bluuebunny/crossref_metadata_2025 huggingface dataset:
Localization and Regulation of Pregnancy-Associated Plasma Protein A Expression in Healing Human Skin
Authors: Chen Bing-Kun , Leiferman Kristin M. , Pittelkow Mark R. , Overgaard Michael T. , Oxvig Claus , Conover Cheryl A.
Published: September 2003

Pregnancy-associated plasma protein A (PAPP-A) is an IGF-binding protein-4 (IGFBP-4) metalloproteinase that cleaves inhibitory IGFBP-4 to amplify local IGF-I bioavailability in vitro. Thus it has functional implications in injury/repair responses. In this study we determined PAPP-A expression in healing human skin. Wounds were induced with a scalpel on the forearms of three normal subjects and were allowed to heal by first intention. Biopsies obtained on d 0, 2, 8, and 14 were processed for immunohistochemical detection of PAPP-A, IGF-I, and IGFBP-4. In uninjured skin (d 0), strong staining for PAPP-A was present in the epidermis, sweat and sebaceous gland epithelial cells, hair follicles, and blood vessels; no PAPP-A was detected in dermal fibroblasts or with mature collagen bundles. IGF-I localized strongly to epithelial cells of skin glands was weak to moderate in epidermis and blood vessels, and was absent in dermal cells. Weak focal staining for IGFBP-4 was found within uninjured epidermis. During wound healing, PAPP-A expression was induced in dermal granulation tissue within and adjacent to the injury. PAPP-A was present in dermis on d 2 and was increased in intensity and extent on d 8 and 14. PAPP-A expression also increased in the epidermis. PAPP-A expression in cells of granulation tissue colocalized with α-smooth actin staining of myofibroblasts and new blood vessels as well as with CD68 staining of macrophages and was associated with the compact, newly synthesized collagen of the healing wound. IGF-I staining was enhanced in the epidermis localized to the area of the incision and in granulation tissue associated with lymphoid cells. IGFBP-4 staining of the epidermis remained unchanged during wound healing, but was induced in the fibroblastic cells of granulation tissue over time. These data demonstrate localized and regulated expression of PAPP-A in human skin and suggest that PAPP-A may play an important role in an integrated IGF system in wound healing and tissue remodeling in vivo.
The eukaryotic genome: a system regulated at different hierarchical levels
Authors: van Driel Roel , Fransz Paul F. , Verschure Pernette J.
Published: September 2003

Eukaryotic gene expression can be viewed within a conceptual framework in which regulatory mechanisms are integrated at three hierarchical levels. The first is the sequence level, i.e. the linear organization of transcription units and regulatory sequences. Here, developmentally co-regulated genes seem to be organized in clusters in the genome, which constitute individual functional units. The second is the chromatin level, which allows switching between different functional states. Switching between a state that suppresses transcription and one that is permissive for gene activity probably occurs at the level of the gene cluster, involving changes in chromatin structure that are controlled by the interplay between histone modification, DNA methylation, and a variety of repressive and activating mechanisms. This regulatory level is combined with control mechanisms that switch individual genes in the cluster on and off, depending on the properties of the promoter. The third level is the nuclear level, which includes the dynamic 3D spatial organization of the genome inside the cell nucleus. The nucleus is structurally and functionally compartmentalized and epigenetic regulation of gene expression may involve repositioning of loci in the nucleus through changes in large-scale chromatin structure.
Structural basis of urothelial permeability barrier function as revealed by Cryo-EM studies of the 16 nm uroplakin particle
Authors: Min Guangwei , Zhou Ge , Schapira Matthieu , Sun Tung-Tien , Kong Xiang-Peng
Published: September 2003

The apical surface of terminally differentiated mammalian urothelial umbrella cells is covered by numerous plaques consisting of two-dimensional (2D) crystals of hexagonally packed 16 nm uroplakin particles, and functions as a remarkable permeability barrier. To determine the structural basis of this barrier function, we generated, by electron cryo microscopy, a projection map of the isolated mouse urothelial plaques at 7 Å and a 3D structure at 10 Å resolution. Our results indicate that each 16 nm particle has a central 6 nm lipid-filled `hole' surrounded by 6 inverted U-shaped subunits, each consisting of an inner and an outer subdomain connected via a distal joint. The transmembrane portion of each subdomain can fit about 5 helices. This finding, coupled with our STEM and EM data, suggests that uroplakin pairs Ia/II and Ib/III are associated with the inner and outer subdomains, respectively. Since the inner subdomains interconnect to form a ring, which can potentially segregate the lipids of the central hole from those outside, the 2D crystalline uroplakin network may impose an organized state and a severely restricted freedom of movement on the lipid components, thus reducing membrane fluidity and contributing to the barrier function of urothelial plaques. Our finding that distinct uroplakin substructures are in contact with the cytoplasmic and exoplasmic leaflets of the plaque suggests that the two leaflets may have different lipid composition and contribute asymmetrically to the barrier function. We propose that the crystalline lattice structure of uroplakin, through its interactions with specialized lipids, plays a major role in the remarkable permeability barrier function of urothelial apical surface. Our results also have implications for the transmembrane signal transduction in urothelial cells as induced by the binding of uropathogenic E. coli to its uroplakin receptor.
Prediction of pressure drop for turbulent fluid flow in 90° bends
Authors: Crawford N M , Cunningham G , Spedding P L
Published: September 2003

The pressure drop for turbulent single-phase fluid flow around sharp 90° pipe bends has proven to be difficult to predict owing to the complexity of the flow arising from frictional and separation effects. Existing models accurately predict the frictional effects, but no precise models are available to predict the flow due to separation. It is the purpose of this work to propose a model capable of such prediction. The proposed model is presented and added to an existing model to predict pressure losses over the turbulent Reynolds number range up to 3 × 105. The predicted data is within a spread of + 3 to − 2 per cent of existing experimental data. Future work will validate this model experimentally and computationally
Designing an optimal controller for rectangular natural circulation loops
Authors: Cammarata L , Fichera A , Pagano A
Published: September 2003

Controlling the dynamics of natural circulation loops represents a major task for the widespread use of this kind of system in safe industrial applications. This paper aims to design an innovative model-based optimal controller for the suppression of unstable oscillations and flow reversals, which affect the dynamical behaviour of a closed-loop thermosyphon at high heating rate. The key idea is to define a multivariable control law aiming to minimize an objective function taking into account both the stability of the system and the cost of control. The design of the proposed controller has been based on a model approximating to the first three modes of the dynamics of rectangular circulation loops with imposed heat fluxes at the boundaries. The capability of the proposed controller in suppressing undesired dynamics has been experimentally demonstrated.
Plug force monitoring for the control and optimization of the thermoforming process
Authors: Harron G W , Harkin-Jones E M A , Martin P J
Published: September 2003

Thermoforming processes generally employ sheet temperature monitoring as the primary means of process control. In this paper the development of an alternative system that monitors plug force is described. Tests using a prototype device have shown that the force record over a forming cycle creates a unique map of the process operation. Key process features such as the sheet modulus, sheet sag, and the timing of the process stages may be readily observed, and the effects of changes in all of the major processing parameters are easily distinguished. Continuous, cycle-to-cycle tests show that the output is consistent and repeatable over a longer time frame, providing the opportunity for development of an on-line process control system. Further testing of the system is proposed.
An investigation of particle degradation by impact within a centrifugal accelerator type degradation tester
Authors: Abou-Chakra H , Tüzün U , Bridle I , Leaper M , Bradley M S A , Reed A R
Published: September 2003

There are several testing devices that are used throughout the world for quantifying particle degradation by impact against a solid surface. Some devices use pressurized air to accelerate particles so that they impinge upon a target, some use a vacuum system or mechanical devices to accelerate the particles. Others attempt to drop particles from a height to achieve the required velocity. All previous testers have some disadvantage associated with them, the most common being poor control over particle velocity. Because it is well known that impact velocity is the single most important controlling factor in particle degradation, this is a major disadvantage. The second major disadvantage of most previous work is that it involves only single or small numbers of particles, making it very difficult to scale to bulk. The purpose of this work was to design and construct an improved testing method in a pilot bench-scale unit for assessing degradation by impact. This test facility can control both the velocity of the particles and the angle of impact. Benefits associated with this facility are that the particle velocity is very closely controlled, the tester is portable, and only a small quantity of test material is required for each test.
Experimental study on elastic engagement and friction-coupled transmission
Authors: Xu Luohua , Huang Ping
Published: September 2003

A new type of mechanical transmission, elastic engagement and friction-coupled (EEFC) transmission, is studied. The surfaces of the transmission pairs consist of a large number of elastic clusters, through which power is transmitted from the driving part to the driven part. The experiments are carried out to test the performance of the EEFC transmission as clutch transmission and as belt transmission. The EEFC belt transmission is compared with a V-belt transmission.
Inverse approach for estimating pressure and viscosity in the elastohydrodynamic lubrication of circular contacts
Authors: Lee Rong-Tsong , Chu Hsiao-Ming , Chiou Yuang-Cherng
Published: September 2003

The film thickness under steady state conditions can be measured by using an optical interferometer. An inverse approach is proposed for estimating the pressure distribution on the basis of film thickness measurement in elastohydrodynamic lubrication (EHL) circular contacts. This approach is constructed from the approximated model of elastic deformation and force balance equations. To obtain an accurate pressure, it is necessary to divide the domain into a few regions on account of the singularity at the pressure spike. The principle of measuring point selection is proposed, and the problem of pressure fluctuation is overcome. On the basis of the smoothed pressure distribution, the apparent viscosity of the film can be obtained from the Reynolds equation. The least-squares method is used to compute the optimum value of the pressure-viscosity index. Results show that the best region for estimating the pressure-viscosity index is along the x axis because the Poiseuille term becomes zero in the Reynolds equation on account of the symmetry. In this region, the estimated pressure-viscosity index shows very good agreement with the exact value when measurement errors are neglected. When measurement errors are taken into account, the close agreement shows the potential of the proposed approach in estimating accurate values of the pressure-viscosity index. Generally, the error in estimating the pressure-viscosity index increases with increasing standard deviation of the measurement error, load, speed, material parameter and absolute error of the measured film thickness. The inverse approach can also be used to estimate the pressure distribution on a film thickness map obtained from an optical EHL tester. Moreover, the agreement between the actual and the estimated values of z is quite good.
Prevention of interfacial slippage in isothermal pure rolling line contact elastohydrodynamic lubrication under heavy loads
Authors: Zhang Yongbin
Published: September 2003

The contact-lubricant interfacial slippage, near and in the inlet zone, significantly reduces the load-carrying capacity of elastohydrodynamic lubrication (EHL) in isothermal pure rolling line contacts under heavy loads. The EHL load-carrying capacity can be significantly improved by the prevention of this interfacial slippage. Equations are derived for predicting the critical interfacial limiting shear stress, which is the least for preventing this interfacial slippage. These equations can be used for designing the EHL system of which the load-carrying capacity is not reduced by this slippage.
Formation and Structure of Protonated Tetrasilatetrahedrane-monooxide, (tert-Bu3Si)4Si4OH+
Authors: Ichinohe Masaaki , Takahashi Nobuyuki , Sekiguchi Akira
Published: August 2003

The reaction of tetrakis(tri-tert-butylsilyl)tetrasilatetrahedrane (1) with trityl tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (TFPB) gave protonated tetrasilatetrahedrane-monooxide, (tert-Bu3Si)4Si4OH+ (2+), whose structure was determined by X-ray crystallography.
Highly Diastereoselective Addition Reaction of Ketene Silyl Acetals to Imines Catalyzed by Samarium(III) Iodide
Authors: Hayakawa Ryuuichirou , Shimizu Makoto
Published: August 2003

In the presence of a catalytic amount of a samarium(III) iodide, the addition reaction of ketene silyl acetal to imine afforded the corresponding β-aminoester with high anti-selectivity. The reaction of chiral imine under the same conditions gave β-aminoester with high diastereoselectivity.
Hydroxy Group-Directed Homolytic Hydrostannylation of Alkenols with Dibutylchlorostannane
Authors: Miura Katsukiyo , Saito Hiroshi , Uchinokura Shingo , Hosomi Akira
Published: August 2003

In homolytic hydrostannylation of allyl alcohol 1a or homoallyl alcohol 1b, dibutylchlorostannane (Bu2ClSnH) exhibited a much higher reactivity than tributylstannane (Bu3SnH). Competitive reaction of 1a  vs. 1-octene with Bu2ClSnH led to the selective formation of γ-stannylated alcohol 3a. Hydrostannylation of 1,5-hexadien-3-ol (8) with Bu2ClSnH favored 1-stannylated product 9 over 6-stannylated product 10, while the use of Bu3SnH decreased the regioselectivity.
First Determination of Absolute Stereochemistry of N-Naphthylmaleimide Polymer
Authors: Oishi Tsutomu , Onimura Kenjiro , Isobe Yukio , Tsutsumi Hiromori
Published: August 2003

Chirality of N-1-naphthylmaleimide polymer (poly(1-NMI)) was attributed to difference between (S,S) and (R,R) configuration in threo-diisotactic structures. According to the exciton chirality method, relationships between specific rotation and configuration of poly(1-NMI) were found to be as follows: (+)-poly(1-NMI) contains (S,S) more than (R,R)-configuration, (−)-poly(1-NMI) contains (R,R) more than (S,S)-configuration.
Experimental Evidence for Helical Conformation of Poly(methylphenylsilylene) in Solution
Authors: Toyoda Seiji , Fujiki Michiya
Published: August 2003

This paper describes a simple methodology designed to prove that poly(methylphenylsilylene) (1) in solution has a helical conformation by a comparing the optical properties of optically inactive 1 with those of its optically active copolymer derivative. This approach can clarify the main-chain conformation from spectroscopic evidence.
Rhodium Catalyzed Transformation of 4-Pentynyl Cyclopropanes to Bicyclo[4.3.0]nonenones via Cleavage of Cyclopropane Ring
Authors: Koga Yuji , Narasaka Koichi
Published: August 2003

By using [RhCl(CO)2]2 as a catalyst, bicyclo[4.3.0]-nonenones are prepared from 4-pentynyl cyclopropanes under CO atmosphere via cleavage of cyclopropane ring.
The combined impact of future space‐based atmospheric sounding instruments on numerical weather‐prediction analysis fields: A simulation study
Authors: Collard A. D. , Healy S. B.
Published: September 2003

Previous studies have illustrated that assimilation into numerical weather prediction models of both space‐based radio‐occultation and advanced‐infrared‐sound er measurements will add significantly to our knowledge of the atmospheric state. In this study we show the degree to which the information contained in these data are complementary or whether there is significant redundancy between the observations.

Initially we examine the retrieval performances based on linear retrieval theory, from which we conclude that the radio‐occultation and advanced‐infrared‐soun der observations contribute their greatest impacts to different parts of the atmospheric temperature and humidity fields. Sequential one‐dimensional variational data assimilation (1DVar) simulations using simulated observations are then used to confirm these conclusions. The results of the 1DVar experiments are in very close agreement with the linear error analyses, and show that the information from the two types of observation are not only important but complementary. © Crown copyright, 2003. Royal Meteorological Society
Do forest fires affect lightning?
Authors: Smith J. A. , Baker M. B. , Weinman J. A.
Published: September 2003

Lightning statistics are analysed downwind of forest fires in 1998 and 2000. The previously studied 1998 case shows anomalously high frequencies of positive cloud‐to‐ground lightning (+CG%) in the southern Great Plains region of the USA, coincident with the smoke plume from forest fires in Central America. Fires in the northwestern USA in summer 2000 produced a smoke pall commensurate with the 1998 fires, but were not accompanied by statistically significant lightning anomalies. Analyses of meteorological data reveal that the southern Great Plains region was abnormally dry and hot during the period of anomalous lightning in 1998.

Using a 1.5‐dimensional thunderstorm model on a day with high +CG%, 15 May 1998, we find that whereas the percentage of positive cloud‐to‐ground lightning did not change significantly with changes in cloud condensation nuclei, adding moisture to the model significantly decreases the percentage of positive cloud‐to‐ground lightning, making it closer to the climatological norm. Copyright © 2003 Royal Meteorological Society
Removal of protein-bound and unbound unconjugated bilirubin by perfusion of plasma through an anion-exchange resin in a case of Crigler-Najjar syndrome type I
Authors: Ihara Hiroshi , Shino Yoshio , Hashizume Naotaka , Shimizu Norikazu , Aoki Tsugutoshi , Yoshida Mitsutaka
Published: September 2003

Background: Patients with Crigler-Najjar syndrome, type I (CNS-I) have an inherited absence of hepatocellular bilirubin uridine diphosphate-glucuronosyltransferase activity, which results in severe unconjugated hyperbilirubinaemia, often causing kernicterus and death in infancy or childhood.

Methods: Our patient is a 19-year-old Japanese man with CNS-I diagnosed by the complete absence of the hepatocellular enzyme in a liver biopsy and genotyping. The efficacies of the removal of protein-bound (PBB) and unbound (UB) unconjugated bilirubin by phototherapy, plasma perfusion and liver transplantation were compared in the patient.

Results: At the age of 5 years, phototherapy treatment reduced the patient's PBB by 21% and UB by 34%, and 98% of the bilirubin produced daily was removed. At the age of 16 years, plasma perfusion combined with nightly phototherapy completely removed the daily production of bilirubin; however, by 24 h post-treatment, the PBB and UB were again increased. Apparently, these treatments were effective in reducing PBB and UB, but the effect was only temporary. Following liver transplantation, PBB and UB decreased to normal concentrations.

Conclusions: Liver transplantation as a potential cure should be performed at a younger age, particularly in confirmed CNS-I cases for which reliable effects of phototherapy cannot be guaranteed.
Effect of homocysteine on cytokine production by human endothelial cells and monocytes
Authors: Dalal S , Parkin SM , Homer-Vanniasinkam S , Nicolaou A
Published: September 2003

Background: Hyperhomocysteinaemia is an independent risk factor in the development of cardiovascular disease. Although homocysteine has been shown to affect endothelial cell function, the mechanisms by which it induces disease states are still poorly understood. Here, we report the ability of homocysteine to influence inflammatory cytokine/chemokine production by human saphenous vein endothelial cells, peripheral blood monocytes and monocyte-derived macrophages.

Methods: Human saphenous vein endothelial cells, peripheral blood monocytes and monocyte-derived macrophages were treated with homocysteine (0.1-5 mmol/L) for 4 and/or 24h. Tumour necrosis factor (TNF)- α, interleukin (IL)-1 β, IL-6 and IL-8 production was measured in the cell culture media using commercially available enzyme-linked immunosorbent assays.

Results: Interleukin-6 production by human saphenous vein endothelial cells was significantly stimulated following a 24-h treatment with homocysteine, whilst IL-8 concentrations were inhibited after both 4- and 24-h treatments. Homocysteine was also found to stimulate IL-1 β production by human peripheral blood monocytes and TNF- α production by monocyte-derived macrophages.

Conclusions: Overall, results from this study suggest that homocysteine alters the profile of cytokine/chemokine production by endothelial cells and macrophages. This altered profile may be important in the inflammatory events that initiate or enhance the development of atherosclerotic lesions.
Practicability of using vaginal fluid markers in detecting premature rupture of membranes
Authors: Ni Chen Yi , Jia Wang Xue , Yi Wu Min , Feng Lu Hai , Yu Lin Zhi
Published: September 2003

Background: Premature rupture of membranes (PROM) may cause intra-uterine infection and fetal death. A diagnostic tool that is non-invasive, specific and quick is needed to predict PROM. Human chorionic gonadotrophin (hCG), α-fetoprotein (AFP) and interleukin 6 (IL-6), which are present in vaginal fluid, were reported to be potential markers for PROM but have not yet been used in the clinic. This study was designed in a daily routine semi-emergency setting to evaluate the clinical practicability of using these markers in diagnosing PROM.

Methods: Using a random-access automated luminescence immunoassay system, 81 vaginal washing samples collected from third trimester pregnant women (43 from PROM patients, 38 from patients with intact membranes) were analysed for β-hCG, AFP and IL-6 in a semi-emergency setting. The Mann-Whitney U-test was used to test the difference between the two groups. Receiver operator curve (ROC) analysis was used to evaluate the performance of the three markers and to determine the cut-off value for a positive diagnosis.

Results: Vaginal fluid concentrations of the three markers were significantly different ( P < 0.001) between the two groups. ROC analysis indicated that AFP had a 97.7% diagnostic sensitivity and 100% specificity; the other two markers had lower diagnostic sensitivity and specificity (95.3% and 89.5% for β-hCG and 83.7% and 78.9% for IL-6, respectively).

Discussion: This work demonstrates that, of the three markers investigated, AFP has the highest diagnostic sensitivity and specificity. Using the 'stat' function provided by the automated luminescence immunoassay system, the reporting time of the results was less than 1h. We conclude that vaginal fluid AFP measured by random-access automated luminescence immunoassay is an ideal marker for the diagnosis of PROM. The technique could be introduced into the laboratory as a semi-emergency service to meet clinical needs.
Products of advanced glycation in patients with type 2 diabetes and vascular disease
Authors: Turk Z , S̆esto M , Skodlar J , Ferenc̆ak G , Pokupec R , Turk N , Stavljenicć-Rukavina A
Published: September 2003

Background: Non-enzymatic glycation leading to advanced glycation endproduct (AGE) formation is thought to contribute to vascular pathology. In the present study, AGEs and anti-AGE antibodies in free and immune complex-bound form were assayed in the serum of diabetic (DMCAD) ( n = 69) and nondiabetic ( n = 78) patients with coronary artery disease (CAD) and in control subjects ( n = 47) free from vascular disease.

Methods: A blocking enzyme-linked immunosorbent assay (ELISA) was used to test immunoreactivity against AGE epitope(s) and a competitive ELISA was used to measure total AGE content.

Results: Anti-AGE immunoreactivity was significantly higher in diabetic than in control subjects ( P = 0.045). Although a wide range of anti-AGE antibody titres were observed in nondiabetic CAD patients, there was no significant difference from those of control subjects. Both diabetic and nondiabetic CAD patients had a higher concentration of circulating immune complexes containing the AGE moiety as antigen than did control subjects (DMCAD versus control, P = 0.041; CAD versus control, P = 0.047). Study patients showed a positive correlation between serum AGE and AGE-immune complexes (DM, r = 0.29, P = 0.014; CAD, r = 0.26, P = 0.019), whereas no such correlation was recorded in controls ( r = 0.08, P = 0.89).

Conclusion: To our knowledge, this is the first study demonstrating increased AGE-immune complexes in patients with CAD, either with or without diabetes, suggesting that AGE-immune complexes might be involved in the atherosclerotic process, either as the result of it or as part of the pathophysiologic process.
Elevated results in a vitamin B12 assay when using serum separator blood collection tubes
Authors: Lowrey I , Smith G
Published: September 2003

Background: In the light of apparently spurious serum vitamin B12 results in some patients, the effect of serum separator sample tubes on serum vitamin B12 values, assayed by the Bayer Centaur analyser, was examined.

Method: Results of parallel assays of serum vitamin B12 in plain (non-gel) serum tubes and serum separator gel tubes were compared. Serum in previously centrifuged gel tubes was mixed in the tube and the effect of that mixing on assay results quantitated. A limited investigation of the effect of tube cap type was also carried out.

Results: Serum vitamin B12 concentration was 54% higher in samples taken into serum separator tubes after re-mixing the serum in the original tube. This effect could be abolished by re-centrifugation.

Conclusions: Use of serum separator tubes may be associated with spuriously elevated serum vitamin B12 concentrations in the Bayer Centaur assay. Laboratories receiving samples for vitamin B12 assay in serum separator tubes that have already been centrifuged should either re-centrifuge the tubes, or aliquot and re-centrifuge serum from the tubes prior to vitamin B12 assay.
False negative results in the Roche assay for HDL-cholesterol
Authors: Bakker Andries J , Zijlstra Appie , Leemhuis Marten P
Published: September 2003

Measurement of HDL-cholesterol is important in the risk evaluation of cardiovascular disease. Recently, we encountered a 61-year-old man with a negative result for HDL-cholesterol using the Roche assay. Further analysis revealed that this patient had a monoclonal Ig type IgM κ, with an electrophoresis-based concentration of 55.8 g/L, which apparently caused the negative result for HDL-cholesterol. Analysis of serum samples from other patients with monoclonal or polyclonal hypergammaglobulinaemia revealed that false negative results in the Roche assay for HDL-cholesterol may occur incidentally. Since negative results are detected easily in the laboratory, such patients do not pose a problem in daily practice. However, it is reasonable to suppose that false low results could also be caused by monoclonal as well as polyclonal Igs. Since such false low results remain undetected, vascular risk estimates consequently are altered and unnecessary treatment might be started.
The case of stainless statins
Authors: Barth JH , Brownjohn AM , Jamieson DRS
Published: September 2003

Two cases of hypercholesterolaemic patients are presented in whom raised plasma creatine kinase was noted during treatment with statins. The plasma creatine kinase failed to fall following cessation of therapy. Further investigation revealed the aetiology of the raised plasma creatine kinase to be due to previously undiagnosed glycogen storage diseases (McArdle's and Pompe's diseases).
Insulin‐like growth factor‐I increases astrocyte intercellular gap junctional communication and connexin43 expression in vitro
Authors: Åberg N. David , Blomstrand Fredrik , Åberg Maria A.I. , Björklund Ulrika , Carlsson Björn , Carlsson‐Skwirut Christine , Bang Peter , Rönnbäck Lars , Eriksson Peter S.
Published: September 2003

Connexin43 (cx43) forms gap junctions in astrocytes, and these gap junctions mediate intercellular communication by providing transport of low‐molecular‐weight metabolites and ions. We have recently shown that systemic growth hormone increases cx43 in the brain. One possibility was that local brain insulin‐like growth factor‐I (IGF‐I) could mediate the effect by acting directly on astrocytes. In the present study, we examined the effects of direct application of recombinant human IGF‐I (rhIGF‐I) on astrocytes in primary culture concerning cx43 protein expression and gap junctional communication (GJC). After 24 hr of stimulation with rhIGF‐I under serum‐free conditions, the GJC and cx43 protein were analyzed. Administration of 30 ng/ml rhIGF‐I increased the GJC and the abundance of cx43 protein. Cell proliferation of the astrocytes was not significantly increased by rhIGF‐I at this concentration. However, a higher concentration of rhIGF‐I (150 ng/ml) had no effect on GJC/cx43 but increased cell proliferation. Because of the important modulatory role of IGF binding proteins (IGFBPs) on IGF‐I action, we analyzed IGFBPs in conditioned media. In cultures with a low abundance of IGFBPs (especially IGFBP‐2), the GJC response to 30 ng/ml rhIGF‐I was 81%, compared with the average of 25%. Finally, as a control, insulin was given in equimolar concentrations. However, GJC was not affected, which suggests that rhIGF‐I acted via IGF‐I receptors. In summary, the data show that rhIGF‐I may increase GJC/cx43, whereas a higher concentration of rhIGF‐I—at which stimulation of proliferation occurred—did not affect GJC/cx43. Furthermore, IGFBP‐2 appeared to modulate the action of rhIGF‐I on GJC in astrocytes by a paracrine mechanism. © 2003 Wiley‐Liss, Inc.
Fluorocitrate‐mediated astroglial dysfunction causes seizures
Authors: Willoughby John O. , Mackenzie Lorraine , Broberg Marita , Thoren Anna E. , Medvedev Andrei , Sims Neil R. , Nilsson Michael
Published: September 2003

A role for astroglia in epileptogenesis has been hypothesised but is not established. Low doses of fluorocitrate specifically and reversibly disrupt astroglial metabolism by blocking aconitase, an enzyme integral to the tricarboxylic acid cycle. We used cerebral cortex injections of fluorocitrate, at a dose that we demonstrated to inhibit astroglial metabolism selectively, to determine whether astroglial disturbances lead to seizures. Rats were halothane‐anesthetized, and 0.8 nmol of sodium fluorocitrate was injected into the cerebral cortex. Extradural electroencephalogram (EEG) electrodes were implanted, after which the anesthesia was ceased and the animals were observed. In all experiments, 14 of 15 fluorocitrate‐treated animals exhibited epileptiform EEG discharges, with some animals exhibiting convulsive seizures. Discharges commenced as early as 30 min postfluorocitrate injection. Intraperitoneal octanol, but not halothane by inhalation, given to test the possible participation of gap junctions in EEG discharge generation, blocked or delayed the occurrence of discharges after fluorocitrate. These results indicate that focal cerebrocortical astroglial dysfunction leads to focal epileptiform discharges and sometimes to convulsive seizures and that the process possibly depends on effects mediated by gap junctions. © 2003 Wiley‐Liss, Inc.
The effect of hydrophobic analogues of the type I winter flounder antifreeze protein on lipid bilayers
Authors: Tomczak Melanie M. , Hincha Dirk K. , Crowe John H. , Harding Margaret M. , Haymet A.D.J.
Published: September 2003

The effect of four synthetic analogues of the 37‐residue winter flounder type I antifreeze protein (AFP), which contain four Val, Ala or Ile residues in place of Thr residues at positions 2, 13, 24 and 37 and two additional salt bridges, on the binary lipid system prepared from a 1:1 mixture of the highly unsaturated DGDG and saturated DMPC has been determined using FTIR spectroscopy. In contrast to the natural protein, which increases the thermotropic phase transition, the Thr, Val and Ala analogues decreased the thermotropic phase transitions of the liposomes by 2.2°C, 3.4°C and 2.4°C, while the Ile analogue had no effect on the transition. Experiments performed using perdeuterated DMPC showed that the Ala and Thr peptides interacted preferentially with the DGDG in the lipid mixture, while the Val peptide showed no preference for either lipid. The results are consistent with interactions involving the hydrophobic face of type I AFPs and model bilayers, i.e. the same face of the protein that is responsible for antifreeze properties. The different effects correlate with the helicity of the peptides and suggest that the solution conformation of the peptides has a significant role in determining the effects of the peptides on thermotropic membrane phase transitions.
Iron chelation and a free radical scavenger suppress angiotensin II‐induced downregulation of klotho, an anti‐aging gene, in rat
Authors: Saito Kan , Ishizaka Nobukazu , Mitani Haruo , Ohno Minoru , Nagai Ryozo
Published: September 2003

Administration of angiotensin II to rats decreases renal expression of klotho, an aging‐related gene, and also causes abnormal iron deposition in renal cells. Here we have examined the effects of iron overload and iron chelation on renal expression of klotho in untreated rats and rats treated with angiotensin II. Administration of iron–dextran caused a downregulation of klotho expression, and iron chelation suppressed the angiotensin II‐induced downregulation of this gene. In addition, a free radical scavenger (T‐0970), which effectively decreased plasma levels of 8‐epi‐prostaglandin F2α (8‐epi‐PGF2α), suppressed angiotensin II‐induced downregulation of klotho. Collectively, these findings suggest that abnormal iron metabolism and increased oxidative stress are involved in the mechanism of angiotensin II‐mediated modulation of klotho expression.
Placental leucine aminopeptidase/oxytocinase gene regulation by activator protein‐2 in BeWo cell model of human trophoblast differentiation
Authors: Iwanaga Kumi , Nomura Seiji , Ito Tomomi , Ikoma Yoko , Yamamoto Eiko , Okada Mayumi , Itakura Atsuo , Kikkawa Fumitaka , Tsujimoto Masafumi , Mizutani Shigehiko
Published: September 2003

Placental leucine aminopeptidase (P‐LAP) is located preferentially in syncytiotrophoblasts in human placenta. Here we investigated P‐LAP expression and the regulatory mechanisms in BeWo choriocarcinoma cells with forskolin (FSK)‐induced differentiation. Morphologically differentiated cells revealed enhanced P‐LAP staining. FSK significantly increased P‐LAP activity and mRNA. Deletion or mutation of activator protein‐2 (AP‐2) binding site in the footprint‐3 (−216 to −172) of P‐LAP promoter abrogated the stimulatory effects of FSK on luciferase activity of the construct −216/+49. In AP‐2‐deficient Hep‐G2 cells, FSK failed to stimulate luciferase activity of the construct −216/+49. Among the isoforms, BeWo expressed AP‐2α and AP‐2γ, while FSK increased only AP‐2α. These results suggest differentiation‐dependent P‐LAP expression in trophoblasts, which involves increased AP‐2α binding.
Unfolding intermediate of a multidomain protein, calmodulin, in urea as revealed by small‐angle X‐ray scattering
Authors: Yokouchi Tsuyoshi , Izumi Yoshinobu , Matsufuji Tomohiro , Jinbo Yuji , Yoshino Hidenori
Published: September 2003

The denaturation of calmodulin (CaM) induced by urea has been studied by small‐angle X‐ray scattering, which is a direct way to evaluate the shape changes in a protein molecule. In the absence of Ca2+, the radii of gyration (R
g) of CaM are 20.8±0.3 Å in the native state and about 34±1.0 Å in the unfolded state. The transition curve derived from Kratky plots indicates a bimodal transition via a stable unfolding intermediate around 2.5 M urea. In the presence of Ca2+ and in the presence of both Ca2+ and a target peptide, the R
g values are 21.5±0.3 and 18.1±0.3 Å in the native state and 26.7±0.4 and 24.9±0.4 Å at 9 M urea, respectively. The results indicate that a stable unfolding intermediate still persists in 9 M urea. The present results suggest that the shape of unfolding intermediates is an asymmetric dumbbell‐like structure, one in the folded and one in the unfolded state.
Boric acid reversibly inhibits the second step of pre‐mRNA splicing
Authors: Shomron Noam , Ast Gil
Published: September 2003

Several approaches have been used to identify the factors involved in mRNA splicing. None of them, however, comprises a straightforward reversible method for inhibiting the second step of splicing using an external reagent other than a chelator. This investigation demonstrates that the addition of boric acid to an in vitro pre‐mRNA splicing reaction causes a dose‐dependent reversible inhibition effect on the second step of splicing. The mechanism of action does not involve chelation of several metal ions; hindrance of 3′ splice‐site; or binding to hSlu7. This study presents a novel method for specific reversible inhibition of the second step of pre‐mRNA splicing.
Activation in isolation: exposure of the actin‐binding site in the C‐terminal half of gelsolin does not require actin1
Authors: Narayan Kartik , Chumnarnsilpa Sakesit , Choe Han , Irobi Edward , Urosev Dunja , Lindberg Uno , Schutt Clarence E. , Burtnick Leslie D. , Robinson Robert C.
Published: September 2003

Gelsolin requires activation to carry out its severing and capping activities on F‐actin. Here, we present the structure of the isolated C‐terminal half of gelsolin (G4–G6) at 2.0 Å resolution in the presence of Ca2+ ions. This structure completes a triptych of the states of activation of G4–G6 that illuminates its role in the function of gelsolin. Activated G4–G6 displays an open conformation, with the actin‐binding site on G4 fully exposed and all three type‐2 Ca2+ sites occupied. Neither actin nor the type‐l Ca2+, which normally is sandwiched between actin and G4, is required to achieve this conformation.
Molecular assembly and subcellular distribution of ATP‐sensitive potassium channel proteins in rat hearts
Authors: Kuniyasu Akihiko , Kaneko Kazuyoshi , Kawahara Kohichi , Nakayama Hitoshi
Published: September 2003

Cardiac ATP‐sensitive K+ (KATP) channels are proposed to contribute to cardio‐protection and ischemic preconditioning. Although mRNAs for all subunits of KATP channels (Kir6.0 and sulfonylurea receptors SURs) were detected in hearts, subcellular localization of their proteins and the subunit combination are not well elucidated. We address these questions in rat hearts, using anti‐peptide antibodies raised against each subunit. By immunoblot analysis, all of the subunits were detected in microsomal fractions including sarcolemmal membranes, while they were not detected in mitochondrial fractions at all. Immunoprecipitation and sucrose gradient sedimentation of the digitonin‐solubilized microsomes indicated that Kir6.2 exclusively assembled with SUR2A. The molecular mass of the Kir6.2–SUR2A complex estimated by sucrose sedimentation was 1150 kDa, significantly larger than the calculated value for (Kir6.2)4–(SUR2A)4, suggesting a potential formation of micellar complex with digitonin but no indication of hybrid channel formation under the conditions. These findings provide additional information on the structural and functional relationships of cardiac KATP channel proteins involving subcellular localization and roles for cardioprotection and ischemic preconditioning.
Intrapartum chlorhexidine vaginal irrigation and chorioamnion and placental microbial colonization
Authors: Rouse D.J. , Lincoln T. , Cliver S. , Lyon M.D. , Andrews W.W. , Hauth J.C.
Published: September 2003

Objectives: To determine whether intrapartum chlorhexidine vaginal irrigation reduces microbial colonization of the chorioamnion or placenta. Methods: Secondary analysis was made of a randomized trial. Cultures for aerobic and anaerobic bacteria, Mycoplasma species and Ureaplasma urealyticum were performed using standard isolation techniques. Results: The placentas of 83 trial participants allocated to chlorhexidine and 93 allocated to placebo underwent evaluation. These two groups were statistically balanced for risk factors for infection. Aerobic bacteria were isolated from 47% of the chlorhexidine placentas vs. 51% of the placebo placentas (relative risk 0.9, 95% confidence interval 0.7–1.3), anaerobic bacteria from 30% and 35%, respectively (0.8, 0.5–1.3), group B streptococcus from 12% and 15% (0.8, 0.4–1.7), U. urealyticum from 18% and 29% (0.6, 0.4–1.1), Mycoplasma species from 6% and 11% (0.6, 0.2–1.6), and any organism from 57% and 67%, respectively (0.8, 0.7–1.1). Conclusions: Intrapartum chlorhexidine vaginal irrigation was associated with non‐significant reductions in the rates of placental microbial isolation.
Use of Patient Satisfaction Data in a Continuous Quality Improvement Program for Endoscopic Sinus Surgery
Authors: Tai Chih‐Jaan , Chu Chia‐Chen , Liang Shu‐Cheng , Lin Ting‐Fu , Huang Zu‐Jin , Tsai Yao‐Han , Wang Pa‐Chun
Published: September 2003

OBJECTIVE

Continuous quality improvement (CQI) is an effort by health care providers to improve the quality of service by continuously exceeding patients' expectations. Patient satisfaction is one of the measures of the quality of care. The aims of this study were to report the patients' evaluation of endoscopic sinus surgery (ESS) and to explore the feasibility in using patient satisfaction data in the CQI program for ESS.

METHODS

Eighty‐three patients completed a validated patient satisfaction survey (PSS) 1 month after undergoing ESS. Logistic regression models were applied to determine the confounders of patient satisfaction.

RESULTS

In general, 72% of patients were very satisfied with the services. Education level and milder disease correlated with higher overall satisfaction levels (P ≤ 0.01). Anesthesia, the addition of nasal septal surgery, intranasal packing, and postoperative sinuscopy had significant impacts on patient satisfaction (P < 0.05).

CONCLUSION

ESS is a good technique to evaluate for implementing efforts in quality improvement. Confounding factors need to be adjusted before patient satisfaction data can be used in a CQI program.
Dispositional anxiety and the experience of pain: gender‐specific effects
Authors: Jones Allan , Zachariae Robert , Arendt‐Nielsen Lars
Published: September 2003

Aim of Investigation: Increased anxiety is believed to correlate with increased pain sensitivity in men and women. However, one laboratory‐based study and one clinical‐based study have offered evidence to suggest that the effect of anxiety in modulating pain sensitivity is specific to men only. The aim of the present study was to examine further whether anxiety differentially effects men and women's report of experimentally induced pain.

Methods: One hundred forty‐four healthy university students (75 women, 69 men) were exposed to a contact heat pain procedure (ascending method of limits procedure, baseline temperature 30 °C, ±0.2 °C, rate of change 2.0 °C/s, cut‐off limit 52 °C) and a cold pressor pain procedure (constant temperature +1 °C; ±1 °C, cut‐off limit 240 s).

Results: The results agreed with the previous two studies indicating a sex‐specific effect of anxiety on pain report. Male participants scoring above the median on the Trait Anxiety Inventory reported significantly greater pain intensity, unpleasantness and showed lower pain tolerance compared to males scoring below the median on the cold pressor pain procedure, while no such differences in cold pressor pain report were found between high and low anxious women. No effect of anxiety was found on measures taken from the contact heat pain procedure, indicating that the sex‐specific effect of anxiety on laboratory induced pain is dependent upon the method of stimulation used.

Conclusion: Anxiety is an important factor when considering gender differences in pain perception and warrants further investigation.
Personalized pain words and Stroop interference in chronic pain patients
Authors: Andersson Gerhard , Haldrup Deborah
Published: September 2003

Attentional bias in patients with chronic pain was investigated using the emotional Stroop task with personalized pain words. A group of 20 chronic pain patients with 20 matched controls participated in the experiment. Before administration of the emotional Stroop patients were asked to select the five best descriptors of their pain from a list of 19 sensory pain descriptors. These words were later used in the computerized Stroop test. Also included in the Stroop task were threat words and color words with corresponding control conditions. Apart from the emotional Stroop, measures of pain related distress, anxiety, and depression symptoms were included. Results showed a weak Stroop interference effect with slower reaction times to pain words in the patient group, but they did not differ significantly from the controls. Both groups were slower on the threat words and displayed the classical Stroop interference effect for color words. The overall pattern of results are in line with previous Stroop studies on pain patients showing weak support for the attentional bias hypothesis.
Volcanism on Io: Estimation of eruption parameters from Galileo NIMS data
Authors: Davies Ashley Gerard
Published: September 2003

Galileo Near Infrared Mapping Spectrometer (NIMS) data of volcanic thermal emission are analyzed to determine the power output of a number of Ionian volcanoes, from which are calculated volumetric eruption rates. A two‐temperature model is used to determine surface temperatures and power output. Portions of Prometheus and six other volcanoes are found to be in excess of 1100 K: areas of Prometheus are at temperatures close to 1500 K. These are minimum eruption temperatures and are consistent with basaltic silicate volcanism. For the 14 volcanoes in G1INNSPEC01, volumetric eruption rates (E) are constrained between 3 and 300 m3/s for basaltic and ultramafic compositions. Actual E values lie between these limits. The small crack fractions (hot area to warm area ratio) implied from these fits are indicative of a relatively quiescent eruption style, such as the emplacement of a pahoehoe or a‐a flow field. The volumetric eruption rates derived from the NIMS data are greater than those observed in similar styles of volcanism on Earth. It is apparent that for similar eruption styles, the areal extent of activity is greater on Io than on Earth. Derived flow thicknesses range from 0.1 to 13 m.