bluuebunny/crossref_metadata_2025_split huggingface dataset:
The basement membrane matrix in malignancy
Authors: Engbring Jean A , Kleinman Hynda K 
Published: July 2003

AbstractCancer is the second most common cause of death among Americans, although for several age groups it ranks first. Most of these deaths are not due to the primary tumour but rather to tumour cell metastases to distant organs. There are many steps that lead to metastasis, all of which are being studied with the goal of preventing these fatalities. Normally, cells attach to the extracellular matrix to maintain tissue integrity. During cancer progression, cells become more motile and acquire invasive qualities. Tumour cells move along blood and lymph vessels or invade into them to travel to distant sites. Then, the tumour cells must attach to the vessel wall, extravasate from the vessel, invade the new tissue, proliferate, and form a secondary tumour. Angiogenesis, the formation of new blood vessels, is critical to survival of these cells at the new site and is also important for primary tumour growth and spread. Tumour cell metastasis is a complex cascade of sequential steps, each of which is not yet fully understood. Progress has been made in identifying several key activators, one of which is the extracellular matrix. A major tumour promoter is the glycoprotein laminin, which is predominantly found in the extracellular matrix produced by endothelial and epithelial cells. This review will follow the metastatic process with particular attention to the effect of laminin on tumour cells. Copyright © 2003 John Wiley & Sons, Ltd.
Integrins in regulation of tissue development and function
Authors: Danen Erik HJ , Sonnenberg Arnoud 
Published: July 2003

AbstractAn erratum for this article has been published in Journal of Pathology; 201(4): 632–641.Cell adhesion is indispensable for embryonic development and for proper tissue function. In metazoans, integrins are the major adhesion receptors that connect cells to components of the extracellular matrix. Integrins are implicated in assembly of extracellular matrices, cell adhesion and migration on extracellular matrices, and in vertebrates (in which the integrin family has expanded) they can also mediate cell–cell adhesion. Furthermore, integrin‐mediated adhesion can modulate many different signal transduction cascades and support cell survival, proliferation, and influence the expression of differentiation‐related genes. In this review we briefly explain how integrins can affect so many different aspects of cell behavior and discuss evidence for roles of integrins in tissue development, function, and disease. Copyright © 2003 John Wiley & Sons, Ltd.
ECM homeostasis in renal diseases: a genomic approach
Authors: Eikmans M , Baelde JJ , de Heer E , Bruijn JA 
Published: July 2003

AbstractChronic renal disease is in general histologically accompanied by a vast amount of scar tissue, ie glomerulosclerosis and interstitial fibrosis. Scarring results from excessive accumulation of extracellular matrix (ECM) components, a process driven by a plethora of cytokines and growth factors. Studies in experimental renal disease which target these regulators using gene therapy limit or prevent the development of scarring. This review focuses specifically on the role of transforming growth factor‐beta, platelet‐derived growth factor, connective tissue growth factor, hepatocyte growth factor, and epidermal growth factor. The results obtained in animal models hold promise for molecular intervention strategies in human renal disease. Microarray technology allows large‐scale gene expression profiling in kidney tissue to identify common molecular pathways in a step towards discovery of new drug targets. Molecular techniques are expected to be used for diagnostic and prognostic purposes in nephrological practice to supplement renal biopsy. Several studies already show that molecular techniques might be of use in routine diagnostic practice. Improvement of diagnosis and prediction of outcome in renal patients might lead to more efficient and earlier therapeutic intervention. Copyright © 2003 John Wiley & Sons, Ltd.
Microvascular basement membranes in diabetes mellitus
Authors: Tsilibary Effie C 
Published: July 2003

AbstractThe alterations in the microvascular system of diabetes mellitus patients are responsible for the most devastating complications of this widespread disease. In the kidney, the microangiopathy leads to thickening of the glomerular capillary basement membrane but also to the expansion of the mesangial matrix and thickening of the tubular basement membrane. Several mechanisms are implicated in the pathogenesis of diabetic renal microangiopathy. These include increased synthesis of type IV collagen following hyperglycaemia‐induced alteration of the pattern of podocyte–integrin expression, decreased expression of matrix metalloproteinases (MMP‐2 and 3), and increased expression of tissue inhibitor of metalloproteinase (TIMP). An altered morphology of podocytes accompanies these basement membrane alterations. Other factors which may contribute to renal matrix accumulation include vascular endothelial growth factor (VEGF), since treatment with anti‐VEGF antibodies attenuates glomerular basement membrane thickening, platelet‐derived growth factor (PDGF) (B chain) and its receptor, which appear to be highly expressed in mesangial and visceral epithelial cells and might play a role in the development of diabetic nephropathy. Also oxygen radicals/oxidative stress may play a role in matrix accumulation in diabetic nephropathy as aminoguanidine, an inhibitor of the formation of advanced glycation end‐products but with antioxidant properties, attenuates diabetic nephropathy. Retinal diabetic microangiopathy follows much the same principles, be it that microvascular proliferation is a distinctive element in the retina. Nephropathy and retinopathy occur frequently but not always together, indicating that in their multifactorial pathogenesis much remains to be clarified. Copyright © 2003 John Wiley & Sons, Ltd.
Electrospray ionization mass spectrometry coupled to liquid chromatography for detection of cisplatin and its hydrated complexes
Authors: Cui Meng , Mester Zoltán 
Published: July 2003

AbstractElectrospray ionization mass spectrometry (ESI‐MS) coupled to liquid chromatography (LC) has been applied to investigate cisplatin and its hydrated complexes. Three hydrolysis products were identified following incubation of cisplatin in aqueous solution: monohydrated species, dihydrated species and the hydroxo‐bridged dimer, each of which exhibited characteristic mass spectrometric behavior. The technique was employed to investigate the time‐ and pH‐dependent hydrolysis of cisplatin in aqueous solution. The results have demonstrated that LC/ESI‐MS is a powerful technique for the analysis of Pt(II) complexes and for monitoring their hydrolysis reactions. Copyright © 2003 Crown in the right of Canada. Published by John Wiley & Sons, Ltd.
Reversed‐phase ion‐pairing liquid chromatography/ion trap mass spectrometry for the analysis of negatively charged, derivatized glycans
Authors: Gennaro Lynn A. , Harvey David J. , Vouros Paul 
Published: July 2003

AbstractThe significant complexity, similar polarity and lack of ionizable sites make the analysis of glycans an analytical challenge. These compounds are often derivatized and separated by normal‐phase high‐performance liquid chromatography (HPLC) or capillary electrophoresis (CE) followed by UV or fluorescence detection. Due to widespread use of reversed‐phase chromatography coupled to electrospray mass spectrometry as an analytical tool, our laboratory has developed this methodology for the analysis of glycans derivatized with a negatively charged tag, 8‐aminonaphthalene‐1,3,6‐trisulfonic acid (ANTS). It is possible to exploit the ability of this negatively charged tag to interact with a mobile phase ion‐pairing reagent, allowing retention on a reversed‐phase C18 column for subsequent on‐line UV or MS analysis. ANTS‐derivatized samples, including a maltooligosaccharide ladder and glycans released from bovine ribonuclease B, bovine fetuin, and chicken ovalbumin, were analyzed using this method. In addition to reversed‐phase retention, ribonuclease B and ovalbumin derivatives displayed highly desirable isomeric separation. With the use of mass spectrometric detection for glycan identity, this allowed relative quantitation of individual components. Copyright © 2003 John Wiley & Sons, Ltd.
Proton transfer reaction ion trap mass spectrometer
Authors: Prazeller Peter , Palmer Peter T. , Boscaini Elena , Jobson Tom , Alexander Michael 
Published: July 2003

AbstractProton transfer reaction mass spectrometry is a relatively new field that has attracted a great deal of interest in the last few years. This technique uses H3O+ as a chemical ionization (CI) reagent to measure volatile organic compounds (VOCs) in the parts per billion by volume (ppbv) to parts per trillion by volume (pptv) range. Mass spectra acquired with a proton transfer reaction mass spectrometer (PTR‐MS) are simple because proton transfer chemical ionization is ‘soft’ and results in little or no fragmentation. Unfortunately, peak identification can still be difficult due to isobaric interferences. A possible solution to this problem is to couple the PTR drift tube to an ion trap mass spectrometer (ITMS). The use of an ITMS is appealing because of its ability to perform MS/MS and possibly distinguish between isomers and other isobars. Additionally, the ITMS duty cycle is much higher than that of a linear quadrupole so faster data acquisition rates are possible that will allow for detection of multiple compounds. Here we present the first results from a proton transfer reaction ion trap mass spectrometer (PTR‐ITMS). The aim of this study was to investigate ion injection and storage efficiency of a simple prototype instrument in order to estimate possible detection limits of a second‐generation instrument. Using this prototype a detection limit of 100 ppbv was demonstrated. Modifications are suggested that will enable further reduction in detection limits to the low‐ppbv to high‐pptv range. Furthermore, the applicability of MS/MS in differentiating between isobaric species was determined. MS/MS spectra of the isobaric compounds methyl vinyl ketone (MVK) and methacrolein (MACR) are presented and show fragments of different mass making differentiation possible, even when a mixture of both species is present in the same sample. However, MS/MS spectra of acetone and propanal produce fragments with the same molecular masses but with different intensity ratios. This allows quantitative distinction only if one species is predominant. Fragmentation mechanisms are proposed to explain the results. Copyright © 2003 John Wiley & Sons, Ltd.
A rapid and sensitive liquid chromatography/tandem mass spectrometry method for determination of docetaxel in human plasma
Authors: Wang L. Z. , Goh B. C. , Grigg M. E. , Lee S. C. , Khoo Y. M. , Lee H. S. 
Published: July 2003

AbstractA novel, rapid and sensitive isocratic liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for quantification of docetaxel in human plasma with paclitaxel as internal standard. The high sensitivity and specificity of MS/MS detection enabled the use of a small volume of plasma (0.05 mL) and a simple liquid‐liquid extraction procedure. Furthermore, a very short run‐time (3 min) fulfilled the need for monitoring plasma levels of docetaxel from large‐scale clinical studies. The calibration curve for docetaxel was linear over the range 5–1000 ng/mL with coefficients of correlation >0.999 using only 0.05 mL plasma. The intra‐ and inter‐day precisions (CV) of analysis were <7%, and accuracy ranged from 96 to 110%. The applicability of the method was demonstrated in a pharmacokinetic study of a 1‐h infusion of docetaxel with dosages of 75 mg/m2. Possible conjugated metabolites of docetaxel were not detected in patients' samples. Copyright © 2003 John Wiley & Sons, Ltd.
Urine drug testing for opioids, cocaine, and metabolites by direct injection liquid chromatography/tandem mass spectrometry
Authors: Dams Riet , Murphy Constance M. , Lambert Willy E. , Huestis Marilyn A. 
Published: July 2003

AbstractA sensitive and specific liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the simultaneous quantification of opioids, cocaine, and metabolites in urine was developed and validated. A 10‐μL aliquot of urine was injected directly onto the LC/MS/MS system. The lack of sample preparation substantially reduced total analysis time. Separation was performed by reversed‐phase chromatography with gradient elution for all analytes in 26 min. Atmospheric pressure chemical ionization (APCI) was a rugged and efficient ionization technique for basic drugs. Identification and quantification was based on selected reaction monitoring (SRM). Calibration, with deuterated internal standards, was performed by linear regression analysis (weighting factor 1/x). Limits of quantitation (LOQ) were established between 10–100 ng/mL and linearity was obtained up to a maximum of 10 000 ng/mL with an average correlation coefficient (R2) > 0.99. Analytical validation criteria for specificity, precision, accuracy, dilution integrity, matrix effect, and stability were fulfilled. The method proved to be simple and time efficient, and was applicable for illicit drug use monitoring and methadone treatment compliance in clinical research projects at the National Institute on Drug Abuse (NIDA). Published in 2003 by John Wiley & Sons, Ltd.
Making Claims for Power: A New Agenda in Dalit Politics of Uttar Pradesh, 1946-48
Authors: Rawat Ramnarayan S. 
Published: July 2003

‘. . . [T]he awakened untouchable today is repeatedly asking them [the Congress] if they could not remove the ‘social evil’ of their own creation without political power, how do they expect us [the untouchables] to liberate ourselves without political power’. (Shastri, Poona Pact. 1946, p. 24)‘This is 1946, not 1932’. (Shastri, Poona Pact. 1946, p.76)Shankaranand Shastri's statements help us locate two related propositions that came to constitute Dalit politics in Uttar Pradesh in the 1940s. The first proposition deals with claims made by Dalits to acquire political power—specifically in the form of adequate representation in the provincial legislative assemblies and in the Constituent Assembly. They demanded positive discrimination in the form of reservations within legislative and executive institutions. Safeguards for Dalits, it was argued, should be incorporated into the proposed constitution for Indian citizens. The second proposition concerns achhut identity, through which Dalits hoped to reconstitute their polity in UP. The Scheduled Castes Federation (SCF) and even a section of Congress Harijans staked a claim for achhut identity to distinguish their difference from ‘other communities.’ Dalit writings increasingly depicted the Poona Pact as a great betrayal by the Congress and the British. From their experience of the two general elections of 1937 and 1946, they argued that the electoral mechanism worked out under the aegis of the Poona Pact was structured against the Dalits.
Why, then, is it so bright? Towards an aesthetics of peace at a time of war
Authors: Bleiker Roland 
Published: July 2003

Dieter Senghaas, Klänge des Friedens: Ein Hörbericht (Frankfurt: Suhrkamp, 2001), pp. 188.Ekkehart Krippendorff, Die Kunst, nicht regiert zu werden: Ethische Politik von Sokrates bis Mozart (Frankfurt: Suhrkamp, 1999), pp. 467.
Mechanisms underlying the modulatory action of platelet activating factor (PAF) on the upregulation of kinin B1 receptors in the rat paw
Authors: Fernandes Elizabeth S , Passos Giselle F , Campos Maria M , Araújo José G V C , Pesquero Jorge L , Avelllar Maria C , Teixeira Mauro M , Calixto João B 
Published: July 2003

The present study evaluated the ability of the administration of platelet activating factor (PAF) to induce the upregulation of B1 receptors in the rat paw.
Local treatment with PAF resulted in a time‐dependent increase of oedema formation induced by the B1 receptor agonist des‐Arg9‐BK (des‐Arg9‐bradykinin), but not by the B2 receptor agonist tyrosine8‐bradykinin. Functional upregulation of B1 receptors was accompanied by a prominent increase of B1 receptor mRNA expression in the rat paw.
In PAF‐treated paws, des‐Arg9‐BK‐induced oedema formation was significantly inhibited by the B1 receptor antagonists des‐Arg9‐[Leu8]‐BK and R‐715. The effects of PAF pretreatment were receptor operated, as assessed by the effects of the PAF receptor antagonist WEB2086 or by desensitisation of PAF receptors.
The protein synthesis inhibitor cycloheximide, the anti‐inflammatory steroid dexamethasone or the nuclear factor (NF‐κB) blockers pyrrolidine‐dithiocarbamate (PDTC) and Nα‐tosyl‐L‐chloromethylketone significantly blocked the functional upregulation of B1 receptors.
The selectin inhibitor fucoidin, an anti‐CD18 antibody or an anti‐rat neutrophil antiserum, also significantly prevented des‐Arg9‐BK‐induced paw oedema in rats pretreated with PAF.
Intradermal injection of PAF induced a 25‐fold increase of myeloperoxidase activity in the rat paw, a response that was significantly inhibited by fucoidin, anti‐CD‐18, anti‐rat neutrophil antiserum or PDTC.
Local treatment with PAF also resulted in a marked increase of NF‐κB activation, an effect largely prevented by PDTC or by the anti‐rat neutrophil antiserum.
Collectively, the present results indicate that the induction of B1 receptors following treatment with the chemotatic mediator PAF is dependent on the recruitment of neutrophils, an event that is under the control of adhesion molecules, protein synthesis and NF‐κB activation. These findings provide new insights into the role played by cell migration and chemotatic factors on B1 receptor upregulation in vivo.

British Journal of Pharmacology (2003) 139, 973–981. doi:10.1038/sj.bjp.0705314
Central endogenous histamine modulates sympathetic outflow through H3receptors in the conscious rabbit
Authors: Charles Julian , Angus James A , Wright Christine E 
Published: July 2003

This study examined the role of histamine H3receptors in vagal and sympathetic autonomic reflexes in the conscious rabbit, and in rabbit and guinea‐pig isolated right atria.The baroreceptor‐heart rate reflex (baroreflex), Bezold‐Jarisch‐like and nasopharyngeal reflexes were assessed after these treatments (i.v.; with H1and H2receptor block): (i) vehicle (saline;n=11); (ii) H3receptor agonist, (R)‐α‐methylhistamine (R‐α‐MH) 100μg kg−1+100μg kg−1h−1(n=9); (iii) H3receptor antagonist, thioperamide 1 mg kg−1+1 mg kg−1h−1(n=11); (iv)R‐α‐MH and thioperamide (n=6); and (v) H2and H3antagonist, burimamide 6.3 mg kg−1+6.3 mg kg−1h−1(n=4).R‐α‐MH caused a thioperamide‐sensitive fall in mean arterial pressure (MAP) of 8±1 mmHg and tachycardia of 18±2 bpm (P<0.0005). Burimamide was without effect, however thioperamide elicited an increase in MAP of 4±1 mmHg (P<0.01), but no change in heart rate (HR).R‐α‐MH caused a 44% decrease in the average gain of the baroreflex (P=0.0001); this effect was antagonised by thioperamide. Thioperamide caused a parallel rightward shift in the barocurve with an increase in MAP of 5 mmHg (P<0.05). Burimamide had no effect on the baroreflex. The vagally mediated bradycardia elicited by the Bezold‐Jarisch and nasopharyngeal reflexes was unaffected by H3receptor ligand administration.R‐α‐MH (10μM) caused a thioperamide‐sensitive depression of both sympathetic and vagal responses in guinea‐pig atria, but had no effect in rabbit atria.As H3receptor activation caused a significant decrease in baroreflex gain without affecting HR range, the former is unlikely to be simply due to peripheral sympatholysis (supported by the lack of effect in isolated atria). Central H3receptors may have a tonic role in the baroreflex as thioperamide caused a rightward resetting of the barocurve. In contrast, the peripherally acting H3antagonist burimamide was without effect. These findings suggest a role for central histamine H3receptors in cardiovascular homeostasis in the rabbit.British Journal of Pharmacology(2003)139, 1023–1031. doi:10.1038/sj.bjp.0705322
Enhanced anti‐inflammatory potency of a nitric oxide‐releasing prednisolone derivative in the rat
Authors: Turesin Fusun , Del Soldato Piero , Wallace John L 
Published: July 2003

Derivatization of nonsteroidal anti‐inflammatory drugs, such that they release nitric oxide (NO) in small amounts, has been shown to significantly increase their anti‐inflammatory activity and analgesic potency. In this study, we compared the anti‐inflammatory potency of prednisolone to a nitric oxide‐releasing derivative of prednisolone (NCX‐1015).
Carrageenan‐induced inflammation of an airpouch in the rat was used. The rats were pretreated with equimolar doses of prednisolone or NCX‐1015 and the effects on leukocyte infiltration into the airpouch and exudates levels of prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and nitrite (as an index of NO production) were measured 6 h later.
Injection of carrageenan into the airpouch resulted in a progressive increase in leukocyte infiltration, and accumulation of PGE2, LTB4 and nitrite. Carrageenan also induced elevated expression of cyclooxygenase‐1 and ‐2, inducible nitric oxide synthase and 5‐lipoxygenase in the inflammatory exudate.
Prednisolone dose dependently reduced the numbers of leukocytes within the airpouch exudates, as well as reducing PGE2, LTB4 and nitrite levels. NCX‐1015 also reduced leukocyte numbers and inflammatory mediator levels. However, the doses of NCX‐1015 required to produce a maximal reduction of each of these parameters was one‐third to one‐tenth the dose of prednisolone that produced a comparable effect.
The reduction of PGE2 and NO production was likely to be at least in part due to reduced expression of the key enzymes responsible for their synthesis (cyclooxygenase‐2, inducible NO synthase), with NCX‐1015 producing greater suppression than prednisolone at an equimolar dose.
Coadministration of prednisolone with a nitric oxide donor (DETA‐NONOate) resulted in a greater reduction of leukocyte infiltration and inflammatory mediator production than was observed with either drug alone.
These results support the notion that delivery of NO to a site of inflammation can markedly enhance the anti‐inflammatory activity of a glucocorticoid.

British Journal of Pharmacology (2003) 139, 966–972. doi:10.1038/sj.bjp.0705324