bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salt effects on the reactivity of the base‐catalyzed hydrolysis of some novel low‐spin hydrophobic Fe(II)–amino acid azomethine chelates
Authors: Shaker Ali M. , Nassr Lobna A. E. 
Published: September 2003

AbstractSalt effects on the reactivity of base hydrolysis of Fe(II) chelates [naphthylideneisoleucinate (nili), naphthylideneleucinate (nli), naphthylideneserinate (nsi), salicylideneisoleucinate (sili), salicylideneleucinate (sli), salicylidenemethioninate (smi), and salicylidenetryptophanate (sti)] have been investigated in aqueous media containing alkali metal halides and tetra‐n‐butylammonium bromide (TBAB). NaCl and NaBr exhibited different reactivity trends from those of KBr and TBAB.The observed patterns vary markedly with complex hydrophobicity. Generally, the presence of the salt markedly enhances the rate compared to its absence. This behavior agrees with the anionic nature of the transient species. With increasing added NaCl and NaBr, the rate of the reaction decreases. The rate decreases and then increases on increasing the concentration of KBr and TBAB. © 2003 Wiley Periodicals, Inc. Int J Chem Kinet 35: 592–601, 2003
Spectroscopy of hydrothermal reactions, part 26: Kinetics of decarboxylation of aliphatic amino acids and comparison with the rates of racemization
Authors: Li Jun , Brill Thomas B. 
Published: September 2003

AbstractThe kinetics of decarboxylation of six α‐amino acids (glycine, alanine, aminobutyric acid, valine, leucine, and isoleucine) and β‐aminobutyric acid were studied in aqueous solution at 310–330ˆC and 275 bar over the pH25 range 1.5–8.5 by using an in situ FT‐IR spectroscopy flow reactor. Based on the rate of formation of CO2, the first‐order or pseudo‐first‐order rate constants were obtained along with the Arrhenius parameters. The decarboxylation rates of amino acids follow the order Gly > Leu ≈ Ile ≈ Val > Ala > α‐Aib > β‐Aib. Differences in the concentration between 0.05 and 0.5 m had only a minor effect on the decarboxylation rate. The effect of the position of the amino group on the decarboxylation rate was investigated for α‐, β‐, and γ‐aminobutyric acid and the order was found to be α > β ≫ γ. Although the pH dependence is complex, the decarboxylation rates of α‐amino acids qualitatively have the inverse trend of the racemization rates. © 2003 Wiley Periodicals, Inc. Int J Chem Kinet 35: 602–610, 2003
The vascular network of tumours — what is it not for?
Authors: Sivridis Efthimios , Giatromanolaki Alexandra , Koukourakis Michael I 
Published: September 2003

AbstractIt is becoming almost a dogma that tumours cannot grow beyond 1–2 mm3unless they are supported by a rich vascular supply1. It is true that tumours promote angiogenesis and that highly vascularized carcinomas have, in general, a more aggressive clinical course than carcinomas of low vascularization2,3. However, a study of intratumoral angiogenesis reveals that the newly formed vessels are commonly deprived of those structural qualities that would allow them to perform an optimal oxygenation function3. Thus, most tumours, irrespective of their angiogenic status, behave as if they were ‘hypoxic’, urging (via angiogenic mediators) for, what would look paradoxical at first sight, more defective angiogenesis. It is hypothesized that tumour cells can grow into solid neoplasms by exploiting the host's pre‐existing vessels, without the need for new blood vessel formation. Neovascularization, however, may be important for tumours with an exophytic pattern of growth as these, by their very nature, lose the host's sheltering stroma. Shifting to anaerobic glycolysis and activation of anti‐apoptotic pathways are complementary mechanisms for tumour cell survival and growth. Besides, continuous and indiscriminate production of a defective vascular network ensures an increased metastatic potential since the newly formed intratumoral vessels, simulating venular‐like spaces, are easily permeable to tumour cells, facilitating metastases. Copyright © 2003 John Wiley & Sons, Ltd.
Identification of novel proteins associated with hepatocellular carcinomas using protein microarrays
Authors: Tannapfel Andrea , Anhalt Kathrin , Häusermann Philip , Sommerer Florian , Benicke Markus , Uhlmann Dirk , Witzigmann Helmut , Hauss Johann , Wittekind Christian 
Published: September 2003

AbstractCharacterization of the protein profiles expressed by hepatocellular carcinomas (HCCs) may identify the genes involved in hepatocellular carcinogenesis and offers the possibility of elucidating clinical biomarkers. In an effort to discover such proteins and pathways that are deregulated in hepatocellular carcinogenesis, cellular proteomes of matched normal liver cells and carcinoma were analysed by tissue microdissection and protein microarrays. Using protein microarrays made up of 83 different antibodies, it was possible to monitor alterations of the protein levels in HCC and non‐neoplastic liver tissue. Further analysis of altered proteins was performed using western blot analysis and tissue microarrays (TMAs) containing 210 HCC specimens and corresponding liver tissue. The protein microarray approach revealed differential expression between HCC and normal liver of 32 of the 83 proteins examined: 21 of these were up‐regulated and 11 down‐regulated. IGF (insulin growth factor) II, ADAM (a disintegrin and metalloproteases) 9, STAT (signal transducers and activators of transcription) 3, SOCS (suppressors of cytokine signalling) 3, and cyclin D1 were significantly up‐regulated and collagen I, SMAD 4, FHIT (fragile histidine triad), and SOCS1 were down‐regulated. The differential expression of these proteins was confirmed using western blot analysis and TMAs. Correlation of differentially regulated proteins with clinico‐pathological data showed that cyclin D1 and SOCS1 were associated with tumour prognosis in univariate analysis, but not multivariate analysis. These data indicate that the development of an array‐based approach for the determination of protein profiles in HCC may facilitate the identification of new proteins associated with carcinogenesis or prognosis. Copyright © 2003 John Wiley & Sons, Ltd.
The effect of gender on Helicobacter felis‐mediated gastritis, epithelial cell proliferation, and apoptosis in the mouse model
Authors: Court M , Robinson PA , Dixon MF , Jeremy AHT , Crabtree JE 
Published: September 2003

AbstractThe murine Helicobacter felis model has been extensively used to investigate the importance of host factors in the development of chronic gastritis. The effect of gender in this murine model is unknown. Male and female C57BL/6J mice were infected with H felis for up to 1 year. At 4, 8, 19, 36, and 52 weeks post‐infection, gastric histopathology, epithelial cell proliferation, and apoptosis were examined and compared with age‐ and gender‐matched controls. In female mice, infection with H felis resulted in an earlier onset of chronic gastric inflammation, epithelial hyperplasia, and oxyntic cell loss than males. In females, there was a trend towards increased gastric pathology compared with males, with long‐term‐infected female mice having significantly greater (p < 0.05) chronic inflammation than male mice. The histopathological differences in male and female mice did not relate to the density of H felis infection. Female mice infected with H felis had significantly increased gastric epithelial cell proliferation in the cardia and corpus at both 8 and 52 weeks post‐infection (p < 0.05). Epithelial cell apoptosis in the glandular mucosa of the corpus at 36 and 52 weeks post‐infection was significantly increased (p < 0.05) in female mice compared with uninfected gender controls. In contrast, there was no significant increase in epithelial cell proliferation or apoptosis in any area of the stomach at any time point after H felis infection in male mice. These results demonstrate that there are gender differences in the gastric inflammatory and epithelial response to H felis in the murine model. The functional importance of gender should be considered in future murine studies on H felis‐ and H pylori‐induced chronic gastritis. Copyright © 2003 John Wiley & Sons, Ltd.
Expression of AP‐2α, c‐kit, and cleaved caspase‐6 and ‐3 in naevi and malignant melanomas of the skin. A possible role for caspases in melanoma progression?
Authors: Woenckhaus Christian , Giebel Jürgen , Failing Klaus , Fenic Irina , Dittberner Thomas , Poetsch Micaela 
Published: September 2003

AbstractProgression of melanoma is associated with loss of the transcription factor AP‐2α and tyrosine‐kinase receptor c‐kit. However, the mechanisms by which these two proteins are down‐regulated have not been fully elucidated. Fifty non‐selected melanomas comprising ten superficial spreading melanomas (five exhibiting a radial growth phase and five a vertical growth phase), ten primary nodular melanomas, 30 melanoma metastases, and 16 naevi were investigated by direct sequencing analysis of the AP‐2α and c‐kit genes and by immunohistochemistry for the respective proteins. Because it has recently been demonstrated that AP‐2α is preferentially cleaved by caspase‐6 and to a lesser extent by caspase‐3, immunohistochemistry for the cleaved (activated) forms of caspase‐6 (c‐casp‐6) and caspase‐3 (c‐casp‐3) was carried out. No mutations were identified in the c‐kit gene, but three different point mutations were demonstrated in the activation motif of AP‐2α in four tumours: one vertical growth phase superficial spreading melanoma, one nodular melanoma, and two metastases. Immunohistochemistry revealed progressive loss of the AP‐2α and c‐kit proteins in primary melanomas and metastases when compared with naevi. The decrease of both markers was more accentuated in the dermal component of all primary tumours, with c‐kit more affected than AP‐2α. All invasive melanomas and metastases expressed c‐casp‐6. c‐casp‐3 was expressed by 83% of the metastases and in the dermal component of one nodular melanoma. These findings suggest that the loss of AP‐2α protein expression during the progression of melanoma could be related to mutation of the gene in only a small number of tumours, whereas the expression and activation of caspases, most prominently caspase‐6, may be an important factor for the down‐regulation of AP‐2α protein. Furthermore, this study supports recent data that the activation of caspases does not inevitably result in apoptosis, but may also contribute to tumour progression in melanomas. Copyright © 2003 John Wiley & Sons, Ltd.
CD40 ligand is selectively expressed on CD4+ T cells and platelets: implications for CD40–CD40L signalling in atherosclerosis
Authors: Büchner Kerstin , Henn Volker , Gräfe Michael , de Boer Onno J , Becker Anton E , Kroczek Richard A 
Published: September 2003

AbstractAtherosclerosis is a degenerative inflammatory disease of the vascular system. Endothelial cells (ECs), smooth muscle cells, and macrophages, key elements in atherosclerosis, all have the potential to express the CD40 receptor and are thus susceptible to potent pro‐inflammatory signals by CD40 ligand (CD40L)‐bearing cells. CD40L is a TNF‐α‐related membrane protein originally identified on activated T cells. The recent recognition of platelets as an abundant source of CD40L led to a reassessment of the involvement of CD40L in atherosclerosis. In the present report, CD40L+ T cells were identified in the intima of atherosclerotic tissues within macrophage infiltrates and in areas of neovascularization. These CD40L+ T cells were CD4+, CD69+, but negative for CD8, CD25, CD28, and ICOS. In some specimens, CD40L+ platelets were identified in the intima and in plaque ruptures. Contrary to previous reports, CD40L was not observed on ECs, smooth muscle cells, and macrophages in atherosclerotic tissues or in vitro at the protein and mRNA levels. Functionally, flow chamber experiments demonstrated that stimulation of ECs via CD40 is sufficient to recruit neutrophils and T cells from whole blood to ECs and suggested that CD40L+ platelets contribute significantly to the recruitment of inflammatory cells to damaged endothelium in vivo. However, due to the short half‐life of platelet CD40L, the chronic CD40L‐driven inflammatory component can only be sustained by activated CD4+ T cells. Contrary to current understanding, the contribution of CD40L to chronic inflammation in atherosclerosis is thus antigen‐driven and MHC‐dependent. This conclusion has significant therapeutic implications. Copyright © 2003 John Wiley & Sons, Ltd.
Frequent loss of Fas expression and function in human lung tumours with overexpression of FasL in small cell lung carcinoma
Authors: Viard‐Leveugle Isabelle , Veyrenc Sylvie , French Lars E , Brambilla Christian , Brambilla Elisabeth 
Published: September 2003

AbstractFas (CD95) and its ligand FasL signal apoptosis and are involved in tissue homeostasis and the elimination of target cells by cytotoxic T cells. Corruption of this signalling pathway in tumour cells, for example by reduced Fas expression or increased FasL expression, can participate in tumour development and immune escape. The present study has analysed Fas/FasL expression and Fas death signalling function in vivo in lung tumour tissues [57 non‐small cell lung carcinomas and 64 neuroendocrine lung tumours including small cell lung carcinoma (SCLC)] in comparison with normal lung tissue, and in vitro in neuroendocrine tumour cell lines in comparison with normal human bronchial epithelial cells. The Fas expression score was markedly decreased compared with normal lung tissue in 90% of the 121 lung tumours and was completely lost in 24%. The Fas staining pattern suggested cytoplasmic Fas expression in tumours, whereas membrane expression was observed in normal lung tissue. Loss of Fas at the cell surface was also shown in vitro by FACS analysis of neuroendocrine tumour cell lines and was concomitant with the resistance of tumour cells to FasL‐mediated apoptosis according to in vitro cell viability. The lack of cell surface Fas expression in tumour cell lines resulted from the lack of intracellular Fas protein due to impaired Fas gene transcription. The FasL expression score was also decreased in most non‐small cell lung carcinomas compared with normal bronchial cells, whereas 91% of SCLCs had higher expression than normal cells. FasL overexpression was related to advanced tumour stage as well as to a Fas/FasL ratio less than 1. It is concluded that a marked decrease in Fas expression may be part of lung tumourigenesis allowing tumour cells to escape from apoptosis. FasL overexpression in the context of Fas down‐regulation in SCLC predicts the ability of SCLC cells to induce paracrine killing of Fas‐expressing cytotoxic T cells. In lung tumours, Fas restoration may represent a key, although not unique, step in therapeutic strategies to reconstitute the ability of tumour cells to undergo apoptosis. Copyright © 2003 John Wiley & Sons, Ltd.
Inhibition of advanced glycation end‐products protects against retinal capillary basement membrane expansion during long‐term diabetes
Authors: Gardiner TA , Anderson HR , Stitt AW 
Published: September 2003

AbstractThe purpose of this study was to investigate the advanced glycation end‐product (AGE)‐inhibitory properties of aminoguanidine and to determine whether treatment in long‐term diabetic rats can prevent basement membrane lesions of diabetic retinopathy. Four groups of male Wistar rats were studied: untreated diabetics injected with 45 mg/kg streptozotocin, aminoguanidine‐treated diabetics, untreated controls, and aminoguanidine‐treated controls. After 12 months' diabetes, the retinas from six animals were processed for electron microscopy or the retinal microvasculature was isolated using the trypsin digest technique. Stereological analysis was used to estimate quantitative ultrastructural changes in the retinal capillary‐associated basement membrane. Serum AGEs were quantified by competitive AGE‐ELISA, while microvascular‐associated, immunoreactive AGEs were analysed on retinal trypsin digests. Aminoguanidine significantly reduced serum AGEs in the diabetic group (p < 0.001). In the retinal capillaries, there was a marked reduction in AGE immunoreactivity in the aminoguanidine‐treated diabetics when compared with untreated diabetics. The surface area and absolute volume of the retinal capillary basement membrane were significantly increased in the diabetic rats when compared with non‐diabetic controls (p < 0.001 and p < 0.001, respectively). Aminoguanidine treatment of diabetic rats protected against basement membrane expansion when compared with untreated diabetic counterparts. Aminoguanidine treatment prevents the development of diabetes‐induced basement membrane expansion in retinal capillaries. The AGE inhibition properties of aminoguanidine suggest that AGEs play an important role in the complex pathogenesis of basement membrane thickening during diabetic retinopathy. Copyright © 2003 John Wiley & Sons, Ltd.
Mature adipocytes, but not preadipocytes, promote the growth of breast carcinoma cells in collagen gel matrix culture through cancer–stromal cell interactions
Authors: Manabe Yasushi , Toda Shuji , Miyazaki Kohji , Sugihara Hajime 
Published: September 2003

AbstractInteraction between cancer and stromal cells is critical for tumour cell growth and invasion. It has recently been suggested that mature adipocytes, a specific type of stromal cell that is abundant in the breast, affect the biological behaviour of some epithelial cell types. However, the nature of the interaction between mature adipocytes and breast cancer cells remains unclear. The present study has examined the effects of mature rat adipocytes, as the main cell type in adipose tissue, on the growth, apoptosis, and cell adhesion of breast carcinoma cell lines [human oestrogen receptor (ER)‐positive cell lines MCF‐7, ZR75‐1, and T47‐D; and the ER‐negative mouse cell line MMT 060562] by analysing bromodeoxyuridine (BrdU) uptake, apoptotic indices, and immunohistochemical expression of E‐cadherin. As a reference, the effects of rat preadipocytes (immature adipocytes) on the behaviour of the cell lines were examined. The cell lines were cultured in a three‐dimensional collagen gel matrix with mature adipocytes or preadipocytes. Mature adipocytes significantly promoted BrdU uptake by all cell lines other than MMT 060562 cells. Preadipocytes decreased the uptake of T47‐D cells and had no effect on that of MCF‐7, ZR75‐1 or MMT 060562 cells. Mature adipocytes or preadipocytes did not affect the apoptotic indices of any of the cell lines. Mature adipocytes did not influence E‐cadherin expression in any of the cell lines, but preadipocytes clearly promoted E‐cadherin expression by MCF‐7 and T47‐D cells, but not by R75‐1 and MMT 060562 cells. These data suggest that mature adipocytes may be involved in the mechanisms regulating the growth of breast cancer mass through their growth‐promoting effect on ER‐positive tumour cells. Copyright © 2003 John Wiley & Sons, Ltd.
Tight junctional abnormality in multiple sclerosis white matter affects all calibres of vessel and is associated with blood–brain barrier leakage and active demyelination
Authors: Kirk John , Plumb Jonnie , Mirakhur Meenakshi , McQuaid Stephen 
Published: September 2003

AbstractBlood–brain barrier (BBB) hyperpermeability in multiple sclerosis (MS) is associated with lesion pathogenesis and has been linked to pathology in microvascular tight junctions (TJs). This study quantifies the uneven distribution of TJ pathology and its association with BBB leakage. Frozen sections from plaque and normal‐appearing white matter (NAWM) in 14 cases were studied together with white matter from six neurological and five normal controls. Using single and double immunofluorescence and confocal microscopy, the TJ‐associated protein zonula occludens‐1 (ZO‐1) was examined across lesion types and tissue categories, and in relation to fibrinogen leakage. Confocal image data sets were analysed for 2198 MS and 1062 control vessels. Significant differences in the incidence of TJ abnormalities were detected between the different lesion types in MS and between MS and control white matter. These were frequent in oil‐red O (ORO)+ active plaques, affecting 42% of vessel segments, but less frequent in ORO− inactive plaques (23%), NAWM (13%), and normal (3.7%) and neurological controls (8%). A similar pattern was found irrespective of the vessel size, supporting a causal role for diffusible inflammatory mediators. In both NAWM and inactive lesions, dual labelling showed that vessels with the most TJ abnormality also showed most fibrinogen leakage. This was even more pronounced in active lesions, where 41% of vessels in the highest grade for TJ alteration showed severe leakage. It is concluded that disruption of TJs in MS, affecting both paracellular and transcellular paths, contributes to BBB leakage. TJ abnormality and BBB leakage in inactive lesions suggests either failure of TJ repair or a continuing pathological process. In NAWM, it suggests either pre‐lesional change or secondary damage. Clinically inapparent TJ pathology has prognostic implications and should be considered when planning disease‐modifying therapy. Copyright © 2003 John Wiley & Sons, Ltd.
Reduced expression of oestrogen receptor β in invasive breast cancer and its re‐expression using DNA methyl transferase inhibitors in a cell line model
Authors: Skliris George P , Munot Kailas , Bell Sandra M , Carder Pauline J , Lane Sally , Horgan Kieran , Lansdown Mark RJ , Parkes Alicia T , Hanby Andrew M , Markham Alexander F , Speirs Valerie 
Published: September 2003

AbstractTo gain insights into the possible role of oestrogen receptor (ER) β in breast carcinogenesis, immunohistochemical analysis of ER β was performed on 512 breast specimens encompassing normal (n = 138), pure ductal carcinoma in situ (n = 16), invasive cancers (n = 319), lymph node metastases (n = 31), and recurrences (n = 8). Real‐time polymerase chain reaction (PCR) was used to investigate the methylation status of the ER β gene in the ER β negative breast cancer cell lines SkBr3 and MDA‐MB‐435. A gradual reduction in, but not a complete loss of, ER β expression was observed during the transition from normal and pre‐invasive lesions to invasive cancers, where ER β was lost in 21% of cases. This was more pronounced in invasive ductal than in lobular carcinomas, a significantly higher proportion of which were ER β‐positive (74% compared with 91%, respectively, p = 0.0004). Examination of paired primary cancers with their axillary lymph node metastases showed that if ER β was present in the primary tumour, it persisted in the metastasis. Treatment of ER β‐negative cell lines with DNA methyl transferase inhibitors restored ER β expression, providing experimental evidence that silencing of ER β in breast carcinomas could be due to promoter hypermethylation. These results suggest that loss of ER β expression is one of the hallmarks of breast carcinogenesis and that it may be a reversible process involving methylation. Copyright © 2003 John Wiley & Sons, Ltd.