bluuebunny/crossref_metadata_2025 huggingface dataset:
Trigger factor interacts with the signal peptide of nascent Tat substrates but does not play a critical role in Tat‐mediated export
Authors: Jong Wouter S. P. , ten Hagen‐Jongman Corinne M. , Genevaux Pierre , Brunner Josef , Oudega Bauke , Luirink Joen
Published: December 2004

Twin‐arginine translocation (Tat)‐mediated protein transport across the bacterial cytoplasmic membrane occurs only after synthesis and folding of the substrate protein that contains a signal peptide with a characteristic twin‐arginine motif. This implies that premature contact between the Tat signal peptide and the Tat translocon in the membrane must be prevented. We used site‐specific photo‐crosslinking to demonstrate that the signal peptide of nascent Tat proteins is in close proximity to the chaperone and peptidyl‐prolyl isomerase trigger factor (TF). The contact with TF was strictly dependent on the context of the translating ribosome, started early in biogenesis when the nascent chain left the ribosome near L23, and persisted until the chain reached its full length. Despite this exclusive and prolonged contact, depletion or overexpression of TF had little effect on the kinetics and efficiency of the Tat export process.
pH dependence, substrate specificity and inhibition of human kynurenine aminotransferase I
Authors: Han Qian , Li Junsuo , Li Jianyong
Published: December 2004

Human kynurenine aminotransferase I/glutamine transaminase K (hKAT‐I) is an important multifunctional enzyme. This study systematically studies the substrates of hKAT‐I and reassesses the effects of pH, Tris, amino acids and α‐keto acids on the activity of the enzyme. The experiments were comprised of functional expression of the hKAT‐I in an insect cell/baculovirus expression system, purification of its recombinant protein, and functional characterization of the purified enzyme. This study demonstrates that hKAT‐I can catalyze kynurenine to kynurenic acid under physiological pH conditions, indicates indo‐3‐pyruvate and cysteine as efficient inhibitors for hKAT‐I, and also provides biochemical information about the substrate specificity and cosubstrate inhibition of the enzyme. hKAT‐I is inhibited by Tris under physiological pH conditions, which explains why it has been concluded that the enzyme could not efficiently catalyze kynurenine transamination. Our findings provide a biochemical basis towards understanding the overall physiological role of hKAT‐I in vivo and insight into controlling the levels of endogenous kynurenic acid through modulation of the enzyme in the human brain.
Antimicrobial activity of histones from hemocytes of the Pacific white shrimp
Authors: Patat Séverine A. , Carnegie Ryan B. , Kingsbury Celia , Gross Paul S. , Chapman Robert , SCHEY KEVIN L.
Published: December 2004

The role of vertebrate histone proteins or histone derived peptides as innate immune effectors has only recently been appreciated. In this study, high levels of core histone proteins H2A, H2B, H3 and H4 were found in hemocytes from the Pacific white shrimp, Litopenaeus vannamei. The proteins were identified by in‐gel digestion, mass spectrometry analysis, and homology searching. The L. vannamei histone proteins were found to be highly homologous to histones of other species. Based on this homology, histone H2A was cloned and its N‐terminus was found to resemble the known antimicrobial histone peptides buforin I, parasin, and hipposin. Consequently, a 38 amino acid synthetic peptide identical to the N‐terminus of shrimp H2A was synthesized and assayed, along with endogenous histones H2A, H2B, and H4, for growth inhibition against Micrococcus luteus. Histone H2A, purified to homogeneity, completely inhibited growth of the Gram‐positive bacterium at 4.5 µm while a mixture of histones H2B and H4 was active at 3 µm. In addition, a fraction containing a fragment of histone H1 was also found to be active. The synthetic peptide similar to buforin was active at submicromolar concentrations. These data indicate, for the first time, that shrimp hemocyte histone proteins possess antimicrobial activity and represent a defense mechanism previously unreported in an invertebrate. Histones may be a component of innate immunity more widely conserved, and of earlier origin, than previously thought.
Methylthioadenosine phosphorylase from the archaeon Pyrococcus furiosus
Authors: Cacciapuoti Giovanna , Moretti Maria Angela , Forte Sabrina , Brio Assunta , Camardella Laura , Zappia Vincenzo , Porcelli Marina
Published: December 2004

The extremely heat‐stable 5′‐methylthioadenosine phosphorylase from the hyperthermophilic archaeon Pyrococcus furiosus was cloned, expressed to high levels in Escherichia coli, and purified to homogeneity by heat precipitation and affinity chromatography. The recombinant enzyme was subjected to a kinetic analysis including initial velocity and product inhibition studies. The reaction follows an ordered Bi–Bi mechanism and phosphate binding precedes nucleoside binding in the phosphorolytic direction. 5′‐Methylthioadenosine phosphorylase from Pyrococcus furiosus is a hexameric protein with five cysteine residues per subunit. Analysis of the fragments obtained after digestion of the protein alkylated without previous reduction identified two intrasubunit disulfide bridges. The enzyme is very resistant to chemical denaturation and the transition midpoint for guanidinium chloride‐induced unfolding was determined to be 3.0 m after 22 h incubation. This value decreases to 2.0 m in the presence of 30 mm dithiothreitol, furnishing evidence that disulfide bonds are needed for protein stability. The guanidinium chloride‐induced unfolding is completely reversible as demonstrated by the analysis of the refolding process by activity assays, fluorescence measurements and SDS/PAGE. The finding of multiple disulfide bridges in 5′‐methylthioadenosine phosphorylase from Pyrococcus furiosus argues strongly that disulfide bond formation may be a significant molecular strategy for stabilizing intracellular hyperthermophilic proteins.
Cloning, over‐expression, purification and characterization of Plasmodium falciparum enolase
Authors: Pal‐Bhowmick Ipsita , Sadagopan K. , Vora Hardeep K. , Sehgal Alfica , Sharma Shobhona , Jarori Gotam K.
Published: December 2004

We have cloned, over‐expressed and purified enolase from Plasmodium falciparum strain NF54 in Escherichia coli in active form, as an N‐terminal His6‐tagged protein. The sequence of the cloned enolase from the NF54 strain is identical to that of strain 3D7 used in full genome sequencing. The recombinant enolase (r‐Pfen) could be obtained in large quantities (≈ 50 mg per litre of culture) in a highly purified form (> 95%). The purified protein gave a single band at ≈ 50 kDa on SDS/PAGE. MALDI‐TOF analysis gave a mean ± SD mass of 51396 ± 16 Da, which is in good agreement with the mass calculated from the sequence. The molecular mass of r‐Pfen determined in gel‐filtration experiments was ≈ 100 kDa, indicating that P. falciparum enolase is a homodimer. Kinetic measurements using 2‐phosphoglycerate as substrate gave a specific activity of ≈ 30 U·mg−1 and Km2PGA = 0.041 ± 0.004 mm. The Michaelis constant for the reverse reaction (KmPEP) is 0.25 ± 0.03 mm. pH‐dependent activity measurements gave a maximum at pH 7.4–7.6 irrespective of the direction of catalysis. The activity of this enzyme is inhibited by Na+, whereas K+ has a slight activating effect. The cofactor Mg2+ has an apparent activation constant of 0.18 ±0.02 mm. However, at higher concentrations, it has an inhibitory effect. Polyclonal antibody raised against pure recombinant P. falciparum enolase in rabbit showed high specificity towards recombinant protein and is also able to recognize enolase from the murine malarial parasite, Plasmodium yoelii, which shares 90% identity with the P. falciparum protein.
Mercury(II) binding to metallothioneins
Authors: Leiva‐Presa Àngels , Capdevila Mercè , Gonzàlez‐Duarte Pilar
Published: December 2004

With the aim of extending our knowledge on the reaction pathways of Zn‐metallothionein (MT) and apo‐MT species in the presence of Hg(II), we monitored the titration of Zn7‐MT, Zn4‐αMT and Zn3‐βMT proteins, at pH 7 and 3, with either HgCl2 or Hg(ClO4)2 by CD and UV‐vis spectroscopy. Detailed analysis of the optical data revealed that standard variables, such as the pH of the solution, the binding ability of the counter‐ion (chloride or perchlorate), and the time elapsed between subsequent additions of Hg(II) to the protein, play a determinant role in the stoichiometry, stereochemistry and degree of folding of the Hg‐MT species. Despite the fact that the effect of these variables is unquestionable, it is difficult to generalize. Overall, it can be concluded that the reaction conditions [pH, time elapsed between subsequent additions of Hg(II) to the protein] affect the structural properties more substantially than the stoichiometry of the Hg‐MT species, and that the role of the counter‐ion becomes particularly apparent on the structure of overloaded Hg‐MT.
Interaction of an ≈ 40 kDa protein from regenerating rat liver with the −148 to −124 region of c‐jun complexed with RLjunRP coincides with enhanced c‐jun expression in proliferating rat liver
Authors: Ohri Sujata , Sharma Dipali , Dixit Aparna
Published: December 2004

The c‐jun belongs to the family of proto‐oncogenes and encodes for the protein Jun, a component of transcription factor AP‐1 involved in regulation of the expression of genes indispensable for cell proliferation and differentiation. While the role of c‐jun in the regulation of such genes has been well examined, the regulation of c‐jun in proliferating cells is not fully understood. We have earlier reported that the −148 to −124 region of c‐jun is involved in the positive regulation of c‐jun transcription, and interacts with a positive regulatory factor (rat liver jun regulatory protein; RLjunRP) present in rat liver. In this investigation, we report that this region is differentially recognized in proliferating liver as evidenced by the formation of a complex, different from that observed with normal liver extract. The new complex appears as early as 2 h after partial hepatectomy and its appearance coincides with the rise in c‐jun mRNA levels after partial hepatectomy. In regenerating rat liver nuclear extract, an additional protein of ≈ 40 kDa (rRLjunRP) interacts with a pre‐existing dimer of RLjunRP complexed with the −148 to −124 region of c‐jun to form a slow‐migrating complex. rRLjunRP appears to pre‐exist in the cytosol and translocate to the nucleus as indicated by the continued presence of the retarded complex in nuclear extract prepared from partially hepatectomized rats treated with cycloheximide. UV crosslinking studies, South‐Western blot analysis, SDS/PAGE of affinity‐purified factor(s), and 2D‐PAGE analysis clearly demonstrate that the additional factor induced in response to growth stimulus is an ≈ 40 kDa, that binds with the dimer of RLjunRP and enhances the c‐jun transcription.
Aptamers to Escherichia coli core RNA polymerase that sense its interaction with rifampicin, σ‐subunit and GreB
Authors: Kulbachinskiy Andrey , Feklistov Andrey , Krasheninnikov Igor , Goldfarb Alex , Nikiforov VADIM
Published: December 2004

Bacterial RNA polymerase (RNAP) is the central enzyme of gene expression that is responsible for the synthesis of all types of cellular RNAs. The process of transcription is accompanied by complex structural rearrangements of RNAP. Despite the recent progress in structural studies of RNAP, detailed mechanisms of conformational changes of RNAP that occur at different stages of transcription remain unknown. The goal of this work was to obtain novel ligands to RNAP which would target different epitopes of the enzyme and serve as specific probes to study the mechanism of transcription and conformational flexibility of RNAP. Using in vitro selection methods, we obtained 13 classes of ssDNA aptamers against Escherichia coli core RNAP. The minimal nucleic acid scaffold (an oligonucleotide construct imitating DNA and RNA in elongation complex), rifampicin and the σ70‐subunit inhibited binding of the aptamers to RNAP core but did not affect the dissociation rate of preformed RNAP–aptamer complexes. We argue that these ligands sterically block access of the aptamers to their binding sites within the main RNAP channel. In contrast, transcript cleavage factor GreB increased the rate of dissociation of preformed RNAP–aptamer complexes. This suggested that GreB that binds RNAP outside the main channel actively disrupts RNAP–aptamer complexes by inducing conformational changes in the channel. We propose that the aptamers obtained in this work will be useful for studying the interactions of RNAP with various ligands and regulatory factors and for investigating the conformational flexibility of the enzyme.
Structure of the core oligosaccharide of a rough‐type lipopolysaccharide of Pseudomonas syringae pv. phaseolicola
Authors: Zdorovenko Evelina L. , Vinogradov Evgeny , Zdorovenko Galina M. , Lindner Buko , Bystrova Olga V. , Shashkov Alexander S. , Rudolph Klaus , Zähringer Ulrich , Knirel Yuriy A.
Published: December 2004

The core structure of the lipopolysaccharide (LPS) isolated from a rough strain of the phytopathogenic bacterium Pseudomonas syringae pv. phaseolicola, GSPB 711, was investigated by sugar and methylation analyses, Fourier transform ion‐cyclotron resonance ESI MS, and one‐ and two‐dimensional 1H‐, 13C‐ and 31P‐NMR spectroscopy. Strong alkaline deacylation of the LPS resulted in two core‐lipid A backbone undecasaccharide pentakisphosphates in the ratio ≈ 2.5 : 1, which corresponded to outer core glycoforms 1 and 2 terminated with either l‐rhamnose or 3‐deoxy‐d‐manno‐oct‐2‐ulosonic acid (Kdo), respectively. Mild acid degradation of the LPS gave the major glycoform 1 core octasaccharide and a minor truncated glycoform 2 core heptasaccharide, which resulted from the cleavage of the terminal Kdo residues. The inner core of P. syringae is distinguished by a high degree of phosphorylation of l‐glycero‐d‐manno‐heptose residues with phosphate, diphosphate and ethanolamine diphosphate groups. The glycoform 1 core is structurally similar but not identical to one of the core glycoforms of the human pathogenic bacterium Pseudomonas aeruginosa. The outer core composition and structure may be useful as a chemotaxonomic marker for the P. syringae group of bacteria, whereas a more conserved inner core structure appears to be representative for the whole genus Pseudomonas.
The effects of an artificial wetland dominated by free‐floating plants on the restoration of a subtropical, hypertrophic lake
Authors: Rodríguez‐Gallego L. R. , Mazzeo N. , Gorga J. , Meerhoff M. , Clemente J. , Kruk C. , Scasso F. , Lacerot G. , García J. , Quintans F.
Published: December 2004

Lake Rodó (Montevideo, Uruguay) is a small, urban, hypertrophic lake undergoing restoration. In this study, we evaluated the nutrient removal efficiency and water quality improvement attributable to a water recirculation system, consisting of the lake and three connected pools converted to artificial wetlands dominated by free‐floating hydrophytes. Eichhornia crassipes and Spirodela intermedia dominated the hydrophyte community during summer and winter, respectively, with the biomass production being maintained throughout the year. The maximum production values of E. crassipes were 11.3 and 5.6 g DW m−2 d−1 in the summers of 1998 and 2000, respectively, while those of S. intermedia were 2.7 and 0.8 g DW m−2 d−1 in the summers of 1999 and 2000, respectively. The aquatic plant community reduced the concentration of nutrients in the water column but did not significantly affect the sediment concentrations. Harvesting the hydrophytes removed the equivalent of 58–88% and 39–78% of the nitrogen (N) and phosphorus (P) load associated with the water column, respectively. In contrast, the harvests accounted for only 1–2% of the N and P load associated with the sediments. In the pools, the combination of water recirculation and hydrophytes generally diminished the algal biomass and the associated N and P, compared to that observed for the lake. The combined use of adequate aquatic plant harvests and hydraulic management increased the efficiency of the system and, therefore, seems to be a useful tool for restoring small, shallow lakes in tropical and subtropical regions.
Water management of Lake Yogo targeting internal phosphorus loading
Authors: Tsujimura Shigeo
Published: December 2004

Lake Yogo is a small, eutrophic lake located 1.3 km north of Lake Biwa, Japan. The lake, which was originally a natural, closed lake, has a unique water management system. It is replenished with water pumped from Lake Biwa and supplies irrigation water to ≈ 5 km2 of agricultural fields. As a result, Lake Yogo functions as a water storage dam and is artificially controlled. As seen in most stratified lakes in temperate regions, large amounts of phosphate (PO4) are released from the sediment in the hypolimnetic water layer during the summer stratification period. In order to reduce the impacts of internal phosphorus (P) loading, a destratification aeration system was installed in the lake. Although the stratification was weakened concomitant with a temperature increase in the hypolimnetic layers, anoxic conditions were still observed because of the small scale of the aeration system, with cyanobacterial blooms continuing to occur during the summer and autumn of every year. Although the internal P load at the autumn turnover is probably immediately scavenged by its incorporation into ferric oxyhydroxide colloids, the phytoplankton present at that time would doubtless benefit from the temporary, increased PO4 supply because of their rapid uptake rates. Although the PO4 transported continually from the hypolimnetic to the epilimnetic layers by the destratification aeration system should be scavenged as ferric oxyhydroxide colloids, a portion of the PO4 is probably incorporated into the phytoplankton biomass. As a result, an insufficient level of artificial destratification might support phytoplankton growth during the period of thermal stratification in the lake.
The use of the Deaver Retractor to visualize staple line haemorrhage following stapled anopexy
Authors: Forshaw M. J. , Mhandu P. C. , Parker M. C.
Published: December 2004

Postoperative haemorrhage is a recognized complication of any haemorrhoidectomy procedure. It can be difficult to visualize a staple line haemorrhage in the presence of large circumferential haemorrhoids. We describe a technique to aid visualization of the staple line in this situation.
Comparison of rigid vs flexible sigmoidoscopy in detection of significant anorectal lesions
Authors: Rao V. S. R. , Ahmad N. , Al‐Mukhtar A. , Stojkovic S. , Moore P. J. , Ahmad S. M.
Published: December 2004

Objective  Sigmoidoscopy is an essential tool in colorectal clinics in the detection of anorectal lesions including rectosigmoid adenomas and carcinomas. However, rigid sigmoidoscope (RS) is still more widely used than flexible sigmoidoscope (FS) as the primary investigation, despite the fact that the latter is more comfortable to the patient and has greater diagnostic yield. Hence we wanted to compare the two modalities in terms of diagnostic use for picking up significant anorectal lesions.

Methods  A retrospective review of all patients referred to the colorectal clinic who had undergone both rigid and flexible sigmoidoscopy for investigation of colorectal symptoms in 2001 was done. Findings recorded during rigid and flexible sigmoidoscopy including depth of insertion, site of lesion and complications were analysed.

Results  152 patients underwent both rigid and flexible sigmoidoscopy as part of investigation of colorectal symptoms. Of the 115 (75.6%) declared normal by RS, 39 (33.9%) had significant lesions including 7 polyps and 4 malignant lesions within 20 cm of the anal verge during FS. Of the 31 patients (20.4%) in whom RS was not helpful due to faecal loading, 15 (48.4%) had significant lesions including 4 malignancies and 1 polp – all within 20 cm of the anal verge during FS. Only 2 polyps and 1 malignant lesion were picked up by both flexible and rigid sigmoidoscopy. There wre no complications in both procedures.

Conclusion  Since flexible sigmoidoscopy is superior to rigid sigmoidoscopy in terms of patient comfort, diagnostic value and ease of doing procedures like biopsy and polypectomy; it can be used as a front line investigation to exclude colorectal pathology in out patient clinics. The utility of rigid sigmoidoscope is in question and in view of obvious shortcomings, may be replaced by flexible sigmoidoscopy, though obvious resource constraints need to be considered.
Evaluation of a pre‐operative staging protocol in the management of colorectal carcinoma
Authors: Griffiths E. A. , Browell D. A. , Cunliffe W. J.
Published: December 2004

Objective  The optimum strategy for pre‐operative staging of colorectal carcinoma (CRC) has yet to be defined. A protocol for staging CRC patients was set up in this hospital in 1998. The protocol included complete colonic visualization together with assessment of the liver and lung for potential metastatic disease. Pelvic imaging was required to assess the local spread of rectal tumours. Our aim was to evaluate prospectively this protocol.

Patients and methods  Data from all patients diagnosed with primary CRC between January 1999 and December 2002 were prospectively collected and analysed.

Results  There were 295 patients; 56 (19%) patients presented as an emergency and were excluded. The study group consisted of 239 patients (206 had elective surgery and 33 had no resectional surgery). In the patients who presented electively; 88% had complete colonic imaging; 87% chest imaging; 90% had liver imaging; 91% of rectal tumours had pelvic imaging. Overall 75% of the elective patients completed the staging protocol. Reasons for incomplete staging were numerous and most were justifiable. Findings which influenced clinical management included alteration in surgical approach (14), lung metastases (7), primary lung cancers (2), definite liver metastases (25), possible liver metastases (8), neo‐adjuvant radiotherapy required (27), advanced local disease (9) and other incidental findings (12).

Conclusion  Our protocol influenced further management decisions in 39% of patients. Better stratification of patient care is possible, with the ultimate aim to avoid unnecessary surgery. However, complete staging is not always possible to perform.
Outcomes after placement of colorectal stents
Authors: Watson A. J. M. , Shanmugam V. , Mackay I. , Chaturvedi S. , Loudon M. A. , Duddalwar V. , Hussey J. K.
Published: December 2004

Background  Colonic stents are increasingly used to palliate or alleviate large bowel obstruction in patients with colon cancer and other obstructing lesions in whom a definitive surgical procedure is inappropriate. We report on the outcomes of a large group of patients who underwent deployment of a colon stent in a single institution by a single operator.

Patients and methods  This was a retrospective observational cohort study of all patients undergoing colonic stenting between September 1995 and May 2002. Data collected included nature of pathology, type of stent used, procedure morbidity, patient survival and details of any definitive procedures performed after stenting.

Results  One hundred and seven patients were evaluated (58 male) with a median age of 75 years (range 36–99 years). A total of 112 stents were successfully deployed (46 as an emergency). Twelve patients had double stents inserted coaxially and overlapping. In 7 patients the stent could not be safely deployed. Eighty‐seven patients had colorectal cancer, 13 patients had an extra‐luminal malignancy, 5 had diverticular strictures and in 2 patients the pathology was unknown. At last review (May 2002) 18 patients were alive, 82 patients had died and 7 patients had been lost to follow‐up. Of those patients who died, the median survival after stenting alone was 6 weeks (range 4 days – 36 weeks). Ten patients underwent subsequent definitive surgery. Stent complications included, 2 colonic perforations, 3 stent occlusions and 4 stent migrations.

Conclusion  Colonic stenting can be used effectively, with acceptable morbidity, to manage patients presenting with large bowel obstruction. In a smaller number of patients colon stents may safely temporize symptoms while definitive surgery is planned.
Endoscopic laser ablation of advanced rectal carcinoma – a DGH experience
Authors: Rao V. S. R. , Al‐Mukhtar A. , Rayan F. , Stojkovic S. , Moore P. J. , Ahmad S. M.
Published: December 2004

Background  Patients with inoperable advanced rectal carcinoma require palliation for local symptoms. Endoscopic Nd‐Yag laser ablation is a valid palliative treatment option in patients with advanced rectal carcinoma who are poor operative risks due to coexistent multiple comorbidities.

Methods  All patients who cannot undergo radical surgery due to various factors such as tumour size, poor risk patients, distant metastasis and refusal to undergo surgery were offered palliation with endoscopic Nd‐YAG laser ablation. Indications included troublesome bleeding, local recurrence, mucous discharge and impending obstruction. Patients were admitted on the day of treatment, phosphate enema given for bowel preparation and endoscopic ablation done through a flexible sigmoidoscope under intravenous sedation with midazolam. All patients were discharged the next day after overnight observation. Patients were reviewed every 3 months and laser ablation repeated if deemed necessary.

Results  Eleven patients (7 males, 4 females; mean age 83.6 years, range 77–90 years) underwent endoscopic laser ablation in a District General Hospital – 8 for rectal carcinoma, 2 for rectosigmoid tumour and 1 for recurrent tubulovillous adenoma. The number of treatment episodes varied from 1 to 12 with symptom free interval from 2 to 18 months between treatment episodes. There were 3 failures, one patient required defunctioning colostomy, one patient was referred for radiotherapy due to persistent symptoms and in one patient laser treatment had to be abandoned due to local extent. There were no immediate post‐treatment complications, but one patient developed incontinence after 5 episodes which might be attributable to tumour infiltration.

Discussion  Endoscopic laser ablation is a practical and feasible alternative to other palliative treatment modalities in the management of this unfortunate category of patients due to low morbidity and mortality, short hospitalization and low complication rates.
Urinary concentration of transforming growth factor‐β‐inducible gene‐h3(βig‐h3) in patients with Type 2 diabetes mellitus
Authors: Cha D. R. , Kim I. S. , Kang Y. S. , Han S. Y. , Han K. H. , Shin C. , Ji Y. H. , Kim N. H.
Published: December 2004

Aims  The expression of TGFβ‐inducible gene h3(βig‐h3) has been used to assess the biological activity of TGFβ in the kidney. In this study, we investigated whether the urinary concentration of βig‐h3 is associated with diabetic nephropathy in patients with Type 2 diabetes mellitus. We also evaluated the relationship between the urinary concentration of βig‐3 and proteinuria and microalbuminuria (AER) in a normal healthy population and in Type 2 diabetes patients.

Methods  Four hundred and seventy‐nine Type 2 diabetic patients without non‐diabetic kidney diseases and 528 healthy control subjects were enrolled. The study subjects were divided into five groups: a non‐diabetic healthy control group with normal ACR (n = 443), a non‐diabetic healthy control group with microalbuminuria (n = 85), a normoalbuminuric diabetic group (n = 198), a microalbuminuric diabetic group (n = 155) and an overt proteinuria group (n = 126). Urinary levels of βig‐h3 were measured by enzyme‐linked immunosorbent assay.

Results  (i) Urinary excretion of βig‐h3 was significantly higher in the diabetic groups than in the controls, even in the normoalbuminuric stage (25.02 ± 8.84 vs. 18.67 ± 6.56, P = 0.03). In diabetic patients, urinary βig‐h3 levels increased significantly as diabetic nephropathy advanced (25.02 ± 8.84 vs. 34.06 ± 24.55 vs. 169.63 ± 57.33, P < 0.001). (ii) Proteinuria was found to be significantly correlated with urinary βig‐h3 (healthy control; r = 0.137, P = 0.019, diabetic patients; r = 0.604, P < 0.001). ACR was also found to be significantly related with urinary βig‐h3 in diabetic patients (r = 0.383, P = 0.006). (iii) In diabetic patients, urinary βig‐h3 was significantly related with systolic and diastolic blood pressure (systolic blood pressure: r = 0.436, P = 0.024; diastolic blood pressure, r = 0.365, P = 0.042), total cholesterol and HbA1c (cholesterol: r = 0.169, P = 0.03, HbA1c; r = 0.387, P = 0.044). Logistic regression analyses showed that urinary βig‐h3 was associated with a significant increase in the risk of microalbuminuria and proteinuria in diabetic patients.

Conclusions  Longitudinal monitoring of urinary βig‐h3 may improve the likelihood of detecting diabetic nephropathy at an earlier stage and βig‐h3 could be a sensitive marker of diabetic kidney disease progression.
Barriers to following dietary recommendations in Type 2 diabetes
Authors: Vijan S. , Stuart N. S. , Fitzgerald J. T. , Ronis D. L. , Hayward R. A. , Slater S. , Hofer T. P.
Published: December 2004

Aims  To evaluate barriers to following dietary recommendations in patients with Type 2 diabetes.

Methods  We conducted focus groups and surveys in urban and suburban VA and academic medical centres. For the written survey, a self‐administered questionnaire was mailed to a random sample of 446 patients with diabetes. For the focus groups, six groups of patients with diabetes (three urban, three suburban) were conducted, with 6–12 participants in each group. The focus groups explored barriers across various types of diabetes self‐management; we extracted all comments relevant to barriers that limited patients’ ability to follow a recommended diet.

Results  The written survey measured the burden of diabetes therapies (on a seven‐point rating scale). Moderate diet was seen as a greater burden than oral agents (median 1 vs. 0, P = 0.001), but less of a burden than insulin (median 1 vs. 4, P < 0.001). A strict diet aimed at weight loss was rated as being similarly burdensome to insulin (median 4 vs. 4, P = NS). Despite this, self‐reported adherence was much higher for both pills and insulin than it was for a moderate diet. In the focus groups, the most commonly identified barrier was the cost (14/14 reviews), followed by small portion sizes (13/14 reviews), support and family issues (13/14 reviews), and quality of life and lifestyle issues (12/14 reviews). Patients in the urban site, who were predominantly African‐American, noted greater difficulties communicating with their provider about diet and social circumstances, and also that the rigid schedule of a diabetes diet was problematic.

Conclusions  Barriers to adherence to dietary therapies are numerous, but some, such as cost, and in the urban setting, communication with providers, are potentially remediable. Interventions aimed at improving patients’ ability to modify their diet need to specifically address these areas. Furthermore, treatment guidelines need to consider patients’ preferences and barriers when setting goals for treatment.
The association of smoking and subclinical atherosclerosis in Type 2 diabetes: modification by duration of diabetes
Authors: Karim R. , Buchanan T. A. , Hodis H. N. , Li Y. , Mack W. J.
Published: December 2004

Background  Diabetes is a relatively common disease in the United States, and cardiovascular disease is the major cause of morbidity and mortality among persons with diabetes. While smoking is one of the most well‐established risk factors for heart disease and atherosclerosis, the effect of smoking on atherosclerosis among diabetic patients has not been thoroughly investigated. The primary objective of this paper was to evaluate the impact of smoking on atherosclerosis among Type 2 diabetic patients and to evaluate whether smoking associations with atherosclerosis are modified by diabetes‐related variables.

Methods  We used cross‐sectional baseline data from a randomized controlled trial to evaluate the associations between smoking and common carotid artery intima‐media thickness (IMT) in 299 subjects with Type 2 diabetes. There were 34 (11%) current cigarette smokers, 73 (24%) former cigarette smokers, and 192 (64%) subjects who had never smoked regularly.

Results  There was an increasing trend in mean carotid IMT with both longer duration and increased frequency of smoking (adjusted P for trend 0.04 and 0.02, respectively). The mean ± SE carotid IMT was non‐significantly thicker (0.872 ± 0.01 mm) in diabetic patients who had ever smoked than never smokers (0.842 ± 0.01 mm) after controlling for age, gender and other potential confounders (P = 0.08). The negative effects of ever smoking (P = 0.01 for interaction), number of cigarettes smoked daily (P = 0.003 for interaction) and duration of smoking (P = 0.03 for interaction) on carotid IMT were accentuated with longer duration of diabetes.

Conclusion  Smoking is associated with subclinical atherosclerosis in diabetic persons and interacts with duration of diabetes to accentuate atherosclerosis. The association between carotid IMT and duration of diabetes increases with both the frequency and duration of smoking.
Factors predicting the blood glucose lowering effect of a 30‐day very low calorie diet in obese Type 2 diabetic patients
Authors: Jazet I. M. , Pijl H. , Frölich M. , Schoemaker R. C. , Meinders A. E.
Published: December 2004

Objective  To identify factors which predict the blood glucose lowering effect of monotherapy with a 30‐day very low calorie diet (VLCD) in obese Type 2 diabetic patients. A responder was a priori defined as a patient with a fasting plasma glucose (FPG) level < 10 mmol/l on day 30.

Research design and methods  In 17 obese patients (BMI 37.6 ± 5.6 (mean ± SD) kg/m2) with Type 2 diabetes, all blood glucose lowering medication (including insulin) was discontinued on day −1 followed by a 30‐day VLCD. On day 2 and 30 of the VLCD an intravenous glucose tolerance test (IVGTT) was performed.

Results  Of the 14 patients who completed the 30‐day VLCD, eight qualified as responder. Responders and non‐responders could be distinguished by day 2. Responders had a shorter duration of Type 2 diabetes and higher fasting serum insulin, C‐peptide and HOMA‐β‐values. In addition, responders displayed a more prominent second‐phase insulin response following i.v. glucose loading and higher k‐values. In a stepwise discriminant analysis, the change in FPG from day 0 to day 2 (responders +0.64 ± 2.3, non‐responders +4.15 ± 3.3 mmol/l, P = 0.035) in combination with the area under the curve of insulin (AUC) above baseline during an IVGTT on day 2 (responders 571 ± 236, non‐responders 88 ± 65 mU*50 min, P < 0.001), distinguished responders completely from non‐responders.

Conclusion  Preservation of the capacity of β‐cells to secrete insulin predicts a favourable metabolic response to a VLCD in obese Type 2 diabetic patients.
Market Visions: The Interplay of Ideas and Institutions in Chinese Financial Restructuring
Authors: Steinfeld Edward S.
Published: December 2004

In studies of transitional systems, negative economic outcomes are often associated with ‘partial’ or ‘stalled’ reform – a reform that signifies an institutional departure from standard market operation. Such departures are often traced to socio-political contestation or political preferences. Focusing on China's intertwined financial and enterprise reforms, this paper challenges that approach on two fronts. First, it argues that institutional change and resultant economic outcomes are driven less by contestation than by societally held assumptions regarding the nature of economic causation in market contexts. The analytical lenses that actors employ to understand their environment shape expectations about how markets function, influence the manner by which economic problems are diagnosed, and profoundly affect the ultimate institutional evolution of the system. Second, such lenses are necessitated by substantial uncertainties at the theoretical level regarding market function – uncertainties that make characterizations of economic behavior as ‘irrational’ highly problematic.
Globalisation, Ecological Modernisation and New Labour
Authors: Barry John , Paterson Matthew
Published: December 2004

Ecological modernisation (EM) provides the principal framework within which environmental policy reform projects are understood. However, writers using the approach, neglect to explain the political contexts within which it is possible to pursue such projects. Specifically, they ignore how discourses of globalisation structure the attempts of states to introduce environmental policy measures consistent with EM agendas. Through an analysis of the UK government's attempts to introduce policies consistent with an EM approach, we show that New Labour's discourse of globalisation acts to create opportunities for EM in some policy arenas and hinder them in others. We examine the development of a renewable energy strategy, the case of genetically modified foods, and transport policy. By specifying conditions under which EM may be pursued, the analysis reveals the potential, but also the limits, of this approach, which attempts to ignore the deep political questions raised by environmental degradation.
Sustainable Development as a Policy Telos: A New Approach to Political Problem-Solving
Authors: Levy Yoram , Wissenburg Marcel
Published: December 2004

The world seems to be characterized by political pluralization (the emergence of ‘polities’ other than the nation state) in addition to an already existing state of moral pluralism. This severely complicates political attempts at problem-solving on, for example, a global scale. One of the most stressing potential problems is the coexistence of mutually effacing or contradictory systems of political norms. To tackle such problems, we argue that policy teloi – shared conceptions giving direction to cooperative political ventures (particularly sustainable development) – can be helpful. The conditions of success for policy teloi in the case of environmental sustainability are investigated.
Rupture of the uterine scar during term labour: contractility or biochemistry?
Authors: Buhimschi Catalin S. , Buhimschi Irina A. , Patel Shilpa , Malinow Andrew M. , Weiner Carl P.
Published: December 2004

Objective  Vaginal birth after a prior low transverse caesarean section (VBAC) is advocated as a safe and effective method to reduce the total caesarean section rate. However, the risk of uterine rupture has dampened the enthusiasm of practising clinicians for VBAC. Uterine rupture occurs more frequently in women receiving prostaglandins in preparation for the induction of labour. We hypothesised that similar to the cervix, prostaglandins induces biochemical changes in the uterine scar favouring dissolution, predisposing the uterus to rupture at the scar of the lower segment as opposed to elsewhere.

Design  We tested aspects of this hypothesis by investigating the location of uterine rupture associated with prostaglandins and compared it with the sites of rupture in the absence of prostaglandins.

Settings  Two North American University Hospitals.

Population  Twenty‐six women with a prior caesarean section, experiencing uterine rupture in active labour.

Methods  Retrospective review of all pregnancies complicated by uterine rupture at two North American teaching hospitals from 1991 to 2000.

Main outcome measure  Site of the uterine rupture.

Results  Thirty‐four women experienced rupture after a previous caesarean section with low transverse uterine incision. Ten of the women who ruptured (29%) received prostaglandins for cervical ripening (dinoprostone: n= 8 or misoprostol: n= 2) followed by either spontaneous contractions (n= 3) or oxytocin augmentation during labour (n= 7). In 16 women (47%), oxytocin alone was sufficient for the induction/augmentation of labour. Eight (23%) women ruptured at term before reaching the active phase of labour in the absence of pro‐contractile agents or attempted VBAC. There were no differences among the groups in terms of age, body mass index, parity, gestational age, fetal weight or umbilical cord pH measurements. Women treated with prostaglandins experienced rupture at the site of their old scar more frequently than women in the oxytocin‐alone group whose rupture tended to occur remote from their old scar (prostaglandins 90%vs oxytocin 44%; OR: 11.6, 95% CI: 1.2–114.3).

Conclusion  Women in active labour treated with prostaglandins for cervical ripening appear more likely to rupture at the site of their old scar than women augmented without prostaglandins. We propose that prostaglandins induce local, biochemical modifications that weaken the scar, predisposing it to rupture.
Incidence of severe pre‐eclampsia, postpartum haemorrhage and sepsis as a surrogate marker for severe maternal morbidity in a European population‐based study: the MOMS‐B survey
Authors: Zhang Wei‐Hong , Alexander Sophie , Bouvier‐Colle Marie‐Hélène , Macfarlane Alison ,   the MOMS‐B Group
Published: December 2004

Objective  To describe the incidence of three conditions of acute severe maternal morbidity in selected regions in nine European countries.

Design  A population‐based questionnaire survey.

Setting  Eleven regions in nine countries of Europe.

Population  All the pregnant women in each region who had delivered during the period covered by the study.

Methods  Standard definitions of three severe obstetric conditions, pre‐eclampsia, postpartum haemorrhage and sepsis were established by a steering committee. A common questionnaire was used in each participating country. The incidence of the three obstetric conditions and characteristics of the study women were compared.

Main outcome measures  Incidence of three severe obstetric conditions: pre‐eclampsia, postpartum haemorrhage and sepsis.

Results  The study identified 1734 women with at least one of the three conditions, with 847 experiencing severe haemorrhage, 793 experiencing severe pre‐eclampsia and 142 experiencing severe sepsis. There were wide variations in incidence of three conditions combined, ranging from 14.7 per thousand deliveries in Brussels, Belgium to 6.0 per thousand deliveries in Upper Austria.

Conclusions  This study sets a simple and straightforward approach to the definition of three severe obstetric conditions and allows population‐based comparisons between developed countries in Europe, even though difficulties may have been present with applying the definition across countries. The reported incidence of these severe obstetric conditions in general and severe haemorrhage varied significantly between countries. Overall, severe haemorrhage in particular was the most common of the three conditions, followed closely by severe pre‐eclampsia.
A comparison of fetal organ measurements by echo‐planar magnetic resonance imaging and ultrasound
Authors: Duncan Keith R. , Issa Bashar , Moore Rachel , Baker Philip N. , Johnson Ian R. , Gowland Penny A.
Published: December 2004

Objectives  To compare fetal organ size measured using echo‐planar magnetic resonance imaging and 2D ultrasound. To determine the relative accuracy with which each technique can predict fetal growth restriction.

Design  A cross sectional, observational study comparing two different measurement techniques against a gold standard, in a normal clinical population and an abnormal population.

Setting and Population  Seventy‐four pregnant women (33 who were ultimately found to be normal and 37 with fetal growth restricted fetuses) were recruited from the City Hospital Nottingham UK to be scanned once (at various gestations).

Methods  Each fetus had a standard ultrasound biometry assessment followed by magnetic resonance imaging measurement of organ volumes.

Main outcome measures  For each measurement for both techniques, the normal population was plotted with 90% confidence intervals. Fetal growth restricted subjects were compared with the normal population using this plot; 2 × 2 tables were created for each measurement. This was used to calculate the relative sensitivities and positive predictive value of the different measurements. A Bland–Altman plot was used to compare the ultrasound and magnetic resonance imaging measurements of fetal weight.

Results  Brain sparing was seen in ultrasonic head circumference measurements, but an overall reduction in fetal growth restriction brain volume was apparent using magnetic resonance imaging at late gestations. Across the whole range of gestational ages, ultrasound assessment of fetal weight was the best predictor of fetal growth restriction.

Conclusion  Ultrasound fetal weight assessment appears to identify more fetuses with fetal growth restriction than abdominal circumference. The brain sparing apparent in ultrasonic head circumference measurements of fetuses with fetal growth restriction masks a reduction in brain volume observed with magnetic resonance imaging.
Evaluation of endocervical, first‐void urine and self‐administered vulval swabs for the detection of Chlamydia trachomatis in a miscarriage population
Authors: Logan S. , Browne J. , McKenzie H. , Templeton A. , Bhattacharya S.
Published: December 2004

Objective  To compare, in parallel, different approaches of opportunistically screening women with bleeding in early pregnancy for Chlamydia trachomatis.

Design  Cross‐sectional study.

Setting  Early pregnancy assessment unit, University hospital, Scotland, UK.

Population  Over 200 consecutive women admitted to an early pregnancy assessment unit were recruited. All had a positive pregnancy test, a history of vaginal bleeding and were less than 24 weeks of gestation. Women with recent antibiotic use, heavy vaginal bleeding and cervical shock excluded.

Methods  Each women provided two or more of the following specimens: a self‐administered vulval swab, first‐void urine and/or endocervical swab. Following screening, each completed a semi‐structured questionnaire assessing the acceptability of each method undertaken.

Main outcome measure  Subjective rating of the screening methods; prevalence; method performance, including proportion requiring repeat testing.

Results  The majority accepted screening, with moderate prevalence rates (95% CI) 3.9% (2.0–7.4%) identified. All positive women were less than 30 years of age. Parallel screening exposed the potential of reduced test performance with urine. Non‐invasive sampling was more acceptable, but more likely to require repeat testing.

Conclusion  Both acceptability and the effect of bleeding on test performance need further assessment before a particular specimen can be recommended for screening this population of women for C. trachomatis.