bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thyroid autoantibody profiles in ophthalmic dominant and thyroid dominant Graves’ disease differ and suggest ophthalmopathy is a multiantigenic disease
Authors: Goh S. Y. , Ho S. C. , Seah L. L. , Fong K. S. , Khoo D. H. C. 
Published: December 2004

Summarybackground  Thyroid‐associated ophthalmopathy (TAO) occurs in 25–50% of patients with Graves’ disease (GD) and is occasionally seen in hypothyroid Hashimoto's disease or euthyroid individuals. The link between TAO and hyperthyroidism remains unclear. We hypothesized that qualitative or quantitative differences in thyroid antibodies might determine individual predisposition to these features.methods  In a prospective study over 3 years, thyroid antibody levels were measured in all patients diagnosed at the Singapore National Eye Centre to have GD. These patients had no known history of thyroid disease, presented with eye complaints and diagnosis was made by an ophthalmologist. A total of 31 patients were identified. Antibody levels were compared against 71 consecutive patients referred to a thyroid clinic (TC) for thyrotoxic symptoms in whom the diagnosis of GD was confirmed by a thyroidologist.findings  Thyroid autoantibody profiles of patients diagnosed at the ophthalmology centre (OC) and TC differed markedly. OC patients had significantly higher TSI (P = 0·003) but lower TPOAb (P = 0·008) and TgAb levels (P < 0·001). In contrast, TC patients had higher free T4 (P = 0·048) and higher TBII levels (P < 0·001). Antibody levels were correlated with four parameters of ophthalmopathy – chronic lid retraction, lid swelling, proptosis and extraocular myopathy (EOM). On univariate logistic regression analysis, TSI was a positive predictor and TPOAb and TgAb negative predictors of all four features. In the absence of TgAb, the odds ratios for individual TAO features ranged from 2·8 to 7·9, with corresponding values of 3·9–10·2 when TPOAb was absent. In stepwise logistic regression analysis, TSI was the strongest independent predictor of all aspects studied: lid fullness P = 0·001, proptosis P = 0·001, lid retraction P = 0·008, EOM P = 0·009. Among smokers, TPOAb were significantly lower (P = 0·044) but no association between smoking and the other antibodies was observed.interpretation  The study demonstrates markedly different thyroid autoantibody profiles in newly diagnosed GD patients with ophthalmic dominant as opposed to thyroid dominant features. It suggests differing antibody patterns are associated with predisposition to hyperthyroidism and orbitopathy. In addition, an association between smoking and low TPOAb levels was noted.
Strange organelles –Plasmodium mitochondria lack a pyruvate dehydrogenase complex
Authors: Ralph Stuart A. 
Published: December 2004

SummaryOur understanding of the Plasmodium mitochondrion and apicoplast has been greatly assisted by the genome sequence project. Sequence data have seeded recent research showing that the apicoplast is  the  site  of  several  anabolic  pathways  including fatty acid synthesis. The discovery of an active apicoplast pyruvate dehydrogenase complex implies this enzyme generates the acetyl‐CoA needed for fatty acid synthesis. However, the absence of a corresponding mitochondrial complex suggests that energy generation in Plasmodium is considerably different from pathways described in other eukaryotes.
Type IV pilus biogenesis in Neisseria meningitidis: PilW is involved in a step occurring after pilus assembly, essential for fibre stability and function
Authors: Carbonnelle Etienne , Hélaine Sophie , Prouvensier Laure , Nassif Xavier , Pelicic Vladimir 
Published: December 2004

SummaryType IV pili (Tfp) play a critical role in the pathogenic lifestyle of Neisseria meningitidis and N. gonorrhoeae, notably by facilitating bacterial attachment to human cells, but our understanding of their biogenesis, during which the fibres are assembled in the periplasm, then emerge onto the cell surface and are stabilized, remains fragmentary. We therefore sought to identify the genes required for Tfp formation in N. meningitidis by screening a genome‐wide collection of mutants for those that were unable to form aggregates, another phenotype mediated by these organelles. Fifteen proteins, of which only seven were previously characterized, were found to be essential for Tfp biogenesis. One novel component, named PilW, was studied in more detail. We found that PilW is an outer‐membrane protein necessary for the stabilization of the fibres but not for their assembly or surface localization, because Tfp could be restored on the surface in a pilW mutant by a mutation in the twitching motility gene pilT. However, Tfp‐linked properties, including adherence to human cells, were not restored in a pilW/T mutant, which suggests that PilW is also essential for the functionality of the fibres. Together with the finding that PilW is important for the stability of PilQ multimers, our results extend the current model for Tfp biogenesis by suggesting that a multiprotein machinery in the outer‐membrane is involved in the terminal stage of Tfp biogenesis during which growing fibres are not only stabilized, but also become perfectly functional.
The PerR regulon in peroxide resistance and virulence of Streptococcus pyogenes
Authors: Brenot Audrey , King Katherine Y. , Caparon Michael G. 
Published: December 2004

SummaryPrior studies have shown that the catalase‐deficient pathogen Streptococcus pyogenes (group A streptococcus) has a robust ability to resist oxidative stress that partially involves the transcriptional regulator PerR. However, the extent of the PerR regulon and the contribution of the members of this regulon to virulence are unknown. In this study, DNase I footprinting revealed that PerR binds specifically to a single site upstream of the promoter for the gene encoding alkyl hydroperoxide reductase (ahpC). However, analyses of transcript abundance revealed that while ahpC is regulated in response to growth phase, its regulation is independent of PerR. Instead, PerR regulates transcription of a divergent gene cluster that encodes a putative cold shock protein. The gene encoding the Dps‐like peroxide resistance protein MrgA was repressed by PerR, consistent with the presence of a PerR binding site in its promoter. Phenotypic analyses of PerR–, AhpC– and MrgA– mutants revealed that while AhpC is not essential for resistance to challenge with hydrogen peroxide in vitro, AhpC does contribute to scavenging of endogenous hydrogen peroxide and is required for virulence in a murine model of infection. In contrast, a MrgA– mutant was hypersensitive to challenge with peroxide in vitro, but was fully virulent in all animal models tested. Finally, a PerR– mutant was hyper‐resistant to peroxide, yet was highly attenuated for virulence in all murine models. These data demonstrate that while a mutant's capacity to resist peroxide stress did not directly correlate with its ability to cause disease, the appropriate regulation of the peroxide stress response is critical for virulence.
PilX, a pilus‐associated protein essential for bacterial aggregation, is a key to pilus‐facilitated attachment of Neisseria meningitidis to human cells
Authors: Hélaine Sophie , Carbonnelle Etienne , Prouvensier Laure , Beretti Jean‐Luc , Nassif Xavier , Pelicic Vladimir 
Published: December 2004

SummaryThe attachment of pathogenic Neisseria species to human cells, in which type IV pili (Tfp) play a key but incompletely defined role, depends on the ability of these bacteria to establish contacts with the target cells but also interbacterial interactions. In an effort to improve our understanding of the molecular mechanisms of N. meningitidis adherence to human cells, we screened a collection of defined mutants for those presenting reduced attachment to a human cell line. Besides underscoring the central role of Tfp in this process, this analysis led to the identification of mutants interrupted in a novel gene termed pilX, that displayed an adherence as impaired as that of a non‐piliated mutant but quantitatively and qualitatively unaltered fibres. Moreover, the pilX gene, which encodes a pilin‐like protein that copurifies with Tfp fibres, was also found to be essential for bacterial aggregation. We provide here several piece of evidence suggesting that PilX has intrinsic aggregative but no adhesive properties and that the reduced numbers of adherent bacteria seen with a pilX mutant result from the absence of interbacterial interactions. These data extend the current model for Tfp‐facilitated adherence of N. meningitidis to human cells by suggesting that the pili lead to an increase in net initial adherence primarily by mediating a cooperation between the bacteria, which is supported by the finding that a major effect on initial adherence could be observed in a wild‐type (WT) genetic background after a mechanical removal of the bacterial aggregates.
The type IV secretion apparatus protein VirB6 of Agrobacterium tumefaciens localizes to a cell pole
Authors: Judd Paul K. , Kumar Renu B. , Das Anath 
Published: December 2004

Summary Agrobacterium tumefaciens VirB proteins assemble a type IV secretion apparatus for the transfer of DNA and proteins to plant cells. To study the role of the VirB6 protein in the assembly and function of the type IV apparatus, we determined its subcellular location by immunofluorescence microscopy. In wild‐type bacteria VirB6 localized to the cell poles but in the absence of the tumour‐inducing plasmid it localized to random sites on the cell membranes. Five of the 11 VirB proteins, VirB7–VirB11, are required for the polar localization of VirB6. We identified two regions of VirB6, a conserved tryptophan residue at position 197 and the extreme C‐terminus, that are essential for its polar localization. Topology determination by PhoA fusion analysis placed both regions in the cell cytoplasm. Alteration of tryptophan 197 or the deletion of the extreme C‐terminus led to the mislocalization of the mutant protein. The mutations abolished the DNA transfer function of the protein as well. The C‐terminus of VirB6, in silico, can form an amphipathic helix that may encode a protein–protein interaction domain essential for targeting the protein to a cell pole. We previously reported that another DNA transfer protein, VirD4, localizes to a cell pole. To determine whether VirB6 and VirD4 localize to the same pole, we performed colocalization experiments. Both proteins localized to the same pole indicating that VirB6 and VirD4 are in close proximity and VirB6 is probably a component of the transport apparatus.
Sequential binding of SeqA protein to nascent DNA segments at replication forks in synchronized cultures of Escherichia coli
Authors: Yamazoe Mitsuyoshi , Adachi Shun , Kanaya Shigehiko , Ohsumi Katsufumi , Hiraga Sota 
Published: December 2004

SummaryTo demonstrate that sequestration A (SeqA) protein binds preferentially to hemimethylated GATC sequences at replication forks and forms clusters in Escherichia coli growing cells, we analysed, by the chromatin immunoprecipitation (ChIP) assay using anti‐SeqA antibody, a synchronized culture of a temperature‐sensitive dnaC mutant strain in which only one round of chromosomal DNA replication was synchronously initiated. After synchronized initiation of chromosome replication, the replication origin oriC was first detected by the ChIP assay, and other six chromosomal regions having multiple GATC sequences were sequentially detected according to bidirectional replication of the chromosome. In contrast, DNA regions lacking the GATC sequence were not detected by the ChIP assay. These results indicate that SeqA binds hemimethylated nascent DNA segments according to the proceeding of replication forks in the chromosome, and SeqA releases from the DNA segments when fully methylated. Immunofluorescence microscopy reveals that a single SeqA focus containing paired replication apparatuses appears at the middle of the cell immediately after initiation of chromosome replication and the focus is subsequently separated into two foci that migrate to 1/4 and 3/4 cellular positions, when replication forks proceed bidirectionally an approximately one‐fourth distance from the replication origin towards the terminus. This supports the translocating replication apparatuses model.
New insertion sequences of Sulfolobus: functional properties and implications for genome evolution in hyperthermophilic archaea
Authors: Blount Zachary D. , Grogan Dennis W. 
Published: December 2004

SummaryAnalyses of complete genomes indicate that insertion sequences (ISs) are abundant and widespread in hyperthermophilic archaea, but few experimental studies have measured their activities in these hosts. As a way to investigate the impact of ISs on Sulfolobus genomes, we identified seven transpositionally active ISs in a widely distributed Sulfolobus species, and measured their functional properties. Six of the seven were found to be distinct from previously described ISs of Sulfolobus, and one of the six could not be assigned to any known IS family. A type II ‘Miniature Inverted‐repeat Transposable Element’ (MITE) related to one of the ISs was also recovered. Rates of transposition of the different ISs into the pyrEF region of their host strains varied over a 250‐fold range. The Sulfolobus ISs also differed with respect to target‐site selectivity, although several shared an apparent preference for the pyrEF promoter region. Despite the number of distinct ISs assayed and their molecular diversity, only one demonstrated precise excision from the chromosomal target region. The fact that this IS is the only one lacking inverted repeats and target‐site duplication suggests that the observed precise excision may be promoted by the IS itself. Sequence searches revealed previously unidentified partial copies of the newly identified ISs in the Sulfolobus tokodaii and Sulfolobus solfataricus genomes. The structures of these fragmentary copies suggest several distinct molecular mechanisms which, in the absence of precise excision, inactivate ISs and gradually eliminate the defective copies from Sulfolobus genomes.
PfPK7, an atypical MEK‐related protein kinase, reflects the absence of classical three‐component MAPK pathways in the human malaria parasite Plasmodium falciparum
Authors: Dorin Dominique , Semblat Jean‐Philippe , Poullet Patrick , Alano Pietro , Goldring J. P. Dean , Whittle Christina , Patterson Shelley , Chakrabarti Debopam , Doerig Christian 
Published: December 2004

SummaryTwo members of the mitogen‐activated protein kinase (MAPK) family have been previously characterized in Plasmodium falciparum, but in vitro attempts at identifying MAP kinase kinase (MAPKK) homologues have failed. Here we report the characterization of a novel plasmodial protein kinase, PfPK7, whose top scores in blastp analysis belong to the MAPKK3/6 subgroup of MAPKKs. However, homology to MAPKKs is restricted to regions of the C‐terminal lobe of the kinase domain, whereas the N‐terminal region is closer to fungal protein kinase A enzymes (PKA, members of the AGC group of protein kinases). Hence, PfPK7 is a ‘composite’ enzyme displaying regions of similarity to more than one protein kinase family, similar to a few other plasmodial protein kinases. PfPK7 is expressed in several developmental stages of the parasite, both in the mosquito vector and in the human host. Recombinant PfPK7 displayed kinase activity towards a variety of substrates, but was unable to phosphorylate the two P. falciparum MAPK homologues in vitro, and was insensitive to PKA and MEK inhibitors. Together with the absence of a typical MAPKK activation site in its T‐loop, this suggests that PfPK7 is not a MAPKK orthologue, despite the fact that this enzyme is the most ‘MAPKK‐like’ enzyme encoded in the P. falciparum genome. This is consistent with recent observations that the plasmodial MAPKs are not true orthologues of the ERK1/2, p38 or JNK MAPKs, and strengthens the evidence that classical three‐component module‐dependent MAPK signalling pathways do not operate in malaria parasites, a feature that has not been described in any other eukaryote.
Discovery of Late Jurassic fossils inside modern sediments at Gorringe Bank (Eastern Atlantic Ocean) and some geological implications.
Authors: Conti Maria Alessandra , De Alteriis Giovanni , Marino Maria Concetta , Pallini Giovanni , Tonielli Renato 
Published: December 2004

AbstractDuring a recent expedition at the Gorringe Bank (eastern Atlantic, 150 miles SW off Portugal), one of the rare sites in the ocean where mantle rocks crop out at very shallow depths (− 30 m), the Gettysburg and Ormonde seamounts, the two summits on the Gorringe Bank, were surveyed in detail. At Gettysburg seamount, within the modern bioclastic material, which is continually produced on the summit and exported to deep water, several examples of Mesozoic cephalopods were found. These fossils, reworked ‘in situ’, gave an age spanning from Kimmeridgian–Tithonian to Hauterivian (145–155 Ma) and recall some condensed Jurassic sequences of the Thetyan region compatible with shallow water (< 200 m). The serendipitous discovery of such ancient faunas within modern sediments suggests that Gorringe Bank was a seamount at the early opening of the Atlantic Ocean and requires us to reassess the age of rifting along the Iberian margin and the importance of vertical tectonics for non‐volcanic, mantle‐rooted seamounts.
Temperature distribution in karst systems: the role of air and water fluxes
Authors: Luetscher Marc , Jeannin Pierre‐Yves 
Published: December 2004

AbstractA better understanding of heat fluxes and temperature distribution in continental rocks is of great importance for many engineering aspects (tunnelling, mining, geothermal research, etc.). This paper aims at providing a conceptual model of temperature distribution in karst environments which display thermal ‘anomalies’ as compared with other rocks. In temperate regions, water circulation is usually high enough to ‘drain‐out’ completely the geothermal heat flux at the bottom of karst systems (phreatic zone). A theoretical approach based on temperature measurements carried out in deep caves and boreholes demonstrates, however, that air circulation can largely dominate water infiltration in the karst vadose zone, which can be as thick as 2000 m. Consequently, temperature gradients within this zone are similar to the lapse rate of humid air (∼0.5 °C 100 m−1). Yet, this value depends on the regional climatic context and might present some significant variations.
THE 5‐HT2 RECEPTOR ANTAGONIST SARPOGRELATE REDUCES URINARY AND PLASMA LEVELS OF THROMBOXANE A2 AND URINARY ALBUMIN EXCRETION IN NON‐INSULIN‐DEPENDENT DIABETES MELLITUS PATIENTS†
Authors: Ogawa Susumu , Takeuchi Kazuhisa , Sugimura Kazuhiko , Sato Chiharu , Fukuda Motoshi , Lee Ribun , Ito Sadayoshi , Sato Tokutaro 
Published: December 2004

1. Therapeutic effects of a 5‐HT2 receptor antagonist sarpogrelate on microalbuminuria and thromboxane (TX)A2 biosynthesis were examined in non‐insulin‐dependent diabetes mellitus (NIDDM) patients.2. In protocol I, the ankle‐brachial pressure index (API; an indicator of peripheral blood flow) and urinary albumin excretion (UalbV; an indicator of renal function) were determined in 42 NIDDM patients who had been treated with 300 mg/day sarpogrelate for 8 weeks. In an analysis of the results, the NIDDM patients were divided into four groups based on the severity of either vasculopathy or nephropathy as follows: group A, API < 0.9, UalbV ≥ 100 mg/day; group B, API < 0.9, UalbV < 100 mg/day; group C API ≥ 0.9, UalbV ≥ 100 mg/day; and group D, API ≥ 0.9, UalbV < 100 mg/day.3. In protocol II, 10 NIDDM patients with UalbV values > 100 mg/day were divided into two groups to further confirm the effect of sarpogrelate on albuminuria: group E, the sarpogrelate treatment group (n = 5); and group F, the no treatment group (n = 5).4. In protocol I, the incidence of a cold sensation in the lower extremities was reduced from 45.2 to 21.4% following sarpogrelate treatment. In patients with UalbV ≥ 100 mg/day (groups A and C), UalbV was significantly decreased independent of API, while it did not change in patients with UalbV < 100 mg/day (groups B and D). Plasma TXB2 levels were significantly decreased following sarpogrelate treatment, whereas plasma 6‐keto‐prostaglandin F1α levels were not.5. In protocol II, in the sarpogrelate treatment group (group E), albuminuria was significantly improved and both plasma levels TXB2 and urinary TXB2 excretion were significantly decreased. In contrast, in the untreated group (group F), neither plasma levels TXB2 nor urinary TXB2 excretion was changed.6. In conclusion, microalbuminuria was improved by treatment with the 5‐HT2 receptor antagonist sarpogrelate independent of latent vasculopathy. Blockade of 5‐HT2 receptors is suggested to be beneficial for the treatment of nephropathy in NIDDM patients. It is possible that the inhibition of TXA2 biosynthesis is involved in the therapeutic effect of 5‐HT2 receptor antagonists.
Delayed stoma formation in Fournier's gangrene
Authors: Bronder C. S. , Cowey A. , Hill J. 
Published: December 2004

AbstractFournier's gangrene is traditionally treated with prompt surgical debridement and in many cases a diverting colostomy is also fashioned during the same procedure. We present four cases where stoma formation was delayed until the second look procedure. The physiological states at the time of either procedure were compared using POSSUM. The results showed an improvement in the physiological condition in all patients at the time of the second operation, suggesting that a delay can potentially improve prognosis in such cases.
Colorectal surgery: the risk and burden of adhesion‐related complications
Authors: Parker M. C. , Wilson M. S. , Menzies D. , Sunderland G. , Thompson J. N. , Clark D. N. , Knight A. D. , Crowe A. M. ,   Surgical and Clinical Adhesions Research (SCAR) Group
Published: December 2004

AbstractObjectives  Adhesions are associated with serious medical complications. This study examines the real‐time burden of adhesion‐related readmissions following colorectal surgery and assesses the impact of previous surgery on adhesion‐related outcomes.Patients and methods  The study used data from the Scottish National Health Service Medical Record Linkage Database to identify three cohorts of patients who had undergone open colorectal surgery during the financial years 1996–97, 1997–98 and 1998–99. Each cohort was followed up for at least 2 years and the number and category of adhesion‐related readmissions was recorded. The influence of any previous operations on adhesion‐related readmissions was also determined by performing a subanalysis within the 1996–97 cohort of patients who had no record of abdominal surgery within either the previous 5 or 15 years. The relative risk of adhesion‐related readmissions was also assessed.Results  In the 1996–97 cohort, 9.0% of patients were readmitted within a year after surgery; 2.1% had complications directly related to adhesions and 6.9% had complications that were possibly related. After 4 years, 19.0% of patients were readmitted for reasons directly or possibly related to adhesions. Many patients were readmitted on more than one occasion and the relative risk of adhesion‐related complications was 29.7 per 100 initial procedures over 4 years. In the subgroups that had no record of abdominal surgery within the previous 5 or 15 years, the relative risks of adhesion‐related complications were 24.8% and 23.5%, respectively. There was no change in the rate of adhesion‐related readmissions following colorectal surgery between 1996 and 1999.Conclusion  Colorectal surgery is associated with a considerable rate of adhesion‐related readmissions. Preventative measures should be considered to reduce this risk.