bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical processes in a young biomass‐burning plume
Authors: Trentmann Jörg , Andreae Meinrat O. , Graf Hans‐F.
Published: November 2003

The photochemistry in young biomass‐burning plumes depends on the emissions from the fire and their mixing with the background atmosphere as well as on the actinic flux. In the present study a three‐dimensional plume model is used to investigate the photochemical evolution of a biomass‐burning plume during the first tens of minutes after the fire emissions have been released into the atmosphere. The model results represent the evolution of the plume from the Quinault prescribed fire conducted during the Smoke, Cloud, and Radiation‐C (SCAR‐C) experiment. The modeled ozone concentrations of about 70 ppb are close to observations. The main nitrogen reservoir species downwind of the fire are HNO3and peroxyacetyl nitrate, accounting for about ∼60% and ∼30% of the total nitrogen reservoir species, respectively. Photolysis of formaldehyde, which is emitted from the fire, is the primary source of radicals in the plume. Omitting the emissions of oxygenated volatile organic compounds in the modeled fire plume leads to unrealistically low ozone concentrations in the simulations. A nonabsorbing aerosol as well as the lower emission of NOxin the simulations enhance the radical concentration, the photochemical ozone formation, and the oxidation efficiency, at least at the timescales considered here. Further investigations of the atmospheric processes in young biomass‐burning plumes will increase our understanding of the interaction of transport and chemical processes not only in biomass‐burning plumes but also in other convective systems.
Spatiotemporal modeling and prediction of solar radiation
Authors: Bodas‐Salcedo A. , López‐Baeza E. , Martínez F. , Mateu J. , Montes F.
Published: November 2003

The radiation budget in the Earth‐atmosphere system is what drives Earth's climate, and thus measurements of this balance are needed to improve our knowledge of Earth's climate and climate change. In the present paper we focus on the analysis of the surface shortwave radiation budget (SSRB), which is the amount of energy in the solar region of the electromagnetic spectrum (0.2–4.0 μm) absorbed at the surface. The SSRB has to be modeled from the surface to the top of the atmosphere, jointly with information about the state of the atmosphere and the surface. These data come from satellites orbiting the Earth and are often missing or disturbed. Its interest is not only at global scales; rather, regional, high‐spatial‐resolution description is also of interest as an indicator of changes and because of its relationship to aridification from well‐developed vegetation. The goal of this paper is to estimate and predict the spatiotemporal evolution of SSRB data at a regional scale in eastern Spain. Two different spatiotemporal models with covariates are considered: one is based on modeling the spatiotemporal semivariogram and the other uses the Kalman filter technique for spatiotemporal prediction. We present comparisons between these two models with respect to the simpler, purely spatial model. The results show that there is not a great benefit to use the more complicated models, although there is a marginal improvement with complexity.
Optimization of dextran production by Leuconostoc mesenteroides NRRL B‐512 using cheap and local sources of carbohydrate and nitrogen
Authors: Behravan Javad , Fazly Bazzaz B. Seddigheh , Salimi Zohreh
Published: November 2003

Using pure components for the fermentation medium in dextran production imposes high costs on the industry. In the present study, the economic production of dextran using local and cheap sources of carbohydrate and nitrogen was investigated. Different concentrations of molasses and wheat‐bran extract, after filtration, steam sterilization and pH adjustment, were inoculated with a fresh suspension of Leuconostoc mesenteroides. Cultures were incubated, and then diluted with an equal volume of ethanol. The bacteria were pelleted, and an aliquot of the supernatant was diluted with ethanol and dextran was precipitated. The supernatant was removed and the precipitate was dissolved in a minimal volume of water. Activated charcoal was added and the solution was boiled. The solution was filtered and protein impurities removed by 2‐methylbutan‐2‐ol/chloroform extraction. Dextran was again precipitated with cold ethanol as described above, and the precipitate was dried in a desiccator. Optimum conditions and composition of culture media for dextran production using sugar‐beet molasses and wheat bran were determined. The best results were obtained when 20% (w/v) molasses and 15% (w/v) wheat bran were used. The optimal initial pH for dextran production was 7.5.
An improved dual‐expression concept, generating high‐quality antibodies for proteomics research
Authors: Falk Ronny , Agaton Charlotta , Kiesler Eva , Jin Shaobo , Wieslander Lars , Visa Neus , Hober Sophia , Ståhl Stefan
Published: November 2003

A novel, improved dual bacterial‐expression system, designed for large‐scale generation of high‐quality polyclonal antibody preparations intended for proteomics research, is presented. The concept involves parallel expression of cDNA‐encoded proteins, as a fusion with two different tags in two separate vector systems. Both systems enable convenient blotting procedures for expression screening on crude bacterial cell cultures and single‐step affinity purification under denaturing conditions. One of the fusion proteins is used to elicit antibodies, and the second fusion protein is used in an immobilized form as an affinity ligand to enrich antibodies with selective reactivity to the cDNA‐encoded part, common for the two fusion proteins. To evaluate the system, four cDNA clones from putative nuclear proteins from the non‐biting midge Chironomus tentans were expressed. Antibodies to these cDNA‐encoded proteins were generated, enriched and used in blotting and immunofluorescence procedures to determine expression patterns for the native proteins corresponding to the cDNAs. The four antibody preparations showed specific reactivity to the corresponding recombinant cDNA‐encoded proteins, and three of the four antibodies gave specific staining in Western‐blot analysis of nuclear cell extracts. Furthermore, two of the antibody preparations gave specific staining in immunofluorescence analysis of C. tentans cells. We conclude that the dual‐vector concept presented offers a highly stringent strategy for the generation of monospecific polyclonal antibodies, which are useful in proteomics research.
Structure and function of efflux pumps that confer resistance to drugs
Authors: BORGES-WALMSLEY M. Ines , McKEEGAN Kenneth S. , WALMSLEY Adrian R.
Published: November 2003

Resistance to therapeutic drugs encompasses a diverse range of biological systems, which all have a human impact. From the relative simplicity of bacterial cells, fungi and protozoa to the complexity of human cancer cells, resistance has become problematic. Stated in its simplest terms, drug resistance decreases the chance of providing successful treatment against a plethora of diseases. Worryingly, it is a problem that is increasing, and consequently there is a pressing need to develop new and effective classes of drugs. This has provided a powerful stimulus in promoting research on drug resistance and, ultimately, it is hoped that this research will provide novel approaches that will allow the deliberate circumvention of well understood resistance mechanisms. A major mechanism of resistance in both microbes and cancer cells is the membrane protein-catalysed extrusion of drugs from the cell. Resistant cells exploit proton-driven antiporters and/or ATP-driven ABC (ATP-binding cassette) transporters to extrude cytotoxic drugs that usually enter the cell by passive diffusion. Although some of these drug efflux pumps transport specific substrates, many are transporters of multiple substrates. These multidrug pumps can often transport a variety of structurally unrelated hydrophobic compounds, ranging from dyes to lipids. If we are to nullify the effects of efflux-mediated drug resistance, we must first of all understand how these efflux pumps can accommodate a diverse range of compounds and, secondly, how conformational changes in these proteins are coupled to substrate translocation. These are key questions that must be addressed. In this review we report on the advances that have been made in understanding the structure and function of drug efflux pumps.
Dual action of oestrogens on the mouse constitutive androstane receptor
Authors: MÄKINEN Janne , REINISALO Mika , NIEMI Kaisa , VIITALA Pirkko , JYRKKÄRINNE Johanna , CHUNG Hinfan , PELKONEN Olavi , HONKAKOSKI Paavo
Published: November 2003

mCAR (mouse constitutive androstane receptor; NR1I3) controls the expression of cytochrome P450 as well as other enzymes involved in drug and steroid metabolism. The high basal activity of mCAR can be modulated by inhibitory steroids related to androstenol and by activating xenobiotic chemicals such as 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene and chlorpromazine. The ability of oestrogens and some other xenobiotics to activate mCAR is not clear. In the present study, co-transfection assays in HEK-293 cells indicated that oestrogens varied in their efficacy to activate mCAR, depending on variation at the steroid D-ring and position of hydroxy groups. In general, oestrogens were weaker activators of mCAR than 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene and chlorpromazine. Also, the induction of CYP2B10 mRNA by oestrogens was less pronounced in mouse primary hepatocytes. Yeast two-hybrid assays indicated that, unlike androstenol and the established activators, oestrogens attracted both nuclear receptor co-repressors and co-activators to the mCAR ligand-binding domain, thus limiting the extent of mCAR activation. This novel dual action is not limited to oestrogens, but is shared by some xenobiotic CYP2B inducers such as clotrimazole and methoxychlor. These findings offer an alternative explanation for the recently suggested nuclear activation step of mCAR.
Studies on G-protein α·βγ heterotrimer formation reveal a putative S-prenyl-binding site in the α subunit
Authors: DIETRICH Alexander , SCHEER Alexander , ILLENBERGER Daria , KLOOG Yoel , HENIS Yoav I. , GIERSCHIK Peter
Published: November 2003

The α and βγ subunits of heterotrimeric G-proteins contain specific lipid modifications, which are required for their biological function. However, the relevance of these modifications to the interactions within the heterotrimeric G-protein is not fully understood. In order to explore the role of the S-prenyl moiety of the isoprenylated βγ dimer of retinal transducin, βγt, in the formation of the heterotrimeric complex with the corresponding N-acylated α subunit, αt, we employed purified fully processed subunits, which are soluble in aqueous solutions without detergents. Pertussis-toxin-mediated [32P]ADP-ribosylation of αt is strongly stimulated (≈10-fold) in the presence of βγt and can thus serve as a measure for heterotrimer formation. Using this assay, preincubation of αt with S-prenyl analogues containing farnesyl or geranylgeranyl moieties was found to inhibit heterotrimer formation in a dose-dependent manner. The inhibition was competitive and reversible, as indicated by its reversal upon increase of the βγt dimer concentration or by removal of the S-prenyl analogue using gel filtration. The competitive nature of the inhibition is supported by the marked attenuation of the inhibition when the S-prenyl analogue was added to αt together with or after βγt. The inhibition does not involve interaction with the αt acyl group, since an S-prenyl analogue inhibited the [32P]ADP-ribosylation of an unlipidated αt mutant. These data suggest the existence of a hitherto unrecognized S-prenyl-binding site in αt, which is critical for its interaction with prenylated βγt.
Enhanced expression of manganese-dependent superoxide dismutase in human and sheep CLN6 tissues
Authors: HEINE Claudia , TYYNELÄ Jaana , COOPER Jonathan D. , PALMER David N. , ELLEDER Milan , KOHLSCHÜTTER Alfried , BRAULKE Thomas
Published: November 2003

Neuronal ceroid lipofuscinosis type 6 and its sheep model (OCL6) are lysosomal storage disorders caused by mutations in the CLN6 gene product of unknown function. It has been proposed that mitochondrial dysfunction, including defects in mitochondrial protein degradation, organelle enlargement and functional changes in oxidative phosphorylation, may contribute to the disease pathology. To further explore the disease mechanisms underlying CLN6, protein expression was compared between normal and affected tissues. Using two-dimensional electrophoretic separation of proteins, MS and immunoblotting, MnSOD (manganese-dependent superoxide dismutase) was found to be significantly and specifically increased in fibroblasts and brain extracts of both human and sheep affected with CLN6. Both the activity and expression of MnSOD mRNA were enhanced in affected fibroblasts. Confocal fluorescence microscopy and immunohistochemical studies revealed the presence of MnSOD in mitochondria of CLN6 fibroblasts and in CLN6 brain sections within both neurons and hypertrophic astrocytes. These data suggest that oxidative stress and/or the production of pro-inflammatory cytokines are characteristic features of human and sheep CLN6, resulting in elevated expression of MnSOD, which may be important for diagnostic purposes.
Grb2 regulates Stat3 activation negatively in epidermal growth factor signalling
Authors: ZHANG Tong , MA Jing , CAO Xinmin
Published: November 2003

EGF (epidermal growth factor) binding to its receptor (EGFR) induces dimerization and autophosphorylation of the receptor at multiple tyrosine residues, which serve as docking sites for recruitment of proteins with SH2 (Src homology 2) domains that activate multiple downstream signalling pathways. The adaptor protein Grb2 (growth factor receptor-binding protein 2) binds to EGFR, which leads to activation of Ras-MAPK (mitogen-activated protein kinase) cascade. The latent transcription factors, STAT (signal transduction and activator of transcription), can also be activated by EGF in certain cell types. Since Ras-MAPK and STAT pathways are simultaneously stimulated by EGF, and Tyr-1086 and Tyr-1068 of EGFR are reported to be the binding sites for both Grb2 and Stat3, we investigated the possible regulatory role of Grb2 in STAT activation. In the present study, we report that transient expression of Grb2 specifically down-regulates EGF-stimulated tyrosine phosphorylation of Stat3, which leads to a repression of Stat3 transcriptional activity. In contrast, depletion of Grb2 by RNA interference substantially increases Stat3 tyrosine phosphorylation induced by EGF. The inhibition is neither mediated by a direct interaction between Grb2 and Stat3 nor via activation of tyrosine phosphatases. However, the repression was abolished by a mutation in the SH2 domain, but not the SH3 domains of Grb2, suggesting that inhibition involves binding of the receptor. Indeed, Grb2 inhibits the interaction between Stat3 and EGFR by competitive binding to the EGFR. On the other hand, Grb2 does not interact with the same sites as Stat3 on the interleukin-6 receptor and, therefore, has no effect on interleukin-6-induced tyrosine phosphorylation of Stat3. Taken together, our results demonstrate that, in EGF signalling, Grb2 regulates Stat3 activation negatively at the receptor level.
Deglycosylation of glycoproteins with trifluoromethanesulphonic acid: elucidation of molecular structure and function
Authors: EDGE Albert S. B.
Published: November 2003

The alteration of proteins by post-translational modifications, including phosphorylation, sulphation, processing by proteolysis, lipid attachment and glycosylation, gives rise to a broad range of molecules that can have an identical underlying protein core. An understanding of glycosylation of proteins is important in clarifying the nature of the numerous variants observed and in determining the biological roles of these modifications. Deglycosylation with TFMS (trifluoromethanesulphonic acid) [Edge, Faltynek, Hof, Reichert, and Weber, (1981) Anal. Biochem. 118, 131–137] has been used extensively to remove carbohydrate from glycoproteins, while leaving the protein backbone intact. Glycosylated proteins from animals, plants, fungi and bacteria have been deglycosylated with TFMS, and the most extensively studied types of carbohydrate chains in mammals, the N-linked, O-linked and glycosaminoglycan chains, are all removed by this procedure. The method is based on the finding that linkages between sugars are sensitive to cleavage by TFMS, whereas the peptide bond is stable and is not broken, even with prolonged deglycosylation. The relative susceptibility of individual sugars in glycosidic linkage varies with the substituents at C-2 and the occurrence of amido and acetyl groups, but even the most stable sugars are removed under conditions that are sufficiently mild to prevent scission of peptide bonds. The post-translational modifications of proteins have been shown to be required for diverse biological functions, and selective procedures to remove these modifications play an important role in the elucidation of protein structure and function.
Identification and characterization of differentially active pools of type IIα phosphatidylinositol 4-kinase activity in unstimulated A431 cells
Authors: WAUGH Mark G. , MINOGUE Shane , BLUMENKRANTZ Deena , ANDERSON J. Simon , HSUAN J. Justin
Published: November 2003

The seven known polyphosphoinositides have been implicated in a wide range of regulated and constitutive cell functions, including cell-surface signalling, vesicle trafficking and cytoskeletal reorganization. In order to understand the spatial and temporal control of these diverse cell functions it is necessary to characterize the subcellular distribution of a wide variety of polyphosphoinositide synthesis and signalling events. The predominant phosphatidylinositol kinase activity in many mammalian cell types involves the synthesis of the signalling precursor, phosphatidylinositol 4-phosphate, in a reaction catalysed by the recently cloned PI4KIIα (type IIα phosphatidylinositol 4-kinase). However the regulation of this enzyme and the cellular distribution of its product in different organelles are very poorly understood. This report identifies the existence, in unstimulated cells, of two major subcellular membrane fractions, which contain PI4KIIα possessing different levels of intrinsic activity. Separation of these membranes from each other and from contaminating activities was achieved by density gradient ultracentrifugation at pH 11 in a specific detergent mixture in which both membrane fractions, but not other membranes, were insoluble. Kinetic comparison of the purified membrane fractions revealed a 4-fold difference in Km for phosphatidylinositol and a 3.5-fold difference in Vmax, thereby indicating a different mechanism of regulation to that described previously for agonist-stimulated cells. These marked differences in basal activity and the occurrence of this isozyme in multiple organelles emphasize the need to investigate cell signalling via PI4KIIα at the level of individual organelles rather than whole-cell lysates.
Are prenyl groups on proteins sticky fingers or greasy handles?
Authors: MAGEE Anthony I. , SEABRA Miguel C.
Published: November 2003

This Commentary discusses the work of Dietrich et al. in this issue of the Biochemical Journal, which sheds new light on the biological roles of protein-bound prenyl groups by providing evidence that the α-subunit of the heterotrimeric G-protein transducin has a binding site for the geranylgeranyl group of the γ-subunit.
Does interplay between nitric oxide and mitochondria affect hypoxia-inducible transcription factor-1 activity?
Authors: MURPHY Michael P.
Published: November 2003

This Commentary discusses recent results from the laboratory of Salvador Moncada (Mateo et al., in this issue of the Biochemical Journal) that shed light on the interaction of nitric oxide (NO) and the transcription factor hypoxia-inducible factor 1 (HIF-1). Using cells stably transfected with inducible NO synthase (iNOS) under the control of a tetracycline-inducible promoter, they generated a range of NO concentrations and determined how these affected HIF-1α stability. HIF-1α, a component of the heterodimer HIF-1, is rapidly degraded at high oxygen concentrations, and thus HIF-1 is only active as a transcription factor under hypoxic conditions. The authors found a biphasic effect of NO concentration on HIF-1α stability. Close to hypoxia, low NO concentrations destabilized HIF-1α by inhibiting mitochondrial respiration, thereby increasing the local oxygen concentration. In contrast, high NO concentrations stabilized HIF-1α at both high and low oxygen concentrations by a non-mitochondrial pathway. These data resolve reported discrepancies on the effect of NO on HIF-1α stability at low oxygen concentrations and suggest that inhibition of mitochondrial respiration by NO may affect oxygen sensing by HIF-1 in vivo.
T wave peak-to-end interval and QT dispersion in acquired long QT syndrome: a new index for arrhythmogenicity
Authors: YAMAGUCHI Masato , SHIMIZU Masami , INO Hidekazu , TERAI Hidenobu , UCHIYAMA Katsuharu , OE Kotaro , MABUCHI Tomohito , KONNO Tetsuo , KANEDA Tomoya , MABUCHI Hiroshi
Published: November 2003

QT dispersion (QTD) on 12-lead ECGs has been proposed as a marker of malignant ventricular tachyarrhythmias, and increased QTD has been reported in long QT syndrome (LQTS). On the other hand, it has been demonstrated that transmural dispersion is associated with ventricular tachyarrhythmias in an experimental model. However, the precise type of QTD or transmural dispersion that contributes most to ventricular tachyarrhythmias in patients with LQTS remains unclear. We evaluated 27 patients with acquired LQTS. These patients were divided into two groups: group A (n=12), patients with polymorphic ventricular tachycardia [torsades de pointes (TdP)], and group B (n=15), patients without TdP. The QT intervals were corrected using Bazett's formula. QTD was measured as the difference between the maximum and the minimum QT intervals, and T wave peak-to-end interval divided by the QT interval (Tpe) in the V5 lead was measured as a new index. Both the corrected QTD (QTDc) and Tpe were significantly larger in group A than in group B. Logistic regression analysis revealed that a reliable predictor for TdP in the QT variables in these patients was not QTDc but Tpe. Cumulative frequency distributions revealed that a Tpe of 0.28 is a good cut-off point for TdP. Tpe did not correlate with the corrected maximum QT interval, whereas the QTDc did correlate with this parameter. In conclusion, Tpe may be the best predictor for TdP in patients with acquired LQTS.
Central and peripheral haemodynamic effects of hyperglycaemia, hyperinsulinaemia, hyperlipidaemia or a mixed meal
Authors: FUGMANN Andreas , MILLGÅRD Jonas , SARABI Mahziar , BERNE Christian , LIND Lars
Published: November 2003

The aim of the present study was to evaluate the haemodynamic changes during hyperinsulinaemia, hyperglycaemia or hypertriglyceridaemia in relation to those following a mixed meal. Ten subjects were subjected to hypertriglyceridaemia (3.9 mmol/l) for 2 h by an infusion of Intralipid® and heparin. Nine subjects received a hyperglycaemic clamp (12.5 mmol/l) with octreotide and low-dose insulin infusion to maintain normoinsulinaemia (10 m-units/l). Ten subjects received saline for 2 h as a control and, thereafter, 2 h of normoglycaemic hyperinsulinaemic clamp (80 m-units/l). Finally, ten subjects were evaluated for 2 h following an ordinary mixed meal. Calf blood flow was measured by venous occlusion plethysmography and cardiac index by thoracic bioimpedance. Both the mixed meal and normoglycaemic hyperinsulinaemia lowered total peripheral resistance, and increased calf blood flow and cardiac index, whereas blood pressure decreased (P<0.05-0.001). Both hyperglycaemia and hypertriglyceridaemia increased calf blood flow, but blood pressure was unchanged. Total peripheral resistance was unchanged in hypertriglyceridaemia, whereas hyperglycaemia induced a significant increase. Normoglycaemic hyperinsulinaemia induced a haemodynamic pattern similar, but to a lesser extent, to the pattern seen following a mixed meal. Hyperinsulinaemia seems to be a major mediator of the haemodynamic response, but other factors are obviously also of great importance. Hypertriglyceridaemia and hyperglycaemia induced haemodynamic responses that are not similar to those seen following a mixed meal.
Synergistic effect of angiotensin-converting enzyme (ACE) and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibition on inflammatory markers in atherosclerotic rabbits
Authors: OUBIÑA M. Pilar , HERAS Natalia de las , CEDIEL Eva , SANZ-ROSA David , ARAGONCILLO Paloma , DÍAZ Cristina , HERNÁNDEZ Gonzalo , LAHERA Vicente , CACHOFEIRO Victoria
Published: November 2003

In the present study, we compared the effect of atorvastatin (1 mg·kg-1·day-1) and quinapril (0.5 mg·kg-1·day-1) alone or in combination on inflammatory markers, endothelial function, intimal thickening and fibrinolytic balance in rabbits fed with either a control diet or a diet containing 1% (v/v) cholesterol for 12 weeks. Atorvastatin alone or in combination partially prevented the increase in cholesterol plasma levels observed in rabbits fed with the cholesterol-rich diet, but did not modify blood pressure levels. Quinapril administration did not alter any of these parameters in any group. Hypercholesterolaemia increased plasma levels of interleukin-1β, interleukin-6, interferon-γ and C-reactive protein, reduced acetylcholine-induced relaxation and produced intimal thickening. Likewise, atherosclerotic rabbits had reduced plasma tissue-type plasminogen activator activity and D-dimer levels and an increase in plasminogen-activator inhibitor-1 activity. Both drugs enhanced acetylcholine-induced relaxation, reduced intimal thickening and improved fibrinolytic balance in atherosclerotic rabbits in a similar manner. Their combination did not induce additive effects on these parameters. However, only the combination of both drugs was able to prevent the increase in inflammatory markers induced by hypercholesterolaemia. In summary, these data suggest that quinapril and atorvastatin had comparable beneficial effects on the alterations of vascular function and structure as well as fibrinolytic balance in atherosclerotic rabbits. In addition, the combination of atorvastatin and quinapril exerts a synergistic effect on inflammatory markers, which individual treatment, at the doses used, was not able to modify.
Activation of the right ventricular endothelin (ET) system in the monocrotaline model of pulmonary hypertension: response to chronic ETA receptor blockade
Authors: JASMIN Jean-François , CERNACEK Peter , DUPUIS Jocelyn
Published: November 2003

Although activation of the endothelin (ET) system contributes to pulmonary hypertension, modifications of the cardiopulmonary ET system and its responses to chronic ET receptor blockade are not well known. To investigate this, rats were injected with monocrotaline (60 mg/kg intraperitoneal) or saline, followed with treatment with the selective ETA receptor antagonist LU135252 (LU; 50 mg·kg-1·day-1) or with saline. After 3 weeks, haemodynamics, cardiac hypertrophy, ET-1 levels and cardiopulmonary ET-receptor-binding profile were evaluated. Monocrotaline (n=7) elicited marked pulmonary hypertension and right ventricular hypertrophy compared with controls (n=8). Both variables were substantially attenuated by LU therapy (n=8; P<0.05 for both). After monocrotaline, right ventricular ET-1 levels were more significantly increased than in the left ventricle (+198% compared with +127%; P<0.05). ETB receptor density was augmented (3-fold) in the right ventricle, whereas that of ETA receptors was not affected. LU treatment also significantly attenuated these alterations (P<0.05). In the lungs, ET-1 levels were not increased after monocrotaline, whereas the balance of ETB to ETA receptors was altered, with a trend toward a lower percentage of ETB than in the control rats. LU treatment did not affect these variables in the lungs. Therefore monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy are associated with the up-regulation of ET-1 and ETB receptors in the right ventricle. These alterations are attenuated with the reduction of pulmonary hypertension and right ventricular hypertrophy after chronic blockade of the ETA receptors, supporting the role of the ET system in right ventricular hypertrophy.
Functional adaptations of the postcranial skeleton of two Miocene borhyaenoids (Mammalia, Metatheria), Borhyaena and Prothylacinus, from South America
Authors: Argot Christine
Published: November 2003

Two Santacrucian borhyaenoids, Borhyaena tuberata and Prothylacinus patagonicus, are analyzed from a functional‐adaptive perspective. Seven extant placental and marsupial models are examined in order to interpret the locomotor adaptations of the two fossils. These carnivorous models are characterized by various hunting types and locomotor habits, and the association of their skeletal adaptive features with diet, substrate preference, and locomotor performance permits a functional interpretation of the postcranium of Borhyaena and Prothylacinus. The analysis shows that the forelimb of Prothylacinus is modified to provide strength and flexibility for controlled climbing. This taxon exhibits semiplantigrade fore‐ and hind feet. Its vertebral column was flexible, and the hindlimb suggests an active predatory mode of hunting. The tail was muscular, heavy, and was probably used as a balancing organ. By comparison, the forelimb of Borhyaena indicates a more terrestrial mode of life, with a digitigrade forefoot, and more parasagittal movements. The tail was lighter and less muscular than in Prothylacinus. Both fossils are characterized by a powerful neck musculature related to predatory habits.
Inadequate rates are lower when FNAC samples are taken by cytopathologists
Authors: Singh N. , Ryan D. , Berney D. , Calaminici M. , Sheaff M. T. , Wells C. A.
Published: November 2003

Inadequate rates (IR) in FNAC from different sources were compared. The rates were lowest when FNAC was performed by a cytopathologist (12%) and highest when done by a non‐cytopathologist (32%). These differences were mirrored in high IRs in breast cancer cases. IR was not significantly improved when non‐cytopathologist FNAC was attended by a cytotechnician.
Fine needle aspiration in plastic surgery outpatients: a retrospective study
Authors: Pleat J. M. , Dunkin C. S. J. , Tam N. , Buley I. D. , Griffiths P. , Coleman D. J.
Published: November 2003

A survey suggested that fine needle aspiration cytology of masses in plastic surgery outpatient clinics was suboptimal. A cytopathologist gave training in the technique and the effectiveness of this intervention was audited. A total of 236 aspirates were taken from 147 patients in the earlier time period and 215 from 149 in the later period. The overall inadequate aspirate rate remained constant at 43%. The most common reasons for poor aspirates were excess blood, unrepresentative adipose tissue and insufficient cellular material. When the specimen was adequate after training, the sensitivity and specificity of the investigation were 96% and 100%, respectively. We present methods for sample optimization. Alternative strategies may be to limit aspiration to one clinician or to refer the patient to a cytopathologist experienced in the technique.
Thyroid fine needle aspiration: the morphological features on ThinPrep® slide preparations. Eighty cases with histological control
Authors: Cochand‐Priollet B. , Prat J.‐J. , Polivka M. , Thienpont L. , Dahan H. , Wassef M. , Guillausseau P.‐J.
Published: November 2003

This study had several purposes: to define cytomorphological features of thyroid cells that might be modified by alcohol fixation; to optimize May‐Grünwald–Giemsa (MGG) staining on ThinPrep® (TP; Cytyc Inc., Bexborough, MA, USA) slides and to compare the diagnostic accuracy of slides prepared by a liquid‐based method with those obtained by conventional technique. This study included 120 cases of ultrasound‐guided fine needle aspiration (FNA) of the thyroid and 55 FNAs performed on surgically resected thyroid specimens. Histological control was available in 80 cases. In the first group of 120 FNAs, a split‐sample technique was used for the TP. Three screenings were performed: first, an individual screening of the conventional smears (CS) and of the TP, a second screening to compare cells observed on the TP with the histological control and a third screening to assess the previously defined diagnostic criteria. Twenty‐seven TP cases (22%) were considered unsatisfactory for diagnosis compared with 10 in CS (8%). The high rate of unsatisfactory cases with TP is likely to be due to the use of the split‐sample technique. The sensitivity was 94% for CS and 81% for TP. The specificity was 67% and 60% for CS and TP, respectively. Two occult papillary carcinomas were missed by both methods. As for the MGG staining, the modified technique used for TP resulted in the same quality as the standard procedure. Conversely, TP did however induce uncommon morphological features. In this study, sensitivity and specificity levels are higher for CS than for TP; the difference may be explained by the fact that the methanol fixative used for TP induces some cytological alterations, especially in oncocytic tumours and lymphocytic thyroïditis.
Chromosomal abnormalities and DNA image cytometry of haematological neoplasms in fine needle aspirates of lymph nodes
Authors: Borovecki A. , Kardum‐Skelin I. , Sustercic D. , Hitrec V. , Lasan R. , Jaksic B.
Published: November 2003

The current diagnostics of haematological neoplasms along with morphological analysis, immunophenotyping and molecular analysis inevitably includes cytogenetic analysis. In this work the possibility of cytomorphological subclassification of haematological neoplasms from lymph node fine needle aspirates was examined without depending upon the referential histological diagnosis and cytogenetic analysis. In addition, the feasibility of cytogenetic analysis of the material obtained by lymph node fine needle aspiration (FNA) was examined. By analysing the findings of cytogenetic analysis and DNA image cytometry, it was decided to examine the possibility of comparing the findings and supplementing diagnostic possibilities of these methods. In 15 cases cytological diagnoses and cytogenetic analysis of haematological neoplasms were performed on the material obtained by lymph node FNA. In 12 of 15 cases histological diagnosis was made separately. A good cytohistological correlation was available in 9 of 12 cases (75%). Cytomorphological diagnoses in 10 of 15 cases (76%) were confirmed by the finding of a specific chromosomal translocation. In two cases cytological diagnosis did not correlate with the histological diagnosis and was confirmed only with specific chromosomal translocations. The lymphocytes obtained by lymph node FNA were adequate material for cytogenetic analysis – in 15 of 18 (83%) cases mitoses in cell cultures were obtained. In 13 of 15 (87%) cases clonal chromosomal abnormalities were detected, whereas in 2 of 15 (13%) cases a normal karyotype was found. DNA image cytometry was performed on nine samples, whereas in six samples the material was not sufficient. Although a small number of samples was analysed in the cases with identical cytomorphological diagnoses, the analysed histograms regarding the DNA index values showed heterogeneity. In conclusion, a cell culture sampled by FNA of lymph nodes is an adequate method for the chromosomal analysis. The specific cytogenetic abnormality associated with cytological diagnosis provides an opportunity to make a definitive diagnosis and provides a powerful approach when reference diagnosis on biopsy material cannot be obtained.
Towards global poliomyelitis eradication: The successes and challenges for a developed country
Authors: Wood N , Thorley B
Published: November 2003

Abstract:  The Sabin oral polio vaccine (OPV) has been remarkably successful, with three major regions of the world declared polio free. Mutations of the live attenuated poliovirus during genomic replication have resulted in polioviruses with increased neurovirulence. Recently, mutated vaccine‐derived polioviruses have circulated in countries with low OPV vaccination coverage causing outbreaks of poliomyelitis in the islands of Haiti, the Dominican Republic, the Philippines and Madagascar. Ultimately the total eradication of poliomyelitis requires the cessation of OPV use. The current questions of how best to continue polio immunisation and when OPV should be withdrawn are addressed. Prolonged excretion of poliovirus in stools following cessation of vaccination has the potential to infect unimmunized susceptible children. In Australia the change to the use of inactivated polio vaccine (IPV), while more costly, will avoid the very low risk of vaccine associated paralytic poliomyelitis (one case per 2.5 million doses) and maintain immunity against polio. In the future, new vaccines may provide the solution to the problem of OPV cessation.
Pulmonary function and scoliosis in children with spinal muscular atrophy types II and III
Authors: Chng SY , Wong YQ , Hui JH , Wong HK , Ong HT , Goh DY
Published: November 2003

Aims:  The objectives were to evaluate the clinical course of spinal muscular atrophy (SMA) types II and III patients necessitating scoliosis surgery at the National University Hospital, Singapore.

Methods:  A retrospective review of SMA types II and III patients, born over a 10‐year period between 1983 and 1992, was conducted.

Results:  There were eight patients: four with SMA type II and four with SMA type III. The mean age at scoliosis surgery was 9 years 7 months (range 7 years 6 months−12 years 4 months). The mean preoperative Cobb angle was 65.4° (range 43−90°) and the mean postoperative Cobb angle was 22.6° (range 12−45°), with a mean correction of 64.8% (range 47.7−77.8%). The decline in percentage predicted forced vital capacity (FVC) was 7.7% (95% CI: 12.4% to 3.0%) per year preoperatively and this was reduced to 3.8% (95% CI: 5.8% to 1.9%) per year postoperatively. The mean length of preoperative and postoperative lung function follow‐up was 6.3 months (range 0.03−31 months) and 44 months (range 0−110 months), respectively.

Conclusions:  This study suggests that pulmonary function in SMA types II and III continues to decline after scoliosis surgery, though the rate of decline is less marked. Overall, the combined results from this study and all other previously published studies are conflicting in regard to the effect of scoliosis surgery on pulmonary function in SMA types II and IIII, though half of the studies (3 of 6) did demonstrate a continued decline in lung function postoperatively. This decline in pulmonary function despite spinal stabilization is likely secondary to the progressive neuromuscular weakness of the disease.
Monitoring the ‘Strong Women, Strong Babies, Strong Culture Program’: The first eight years
Authors: Tursan d’Espaignet E , Measey ML , Carnegie MA , Mackerras D
Published: November 2003

Objective:  To assess improvements in perinatal health following the introduction of the Strong Women, Strong Babies, Strong Culture (SWSBSC) Program in two groups of Aboriginal communities in the Northern Territory.

Methods:  A comparison of pre and post birthweights in intervention and control communities in rural and remote regions in the Top End of the Northern Territory was performed.

Results:  Significant improvements in birthweight were observed for Group 1 communities with no significant change in Group 2.

Conclusion:  There is a need to better understand how the intervention differed in the two groups of communities.
Congenital malaria in a preterm infant
Authors: Hewson MP , Simmer K , Blackmore T
Published: November 2003

Abstract:  A case of congenital malaria in a preterm newborn infant is presented. The case illustrates the difficulty of early diagnosis, and the atypical nature of presentation in a preterm infant.
Simple dorsal plication near the 12 o’clock position for the correction of congenital ventral penile curvature
Authors: TAN MUSTAFA ÖZGÜR , BİRİ HASAN , GÜROCAK SERHAT , ŞEN İLKER , KÜPELİ BORA , BOZKIRLI İBRAHİM
Published: November 2003

Abstract  Fourteen patients with congenital penile curvature without hypospadias were treated with a modified Essed dorsal plication method between 1998 and 2002 in our clinic. Patient age ranged between 20 and 25 years (mean 22.2). Eight cases (57.1%) had ventral curvature only and six had an additional lateral curvature. There were no significant postoperative complications. One (7.1%) patient had early suture breakage on the 21st postoperative day during erection and underwent re‐operation after 9 months. After a mean follow‐up period of 23.2 months (range 3–46) all patients were satisfied with the procedure except for one patient (7.1%) who had a residual curvature of 20°. Four cases (28.6%) had minimal shortening of the penis. The overall satisfaction rate with the procedure was 93%. Simple dorsal plication near the 12 o’clock position is a minimally invasive and effective method for the treatment of congenital ventral penile curvature.
Questionnaire survey of Japanese urologists concerning the diagnosis and treatment of chronic prostatitis and chronic pelvic pain syndrome
Authors: KIYOTA HIROSHI , ONODERA SHOICHI , OHISHI YUKIHIKO , TSUKAMOTO TAIJI , MATSUMOTO TETSURO
Published: November 2003

Objectives:  We performed a questionnaire survey to investigate various issues in the diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome by Japanese urologists and to clarify the circumstances surrounding prostatitis in Japan.

Methods:  Japanese urologists (n = 1869) were surveyed by mail using a 17‐item questionnaire to determine current diagnostic and treatment practices for prostatitis/chronic pelvic pain syndrome.

Results:  Only 1.5% (11/739) of urologists diagnosed chronic prostatitis/chronic pelvic pain syndrome using the 4‐glass test, while most did so using the 2‐glass test (voided bladder [VB]2 and VB3, or VB2 and expressed prostatic secretion [EPS]). Approximately half (55.2%; 412/746) did not perform urine cultures to differentiate chronic bacterial prostatitis from chronic abacterial prostatitis/chronic pelvic pain syndrome. Approximately half (46%; 343/746) did not count the number of leukocytes in VB2 or VB3/EPS to differentiate chronic abacterial prostatitis from chronic pelvic pain syndrome. Although many urologists (63.8%; 459/720) thought that chronic abacterial prostatitis/chronic pelvic pain syndrome was not an infectious disease, many chose antimicrobial agents as the primary treatment. More than half (52.2%; 384/735) of all urologists felt pessimistic about dealing with chronic prostatitis/chronic pelvic pain syndrome compared to treating benign prostatic hypertrophy or prostate cancer, because of the high number of complaints by patients and their own lack of confidence in diagnosing and treating the condition.

Conclusion:  There is much confusion and frustration among Japanese urologists about chronic prostatitis/chronic pelvic pain syndrome. Further studies are needed to elucidate its etiology and pathogenesis, and to establish guidelines for its diagnosis and treatment.
Role of ureteroscopic biopsy in the management of upper urinary tract malignancy
Authors: SHIRAISHI KOJI , EGUCHI SATOSHI , MOHRI JUN , KAMIRYO YORIAKI
Published: November 2003

Background:  The aim of the study presented here was to examine the accuracy of ureteroscopic biopsy in the diagnosis of upper urinary tract transitional cell carcinoma (TCC) and whether nephron‐sparing management (holmium YAG laser, transurethral resection or partial ureterectomy) is possible or not based on pathological diagnosis.

Methods:  Forty consecutive patients underwent ureteroscopic biopsy with the use of 3‐Fr cold cup forceps. Pathological diagnosis of the biopsy sample and grade or stage of surgically resected tumors were compared. In patients with grade 1 or 2 TCC diagnosed by ureteroscopic biopsy, the disease‐free and survival rates determined whether nephron‐sparing management was performed or not.

Results:  There were no major complications associated with ureteroscopic biopsy. The pathological grading of the biopsy specimen was almost the same as that of the surgically resected specimen. Eighty five percent of grade 2 or 3 TCC showed muscle invasive disease. There were no significant differences in the disease‐free and survival rates between the nephroureterectomy and the nephron‐sparing management groups, except for grade 3 or pT3 tumors.

Conclusion:  Ureteroscopic biopsy is safe and accurate if sufficient tissue sample is obtained. Ureteroscopic biopsy should be performed in patients who require nephron‐sparing management. Nephroureterectomy can be avoided if the tumor is confirmed as low‐grade.
Psychological trauma of circumcision in the phallic period could be avoided by using topical steroids
Authors: YILMAZ ERDAL , BATISLAM ERTAN , BASAR MEHMET MURAD , BASAR HALIL
Published: November 2003

Objective:  The objective of our study was to assess the efficacy of topical steroids in the treatment of phimosis and evaluate patients using the Diagnostic and Statistical Manual‐III‐Revised (DSM‐III‐R) test with the aim of eliminating castration anxiety of circumcision in the phallic period.

Methods:  One hundred and forty‐nine children with phimosis who required circumcision were included the study. The average age of the children was 4.47 years. All children underwent the DSM‐III‐R test and their parents were questioned. Patients were separated randomly into three groups. Group I comprised 51 children who would undergo circumcision; group II comprised 50 children who would be treated with a topical corticosteroid (0.05% bethamethasone cream) twice daily for 1 month; and group III comprised 48 children who would be treated with a topical placebo cream. On the 5th day of treatment, parents were told to retract the prepuce and were given hygiene routine instructions. Patients were seen immediately after treatment and again 2 months later.

Results:  In group II, 16 of the 50 children had non‐retractable prepuce. Forty‐two cases of phimosis were corrected after treatment. Eight patients received further monthly treatment and five benefited from the second course of treatment. In group III, 17 of the 48 patients had non‐retractable prepuce and four had satisfactory results. Forty‐four patients received placebo treatment for another month and eventually, 40 children underwent circumcision in this group. DSM‐III‐R test results showed a significant shift to anxiety in the circumcision group. The were no significant differences in the other groups.

Conclusion:  Topical steroids for the treatment of phimosis is a highly effective treatment alternative to surgery. It avoids or delays circumcision and can be practised during the phallic period to decrease castration anxiety. The treatment is suitable for patients from any religious or cultural background.