bluuebunny/crossref_metadata_2025 huggingface dataset:
The prognostic value of oncogenic antigen 519 (OA‐519) expression and proliferative activity detected by antibody MIB‐I in node‐negative breast cancer
Authors: Jensen Vibeke , Ladekarl Morten , Holm‐Nielsen Peter , Melsen Flemming , Sœrensen Flemming Brandt
Published: June 2005

The prognostic value of oncogenic antigen 519 (OA‐519) expression and tumour proliferative activity was evaluated in a retrospective series of 118 patients with low‐risk breast cancer. Low risk was defined as negative axillary nodes, tumour diameter ⩽50 mm, and no histological evidence of invasion of skin or deep fascia (=T1N0M0 and T2N0M0). The median follow‐up time was 104 months (range 5–143 months). Immunohistochemical analysis of OA‐519 expression was performed on formalin‐fixed, paraffin‐embedded tissue. The proliferative activity was estimated using a Ki‐67 equivalent monoclonal antibody (MIB‐1), which is applicable on formalin‐fixed, paraffin‐embedded tissue after microwave pretreatment. OA‐519 was expressed in about one‐third of the tumours and the percentage of proliferating cells (the MIB‐1 index) ranged between 1 and 72 per cent (median 17 per cent). Using multivariate Cox analysis, both the MIB‐1 index and OA‐519 expression were of independent prognostic value (2p⩽0·01), and the combined immunohistological approach may therefore be useful in selecting patients with node‐negative breast cancer who might benefit from adjuvant therapy.
Correlation of numerical chromosome 11 and 17 imbalance with metastasis of primary breast cancer to lymph nodes
Authors: Herrington C. S. , Leek R. D. , McGee J. O'D.
Published: June 2005

Abnormalities of chromosomes 11 and 17 have been widely reported in invasive carcinoma of the breast. Interphase cytogenetics using pericentromeric repeat probes allows the evaluation of numerical chromosomal aberrations in tumour cell populations. We have developed a method for interphase cytogenetics on fine needle aspirates taken from breast tumours and have applied it to the analysis of chromosomes 11 and 17 in 49 cases of invasive adenocarcinoma. Frequency distributions of signal number were generated for each case and no correlation was found between modal signal number and tumour size at presentation, nodal status or tumour differentitation. In 14 cases, two copies of each of chromosomes 11 and 17 were equal but abnormal. In 14 cases, the chromosome 11 number was greater than chromosome 17 and in 7 cases, the chromosome 17 number was greater than chromosome 11. Chromosome inequality correlated with the presence of lymph node metastases or disseminated disease at presentation and the absence of in situ carcinoma. There was no relationship with the presence of vascular invasion. These data suggest that numerical chromosome 11 and 17 imbalance may indicate the ability of breast cancers to metastasize rather than invade vessels. The pattern of numerical chromosome abnormality described may define a subgroup of tumours with a greater tendency for metastasis.
p53 gene alterations in special types of breast carcinoma: A molecular and immunohistochemical study in archival material
Authors: Karameris A. M. , Worthy E. , Gorgoulis V. G. , Quezado M. , Anastassiades O. Th.
Published: June 2005

The p53 locus on the short arm of chromosome 17 at 17p13.1 was examined for small genomic deletions and mutations in 23 formalin‐fixed, paraffin‐embedded cases of special types of breast carcinoma (six medullary, seven apocrine, five differentiated tubular, and five papillary). p53 mutations in the evolutionarily conserved exons 5–9 were detected in 11 cases (four apocrine, two papillary, two medullary, and three differentiated tubular), using the novel non‐radioactive PCR‐based Hydrolink mutation detection enhancement (MDE) method, and confirmed by direct sequencing of the PCR products. Missense mutations causing amino acid substitutions were evenly distributed among exons. One case of apocrine carcinoma showed a polymorphism at codon 213 (CGA→CGG). Twelve out of 23 cases were found to express a strong nuclear signal against CM‐1 and DO‐7, two anti‐p53‐specific antibodies. Small genomic deletions in the vicinity of the p53 locus were detected in 11 tumours (three papillary, three differentiated tubular, two medullary, and three apocrine carcinomas), using the multiplex PCR method. No statistical correlation was found between deletions at 17p13.1 and p53 mutations (P<0·5). In addition, p53 mutations and immunoexpression correlated with the c‐erbB‐2 gene product, an oncogenic protein that has been implicated in cell cycle control (P<0·001). Our findings suggest that genomic alterations of the p53 gene are quite common events associated with special types of breast carcinoma, particularly of the apocrine subtype, but the prognostic value is unlikely to be of clinical importance.
The lymphoepithelial organization of the tonsil: An immunohistochemical study in chronic recurrent tonsillitis
Authors: Ruco Luigi P. , Uccini Stefania , Stoppacciaro Antonella , Pilozzi Emanuela , Morrone Stefania , Gallo Andrea , De Vincentiis Marco , Santoni Angela , Baroni Carlo D.
Published: June 2005

Interactions between leukocytes and crypt epithelium were extensively investigated in 12 cases of chronic recurrent tonsillitis, using immunohistochemistry and cytofluorimetric analysis of cell suspensions. Intraepithelial leukocytes are a mixed cell population composed of 50 per cent CD20‐positive B lymphocytes, 40 per cent T lymphocytes with a 2.7 CD4/CD8 ratio, and 10 per cent CD68‐positive macrophages. About 4 per cent of intrepithelial leukocytes are proliferating cells, as indicated by Ki‐67 staining. Leukocyte infiltration is associated with expression on epithelial cells of the adhesion molecules ICAM‐1 and VCAM‐1. Crypt epithelium is supported by a basement membrane showing frequent interruptions and connected with the reticular stroma of the lymphoid tissue, which was stained for fibronectin, tenascin, collagen, and laminin. Extracellular matrix (ECM) distribution was correlated with integrin expression on B and T lymphocytes. It was found that the ECM was arranged differently in the follicles and in the extrafollicular area and that B and T lymphocytes exhibited different patterns of integrin expression.
Artefacts in electron microscopy: Ultrastructural features of chrysiasis
Authors: Culora G. A. , Barnett N. , Theaker J. M.
Published: June 2005

Eleven cases of chrysiasis have been studied ultrastructurally and by electron probe microanalysis. Tissue samples were examined both with and without osmium and urany1 acetate staining. There was a significant morphological difference in the appearances of the gold deposits within aurosomes between the two groups. The untreated group showed finely granular deposits, often arranged in a linear fashion. Aurosomes from samples treated with osmium and urany1 acetate showed more electron‐dense deposits and star‐like formations. We propose that treatment of the tissue with osmium and urany1 acetate causes a change in the electron microscopic appearance of aurosomes, including the formation of the characteristic star‐like aurosomes.
Apoptosis suppressing protein bcl‐2 is expressed in well‐differentiated breast carcinomas with favourable prognosis
Authors: Lipponen P. , Pietiläinen T. , Kosma V.‐M. , Aaltomaa S. , Eskelinen M. , Syrjäunen K.
Published: June 2005

The expression of bcl‐2 protein was analysed immunohistochemically in 202 female breast carcinomas. The intensity of bcl‐2 expression was inversely related to tumour grade (P<0·0001), tumor necrosis (P<0·0001), mitotic index (P<0·0001), oestrogen receptor content (P<0·0001), progesterone receptor content (P=0·0007), S‐phase fraction (P=0·00047), and apoptotic index (P=0·087). A high fraction of bcl‐2‐positive cells was related to ductal or lobular type (P=0·03) and slight nuclear pleomorphism (P=0·03). Heterogeneous expression of bcl‐2 protein was associated with high grade (P=0·02), severe nuclear pleomorphism (P=0·02), DNA aneuploidy (P=0·018), high S‐phase fraction (P=0·05), and early metastasis (P=0·03). Intense expression of bcl‐2 protein was significantly related to favourable outcome in the entire cohort (P=0·0013), as well as in axillary lymph node‐negative (ANN) tumours (P=0·0124). Long recurrence‐free periods in the entire cohort (P=0·037) and in ANN tumours (P=0·08) were confined to cases with intense expression of bcl‐2 protein. In multivariate analysis, bcl‐2 expression had no independent prognostic value in the entire cohort or in axillary lymph node‐negative breast carcinomas, whereas it was a weak independent prognostic factor in axillary lymph node‐positive breast carcinomas.
Microvessel count predicts metastatic disease and survival in non‐small cell lung cancer
Authors: Fontanini Gabriella , Bigini Daniela , Vignati Silvana , Basolo Fulvio , Mussi Alfredo , Lucchi Marco , Chine Silvana , Angeletti Carlo Alberto , Harris Adrian L. , Bevilacqua Generoso
Published: June 2005

The growth of newly formed vessels, or neoangiogenesis, represents an important step in both physiological and pathological situations: in particular, tumour growth and metastasis require angiogenesis. Microvessel count (MC), which represents a measure of tumour angiogenesis, has been associated with metastatic spread in cutaneous, mammary, prostatic, head and neck, and early‐stage lung cancer. In this study, the role of tumour angiogenesis as a prognostic indicator was examined in 253 primary non‐small cell lung cancer (NSCLC) patients. Microvessels were counted by highlighting endothelial cells with anti‐Factor VIII monoclonal antibody (MAb) in methacarn‐fixed tumour samples. In univariat analysis, MC (P<0·000001), sex (P=0·0036), histotype (P<0·014), tumour status (P<0·007), and vessel invasion (P<0·019) were significantly related to hilar and/or mediastinal nodal involvement. However, in the stepwise logistic regression analysis, MC (P<0·000003) retained the most important influence on nodal metastasis. The overall survival analysis calculated by the Kaplan‐Meier method revealed that tumours with high MC (>25 vessels/field) were significantly associated with increased death risk (log‐rank test P=0·00067; Cox's test P=0·00046; Gehan's Wilcoxon test P=0·00108). In 94 patients, the development of metastatic disease during follow‐up was significantly related to MC. Indeed, patients who developed metastasis during follow‐up showed a higher MC, either as a dichotomous (P=0·01) or as a continuous (P=0·003) variable, than patients who had developed no metastasis at the time of the analysis. Moreover, in the stepwise logistic regression analysis, MC retained the most important influence on distant metastases. Microvessel count, as a method for the quantitation of tumour angiogenesis, has an important prognostic role in non‐small cell lung carcinomas.
The hypotransferrinaemic mouse: Ultrastructural and laser microprobe analysis observations
Authors: Iancu Theodore C. , Shiloh Hanna , Raja Kishor B. , Simpson Robert J. , Peters Timothy J. , Perl Daniel P. , Hsu Amy , Good Paul F.
Published: June 2005

Homozygote hypotransferrinaemic mice (hpx/hpx) have cytopathological features similar to those of human congenital atransferrinaemia, genetic haemochromatosis, and neonatal haemochromatosis. These conditions all have in common high levels of cytotoxic non‐transferrin‐bound serum iron. This study describes the ultrastructural features of iron overload in liver, pancreas, heart, and small intestine of 2‐ and 12‐month‐old hypotransferrinaemic mice. Electron microscopic studies of unstained sections showed early parenchymal cell siderosis, with accumulation of numerous ferritin particles and clusters in the cytosol, as well as ferritin and haemosiderin in lysosomes (siderosomes). In the 12‐month‐old animals, iron was also found in Kupffer cells and macrophages in other tissues. In addition, there were conspicuous iron‐containing compounds in the bile canaliculi, and marked iron deposition in the pancreas and heart. Laser microprobe mass analysis (LAMMA) enabled localization and relative quantitation of iron deposition in subcellular compartments providingin situdocumentation of iron accumulation in siderosomes and contributed in assessing total cytosolic iron in various cell types. Moreover, it demonstrated the importance and magnitude of the biliary route for iron excretion in these animals.
An infarct‐like myocardial lesion experimentally induced in wistar rats with Africanized bee venom
Authors: Ferreira Dirceu B. , Costa Roberto S. , De Oliveira J. A. Mello , Muccillo Gerson
Published: June 2005

There is evidence in the literature that death following a bee or wasp sting may result from cardiac involvement. This study describes acute cardiac lesions experimentally induced in Wistar rats submitted to intravenous inoculation of Africanized bee venom (ABV) and killed 1, 4, and 24 h after inoculation. Significant increases in serum enzyme levels were detected; light microscopy showed necrosis of the myocardium; and enzyme histochemistry showed inactivation of enzymes in and around the areas of necrosis. This is the first report of an acute necrotizing cardiac lesion, similar to human myocardial infarction, produced by the inoculation of ABV.
Detection of loss of heterozygosity of p53 gene in paraffin‐embedded breast cancers by non‐isotopic PCR–SSCP
Authors: Chen Yi‐Hua , Li Chun‐De , Yap Eric P. H. , McGee James O'D.
Published: June 2005

A rapid non‐isotopic PCR‐SSCP (polymerase chain reaction‐single‐stranded conformation polymorphism) method was developed in this study to detect polymorphism and loss of heterozygosity (LOH) of p53 in formalin‐fixed and paraffin‐embedded samples of normal breast tissue and of breast cancer. p53 expression was also examined by immunohistochemistry. In 35 paired samples, heterozygosity in exon 4 of p53 was detected in 17 cases (49 per cent) and LOH of the p53 gene in breast cancer tissues was observed in 7 out of 15 informative cases (47 per cent). The correlation of LOH of p53 with positive p53 immunostaining did not reach statistical significance, but all immunostaining‐positive tumours among informative cases had LOH of p53. The results support the hypothesis that in most cases the allelic deletion of p53 may uncover the ‘recessive mutation’ in the remaining allele. However, LOH of p53 was more frequent than positive immunostaining and was significantly associated with poor differentiation of breast cancer (P<0·05). The results suggest that the allelic deletion of p53 may also contribute to the development and progression of breast cancer by reducing the amount of normal p53 protein. These results show that non‐isotopic PCR‐SSCP is a simple, fast, and effective method for detecting polymorphism and LOH of the p53 gene, which is especially useful for retrospective studies.
Expression of bcl‐2 oncogene protein is prevalent in small cell lung carcinomas
Authors: Jiang Shi‐Xu , Sato Yuichi , Kuwao Sadahito , Kameya Toru
Published: June 2005

To investigate the frequency of bcl‐2 oncogene protein expression in small cell lung carcinoma (SCLC), immunohistochemical staining with a mouse‐anti‐human monoclonal antibody, bcl‐2/124, was carried out on 60 formalin‐fixed, paraffin‐embedded SCLC samples obtained from surgical biopsy, and autopsy cases. bcl‐2 protein was detected in 54 out of the 60 SCLCs. In 47 cases, more than half of the tumour cells stained positively. The staining intensity of the tumour cells was comparable to that of infiltrating lymphocytes in 37 cases, but varied from area to area and even from cell to cell. Negative data in six cases were found to be due to unsuitable fixation or embedding procedures rather than the absence of the antigen. bcl‐2 oncogene protein may thus be expressed in most if not all SCLCs. bcl‐2 may have potential diagnostic and therapeutic importance in SCLCs and non‐SCLCs. Previous cytogenetic and molecular genetic analyses indicate that SCLCs carry a number of chromosomal abnormalities and it would follow from tpresent results that the abnormal expression of bcl‐2 may also play a role in the pathogenesis of SCLC, by increasing tumour mass through inhibition of apoptosis as previously proposed. The diagnostic, prognostic, and therapeutic implications of these findings should be studied in greater detail.
The immunohistochemical localization of drug‐metabolizing enzymes in prostate cancer
Authors: Murray Graeme I. , Taylor Valerie E. , McKay Judith A. , Weaver Richard J. , Ewen Stanley W. B. , Melvin William T. , Burke M. Danny
Published: June 2005

The major groups of enzymes involved in activating and detoxifying therapeutic drugs, not least several anti‐cancer drugs, include the cytochromes P450 (P450s), epoxide hydrolase, and glutathione S‐transferases (GSTs). The expression of these enzymes in malignant tumours is one possible mechanism of anti‐cancer drug resistance. This study has investigated the presence, cellular localization, and distribution of drug‐metabolizing enzymes in prostate cancer. The P450 subfamilies CYP1A, CYP2C, and CYP3A were present in 63, 25, and 61 per cent of tumours, respectively. Epoxide hydrolase was identified in 96 per cent of tumours. GST‐α and GST‐μ were expressed in 29 and 41 per cent of tumours, respectively, while there was no immunoreactivity for the π form of GST. The absence of GST‐μ in prostate cancer contrasts with the frequent expression of GST‐π observed in other types of malignant tumour. In non‐neoplastic prostatic epithelium, there was expression of CYP1A, CYP2C, epoxide hydrolase, and the different forms of GST, while there was no apparent immunoreactivity for CYP3A.
Prostatic intraepithelial neoplasia (PIN). Performance of bayesian belief network for diagnosis and grading
Authors: Montironi Rodolfo , Bartels Peter H. , Thompson Deborah , Scarpelli Marina , Hamilton Peter W.
Published: June 2005

Prostatic intraepithelial neoplasia (PIN) diagnosis and grading are affected by uncertainties which arise from the fact that almost all knowledge of PIN histopathology is expressed in concepts, descriptive linguistic terms, and words. A Bayesian belief network (BBN) was therefore used to reduce the problem of uncertainty in diagnostic clue assessment, while still considering the dependences between elements in the reasoning sequence. A shallow network was used with an open‐tree topology, with eight first‐level descendant nodes for the diagnostic clues (evidence nodes), each independently linked by a conditional probability matrix to a root node containing the diagnostic alternatives (decision node). One of the evidence nodes was based on the tissue architecture and the others were based on cell features. The system was designed to be interactive, in that the histopathologist entered evidence into the network in the form of likelihood ratios for outcomes at each evidence node. The efficiency of the network was tested on a series of 110 prostate specimens, subdivided as follows: 22 cases of non‐neoplastic prostate or benign prostatic tissue (NP), 22 PINs of low grade (PINlow), 22 PINs of high grade (PINhigh), 22 prostatic adenocarcinomas with cribriform pattern (PACcri), and 22 prostatic adenocarcinomas with large acinar pattern (PAClgac). The results obtained in the benign and malignant categories showed that the belief for the diagnostic alternatives is very high, the values being in general more than 0·8 and often close to 1·0. When considering the PIN lesions, the network classified and graded most of the cases with high certainty. However, there were some cases which showed values less than 0·8 (13 cases out of 44), thus indicating that there are situations in which the feature changes are intermediate between contiguous categories or grades. Discrepancy between morphological grading and the BBN results was observed in four out of 44 PIN cases: one PINlow was classified as PINhigh and three PINhigh were classified as PINlow. In conclusion, the network can grade PIN lesions and differentiate them from other prostate lesions with certainty. In particular, it offers a descriptive classifier which is readily implemented and which allows the use of linguistic, fuzzy variables.
Spatial arrangement of IgA and C3 as a prognostic indicator of IgA nephropathy
Authors: Muda Andrea Onetti , Feriozzi Sandro , Rahimi Siavash , Faraggiana Tullio
Published: June 2005

The histological picture of primary glomerulonephritis with glomerular IgA deposition (IgA nephropathy and Henoch‐Schönlein disease) can vary from minimal mesangial involvement to severe endocapillary and/or extracapillary proliferation. Local activation of the complement cascade by glomerular IgA deposits and release of anaphylactoid factors are considered to be major triggers of inflammation, but clear‐cut correlations between the severity of the histological findings and the intensity of glomerular deposition of immunoglobulin and complement fractions are still lacking. The purpose of this study was to investigate the spatial distribution of IgA and complement in mesangial deposits with confocal laser scanning microscopy (CLSM) and to correlate specific patterns of IgA‐complement interaction with glomerular damage. Two groups of patients have been studied, one with mild to moderate diffuse mesangial proliferation and the other with diffuse proliferative endocapillary and/or extracapillary patterns. In milder forms of the disease, the majority of the immune deposits are composed of both IgA and C3, coated by an outer layer of IgA alone. Large C3 deposits, or deposits composed of IgA and C3 without an outer coat of IgA, were associated with more severe histological lesions. The results suggest that free access of active complement components to cell and/or mesangial matrix receptors could trigger a cytolytic reaction and that immunoglobulins seem to act as a protective layer on C3 components.
A cautionary note regarding the application of Ki‐67 antibodies to paraffin‐embedded breast cancers
Authors: Gee Julia M. W. , Douglas‐Jones Anthony , Hepburn Peter , Sharma Anup K. , McClelland Richard A. , Ellis Ian O. , Nicholson Robert I.
Published: June 2005

Immunocytochemical studies examining the Ki‐67 proliferation marker in paraffin‐embedded material have recently been made possible by the availability of several antibodies, notably MIB‐1, which are readily applicable to microwaved sections. Using breast cancer material, the present study examines correlations shown by these new paraffin assays and also by PCNA (proliferating cell nuclear antigen), an existing marker of proliferation, with the established Ki‐67 cryosection assay. Paraffin sections were microwaved prior to incubation with Ki‐67 or MIB‐1 antibodies. Signal detection was carried out with a biotinylated secondary antibody, peroxidase‐conjugated streptavidin, and DAB/H2O2 chromogen. The results suggest that caution is required when studying proliferation in paraffin‐embedded breast cancers by immunostaining using Ki‐67 antibodies. Nuclear staining in wax sections (Ki‐Par, MIB‐1, PCNA) greatly exceeded that in cryosections (Ki‐Froz) and thus correlations were notably absent between Ki‐Par or PCNA immunostaining and the routine Ki‐Froz assay. Immunostaining with MIB‐1 or PCNA may, however, be useful to assess proliferation if cut‐offs are applied to eliminate weak immunostaining associated with wax sections. Thus, an approximately linear relationship was seen between MIB‐1/Ki‐Froz, which was improved if only moderately or moderately/strongly MIB‐1‐positive cells were scored. Similarly, a significant correlation was also revealed between PCNA/Ki‐Froz if such a cut‐off was applied.
Cytogenetic and pathogenic effects of long and short amosite asbestos
Authors: Donaldson Kenneth , Golyasnya Nadya
Published: June 2005

This study utilized two samples of amosite asbestos which differ in their length, but not in their diameter and which have been shown previously to have very different abilities to cause pathology in rats exposed by instillation or inhalation. The activity of these amosite samples in causing chromosomal aberrations in Chinese hamster ovary cells in culture was examined, along with the effect of the glutathione (GSH) synthesis‐inhibiting agent buthionine sulphoximine. The incidence of chromosomal aberrations in cells treated with the short fibre sample was similar to control levels; the long amosite sample caused significantly more chromosomal aberrations than the short fibre sample. When cells were treated with buthionine sulphoximine to decrease the levels of intracellular glutathione, the incidence of chromosomal aberrations was increased in the control cells, but also on treatment with both short and long amosite, the long sample again being considerably more active than the short. The pathogenicity of the long amosite may result from the ability of the fibres to cause chromosome damage, while the enhancement of this damage caused by decreasing intracellular glutathione suggests that the asbestos fibres may impose an oxidant stress on the cells which contributes to these aberrations.
Low versus high cell turnover in diffusely growing non‐Hodgkin's lymphomas
Authors: Spina Donatella , Leoncini Lorenzo , Del Vecchio Maria T. , Megha Tiziana , Minacci Chiara , Poggi Simonetta A. , Piler Stefano , Tosi Piero , Kraft Rainer , Laissue Jean A. , Cottier Hans
Published: June 2005

Cell loss, perhaps as important as cell production in determining the size of an expanding cell population, has not usually been registered in quantitative cellular kinetic analyses of neoplastic disorders. The present retrospective study on various types and subtypes of non‐Hodgkin's lymphomas (NHLs;n=170) was designed to test the usefulness of a novel additional parameter, the ‘turnover index’ (TI), which is the sum per case of the mitotic index and the apoptotic index. Results document that TIs clearly distinguished between categories and subtypes of NHLs according to the Kiel classification. Cluster analysis of TIs plotted against the percentage of Ki‐67‐positive cells per case revealed that about one‐third of the high‐grade malignancy lymphomas actually belonged to the low‐turnover lymphomas. Overall survival was longer in the low‐ than in the high‐turnover group of lymphomas. Assessment of TIs can, for practical diagnostic purposes, be replaced by counting mitotic figures and apoptotic cells in several high‐power fields. The TI concept may help to interpret the kinetics of NHLs in terms of accumulation vs. proliferation of cells.
Standard and variant CD44 isoforms are commonly expressed in lung cancer of the non‐small cell type but not of the small cell type
Authors: Ariza Aurelio , Mate José L. , Isamat Marc , López Dolores , Von Uexküll‐Güldeband Claudia , Rosell Rafael , Fernández‐Vasalo Angela , Navas‐Palacios José J.
Published: June 2005

Cluster of differentiation 44 (CD44) encompasses a polymorphic family of cell membrane glycoproteins involved in the mechanism of tumour invasion and metastasis. Since non‐small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) display very different rates of progression, a significant discrepancy in their CD44 expression profiles is to be expected. An immunohistochemical study was undertaken on the expression of standard CD44 (CD44s) and the variant isoforms containing the domains encoded by variant exon 3 (CD44v3) or variant exon 6 (CD44v6) in paraffin‐embedded bronchial biopsy specimens from 32 NSCLC cases and 11 SCLC cases. An absolute lack of immunoreactivity for CD44s, CD44v3, and CD44v6 was obtained in every case of SCLC, whereas 28 of the 32 NSCLC cases showed a positive immunoreaction for at least one of the three epitopes investigated. In conclusion, the occurrence of standard and variant CD44 isoforms in NSCLC and their absence in SCLC suggest the possibility that CD44 is in some way instrumental in conditioning the biological behaviour of NSCLC, but not of SCLC, whose metastatic cascade would be set in motion by the activation of hitherto unidentified, CD44‐independent pathways.
The increased expression of adhesion molecules ICAM‐3, E‐ and P‐selectins on breast cancer endothelium
Authors: Fox S. B. , Turner G. D. H. , Gatter K. C. , Harris A. L.
Published: June 2005

Sequential interaction of neoplastic cells with the endothelium of tumour neovasculature is believed to be a significant step in tumour metastasis. Increasing evidence suggests that inducible endothelial adhesion molecules are intimately involved in this process. An immunohistochemical approach was used to examine the expression of adhesion molecules in 14 normal controls and a series of 64 invasive breast carcinomas. Endothelium in normal breast showed constitutive expression of PECAM (100 per cent), ICAM‐2 (100 per cent), and P‐selectin (64 per cent); variable and focal expression of ICAM‐1 (71 per cent); and only weak staining for E‐selectin (21 per cent). No ICAM‐3 or VCAM‐1 expression was observed. Similarly to normal breast endothelium, widespread and intense immunoreactivity on the endothelium of tumour‐associated vessels was seen for PECAM (100 per cent), ICAM‐1 (69 per cent), and ICAM‐2 (95 per cent). In contrast to normal tissues, E‐ and P‐selectins showed increased intensity of staining (52 and 67 per cent of cases, respectively) and expression of E‐ and P‐selectins was more prominent at the tumour periphery. ICAM‐3 expression was increased on tumour endothelium (15 per cent of cases), but in common with VCAM‐1 (10 per cent) expression was focal. A previously unreported finding was the immunoreactivity of the neoplastic epithelial cells for the non‐epithelial lineage markers ICAM‐1 (34 per cent), ICAM‐3 (10·9 per cent), PECAM (1·6 per cent), and E‐ and P‐selectins (7 and 37 per cent of cases, respectively). These findings show that tumour endothelium displays significant heterogeneity and can assume a pro‐inflammatory phenotype, probably as a result of cytokine stimulation. Upregulation of adhesion molecules might contribute to changes in invasive phenotype by promoting endothelial cell adhesion and angiogenesis, as well as forming a substratum for tumour cells to assemble and attract macrophages.
Identification of a low‐risk group of stage I breast cancer patients by cytometrically assessed DNA and nuclear texture parameters
Authors: Aubele M. , Auer G. , Falkmer U. , Voss A. , Rodenacker K. , Jütting U. , Höfler H.
Published: June 2005

Image cytometrical measurements were performed on Feulgen‐stained cells from 329 stage I breast cancers (pT1pN0,M0,R0). For each patient, several DNA (ploidy, S‐phase fraction, exceeding rates, 2c deviation index, ploidy balance, entropy, and histogram typing), morphometric (area and radius of nuclei), and textural parameters (mainly co‐occurrence and run‐length) were calculated. The prognostic value of these parameters was investigated by multivariate Cox regression analysis, considering a distant recurrence‐free survival of 8 years as the prognostic criterion. In the multivariate analysis, one DNA parameter (histogram type) and two textural parameters (co‐occurrence and variation of the average heterochromatin area) were proven to have independent prognostic value. Using a linear combination of these variables, a prognostic factor was calculated for each individual patient. Patients were stratified using this factor into several groups according to their risk for distant recurrence. Thus, a low‐risk group of stage I patients was identified, remaining distant recurrence‐free for 8 years. In addition, a group of patients with a worse prognosis and an 8‐year recurrence rate of about 26 per cent was identified, compared with the average distant recurrence rate of all stage I patients of 13 per cent. A combination of DNA and textural parameters can provide powerful prognostic information in stage I breast carcinomas and may allow a better selection of patients for different therapy protocols.
Grading of precancerous laryngeal lesions by multiparameter image analysis at separate epithelial layers
Authors: Dreyer Thomas , Popella Christian , Hinrichs Bernd , Bohle Rainer M. , Pohlmann Ulrike , Schulz Andreas , Glanz Hiltrud
Published: June 2005

In order to detect early precancerous changes which do not involve the whole thickness of the epithelium, we used a novel image analysing program based on an IBAS system (Kontron, Germany) to determine nuclear DNA content (NC) as well as average nuclear area (NA) and variation of nuclear area (VA), in the entire epithelium and in three sublayers, parabasal, intermediate, and superficial. DNA aneuploidy was found in only half of the cases classified as ‘high‐grade’ (HG) lesions, comprising carcinoma in situ (CIS) and severe epithelial dysplasias (EDIII), and was chiefly demonstrable in the parabasal third of the epithelium. The other lesions were DNA euploid. HG lesions showed highly significant increases of NA and VA at the lower levels of the epithelium when compared with ‘low‐grade’ (LG) lesions comprising moderate and mild epithelial dysplasias (EDII and EDI). Our data show that the combination of multiparameter image analysis with conventional morphology assists in the objective grading of precancerous lesions and permits the reliable detection of high‐grade lesions.
Distribution of CD1A‐positive langerhans cells and lymphocyte subsets in transitional cell carcinoma of the urinary bladder. An immunohistological study on frozen sections
Authors: Ioachim‐Velogianni Elli , Stavropoulos Nickolaos E. , Kitsiou Evangelia , Stefanaki Stella , Agnantis Niki J.
Published: June 2005

The distribution of CD1a‐positive Langerhans cells, CD4‐positive T‐helper cells, and CD8‐positive T‐suppressor cells in 36 patients with transitional cell carcinoma of the urinary bladder was studied immunohistochemically on frozen sections. Multiple tissue specimens from the tumour, the adjacent mucosa, and random bladder wall biopsies were examined. Langerhans cells were mainly interspersed among the tumour cells, whereas T‐helper cells were present in aggregates in the stroma. T‐suppressor cells were present both in aggregates in the stroma and among the tumour cells. There was a marginal relationship between the density of Langerhans cells and the density of T‐helper/inducer cells and a good relationship with CD8‐positive cells. There was no statistically significant difference in the population density of Langerhans cells associated with the various clinicopathological variables, including growth pattern, histological grade and stage, or patient's age and sex. On the contrary, a statistically significant difference was found in the CD1a/CD4 ratio among specimens of different grades. These results show that CD1a cell populations correlate with T‐cell populations in bladder cancer, suggesting that Langerhans cells take part in the immune response carried out by T lymphocytes, their task being apparently antigen presentation.
Pulmonary eosinophilia in sudden infant death syndrome
Authors: Baxendine Julia A. , Moore Isabella E.
Published: June 2005

A recent immunohistochemical study found increased numbers of eosinophils, but no mast cells, in the pulmonary parenchyma of infants who died of sudden infant death syndrome (SIDS). The present study tested the hypothesis that this pulmonary eosinophilia could be IgE‐mediated. Histomorphometry was used to compare the numbers of eosinophils, mast cells, and IgG‐, IgA‐, IgM‐ and IgE‐expressing lymphoid cells in the lungs of two groups of infants. Twenty‐eight subjects aged less than 1 year were selected from post‐mortem records of infant deaths between 1989 and 1992. Fourteen were cases of SIDS and these infants were matched for age and gender to 14 controls who died of other non‐pulmonary conditions. Immunohistochemical stains were used and positive cells were counted on six peribronchial and six subpleural fields. The numbers of eosinophils in both peribronchial and subpleural regions were significantly higher in SIDS compared with controls (P=0·0071 and P=0·041, respectively). The numbers of IgA‐expressing lymphoid cells were also significantly increased in SIDS cases (P=0·042). There were no differences in IgG, IgM or IgE expression or in mast cell numbers. These results confirmed that pulmonary eosinophils are increased in SIDS, but not through an IgE‐mediated pathway.
Transmural changes in mast cell density in rat heart after infarct induction in vivo
Authors: Engels Wim , Reiters Pascalle H. C. M. , Daemen Mat J. A. P. , Smits Jos F. M. , Van Der Vusse Ger J.
Published: June 2005

The cardiac distribution of mast cells was investigated after the induction of acute myocardial infarction in the rat. The left anterior descending coronary artery (LAD) was occluded by ligation in the infarct group, whereas in sham rats only a superficial ligature was placed beside the LAD. Rats of both groups were killed at 4, 7, 14, 21, 35, and 85 days following surgery. Hearts were excised and formalin‐fixed. Mast cell densities were monitored in subepicardial and subendocardial layers of the left ventricle (LV) in 6 μm thick toluidine blue‐stained cross‐sections. In control (non‐operated) animals, mast cell densities were comparable in the LV subepicardial and subendocardial layers (1·5–2·0 cells per mm2). Following infarction, the mast cell density at the subepicardial site of the infarction gradually increased, reaching a maximum of 25 cells per mm2 on day 21, while a non‐significant increase was observed at the subendocardial site. In the non‐infarcted regions, the mast cell density increased transiently to reach a maximum of 7 cells per mm2 on day 35 in the subepicardial layer. Again, changes in mast cell density in the subendocardial layer were non‐significant. In the sham group, a gradual increase to 9 cells per mm2 on day 21 and a subsequent decrease to 5 cells per mm2 on day 85 were observed in the subepicardial layers. These findings indicate a massive accumulation of mast cells in the subepicardial layers of the infarcted region and a small but significant effect of the surgical procedure on cardiac mast cell deposition, especially in the outer layers of the left ventricle.
Angiotensin converting enzyme inhibition prevents polyploidization of cardiomyocytes in spontaneously hypertensive rats with left ventricular hypertrophy
Authors: Panizo‐Santos A. , Sola J. J. , Pardo‐Mindán F. J. , Hernández M. , Cenarruzabeitia E. , Díez J.
Published: June 2005

Polyploidization of cardiomyocyte nuclei is a physiological phenomenon that increases in pathological conditions such as myocardial hypertrophy. The purpose of this study was to evaluate the potential benefit of the angiotensin converting enzyme (ACE) inhibitor quinapril in reversing the polyploidization of cardiomyocyte nuclei in spontaneously hypertensive rats (SHR) with established left ventricular hypertrophy (LVH). Sixteen week‐old male SHR were treated with oral quinapril (average dose 10 mg/kg per day) for 20 weeks. Sixteen‐ and 36‐week‐old untreated SHR and 16‐ and 36‐week‐old normotensive Wistar‐Kyoto (WKY) rats were used as controls. Nuclear polyploidization was determined by DNA flow cytometry of frozen tissues from the left ventricle, at least 20 000 nuclei being measured in each sample. The rates of tetraploidy in the 16‐ and 36‐week‐old SHR groups were 2·8 per cent (range 2·16‐3 per cent) and 5·4 per cent (range 4·9–5·9 per cent), respectively. Treated SHR had a similar rate of DNA tetraploidy to the 16‐ and 36‐week‐old WKY rat groups: 1·8 per cent (range 1·5–2·3 per cent), 1·55 per cent (range 1·5–1·6 per cent), and 1·5 per cent (range 1·4–1·6 per cent), respectively. The differences in the percentage of tetraploid cardiomyocytes between the SHR untreated groups and the SHR treated group were statistically significant (P<0·05). Regression of LVH and normalization of blood pressure were observed in treated rats. These results indicate that DNA tetraploidy in the myocardium of SHR increases with hypertrophy and decreases on quinapril treatment. It is suggested that ACE inhibition modifies nuclear processes involved in myocyte growth in arterial hypertension.
A step toward DSM‐V: cataloguing personality‐related problems in living
Authors: McCrae Robert R. , Löckenhoff Corinna E. , Costa Paul T.
Published: June 2005

Intractable problems with DSM‐IV's Axis II mandate an entirely new approach to the diagnosis of personality‐related pathology. The Five‐Factor Model of personality provides a scientifically grounded basis for personality assessment, and Five‐Factor Theory postulates that personality pathology is to be found in characteristic maladaptations that are shaped by both traits and environment. A four‐step process of personality disorder (PD) diagnosis is proposed, in which clinicians assess personality, problems in living, clinical severity, and, optionally, PD patterns. We examine item content in five problem checklists to update the list of personality‐related problems used in Step 2 of the four‐step process. Problems were reliably assigned to relevant factors and facets, and a number of additions were made to an earlier catalogue. The four‐step process can be used by clinicians, and may be incorporated in a future DSM. This article is a U.S. government publication and is in the public domain in the United States.
Incremental validity of the Structured Interview for the Five‐Factor Model of Personality (SIFFM)
Authors: Stepp Stephanie D. , Trull Timothy J. , Burr Rachel M. , Wolfenstein Mimi , Vieth Angela Z.
Published: June 2005

This study examined the incremental validity of the Structured Interview for the Five‐Factor Model (SIFFM; Trull & Widiger, 1997) scores in the prediction of borderline, antisocial, and histrionic personality disorder symptoms above and beyond variance accounted for by scores from the Schedule for Nonadaptive and Adaptive Personality (SNAP; Clark, 1993), a self‐report questionnaire that includes items relevant to both normal (i.e. Big Three) and abnormal personality traits. Approximately 200 participants (52 clinical outpatients, and 149 nonclinical individuals from a borderline‐features‐enriched sample) completed the SIFFM, the SNAP, and select sections of the Personality Disorder Interview—IV (PDI‐IV; Widiger, Mangine, Corbitt, Ellis, & Thomas, 1995). We found support for the incremental validity of SIFFM scores, further indicating the clinical utility of this instrument. However, results also supported the incremental validity of SNAP scores in many cases. We discuss the implications of the findings in terms of dimensional approaches to personality disorder assessment. Copyright © 2005 John Wiley & Sons, Ltd.
Structure and properties of PBO–PEO diblock copolymer modified epoxy
Authors: Wu Junxian , Thio Yonathan S , Bates Frank S.
Published: June 2005

Amphiphilic poly(n‐butylene oxide)‐b‐poly(ethylene oxide) (PBO–PEO) diblock copolymers of various compositions were synthesized and studied as modifiers for epoxy resins. In blends of PBO–PEO, epoxy resin, and curing agent, the copolymers formed well‐defined microstructures that persisted upon curing of the epoxy. The resulting morphologies were vesicles, worm‐like micelles, and spherical micelles (in order of increasing size of PEO block), as well as transitional morphologies. Addition of 5% by weight of these block copolymers improved the fracture toughness of the epoxy by as much as 19 times with relatively small reduction in the elastic modulus. The highest level of toughness was measured in a system containing branched worm‐like micelles. Close examination of the fracture surfaces of these compositions suggests that although all the dispersed morphologies played a similar role to inclusions in particle‐toughened thermosets, crack deflection toughening contributed to the significantly higher levels of toughness in the worm‐like micelle systems. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Chem 43: 1950–1965, 2005
Development of a liquid chromatography/tandem mass spectrometry method for the quantification of fumonisin B1, B2 and B3 in cornflakes
Authors: Paepens C. , De Saeger S. , Van Poucke C. , Dumoulin F. , Van Calenbergh S. , Van Peteghem C.
Published: June 2005

A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the determination of fumonisin B1 (FB1), B2 (FB2) and B3 (FB3) in cornflakes is described. During method development, special attention was paid to the selection of a suitable internal standard (IS) in order to offer a good alternative for deuterated FB1. In this respect, the C12‐sphinganine analogue (2S,3R)‐2‐aminododecane‐1,3‐diol was chosen because of its structural similarity to the fumonisin backbone and its chromatographic elution between the target analytes. For the extraction of the fumonisins from the cornflakes matrix, MeOH/H2O (adjusted to pH 4 with 0.1 M HCl; 70:30, v/v), ACN/MeOH/H2O (25:25:50, v/v/v) and acidified ACN/MeOH/H2O (25:25:50, v/v/v; pH 4) were evaluated. Preference was given to acidified MeOH/H2O (70:30, v/v) with mean recoveries (n = 12) for FB1, FB2 and FB3 of, respectively, 84 ± 10, 78 ± 7 and 85 ± 9%. Cleanup was performed using immunoaffinity columns (FumoniTest®, VICAM). The chromatography was performed under isocratic conditions at a flow of 0.3 mL min−1 with a mobile phase consisting of ACN/H2O (60:40, v/v) containing 0.3% formic acid. The mass spectrometer was operated in the positive electrospray ionization (ESI+) mode using multiple reaction monitoring (MRM). An intralaboratory validation was conducted with fortified samples determining limits of detection (LOD), limits of quantification (LOQ), precision, trueness, specificity and measurement uncertainty. The LOD concentrations for FB1, FB2 and FB3 were 20, 7.5 and 12.5 µg/kg. The LOQs were 40 µg/kg for FB1, 15 µg/kg for FB2 and 25 µg/kg for FB3. The coefficients of variation (CVs) under repeatability conditions varied from 11 to 13% for FB1, from 9 to 14% for FB2 and from 7 to 10% for FB3. Under within‐laboratory reproducibility conditions, the CVs ranged from 12 to 17% for FB1, from 9 to 16% for FB2 and from 7 to 13% for FB3. The percent bias for FB1 varied from −12 to −10%, while for FB2 and FB3 bias ranged, respectively, from −4 to −2% and from −12 to −5%. The expanded measurement uncertainties for FB1, FB2 and FB3 were, respectively, 19, 18 and 22%. Copyright © 2005 John Wiley & Sons, Ltd.
Asymptotic behavior of random heaps
Authors: Hough J. B.
Published: June 2005

We consider a random walk Wn on the locally free group (or equivalently a signed random heap) with m generators subject to periodic boundary conditions. Let #T(Wn) denote the number of removable elements, which determines the heap's growth rate. We prove that limn→∞𝔼(#T(Wn))/m ≤ 0.32893 for m ≥ 4. This result disproves a conjecture (due to Vershik, Nechaev and Bikbov [Comm Math Phys 212 (2000), 469–501]) that the limit tends to 1/3 as m → ∞. © 2005 Wiley Periodicals, Inc. Random Struct. Alg., 2005
Simultaneous labeling of mast cell proteases and protease mRNAs at the bone–implant interface of aseptically loosened hip implants
Authors: Qiu J. , Beckman M. J. , Qian J. , Jiranek W.
Published: June 2005

Human mast cells (MC) exhibit two distinct phenotypes based on the protease content of their secretory granules. MCTC cells express tryptase, chymase, cathepsin G, and mast cell carboxypeptidase, while MCT cells express only tryptase. Both mast cell phenotypes were assessed near regions of osteolysis in uninfected failed joint implants by immunohistochemistry with antibodies to tryptase and chymase, and by in situ hybridization with anti‐sense RNA probes for the respective mRNA molecules. Specimens from the interface membrane of 32 aseptically loosened total hip implants were studied, 28 of which had mast cells of the MCTC type. Most of these mast cells were aligned along the bone–prosthesis interface adjacent to loosened implants, suggesting involvement in the chronic inflammatory response that leads to bone resorption. Further ultrastructural evidence of mast cells in tissues from failed joint interface membranes was shown by transmission electron microscopy, and detection by staining after magnetic activated cell sorting. The presence of MC at the periprosthetic interface of eroded bone suggests MC degranulation and activity are associated with osteolysis in failed joint prostheses. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.