking tasks. Half of the participants received a divergent thinking training (over a time period of 2 weeks) which was composed of exercises structurally similar to those used in the pre‐ and post‐test. Analyses revealed that the training group displayed higher task‐related synchronization of frontal alpha activity (i.e. increases in alpha power from the pre‐stimulus reference to the activation interval) than the control group. These findings are in line with the view of frontal alpha synchronization as a selective top–down inhibition process that prevents internal or top–down information processing being disturbed by incoming external input.
Diagnosis and management of hypertension in obesity
Authors: Narkiewicz K.
Published: April 2006

Cardiovascular risk in a patient with obesity hypertension increases with the extent of risk factor clustering. It is therefore important to determine the global risk of a patient with hypertension rather than to focus solely on blood pressure. Every hypertensive should be screened for other than blood pressure risk factors, target organ damage and concomitant diseases or accompanying clinical conditions. Assessment of blood pressure and target organ damage might be more difficult in obese hypertensives than in normal‐weight patients. Intensive lifestyle interventions can reduce weight, and decrease blood pressure and cardiovascular risk in obese hypertensive patients. Current guidelines do not provide specific recommendation for pharmacological management of the hypertensive patients with obesity. Recent trials have consistently shown that therapy involving beta‐blockers and diuretics may induce more new‐onset diabetes compared with other combination therapies. Several lines of evidence suggest that anti‐hypertensive agents that block the renin‐angiotensin system may be especially beneficial in treating obese hypertensive patients. Hypertension management in obese individuals is complicated by poorer response to treatment, and the increased need for multiple medications. It is important to consider obstructive sleep apnoea in the differential diagnosis of hypertensive patients who respond poorly to combination therapy with anti‐hypertensive medications.
World Bank Independence: A Model and Statistical Analysis of US Influence
Authors: Fleck Robert K. , Kilby Christopher
Published: April 2006

This paper develops a model to test whether World Bank lending caters to US interests. We use country‐level panel data to examine the geographic distribution of World Bank lending to 110 countries from 1968 to 2002. After controlling for country characteristics expected to influence the distribution of lending in a manner consistent with the World Bank's charter and stated allocation mechanisms, we introduce variables reflecting US interests. The empirical results are consistent with a significant US influence, but one which varies across presidential administrations. These findings have important implications because donor influence may reduce the credibility, and hence the development effectiveness, of multilateral aid organizations.
Anger, hostility and aggression in the first days of acute stroke
Authors: Santos C. O. , Caeiro L. , Ferro J. M. , Albuquerque R. , Luísa Figueira M.
Published: April 2006

In acute stroke patients, anger can disturb management and rehabilitation and creates a stressful situation for family, health‐care providers and other patients. We aim to describe the presence of anger and its association with demographic, clinical, psychiatric, lesion variables and functional outcome in acute stroke patients. We screened anger prospectively in 202 consecutive acute stroke patients (≤4 days) using eight items from three psychiatric scales (Catastrophic Reaction Scale, Mania Rating Scale and Comprehensive Psychopathological Rating Scale). Anger was present if the patient scored in at least one item. Anger was detected in 71 (35%) patients and 26 of these were severely angry (≥4 points). There was no association between anger and the considered variables. Analysis of the items extracted two factors: (i) the emotional‐cognitive and (ii) the behavioural components of anger. These components were independent of each other in 26 patients. In 38 patients we found a dissociation between clinical observation and patients’ subjective expression. Anger was frequent in acute stroke patients. Anger was probably triggered by the brain lesion, which interfered with the emotional control. The lack of an association with clinical and imaging variables suggests a contribution of psychological/psychosocial dimensions.
Magnetic brainstem stimulation of the hypoglossal nerve in normal subjects
Authors: Lo Y. L. , Fook‐Chong S.
Published: April 2006

Electrophysiological evaluation of motor pathways to the lingual muscles is technically challenging. Previous studies utilizing transcranial magnetic stimulation (TMS) of the parieto‐occipital region with a round coil reported difficulties in eliciting tongue motor responses. In this study, we utilized TMS with a double cone coil at the posterior head region to obtain tongue motor evoked potentials. Our findings suggest activation at or distal to the hypoglossal nuclear level, but proximal to the hypoglossal canal region. Our method can be usefully applied in future studies of brainstem and cranial nerve function.
A Comparison of Sexual and Violent Offenders in a German Youth Prison
Authors: HOSSER DANIELA , BOSOLD CHRISTIANE
Published: April 2006

Abstract: This study compares young adult sexual delinquents and violent offenders via relevant psychological variables of two main areas: (i) anti‐social personality factors (aggression, impulsivity, hostility), and (ii) predisposing personality factors (self‐esteem, self‐efficacy, empathy, neutralisation). Participants are 78 violent and 27 sexual offenders (14 rapists, 13 child abusers), between 17 and 24 years of age. They were incarcerated in a German youth prison and interviewed during their prison term. Sexual offenders show significantly lower levels in anger cognitions, self‐esteem and self‐efficacy. Those convicted of rape do not differ from those convicted of child abuse.
Headache Features in Patients with Dengue Virus Infection
Authors: Domingues RB , Kuster GW , de Castro FL Onuki , Souza VA , Levi JE , Pannuti CS
Published: April 2006

The aim of this study was to describe the frequency and features of headache among patients with confirmed dengue virus infection and to compare the headache features in patients with dengue fever and dengue haemorrhagic fever, primary and secondary dengue infection, and patients with and without neurological involvement. Patients with classic dengue fever had a more intense headache than those with the more severe form of the disease, dengue haemorrhagic fever.
UVB in the management of early stage mycosis fungoides
Authors: Pavlotsky F , Barzilai A , Kasem R , Shpiro D , Trau H
Published: April 2006

Background  Several options for treatment of early mycosis fungoides (MF) offer similar success rates. Previous small studies have shown UVB to be at least as effective as PUVA.

Objective  To summarize our experience with UVB treatment of early MF.

Methods  A retrospective analysis of early‐stage MF patients treated by narrow band (NB) or broad band (BB) UVB in our institution between 1996 and 2002. Most patients achieving complete response (CR) were put on maintenance until natural sun exposure was possible and followed up every 3–6 months. The results were compared to those previously reported regarding PUVA.

Results  Sixty‐eight and 43 patients were treated by NB and BB UVB, respectively. Eighty‐six per cent (84 and 89% in NB and BB UVB groups, respectively) of IA and 71% (78 and 44% in NB and BB UVB groups, respectively) of IB patients achieved CR within a mean of 12.8 and 10.6 weeks, respectively. When maintenance was stopped, 65 and 30% had not relapsed after an average follow up of 27 and 222 weeks, respectively. Non‐relapse rate was 33 and 48% for those having had vs. those not having had maintenance, respectively.

Conclusions  Our results are comparable to all previously reported for skin‐targeted treatments, including PUVA and, to our belief, reflect the nature of early MF, in which CR can probably be achieved in most of the patients. Among the responding patients there is no relapse during prolonged follow‐up in about one third of the cases. Thus, we believe treatment should be stopped completely following first CR induction and maintenance treatment should be considered for relapsing patients only. Both broad and narrow UVB options are good and future choices should be made on the basis of short‐ and long‐term side‐effects.
Reversing the export of people with learning disabilities and complex health needs
Authors: Pritchard Andrew , Roy Ashok
Published: April 2006

Background  There is an increase in people with learning disabilities with offending and other disturbed behaviour who are placed in the local community and out of their area of origin.

Aims  To compare clients placed locally and out of area.

Method  All authorities in an English region were surveyed and interviewed about their clients placed locally and out of area.

Results  External placements were common place and expensive especially for clients with complex needs. Information regarding these clients was variable as was the joint commissioning process. The population was predominantly young and male requiring high levels of long term funding.

Conclusions  To reduce flows of high cost clients out of area, there is a need to develop joined up commissioning, and monitoring of services and partnerships with local providers to increase capacity and improve quality. Better information would enable commissioning to become less reactive.
Genetic Change in the Polynesian Population of Easter Island: Evidence from Alu Insertion Polymorphisms
Authors: González‐Pérez E. , Esteban E. , Via M. , García‐Moro C. , Hernández M. , Moral P.
Published: April 2006

The origin of Pacific islanders is still an open issue in human population genetics. To address this topic we analyzed a set of 18 Alu insertion polymorphisms in a total of 176 chromosomes from native Easter Island inhabitants (Rapanui). Available genealogical records allowed us to subdivide the total island sample into two groups, representative of the native population living in the island around 1900, and another formed by individuals with some ancestors of non‐Rapanui origin. Significant genetic differentiation was found between these groups, allowing us to make some biodemographic and historical inferences about the origin and evolution of this geographically isolated island population. Our data are consistent with equivalent and recent contributions from Amerindian and European migrants to the 1900s Rapanui population, with an accelerated increase in the European gene flow during the 20th century, especially since the 1960s. Comparative analysis of our results with other available Alu variation data on neighbouring populations supports the “Voyaging Corridor” model of Polynesian human settlement, which indicates that pre‐Polynesians are mainly derived from Southeast Asian and Wallacean populations rather than from Taiwan or the Philippines. This study underlines the importance of sampling and taking into account historical information in genetic studies to unravel the recent evolution of human populations.
The A370T Variant (StuI Polymorphism) in the LDL Receptor Gene is not Associated with Plasma Lipid Levels or Cardiovascular Risk in UK Men
Authors: Vieira José Ricardo S. , Whittall Ros A. , Cooper Jackie A. , Miller George J. , Humphries Steve E.
Published: April 2006

Over 800 different missense mutations in the low density lipoprotein (LDL) receptor gene (LDLR) have been identified in patients with familial hypercholesterolaemia (FH). Only two of them, including the Alanine to Threonine change at position 370 (A370T), have been discovered in FH patients but do not cause FH. The frequency of the 370T allele has been reported worldwide to be between 0.022 and 0.070, with no clear association with high cholesterol levels or risk for coronary heart disease (CHD) and stroke. To explore this relationship in more detail we have determined this genotype in 2,659 healthy middle‐aged (50–61 years) men participating in the prospective Second Northwick Park Heart Study, with 236 CHD and 67 stroke incident events. The genotype distribution was in Hardy‐Weinberg equilibrium and in the no‐event group the frequency of 370T was 0.046 (95% CI 0.040–0.052). Overall, there was no significant association of the 370T allele with any measured plasma lipid trait, and there was no difference in genotype distribution or allele frequency between the no‐event and CHD (0.059; 95% CI 0.040–0.085) or stroke (0.037; 95% CI 0.012–0.085) groups ( p= 0.18 and 0.65, respectively). There was evidence for significant interaction ( p= 0.006) between body mass index (BMI) and genotype on CHD risk, with 370A homozygotes showing the expected higher CHD risk for those with higher BMI, whilst risk for 370T allele carriers was highest in men in the lowest tertile of BMI. The explanation for this association is unclear, and may simply be chance. Thus, these data confirm the absence of a significant impact of the A370T polymorphism on LDL receptor function, at least as measured by the effect on plasma lipid levels and CHD risk.
Nidamental glands in males of the oceanic squid Ancistrocheirus lesueurii (Cephalopoda: Ancistrocheiridae) – sex change or intersexuality?
Authors: Hoving H. J. T. , Roeleveld M. A. C. , Lipinski M. R. , Videler J. J.
Published: April 2006

This is the first record of intersexuality to have been found within the Cephalopoda. Seven out of 16 sexually mature Ancistrocheirus lesueurii males from southern African waters had nidamental glands in the mantle cavity in addition to a normally developed male reproductive system (spermatophoric complex, testis and hectocotylus). The frequency of occurrence suggests that feminization in male A. lesueurii is not a rare phenomenon in the south‐eastern Atlantic. Normal A. lesueurii shows sexual size dimorphism, with females growing larger than males. The intersexual males formed a distinct size group intermediate between normal males and females, and their testis mass and spermatophore length were significantly larger than in normal males. The absence of oocytes and oviducts in intersexual males indicates that feminization represents pseudohermaphroditism. Intersexuality does not seem to affect male functionality and is apparently advantageous in that larger body size is accompanied by larger testis and spermatophores.
Nitric oxide‐producing microglia mediate thrombin‐induced degeneration of dopaminergic neurons in rat midbrain slice culture
Authors: Katsuki Hiroshi , Okawara Mitsugi , Shibata Haruki , Kume Toshiaki , Akaike Akinori
Published: April 2006

Activated microglia are considered to play important roles in degenerative processes of midbrain dopaminergic neurons. Here we examined mechanisms of neurotoxicity of thrombin, a protease known to trigger microglial activation, in organotypic midbrain slice cultures. Thrombin induced a progressive decline in the number of dopaminergic neurons, an increase in nitric oxide (NO) production, and whole tissue injury indicated by lactate dehydrogenase release and propidium iodide uptake. Microglia expressed inducible NO synthase (iNOS) in response to thrombin, and inhibition of iNOS rescued dopaminergic neurons without affecting whole tissue injury. Inhibitors of mitogen‐activated protein kinases (MAPKs) such as extracellular signal‐regulated kinase (ERK), p38 MAPK and c‐Jun N‐terminal kinase (JNK) attenuated thrombin‐induced iNOS induction and dopaminergic cell death. Whole tissue injury was also attenuated by inhibition of ERK and p38 MAPK. Moreover, depletion of resident microglia from midbrain slices abrogated thrombin‐induced NO production and dopaminergic cell death, but did not inhibit tissue injury. Finally, antioxidative drugs prevented thrombin‐induced dopaminergic cell death without affecting whole tissue injury. Hence, NO production resulting from MAPK‐dependent microglial iNOS induction is a crucial event in thrombin‐induced dopaminergic neurodegeneration, whereas damage of other midbrain cells is MAPK‐dependent but is NO‐independent.