bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in the distribution pattern of gelatin‐binding protein of 28 kDa (adiponectin) in myocardial remodelling after ischaemic injury
Authors: Ishikawa Y , Akasaka Y , Ishii T , Yoda‐Murakami M , Choi‐Miura N‐H , Tomita M , Ito K , Zhang L , Akishima Y , Ishihara M , Muramatsu M , Taniyama M 
Published: December 2004

Aims:  Gelatin‐binding protein of 28 kDa (GBP28) is a collagen‐like plasma protein having a binding capacity with collagens. We investigated GBP28 role on myocardial remodelling as well as the diagnostic significance of GBP28 immunostaining in myocardial infarction.Methods and results:  Myocardial tissues obtained from 47 autopsied hearts with infarction were immunostained with antibodies against GBP28, fibronectin, type III and IV collagens, and prolyl 4‐hydroxylase. GBP28 was distributed in interstitium of infarcted lesions at an early stage. GBP28 was linearly found both along the border with vital myocardium and at the periphery of surviving cardiomyocyte around the lesion at granulative stage. However, it was not observed in the scar. GBP28 distribution patterns were similar to those of fibronectin in infarcted lesions and those of type IV collagen at the periphery of cardiomyocyte. Type III collagen was not recognized in the early‐stage lesion but increased along with scar maturation. Prolyl 4‐hydroxylase was found in surviving cardiomyocytes around the lesion during all stages and in interstitial cells appeared in granulation tissue.Conclusion:  GBP28 plays a role as a scaffold of newly formed collagen in myocardial remodelling after ischaemic injury, and GBP28 immunostaining may assist in a diagnosis of healing stage.
Cellular differentiation status of epithelial polyps of the colorectum: the gastric foveolar cell‐type in hyperplastic polyps
Authors: Koike M , Inada K , Nakanishi H , Matsuura A , Nakamura S , Tatematsu M 
Published: December 2004

Aims:  The ‘metaplastic’ polyp of the colorectum, a synonym for the hyperplastic polyp, was named based only on features of the crypt epithelium. It is considered non‐neoplastic, but the precise cellular differentiation status remains to be proven.Methods and results:  Forty‐eight hyperplastic polyps, 12 serrated adenomas, 45 tubular adenomas and five juvenile polyps were studied for their phenotypic expression using gastric (foveolar or pyloric gland cell), small intestinal (goblet cell), and colonic (goblet cell) cellular markers by immunohistochemical and mucin histochemical techniques. Gastric foveolar cell‐type differentiation was significantly expressed in hyperplastic polyps, while colonic differentiation was also consistently preserved. Neither gastric pyloric‐type nor small intestinal differentiation was observed. The same cell differentiation status as hyperplastic polyps was observed in serrated adenomas but not in tubular adenomas or juvenile polyps.Conclusions:  A large proportion of hyperplastic polyps are composed of hybrid epithelium, with bidirectional differentiation to both gastric foveolar and colonic epithelial cells in the same crypt. Therefore hyperplastic polyps might be interpreted as the outcome of abnormal cell differentiation of stem cells. The same phenotypic expression suggests that hyperplastic polyps and serrated adenomas share the same cell lineage.
p53 expression in normal paraffin‐embedded tissue using different antibodies and antigen retrieval buffer systems
Authors: Pillai G , Roberts H , Gatter K , Pezzella F 
Published: December 2004

Aims:  The study was undertaken to demonstrate wild‐type p53 in normal paraffin‐embedded tissues using two widely used antibodies, DO7 and 1801 and two different antigen retrieval buffer systems.Methods and results:  Formalin‐fixed paraffin‐embedded normal tissue samples were obtained from the archives of the John Radcliffe Hospital, Oxford. Antigen retrieval was performed by microwaving using two different buffer systems: (i) the commercially available Dako target retrieval solution (Cat. no. 1699) (pH 9.8–9.9), (ii) freshly prepared buffer consisting of 0.1 m EDTA with 0.1% Tween pH 6.0, and (iii) freshly prepared buffer consisting of 0.1 m EDTA with 0.1% Tween pH 8.0. Staining was performed with DO7 and 1801 antibodies using the Dako Envision kit (peroxidase/DAB). DO7 antibody elicited strong nuclear staining in the mucosal cells of the small and large intestine, lymphoid cells, decidua, neurones such as Purkinje cells of the cerebellum, glandular epithelial cells and stromal cells of the prostate, cardiac myocytes and bronchial epithelial cells. Cytoplasmic staining was noted in Purkinje cells, glandular epithelium of prostate, exocrine pancreas and renal tubular epithelium. The 1801 antibody did not produce staining in any of these tissues.Conclusions:  Our study demonstrates the presence of p53 in normal paraffin‐embedded tissue with nuclear and/or cytoplasmic localization in some instances. In our view, DO7 appears to be better suited for such detection.
Clinicopathological features of nine cases of non‐cirrhotic portal hypertension: current definitions and criteria are inadequate
Authors: Ibarrola C , Colina F 
Published: December 2004

Aims:  The clinicopathological features of nine patients with non‐cirrhotic portal hypertension were studied and an attempt was made to apply the descriptive criteria of experts to the morphological alterations of the livers in order to classify them adequately.Methods and results:  Clinical and biochemical data and the alterations in livers resected at transplantation (n=7) or at autopsy (n=2) were gathered in five males and four females (ages 15–78 years) without aetiological factors for chronic hepatic disease who had oesophageal varices and splenomegaly in the absence of typical cirrhosis. Noting the luminal obstruction of the three hepatic vascular trees, hyperplastic nodule size and distribution, and the density of fibrosis, an attempt was made to assign each case to one of the following diagnostic categories: idiopathic portal hypertension, diffuse nodular regenerative hyperplasia, partial nodular transformation and incomplete septal cirrhosis. When a case could not be categorized into one of these groups, it was listed as non‐cirrhotic irregular architectural transformation. Only three cases could be assigned to one pure diagnostic category (two diffuse nodular regenerative hyperplasias and one incomplete septal cirrhosis). Three other cases could not be classified due to the heterogeneity of their lesions. In the remaining three cases, the hepatic morphology was a mixture of hilar partial nodular transformation combined with another abnormal architectural pattern in the peripheral parenchyma: diffuse nodular regenerative hyperplasia in two cases and idiopathic portal hypertension in the other. In seven cases, old thromboses in the hilar portal tree were observed. Stenoses were observed in some of the arterial branches in five cases and in some hepatic venous branches in four. However, no obstructions could be discovered in small or large portal veins in the two classical diffuse nodular regenerative hyperplasia cases.Conclusions:  The hepatic morphology in this group of non‐cirrhotic portal hypertension patients was an abnormal remodelling of the liver associated with the frequent development of irregular hyperplastic nodules and frequent obstructions of the pre‐ and intrahepatic vascular lumens. It was very difficult to apply the nomenclature proposed by international experts.
The immunohistochemical expression pattern of Chk2, p53, p19INK4d, MAGE‐A4 and other selected antigens provides new evidence for the premeiotic origin of spermatocytic seminoma
Authors: Rajpert‐De Meyts E , Jacobsen G K , Bartkova J , Aubry F , Samson M , Bartek J , Skakkebæk N E 
Published: December 2004

Aims:  Spermatocytic seminoma is a rare germ cell derived tumour of the testis that occurs mainly in older men. We analysed the expression of recently discovered markers for germ cell differentiation and the mitosis–meiosis transition in order to define the antigen profile for diagnostic purposes and to clarify the biology and histogenesis of spermatocytic seminoma.Methods and results:  Twenty‐five spermatocytic seminomas were examined for immunohistochemical expression of germ cell‐specific onco‐fetal antigens and proteins involved in regulation of germ cell division, DNA repair and differentiation. The panel included Chk2, p19INK4d, p53, MAGE‐A4, KIT, TRA‐1‐60, neurone‐specific enolase and placental‐like alkaline phosphatase. Four of these proteins/antigens have never before been investigated in spermatocytic seminoma. Proteins highly expressed in gonocytes and spermatogonia, such as Chk2, MAGE‐A4 and neurone‐specific enolase, were consistently present in spermatocytic seminoma. Antigens expressed in embryonic germ cells but not in the normal adult testis, e.g. TRA‐1‐60, were undetectable, with the exception of p53 protein, which was demonstrated in 80% of cases. A proto‐oncogene p19INK4d, which is involved in the transition from mitotic to meiotic division in germ cells, was not detected in spermatocytic seminoma.Conclusions:  The investigation provided new information concerning the expression of Chk2, MAGE‐A4, neurone‐specific enolase and p19INK4d in spermatocytic seminoma. The pattern of expression is highly consistent with the origin of spermatocytic seminoma from a premeiotic germ cell, which has lost embryonic traits and has committed to spermatogenic lineage but has not yet passed the meiotic checkpoint, most probably from the spermatogonium of the adult testis.
Differential expression of S100 calcium‐binding proteins in epidermoid cysts, branchial cysts, craniopharyngiomas and cholesteatomas
Authors: Pelc P , Vanmuylder N , Lefranc F , Heizmann C W , Hassid S , Salmon I , Kiss R , Louryan S , Decaestecker C 
Published: December 2004

Aims: To investigate whether epidermoid cysts, branchial cysts, craniopharyngiomas and cholesteatomas express S100 proteins differentially by immunohistochemical assaying the presence of S100A1, S100A2, S100A3, S100A4, S100A5, S100A6 and S100B.Methods and results: Immunopositivity/negativity was recorded for each S100 protein in a series of 52 cases consisting of 12 epidermoid cysts, 12 branchial cysts, 15 adamantinomatous craniopharyngiomas and 13 acquired cholesteatomas. Except in the case of the craniopharyngiomas, immunoreactivity was assessed independently in the basal membrane and the basal, the internal and the keratin layers. Our data show that in contrast to S100B, which was rarely expressed, S100A1, S100A2, S100A4 and S100A5 were often present in these four types of epithelial lesions. S100A3 and S100A6 and, to a lesser extent, S100A5 were the most differentially expressed proteins across the different histopathological groups analysed. These three proteins are expressed more often in craniopharyngiomas and cholesteatomas, the two more aggressive types of lesions.Conclusions: This is the first study to report data on the expression of seven S100 proteins in different histopathological groups of epithelial head and neck lesions, whose precise embryological origins are still a matter of debate. S100 proteins could possibly be used as markers to target this embryonic origin, since our results show that S100A3 and S100A6 (and, to a lesser extent, S100A5) are expressed differentially across these different groups of epithelial lesions.
Expression of cyclin A and topoisomerase IIα of oligodendrogliomas is correlated with tumour grade, MIB‐1 labelling index and survival
Authors: Park S‐H , Suh Y‐L 
Published: December 2004

Aims:  This study was designed to investigate immunoexpression of cyclin A and D1, and topoisomerase IIα in oligodendrogliomas and to evaluate the correlation with MIB‐1 (Ki67), tumour grade, and survival of the patients.Methods and results:  Forty cases of oligodendrogliomas (20 high‐ and 20 low‐grade) were studied immunohistochemically with the above‐mentioned monoclonal antibodies.Results:  Normal brain tissues included in tumour sections did not express any of cyclin A, MIB‐1 and topoisomerase IIα except cyclin D1, which was shown in perineuronal and interfascicular normal oligodendroglial cells. In low‐grade and high‐grade oligodendrogliomas, the mean cyclin A labelling index (LI) was 1.18 ± 0.98% versus 4.65 ± 1.99%, respectively; the mean topoisomerase IIα LI was 1.32 ± 1.04% versus 6.63 ± 4.31%, respectively; and the mean MIB‐1 LI was 1.69 ± 1.55% versus 9.46 ± 4.66%, respectively. Interestingly, cyclin D1 was not expressed in any oligodendrogliomas. Both cyclin A and topoisomerase IIα LI showed a significant positive correlation with MIB‐1 LI and histological grade of oligodendrogliomas (P < 0.01) and an inverse correlation with overall survival (P < 0.01). Univariate analysis showed that cyclin A and topoisomerase IIα LIs with a cut‐off point at 3% were a significant prognostic factor (P: cyclin A = 0.0040, topoisomerase IIα = 0.0033).Conclusion:  Cyclin A and topoisomerase IIα expression are closely correlated with anaplastic oligodendrogliomas and worse clinical outcomes. Cyclin D1 seems not to be involved in the tumorigenesis of oligodendrogliomas.
Pathological significance of oxidative cellular damage in human alcoholic liver disease
Authors: Seki S , Kitada T , Sakaguchi H , Nakatani K , Wakasa K 
Published: December 2004

Aims: To investigate the pathological significance of oxidative stress‐induced lipid peroxidation and oxidative DNA damage in alcoholic liver disease.Methods and results: Hepatic expression of 4‐hydroxy‐2′‐nonenal (HNE) adducts and 8‐hydroxydeoxyguanosine (8‐OHdG) as reliable markers of lipid peroxidation and oxidative DNA damage, respectively, was analysed immunohistochemically and compared with histological findings in alcoholic liver disease. While no HNE adducts were observed in control livers, HNE adducts were frequently (37 of 40 cases, 92.5%) detected in alcoholic liver disease. The localization of HNE adducts was the cytoplasm of hepatocytes and sinusoidal cells in zone 3. As for 8‐OHdG, 29 of 40 cases (72.5%) with alcoholic liver disease exhibited positive immunolabelling for 8‐OHdG, while 8‐OHdG expression was not evident in control livers. The nuclear expression of 8‐OHdG was mainly detected in the hepatocytes within the areas of active inflammation. Among histological parameters, the grade of necro‐inflammation activity as well as the presence of Mallory bodies were significantly associated with the expression of HNE adducts and 8‐OHdG. In addition, the severity of steatosis also correlated with HNE adduct expression.Conclusions: Lipid peroxidation and oxidative DNA damage occur widely and may be associated with certain pathological features in human alcoholic liver disease.
How to improve microscopic images obtained with consumer‐type digital cameras
Authors: Regitnig P , Van Paasen R , Tsybrovskyy O 
Published: December 2004

Aim: Digital imaging is useful in conventional photography because it immediately provides images, and the image quality can be improved afterwards by the use of computer programs. The major disadvantages of consumer‐type digital cameras mounted on microscopes are (i) unequal illumination through the image, and (ii) a coloured background. A computer program was specifically adapted and refined to improve images obtained with consumer‐type digital cameras mounted on microscopes.Methods and results: An approach using a division operation between the specimen image and a background image leads to homogeneous illumination throughout the image, with automatically corrected brightness and white background. The correct colour spectrum is preserved by correction of the histogram. This approach was obtained from the freeware computer program ‘Image Arithmetic’. In a test, three different consumer‐type digital cameras (Sony, Nikon, Olympus) on different microscopes were used to obtain images of different types of histological specimens (cervical smear, bone marrow biopsy, and colonic biopsy). The computer program dramatically improved the quality of images obtained with all tested cameras.Conclusion: Using this approach, even low‐cost digital cameras mounted on microscopes produce brilliant images with homogeneous illumination and a white background, the image quality being comparable with expensive cameras especially designed for microscopes.
p53 mutation and MDM2 amplification in inflammatory myofibroblastic tumours
Authors: Yamamoto H , Oda Y , Saito T , Sakamoto A , Miyajima K , Tamiya S , Tsuneyoshi M 
Published: December 2004

Aims:  The pathogenic mechanism and predictive indicators of biological behaviour of inflammatory myofibroblastic tumour are poorly understood. We investigated molecular abnormalities of p53 and MDM2 in order to assess whether these play an important role in pathogenesis, and whether they also contribute to clinicopathological aggressive phenotype in inflammatory myofibroblastic tumour.Methods and results:  We compared the immunohistochemical expression of calponin, h‐caldesmon, ALK, and p53 gene mutation and MDM2 gene amplification with clinicopathological findings in 15 cases of inflammatory myofibroblastic tumour. Histologically, cellular atypia was observed in five (33.3%) out of 15 cases. Local recurrences were observed in two (14.3%) of 14 informative cases, but no distant metastasis was observed. The expression of calponin (9/14; 64%) but not h‐caldesmon (0/14; 0%) was seen, which suggested myofibroblastic differentiation. ALK expression was seen in eight (53.3%) out of 15 cases, particularly in patients under 40 years old. Nuclear expression of p53 protein was recognized in only one (6.7%) of 15 cases, and polymerase chain reaction single‐strand conformation polymorphism followed by direct sequencing revealed p53 gene missense mutations in two (13.3%) of 15 cases. Nuclear expression of MDM2 was seen in four (26.7%) of 15 cases, and the MDM2 gene amplification was observed in two of the four cases.Conclusion:  Inflammatory myofibroblastic tumour shows a wide spectrum of cellular atypia and biological behaviour with p53 and MDM2 expression. However, the alterations in the p53 pathway seem not to play a major role in the pathogenesis of inflammatory myofibroblastic tumour.
Gastric‐type mucin and TFF‐peptide expression in Barrett's oesophagus is disturbed during increased expression of MUC2
Authors: Van de Bovenkamp J H B , Korteland‐Van Male A M , Warson C , Büller H A , Einerhand A W C , Ectors N L E Y , Dekker J 
Published: December 2004

Aims:  Barrett's oesophagus constitutes metaplastic epithelium, often diagnosed by mucin histochemistry. We determined the mucins and trefoil factor family (TFF)‐peptides that were expressed in Barrett's oesophagus, in order to study changes in protein expression in early stages of Barrett's oesophagus development.Methods and results:  Biopsy specimens of 71 Barrett's oesophagus patients were collected, and sections were stained for secretory mucins by histochemistry. Immunohistochemistry was performed for secretory mucins (MUC2, MUC5AC, MUC5B, MUC6), TFFs (TFF1, TFF2, TFF3), and proliferation (Ki67). Protein expression in the tissue was measured semiquantitatively. MUC5AC and TFF1 showed high levels and strong colocalization in the surface epithelium, whereas MUC6, MUC5B and TFF3 were found in the deeper glandular structures. TFF2 was found in both surface and glandular epithelium. The co‐ordinate expression patterns of these six markers were similar to gastric antrum epithelium. MUC2 expression was ubiquitously associated with goblet cells within intestinal metaplasia, occurring in 68% of patients, and was correlated with increasing proliferation in the epithelium.Conclusions:  Virtually all cells in Barrett's oesophagus epithelium displayed a secretory phenotype, demonstrating a co‐ordinate gastric‐type MUC and TFF expression. When MUC2 expression was more pronounced, the expression patterns of the other MUCs and the TFFs were increasingly disturbed. MUC2 expression may constitute a marker for early change in the phenotype of Barrett's oesophagus as a precancerous lesion.
Cutaneous breast cancer deposits show distinct growth patterns with different degrees of angiogenesis, hypoxia and fibrin deposition
Authors: Colpaert C G , Vermeulen P B , Van Beest P , Soubry A , Goovaerts G , Dirix L Y , Harris A L , Van Marck E A 
Published: December 2004

Aims:  We postulated that skin metastases and cutaneous local recurrences from breast adenocarcinoma show different growth patterns with distinct angiogenic profiles.Methods and results:  Fifty‐one surgically resected dermal breast cancer deposits were evaluated for growth pattern, E‐cadherin expression, presence of necrosis and a fibrotic focus, fibrin deposition, carbonic anhydrase IX expression (CA IX), microvessel density, endothelial cell proliferation and blood vessel immaturity. Growth patterns were infiltrative, with carcinoma cells infiltrating the dermis without significant disturbance of the pre‐existing architecture, expansive, meaning that a nodule of carcinoma cells and desmoplastic tissue pushed aside the pre‐existing dermal structures, or mixed. All lobular carcinomas showed an infiltrative growth and lacked membranous E‐cadherin expression. Different growth patterns in the ductal carcinomas were not correlated with differences in E‐cadherin expression. The presence of necrosis and/or a fibrotic focus and the expression of the hypoxia marker CA IX were significantly associated with an expansive growth. Fibrin was present in all expansive deposits and less frequently in the other growth patterns. There was a positive association between fibrin deposition, CA IX expression and microvessel density. The latter was significantly higher in the expansive and mixed growth patterns than in the infiltrative pattern. Endothelial cell proliferation was highest in the expansive growth pattern and was positively correlated with the presence of a fibrotic focus and with fibrin deposition. The maximum percentage of immature blood vessels was higher in the expansive and mixed growth patterns than in the infiltrative one.Conclusion:  The recognition of different subgroups of cutaneous breast cancer deposits with different degrees of hypoxia‐driven angiogenesis may have important implications for the usefulness of anti‐angiogenic therapy.
The angiogenic receptor KDR is widely distributed in human tissues and tumours and relocates intracellularly on phosphorylation. An immunohistochemical study
Authors: Stewart M , Turley H , Cook N , Pezzella F , Pillai G , Ogilvie D , Cartlidge S , Paterson D , Copley C , Kendrew J , Barnes C , Harris A L , Gatter K C 
Published: December 2004

Aims:  Angiogenesis is an important factor in tumour growth and metastasis. Vascular endothelial growth factor receptor 2 (VEGFR‐2) or KDR plays a crucial role in angiogenesis. The aim of this study was to raise and characterize antibodies against phosphorylated KDR which could be used for studies on human tissues to assess KDR activation and novel inhibitors of KDR activation in clinical trials.Methods and results:  Three monoclonal antibodies and one rabbit polyclonal antiserum were produced. The specificity of the antibodies was confirmed by ELISA. One of the mouse antibodies and the rabbit polyclonal antiserum reacted with a 200‐kDa band on a Western blot of human umbilical vein endothelial cell (HUVEC) lysates, the molecular weight of KDR. Immunohistochemical staining showed that phosphorylated KDR is present in a wide variety of normal tissues including liver, colon and placenta, and is not restricted to endothelium. It was also present in a number of human tumours including breast carcinomas, colonic carcinomas and non‐Hodgkin's lymphomas. The pattern of staining was membranous, cytoplasmic and nuclear.Conclusions:  This study has shown that phosphorylated KDR is present in a wide variety of tumour and tissue types and is not confined to endothelium.