bluuebunny/crossref_metadata_2025 huggingface dataset:
Is immunohistochemical analysis of oestrogen and progesterone receptors in endometrial carcinoma superior to the radioligand binding assay?
Authors: Snijders Marc P. , De Goeij Antony F. , Koudstaal Johan , Rousch Mat J. , Scheres Hubert M. , Stoot Jan E. , Bosman Fred T.
Published: June 2005

The aim of this study was to evaluate tissue and steroid receptor heterogeneity in endometrial carcinoma specimens as a possible source of discordance between biochemically assayed receptor status and response to endocrine treatment. For this purpose the oestrogen receptor (OR) and progesterone receptor (PR) levels in specimens from 16 endometrial carcinoma patients were analysed on adjacent tissue sections using both a radiochemical and an immunohistochemical assay. With immunohistochemical receptor analysis extensive tissue and tumour cell receptor heterogeneity was observed. Many tumour samples revealed up to 75 per cent contamination with benign tissue. In the majority of cases, evaluation of immunoreactivity in normal tissue elements of the specimen could explain the apparent discordance between semiquantitative immunohistochemical receptor scoring of tumour cells and radiochemical receptor assay.

Immunohistochemical analysis of OR and PR in endometrial carcinoma specimens allows a more specific determination of tumour cell receptor content and hence may yield a more accurate prediction of response to endocrine therapy than the biochemical assay.
Mast cells, nerves and fibrosis in the appendix: A morphological assessment
Authors: Stead Ron H. , Franks Antony J. , Goldsmith Charles H. , Bienenstock John , Dixon Michael F.
Published: June 2005

Mast cells are closely associated with nerves in the mucosa of the appendix vermiformis, and obliteration of the appendiceal lumen by fibrous tissue is accompanied by neurogenous hyperplasia. However, changes in the density of mast cells in this process have not been reported. Accordingly, fibrosis was graded in haematoxylin and eosin sections from 46 samples of human appendix. This was compared with mast cell number in toluidine blue‐stained slides and nerve density in PGP9.5‐immunoreactive sections. In the mucosa, the mast cell number in the samples with minimal fibrosis was three times greater than in those classified as normal (P<0.0001), and this declined in the more fibrotic samples. The mucosal nerve scores paralleled the mucosal mast cell changes, and stereological analysis revealed a correlation of mast cell number and nerve density within the lamina propria of the same specimens (r=0.49–0.90). In the submucosa, mast cell numbers and nerve scores were not significantly different in the different histological grades and obliterated samples resembled normal submucosa, except that a dense axial block of nerve staining was often present. The progressive fibrotic changes in appendices provide a human model for studying the relationships of nerves, mast cells, and fibrosis in the gastrointestinal tract.
The sweat gland in graft versus host disease
Authors: Akosa A. B. , Lampert I. A.
Published: June 2005

Sweat gland abnormalities occur much more frequently than hitherto described in cutaneous graft versus host disease (GVHD). Two patterns of abnormalities were identified in 80 per cent of cases of acute GVHD: a cytopathic pattern consisting of a combination of basal vacuolopathy with or without lymphocytic infiltration and basal cell degeneration, and a proliferative pattern consisting of basal cell hyperplasia. In chronic GVHD, complete sweat gland destruction with fibrosis was commonly observed. Squamous metaplasia and dilatation of the sweat glands were less frequently identified. Ki67 immunostaining confirmed proliferative activity in the basal cells of the distal duct. HLA‐DR antigens were expressed on the basal cells of the duct and secretory glands in acute GVHD but not in normal skin. Langerhans cells were absent in both normal and abnormal sweat glands. The role of HLA‐DR or Langerhans cells in the initiation of GVHD is questioned in the light of the new data and the primary involvement of proliferating cells is confirmed.
Fibronectin degradation; An in‐vitro model of neutrophil mediated endothelial cell damage
Authors: Forsyth Kevin D. , Levinsky Roland J.
Published: June 2005

We have observed that fibronectin has a characteristic fibrillar morphology within the extracellular matrix surrounding endothelial cells. This morphology, which is easily recognizable by conventional immunoperoxidase techniques, is disrupted if neutrophils are induced to degranulate on endothelial monolayers. Loss of the fibrillar morphology (degraded fibronectin) is characterized by fragmentation and diffuse spreading of fibronectin over the surface of the endothelial cells. Loss of the normal fibronectin architecture following neutrophil degranulation is more rapid and extensive in endothelium pretreated with Interleukin‐1 (IL‐1). In addition, there is loss from the fibronectin molecule of a chymotryptic protease‐sensitive epitope recognized by a cellular fibronectin specific antibody.

Degraded fibronectin is stimulatory for neutrophils, and is likely to induce further fibronectin breakdown. This sequence has the potential to set up an amplification inflammatory loop with neutrophil mediated loss of vascular homeostasis. Alteration of fibronectin architecture is a useful marker of endothelial injury, and has important pathophysiological consequences.
Alpha‐smooth muscle actin as a marker for soft tissue tumours: A comparison with desmin
Authors: Jones Hugh , Steart Phillip V. , Boulay Clair E. H. Du , Roche William R.
Published: June 2005

The immunoreactivity of a range of vascular and non‐vascular smooth muscle tumours, rhabdomyosarcomas, and non‐myoid lesions has been examined with the use of a monoclonal antibody to smooth muscle‐specific actin and the muscle intermediate filament, desmin. In all cases of smooth muscle‐derived tumours, the alpha‐actin antibody yielded superior results. Staining of the myofibroblasts of fibromatoses was also seen. In contrast to desmin, immunoreactivity was not exhibited by rhabdomyosarcomas. We propose that this monoclonal antibody to alpha‐smooth muscle actin is a useful addition to the panel of reagents used for the characterization of soft tissue proliferations and tumours. The technical aspects of the application of this monoclonal antibody to immunohistochemistry are discussed.
Silver stained nucleolar organizer region proteins (Ag‐NORs) as a predictor of prognosis in colonic cancer
Authors: Öfner D. , Tötsch M. , Sandbichler P. , Hallbrucker Chr. , Margreiter R. , Mikuz G. , Schmid K. W.
Published: June 2005

Using a one‐step silver nitrate staining technique, routinely processed tumour tissues of 49 carcinomas of the colon were investigated to demonstrate silver‐stained nucleoli (Ag‐nus) and argyrophilic proteins associated with the so‐called nucleolar organizer regions (Ag‐NORs). Patients with attempted curative resections and tumour stages Dukes' A, B, C1 and C2, with an uneventful follow‐up period of at least 48 months (N = 17), showed a statistically significant (P = 0·0001) lower mean number of scattered Ag‐NORs (3·04; SD: 1·08) compared to patients who developed metastases during their follow‐up period (N = 15; 5·40; SD: 1·28), as well as to patients who underwent palliative surgical treatment (N = 17; 4·48; SD: 1·67). Mean numbers of scattered Ag‐NORs per nucleus and staging of the tumour were strongly related (P = 0·0001) to cancer‐specific survival. The results indicate that the evaluation of silver‐stained particles according to their different distribution patterns is of great value with regard to the clinical outcome of colonic carcinoma and may even allow a more accurate prognostic assessment of these patients than the WHO grading system, UICC staging system, the so‐called Jass‐scoring system, and Dukes' classification.
A Morphometrically‐based classification rule for the diagnosis of primary mesothelial lesions
Authors: Robutti Flavio , Betta Pier‐Giacomo , Donna Adalberto , Pavesi Mansueto
Published: June 2005

A computer‐aided morphometrical study was performed on histological specimens of reactive hyperplastic (n =10) and malignant (n=17) mesothelium. For each cell, seven nuclear features were measured and 13 parameters computed. Using stepwise variable selection, discriminant analysis chose the nuclear contour index, the standard deviation of the nuclear area, and the mean of the nuclear perimeter as discriminating features between hyperplastic and malignant mesothelium. The coefficients of these variables were included in a discriminant function which gave perfect discriminantion between the two groups of lesions. When the function was assessed on a test set of hyperplastic (n = 10) and egories was achieved. This classification rule may help to increase the level of confidence with which a histological diagnosis of mesothelioma can be established.
Distribution of type I collagen in human kidney diseases in comparison with type III collagen
Authors: Yoshioka Kazuo , Tohda Machi , Takemura Tsukasa , Akano Norihisa , Matsubara Kazunori , Ooshima Akira , Maki Sunao
Published: June 2005

The distribution of type I collagen in normal and diseased renal tissues was studied using immunofluorescence and immunoelectron microscopy, and was compared with that of type III collagen. In normal human kidneys, a monoclonal antibody against type I or type III collagen reacted with the renal interstitium, but not with the intra‐glomerular structures. In various types of glomerulonephritis, immunofluorescent staining for type I collagen was positive in the fibrocellular and fibrous crescents, sclerosed glomeruli, and infrequently within the glomerular mesangium. In the crescents and sclerosed glomeruli, type I collagen was co‐localized with type III collagen. The staining intensity of type I collagen in those areas was generally stronger than that in the interstitium. Mesangial staining for type I collagen was Present within the glomeruli, particularly with a marked mesangial matrix increase, but was less in amount and frequency compared with type III collagen staining.

These findings indicate that the fibrosclerotic process in damaged glomeruli is accompanied by the appearance of interstitial collagens, and that participation of type I collagen is prominent in crescent organization and global glomerular sclerosis, but is less frequent in mesangial expansion, compared with type III collagen.
Deduction from Wilms' tumour that glomerular podocytes produce the basement membrane material bearing goodpasture determinants
Authors: Droz Dominique , Diebold Nicole , Jan Dominique , Jaubert Francis
Published: June 2005

Using an indirect immunoperoxidase technique, we tested frozen specimens from one Wilms' tumour composed of numerous glomeruloid bodies devoid of blood vessels, with monoclonal antibodies directed against vimentin, cytokeratin, CALLA/CD10, CD24, CR1/CD35, endothelium factor VIII, class I and II MHC molecules, laminin, fibronectin, and non‐collagenic domain NC1 of type IV collagen. Two reagents against Goodpasture determinants were used: P1 monoclonal antibody and serum IgG (GP antibodies) from a biopsy‐proven Goodpasture patient.

Glomeruloid bodies comprised two cell types: a peripheral layer of parietal epithelial cells (cytokeratin and CD24‐positive) and central cell clumps of podocytes (vimentin and CALLA‐positive). The basal lamina surrounding the glomeruloid bodies contained laminin and NC1 domain of type IV collagen, while that present between the podocytes reacted strongly with laminin, and P1 and GP antibodies. Endothelium factor VIII was not detected within the glomeruloid bodies and CR1 molecules bound to the basement membrane material within them.

These data favour the hypothesis that podocytes produce the basement membrane material which bears Goodpasture determinants recently identified as a novel chain, named the α3 chain, of type IV collagen.
Adenomatous hyperplasia of the rete testis in the undescended testis
Authors: Cooper Kumarasen , Govender Dhirendra
Published: June 2005

Multiple foci of micronodular or tubulopapillary structures were noted in the rete testis of 13 cases of undescended testes. These structures were lined by low columnar to cuboidal epithelium, showed back‐to‐back crowding, and were supported by a thin lamina propria. These changes, referred to as adenomatous hyperplasia of the rete testis, appear to be a frequent finding in the undescended testis. An age‐matched control group did not show any of these features.
The fate of vacuolation in liver cells with special reference to hyaline globules
Authors: Shibayama Yuro , Yahara Miyakichi , Nakata Katsuji
Published: June 2005

This study was undertaken in rats to clarify the mechanisms and time necessary for recovery from vacuolation in liver cells. Vacuoles were produced by congestion of the liver due to constriction of the inferior vena cava just below the diaphragm, and changes in vacuoles were examined quantitatively and qualitatively until 24 h after release of the constriction. Vacuoles in liver cells decreased in number by half within 5 min after recovery from congestion. The remaining vacuoles metamorphosed to hyaline globules by condensation of the contents. The number of hyaline globules increased with a peak occurring at 3–6 h after recovery from congestion, although the number of vacuoles decreased gradually. Only a few small vacuoles and hyaline globules were found in liver cells in pericentral areas at 24 h after recovery from congestion. These data indicate that vacuoles may be discharged promptly from the liver cell cytoplasm after recovery from congestion, and the remaining vacuoles may metamorphose to hyaline globules by condensation of the contents and finally fade into the cytoplasm.
Translocation (11;14): A cytogenetic anomaly associated with B‐cell lymphomas of non‐follicle centre cell lineage
Authors: Vandenberghe Elisabeth , De Wolf‐Peeters Chris , Van Den Oord Joost , Wlodarska Ivonna , Delabie Jan , Stul Michel , Thomas José , Michaux Jean‐Louis , Mecucci Cristina , Cassiman Jean‐Jacques , Van Den Berghe Herman
Published: June 2005

Nine patients with t(11;14) and B non‐Hodgkin's lymphomas composed of small to intermediately sized cells with irregular nuclei are described. Immunophenotyping was performed on seven cases, which were M+, D− with light chain restriction, CD5+, CD10−, and CD20+, suggesting that they were non‐follicle centre cell lymphomas. The translocation (11;14) (in three cases the only cytogenetic anomaly) was associated with rearrangement of bcl‐1 in four of the five cases investigated. Translocation (11;14) has been described in an apparently heterogeneous group of low‐grade lymphoid malignancies which we suggest have a non‐follicle centre cell lineage in common. This translocation may be associated with these lymphomas in the same way that t(14; 18) is associated with follicle centre cell lymphomas.
Histopathological grading of soft tissue tumours. Prognostic significance in a prospective study of 278 consecutive cases
Authors: Jensen Olaf Myhre , Høgh Jørgen , Østgaard Svend E. , Nordentoft Axel Munck , Sneppen Otto
Published: June 2005

A consecutive 10‐year series of 278 soft tissue sarcomas was prospectively graded, using a system based on the number of mitoses and taking into account parameters such as cellularity, anaplasia, necrosis, and histogenetic type and subtype of tumour. Prognostic factors in relation to metastasis‐free survival were studied by uni‐ and multivariate analysis.

Fifty‐seven (20·5 per cent) were low‐grade tumours, 43 (15·5 per cent) were intermediate, and 178 (64 per cent) were high grade. High‐grade tumours were divided into two groups; 80 (29 per cent) grade 3A (=5–20 mitoses per 10 high power fields (HPF)) and 78 grade 3B (28 per cent) (=more than 20 mitoses/10 HPF); 10 HPF corresponds to 2·5 mm2. Twenty (7·2 per cent) high‐grade tumours could not be further subdivided.

Grading was found to be the prognostic factor associated with the strongest predictive value. Five‐year survival in low‐grade and intermediate tumours (95 and 86 per cent, respectively) differed significantly (P < 0·0001) from high grade (50 per cent) and (P = 0·0018) between grade 3A (64 per cent) and grade 3B (41 per cent). Other prognostic indicators of importance in high‐grade tumours were age, local recurrence at presentation (primary operation outside the Centre), and localization (superficial vs. deep).
‘Neuroendocrine’ differentiation in primary neoplasms of the liver
Authors: Wang Jiahua , Dhillon Amar P. , Sankey Elizabeth A. , Wightman A. Kay , Lewin Jackie F. , Scheuer Peter J.
Published: June 2005

Thirty primary liver neoplasms (16 hepatocellular, nine biliary, and five epithelioid haemangioendotheliomas) were studied for the expression of the general ‘neuroendocrine’ markers, neurone specific enolase (NSE) and protein gene product 9·5 (PGP 9·5). Grimelius silver staining for neurosecretory granules and immunostaining for S100 protein, HMB‐45, vasoactive intestinal polypeptide (VIP), and calcitonin were also performed. Eleven of the 16 hepatocellular carcinomas stained positively for PGP 9·5, four for NSE, six for HMB‐45, and two for S100 protein. Seven exhibited granular staining by the Grimelius method; eight showed immunostaining for VIP, and two for calcitonin. Three of the five haemangioendotheliomas demonstrated positive immunostaining for PGP 9·5, and two for NSE; of the nine biliary carcinomas, two showed staining for PGP 9·5 and NSE, and four contained cells staining with the Grimelius technique. Primary neoplasms of liver may show ‘neuroendocrine’ differentiation and this aspect of their phenotypic expression has to be considered before predicting the site of origin of a tumour in the liver.
Binding of ubiquitin to experimentally induced murine AA amyloid
Authors: Chronopoulos Soula , Alizadeh‐Khiavi K. , Normand Josée , Ali‐Khan Z.
Published: June 2005

Amyloid enhancing factor (AEF) activity has recently been demonstrated in ubiquitin purified from amyloidotic murine tissues and Alzheimer brain extract. Since AEF is known to bind to amyloid fibrils and ‘fibril‐AEF’ on passive transfer induces accelerated amyloidogenesis in the recipient animals, it was of interest to investigate whether ubiquitin binds to amyloid. Immunohistological studies were carried out on liver sections from amyloidotic mice. Biotin–strepavidin–peroxidase methods using monospecific rabbit anti‐mouse AA amyloid IgG (RAAG) and rabbit anti‐bovine ubiquitin IgG (RABU) antibodies were employed to immunostain the amyloid and ubiquitin deposits, respectively. RABU‐treated liver sections were counterstained with thioflavine S. RAAG reacted strongly with the amyloid, indicating that it is AA type, and RABU‐positive immunodeposits were found bound to the thioflavine‐S‐positive AA deposits. Treatment of the liver sections with 0·1 M sodium acetate containing 0·5 M NaCl, pH 4, for 2–3 h at 37°C nearly completely desorbed the AA amyloid‐bound ubiquitin. Since ubiquitin demonstrates AEF activity in vivo and binds non‐covalently to AA amyloid, we suggest that ubiquitin may indeed be ‘fibril‐AEF’ and may play a crucial role in the pathogenesis of amyloidosis. To our knowledge, this is the first time that ubiquitin bound to extracellularly deposited amyloid has been demonstrated.
Is focal chronic autoimmune thyroiditis an age‐related disease? Differences in incidence and severity between Japanese and British
Authors: Okayasu Isao , Hatakeyama Shigeru , Tanaka Yasukazu , Sakurai Tetsushi , Hoshi Kazuo , Lewis Paul D.
Published: June 2005

The incidence of chronic lymphocytic thyroiditis in autopsy material from Japanese and British subjects was evaluated. Lymphocytic infiltration in representative thyroid sections from 1826 Japanese cases collected from four different institutions was analysed. The overall incidence of lymphocytic infiltration was significantly higher in females (22·2 per cent) than in males (13·9 percent). In females, the incidence reached 23·2 percent in the fourth decade and showed no increase with age thereafter. The overall incidence of lymphocytic infiltration in thyroid sections from 810 British cases was 42·5 per cent in females and 19·4 per cent in males: an increase in the incidence of thyroiditis from the sixth decade onwards was noted in British females, the figure reaching 50·0 per cent in those aged over 70 years. These findings suggest possible racial differences in susceptibility to chronic thyroiditis. The disorder is not necessarily related to age, increasing severity of disease with age being found only in British females.
Distribution of β1, α1, α2 and α3 integrin chains in basal cell carcinomas
Authors: Stamp G. W. H. , Pignatelli M.
Published: June 2005

The integrins are αβ heterodimeric transmembrane proteins mediating cell–substratum as well as cell‐cell interactions. Changes in their expression and/or function seem to occur in a number of malignant epithelial neoplasms and may in part explain their abnormal patterns of growth and differentiation. Using monoclonal antibodies to the β1 (DH12), α1 (TS2/7), α2 (B1.515), and α3 (E1.56) integrin chains, the α1β1 (VLA‐1), α2β1 (VLA‐2), and α3β1 (VLA‐3) integrin receptors were studied on cryostat sections of 22 basal cell carcinomas (BCCs) and adjacent normal tissues by a standard peroxidase‐antiperoxidase technique. In non‐neoplastic skin, VLA‐2 and VLA‐3 were found in the basal layer, eccrine glands, and cells of the outer root sheath in which VLA‐1 was detected. In BCCs, there was a considerably higher expression of VLA‐2 and VLA‐3 compared with epidermal basal cells but similar to that seen in hair bulb and outer root sheath. In two cases of nodular BCC showing evidence of regression, both VLA‐2 and VLA‐3 were completely negative, in contrast to non‐regressing foci which were strongly positive.

The high level of expression of two adhesion molecules (VLA‐2 and VLA‐3) involved in cell‐substratum as well as cell‐cell interactions may account for the more indolent pattern of growth characteristic of BCC and perhaps reflect its high degree of differentiation towards the hair follicle.
A new monoclonal antibody, PM‐2K, specifically recognizes tissue macrophages but not blood monocytes
Authors: Takeya Motohiro , Tsuchiya Tatsuaki , Shimokawa Yasuhiro , Takahashi Kiyoshi
Published: June 2005

A new monoclonal antibody, PM‐2K, was raised against 24‐h cultured human peritoneal macrophages. Immunohistochemically, PM‐2K recognized most tissue macrophages in lymphoreticular organs such as the thymus, spleen, lymph node, and tonsil. Kupffer cells of the liver, alveolar macrophages, and macrophages in the interstitial tissue of the kidney, pancreas, and many other organs were also positively labelled. On the other hand, PM‐2K failed to recognize blood monocytes, freshly isolated peritoneal macrophages, microglial cells, osteoclasts, and dendritic cells such as Langerhans cells, interdigitating cells, and follicular dendritic cells. In various pathological conditions. PM‐2K labelled a wide variety of proliferating macrophages. Reaction products of PM‐2K were observed by immunoelectron microscopy on the cytoplasmic membrane of cultured peritoneal macrophages. The molecular weight of the antigen recognized by PM‐2K was determined to be 150 kD by Western blotting. As no cells other than macrophages were reactive with PM‐2K, this antibody is considered to be very useful not only in the investigation of macrophage differentiation and maturation, but also in the diagnosis of various proliferative disorders of macrophages.
p53 expression in human breast cancer related to survival and prognostic factors: An immunohistochemical study
Authors: Ostrowski J. L. , Sawan A. , Henry L. , Wright C. , Henry J. A. , Hennessy C. , Lennard T. J. W. , Angus B. , Horne C. H. W.
Published: June 2005

In a study of 90 breast cancer patients, tumour p53 protein expression was determined by immunohistochemistry using the monoclonal antibody PAb1801. Patient lymph node status and Bloom's grade were determined, and both oestrogen and progesterone status assessed, also by immunohistochemistry. Lymph node status, tumour grade, and progesterone receptor status all had a significant influence on survival. Patients with p53‐positive tumours showed poorer survival but this did not achieve significance. p53 protein expression showed a significant relationship to high tumour grade and a weak correlation with negative oestrogen receptor status. The data suggest taht p53 protein expression may be a marker of more aggressive carcinomas but that the prognostic power of expression is likely to be weak and unlikely, therefore, to be of clinical value. The results do not resolve whether detectable p53 protein expression represents a random product of dedifferentiation, or an important feature of the malignant phenotype, playing a key role in tumour behaviour. The number of patients in our study is small, however, and investigation of a larger series is clearly indicated.
Histopathological studies on the local reactions induced by complete fReund's adjuvant (CFA), bacterial lipopolysaccharide (LPS), and synthetic lipopeptide (P3C) conjugates
Authors: Wiedemann Frank , Link Ralf , Pumpe Konrad , Jacobshagen Ulrich , Schaefer Hans E. , Wiesmüller Karl‐Heinz , Hummel Rolf‐Peter , Jung Günther , Bessler Wolfgang , Böltz Traudel
Published: June 2005

The inflammatory reactions following subcutaneous application of adjuvants revealed characteristic pathological patterns. The injection of complete Freund's adjuvant (CFA) resulted in the formation of large lipid deposits encircled by an inflammatory reaction and concentrically arranged collagen bundles. Bacterial lipopolysaccharide (LPS) caused granulomatous aggregations of mononuclear cells with thrombotic vessel occlusions. Inoculation of the lipopeptide adjuvants induced accumulation of mononculear cells with only minimal fibrotic changes which were resolved after day 28. Lipopeptide conjugates based on the head group tripalmitoyl‐S‐glyceryl‐cysteinyl‐serin (P3CS) can thus be used as effective immunogens and adjuvants without long‐term tissue damage.
Phenotypic modulation in lipocytes in experimental liver fibrosis
Authors: Tanaka Yujiro , Nouchi Toshihiko , Yamane Michio , Irie Tetsuya , Miyakawa Happei , Sato Chifumi , Marumo Fumiaki
Published: June 2005

The presence of a‐smooth muscle actin (smA)‐positive cells has recently been reported in the fibrotic liver. Lipocytes have been considered to play important roles in hepatic fibrosis. However, the relation of the a‐smA‐positive cells and lipocytes has not been determined. The biological implication of a‐smA expression remains unknown. To study these questions, we carried out double immunofluorescent staining of a‐smA and desmin (a marker for lipocytes), or a‐smA and collagen, and double immunohistochemical staining of a‐smA and 5‐bromo‐2′‐deoxyuridine (BrdUrd) in carbon tetrachloride‐induced fibrotic rat livers. In normal and control livers, a‐smA‐positive cells were not seen in the lobules, whereas scattered desmin‐positive cells were present. With the development of hepatic fibrosis, a‐smA was expressed only in a portion of desmin‐positive cells located predominantly around collagen bundles. A number of a‐smA‐positive cells in the lobules were labelled with BrdUrd. These results suggest phenotypic modulation in lipocytes and differentiation of lipocytes towards myofibroblast‐like cells, since a‐smA is expressed with desmin in myofibroblasts in scar tissue. The expression of a‐smA may be related to events of the fibrotic process, such as tissue contraction or fibrogenesis per se.
Low expression of β1, α2 and α3 subunits of VLA integrins in malignant mammary tumours
Authors: Pignatelli Massimo , Hanby Andrew M. , Stamp Gordon W. H.
Published: June 2005

The Very Late Antigens (VLAs) are αβ heterodimeric transmembrane proteins mediating cell–substratum as well as cell–cell interactions. Changes in their expression and/or function seem to occur in a number of invasive carcinomas and may at least in part explain their abnormal patterns of growth and differentiation. Using monoclonal antibodies to the β1 (DH12, A1A‐5), α2 (B1.515) and α3 (E1.56) chains, VLA‐2 (α2β1) and VLA‐3 (α3β1) were studied on cryostat sections of three fibroadenomas and 43 invasive breast carcinomas (29 ductal, 14 lobular) by the avidin–biotin complex immunoperioxidase technique. In non‐neoplastic breast tissue and in fibroadenomas VLA‐2 and VLA‐3 were expressed by myoepithelial cells and on the basolateral surface of the luminal cells. There was weak or absent expression of α2, α3 and the common β1 chain in the majority of invasive carcinomas compared to the adjacent normal breast epithelium and preinvasive (in‐situ) carcinomas. In addition, the expression of the α2 chain of VLA‐2 was reduced significantly (P < 0.005) in the poorly differentiated ductal breast carcinomas (Grade III) compared to the well (Grade I) and moderately (Grade II) differentiated ductal tumours. These data give further evidence that loss or down‐regulation of VLA‐2 and VLA‐3 occur relatively frequently in invasive cancers, and, at least in the invasive ductal breast carcinomas. Loss of an extracellular matrix receptor controlling growth and differentiation seems to be one of the abnormalities underlying the progression towards an undifferentiated morphology.
Unilateral papillary necrosis complicating renal artery stenosis—evidence of activation of the intrarenal renin–angiotensin system?
Authors: Lindop George B. M. , Raweily Essam A. , Graham Patricia C.
Published: June 2005

We report an association between renal artery stenosis and papillary necrosis. We studied three kidneys with renal artery stenosis, two of which showed ipsilateral acute papillary necrosis. In all three cases there had been a sudden fall in perfusion of the ischaemic kidney. In the case with intact papillac, immunostainable renin was normal in amount and distribution, whereas both kidneys with papillary necrosis showed hyperplasia of renin‐containing cells, and these were mainly in the JGAs of the juxtamedullary cortex. Since the contralateral kidneys were spared, we suggest that in an ischaemic kidney with hyperplasia of renin‐secreting cells in the deep cortex, local activation of the renin‐angiotensin system could cause acute papillary necrosis due to vasoconstriction.
A comparison of immunohistochemical markers of cell proliferation with experimentally determined growth fraction
Authors: Scott R. J. , Hall P. A. , Haldane J. S. , Van Noorden S. , Price Y. , Lane D. P. , Wright N. A.
Published: June 2005

The relationship between immunoreactivity for cell proliferation markers (Ki67 and PCNA) and the growth fraction as determined by the fraction of labelled mitoses method was assessed in xenograft tumours grown from the LoVo cell line in nude mice. FLM curves were constructed by injecting tritiated thymidine and then preparing autoradiographs from the tumours. From this data an estimate of growth fraction and cell cycle time were made. Using frozen material from the same tumours, the Ki67 index was determined by immunostaining. PCNA staining was determined in the fixed material which had been used for the autoradiographs. The results show that Ki67 staining follows the same trend as the FLM‐determined growth fraction as the tumour increases in size and the rate of growth decreases. However the Ki67 index does produce a consistent overstimate of the growth fraction in this in‐vivo system, as compared to observations in cell culture. PCNA staining showed virtually 100 per cent positive staining in all the tumours, which is likely to reflect the long half‐life of the antigen, compared to the very fast cell‐cycle time of the xenograft tumours. These results show that staining with proliferation markers is not a precise determinant of growth fraction. Ki67 staining is a method that can be usefully applied as an operational marker of cell proliferation, but should not be used uncritically. Further caution is necessary in the use of PCNA. The findings also demonstrate the need to use a range of methods when assessing a new proliferation marker.
Morphometric analysis of Mycobacterium tuberculosis infection in mice suggests a genetic influence on the generation of the granulomatous inflammatory response
Authors: Orrell J. M. , Brett S. J. , Ivanyi J. , Coghill G. , Grant A. , Beck J. Swanson
Published: June 2005

There is evidence in natural human disease and experimental infection in mice that host genetic factors influence susceptibility to infection with Mycobacterium tuberculosis and the progress of the disease. In mouse models, both H‐2 and non‐H‐2 genes have been implicated. In this study, four inbred strains of mice (Balb/b, Balb/k, B10, B10.BR), selected for combinations of two different H‐2 haplotypes on two different non‐H‐2 backgrounds, were inoculated with M. tuberculosis, strain H37Rv, by intraperitoneal injection. The histological features of the granulomatous inflammatory response in the liver and lungs were investigated during the first 18 weeks of the infection. Granuloma fraction, mean granuloma area, bacillary load, and the density of acid‐fast bacilli within granulomata were measured. Animals of all four strains showed the same general pattern of infection with an early, and later self‐limiting, infection of the liver and delayed onset, but progressive, infection of the lung. The non‐H‐2 related genetic background appears to influence the morphology of the granulomatous inflammatory response. In comparison, H‐2 differences appeared to be small and inconsistent.
Rapid acinar to ductal transdifferentiation in cultured human exocrine pancreas
Authors: Hall P. A. , Lemoine N. R.
Published: June 2005

Experiments have been performed to define conditions for the primary culture of human exocrine pancreas, as a first step towards molecular reconstruction experiments of pancreatic neoplasia. Normal human exocrine pancreas was digested using collagenase and dispase and the resulting cellular aggregates were cultured in vitro. The phenotype of the digested pancreatic cells was almost exclusively acinar (amylase‐positive, keratin 19 and mucin antigens‐negative), Yet within 4 days of culture the cells had taken on a ductal phenotype (amylase‐negative, keratin 19 and mucin antigens positive). The kinetics of these observations exclude the possibility of overgrowth of the acinar population by a ductal sub‐population, and selective adherence is excluded by examination of those cells that do not adhere, which are representative of the initiating population. We interpret these data as indicating that, under the conditions of culture, the acinar cell phenotype is not stable and can transdifferentiate to a ductal phenotype. Taken together with recent data from transgenic animals, this in vitro observation has possible implications for our view of the pathogenesis of pancreatic neoplasia.
T‐Cell receptor variable (V) gene usage by lymphoid populations in T‐cell lymphoma
Authors: Smith John L. , Lane Andrew C. , Hodges Elizabeth , Reynolds Wendy M. , Howell William M. , Jones David B. , Janson Carl H.
Published: June 2005

A panel of monoclonal antibodies specific for TcR V gene families was used to study TcR V region expression in 28 cases of malignant and reactive T‐cell expansions including four cases of mixed cellularity Hodgkin's disease (HD) and five reactive cases. TcR Vβ5 gene products were represented in three cases of lymphoblastic malignancy (Vβ5.1, Vβ5.2) and two cases of peripheral T‐cell lymphoma (PTCL) (Vβ5.1). In the PTCL cases, the expanded family was found in the absence of clonal TcR gene rearrangements and in one of these cases with Ig JH and Ck clonal gene rearrangements consistent with the presence of a phenotypically and histologically undetectable clonal B‐cell population. In a third PTCL case not investigated for genotype, the TCR Va12 family was overrepresented. Expanded TcR Va2 and Vβ5.1 families were identified in HD and Vβ8 and Vβ5.2/Vβ5.3 families in a reactive lymph node and CD3 and CD8‐positive blood lymphocytosis respectively. Further study of PTCL and related entities are needed to establish whether expanded TcR families are common in those cases that fail to exhibit clonal TcR gene rearrangement.
A novel lamina lucida component of epithelial and endothelial basement membranes detected by LH39 monoclonal antibody
Authors: Almeida Bernice M. , Challacombe Stephen J. , Eveson John W. , Smith Colin G. , Leigh Irene M.
Published: June 2005

The murine monoclonal antibody, LH39 was characterized in this study and appeared to bind to a novel basement membrane epitope. This antigen was expressed in the epithelial basement membrane of human tissue derived from all three germ cell layers and in basement membranes surrounding small blood vessels within the stroma of all organs examined. LH39 antigen could be first detected in fetal skin at the dermo‐epidermal junction at 7 weeks estimated gestational age but was not present in the dermal vasculature until 16 weeks. When tested against tissue from a range of lower mammalian species, LH39 antigen appeared to be primate‐specific. The epithelial basement membrane zone in organotypical cultures, where there is de novo synthesis of basement membrane components, contained abundant LH39 antigen in contrast to other basement membrane components, type IV collagen, laminin, and type VII collagen. Ultrastructural localization of LH39 epitope, using immunogold electron microscopy on unfixed freshly frozen tissue, was to the lamina lucida. No cross‐reactivity could be detected between LH39 and laminin, fibronectin, and collagens I, III, IV, and V using the ELISA assay. In vitro studies with a range of proteolytic enzymes suggested that the antigen was non‐collagenous in nature. LH39 precipitated a polypeptide with a molecular weight of 185 kD from extracts of metabolically labelled cultured keratinocytes, and polypeptides of 185 and 200 kD from the culture medium. The tissue distribution of LH39 antigen suggested that it may be an epitope within anchoring filaments. Potential applications of this antibody include the study of benign and malignant human vascular disorders, diseases and tumours associated with angiogenesis, epithelial neoplasms, and conditions of tissue regeneration and repair, such as wound healing.
Sequential dermal microvascular and perivascular changes in the development of scleroderma
Authors: Prescott Richard J. , Freemont Anthony J. , Jones Carolyn J. P. , Hoyland Judith , Fielding Patricia
Published: June 2005

It has been previously proposed that there is a primary microvascular abnormality in patients with systemic sclerosis. In this study using conventional light and electron microscopy, immunohistochemistry, and labelled adenosine uptake techniques, changes in the dermal microvasculature have been related to the various clinical stages of skin disease in systemic sclerosis.

The earliest pathological changes are seen in clinically normal skin. They constitute changes in endothelial cell function and their consequences. Perivascular oedema is an early feature. With progression in the clinical disease, there is, at first, an inflammatory cell infiltrate into the dermis, particularly the papillary and mid‐dermis, and platelet aggregation within vessels. Further clinical progression is associated with increasing dermal fibrosis, loss of adnexae, and vascular effacement.

It is postulated that the recruitment of different types of mononuclear cells into the dermis is causally linked with the preceding endothelial cell dysfunction and the subsequent induction of fibroblast proliferation and collagen synthesis.
Human coronary microvessels in diabetes and ischaemia. Morphometric study of autopsy material
Authors: Yarom R. , Zirkin H. , Stämmler G. , Rose A. G.
Published: June 2005

The objective of this study was to test the hypothesis that excessive severity of ischaemic heart disease in diabetics is due, in part, to capillary inadequacy. Sections from autopsied hearts of diabetic patients with and without myocardial infarction as well as from those of patients with infarcts and no diabetes were used for morphometric studies of intramural microvessels in areas without infarction. Normoglycaemic patients with normal hearts were also examined. Two to five transverse sections from each of 44 hearts (stained with methenamine silver) were examined for capillary numerical density, capillary to myofibre ratios, and myofibre diameters. Averages for each case and totals for each group were calculated and compared. Normoglycaemic patients with infarcts had increased morphometric values. Diabetics with infarcts had significantly lower capillary densities than the other groups. In conclusion, it is suggested that in diabetes there is an inadequate ischaemia‐induced, reactive angiogenesis. This may contribute towards increased myocardial vulnerability in further ischaemic injury and perhaps to diabetic cardiomyopathy.
Immunoreactivity for the β chain of the platelet‐derived growth factor receptor in malignant mesothelioma and non‐neoplastic mesothelium
Authors: Ramael Marc , Buysse Corinne , Bossche Jan Van Den , Segers Kurt , Van Marck Eric
Published: June 2005

The results of an immunohistochemical study of platelet‐derived growth factor receptor (PDGF‐R)β chain in human non‐neoplastic mesothelium (35 cases) and in malignant mesothelioma (33 cases) using a murine monoclonal antibody are reported. In approximately half of the malignant mesotheliomas, there was immunoreactivity in the cytoplasm of the neoplastic cells for the β chain of the PDGF‐R. In some cases, there was also membrane immunoreactivity. There were no statistically significant differences between the various mesothelioma subtypes. Immunoreactivity for PDGF‐R β chain was absent in non‐neoplastic mesothelium.
GB (guanidinobenzoatase) cell surface protease and serum inhibitors in colorectal neoplasia
Authors: Steven Frank S. , Griffin Margaret M. , Talbot Ian C.
Published: June 2005

Cell surface proteases and their inhibitors are functionally related to the invasive properties and metastatic potential of tumour cells. Epithelial cells of the colorectal mucosa possess a cell surface protease referred to as guanidino‐benzoatase (GB), which is similar, if not identical, to plasminogen activator. GB exists in isoenzymatic forms, one of which is associated with epithelial cells of normal colorectal mucosa and of adenomatous polyps, whilst another isoenzymatic form is associated with colorectal adenocarcinoma cells. Normal serum contains inhibitor proteins which recognize the isoenzymatic form of GB found on normal and adenomatous polyp epithelial cells but this inhibitor does not recognize the isoenzymatic form of GB associated with adenocarcinoma cells. The fluorescent probe 9‐amino‐acridine locates cells possessing active GB in frozen sections of colorectal mucosa. A technique is described which enables colorectal carcinoma cells to be highlighted by fluorescence microscopy whilst normal epithelial cells are distinguished by their lack of fluorescence. This is of biological and possibly diagnostic significance.
Membranous expression of carcinoembryonic antigen (CEA) in the normal cervical squamous mucosa
Authors: Sanders D. S. A. , Stocks S. C. , Milne D. M. , Milne G. A. , Hopwood D. , Kerr M. A.
Published: June 2005

Using a panel of polyclonal and monoclonal antibodies to CEA‐related antigens in paraffin‐processed cervical biopsies, CEA and NCA expression has been demonstrated on the cell membrane of normal mature cervical squames. Cytofluorimetry of disaggregated cervical squames confirmed membranous expression and immunogold labelling of ultrathin cryostat sections localized CEA to the glycocalyx and to within cytoplasmic membrane‐bound vesicles of mature squames. Immunoblotting of cervical tissue showed that most of the CEA reactivity was expressed as a glycoprotein of molecular weight around 180 k, probably CEA itself. Localization of the CEA to the cell membrane of mature cervical squames suggests a key role for these antigens in maintaining the integrity of the squamous mucosa, through the putative function of an adhesion molecule.
Hepatic reinnervation following orthotopic liver transplantation in man
Authors: Boon Andrew P. , Hubscher Stefan G. , Lee John A. , Hines Julie E. , Burt Alastair D.
Published: June 2005

We have studied changes in the pattern of intrinsic hepatic innervation in sequential liver biopsies from 16 patients who underwent orthotopic liver transplantation. Seventy‐one needle biopsies were used, including specimens obtained at the time of transplantation (time zero) and up to 4 years post‐transplantation; five transplant hepatectomy tissue blocks removed 3–32 months after transplantation were also assessed. Paraffin sections were immunostained with anti‐PGP 9.5 and anti‐S‐100 to identify nerve fibres.

All ‘time zero’ biopsies contained portal nerves and all but two showed staining of parenchymal fibres. After 1 week, no subsequent biopsies contained parenchymal fibres. The disappearance of portal fibres was less rapid and showed greater variability between patients, but they had all disappeared by 6 weeks and there was no positive staining between 6 and 60 weeks. Thereafter, a minority of biopsies showed innervation of a few small portal tracts. Samples from the porta hepatis, hepatectomy specimens, and needle biopsies containing large tracts showed persistence of major nerve trunks at all stages. Abnormally large nerve bundles were seen in some of these areas. The pattern of nerve staining showed no obvious relationship to the intensity of rejection changes.

Our results suggest that there is a limited, delayed capacity for regeneration of portal, but not parenchymal, fibres in the transplanted human liver. The physiological significance of this long‐term parenchymal denervation in transplanted livers remains to be determined.
Oral contraceptive use and histopathology of cancerous breasts in young women
Authors: Hulman G. , Trowbridge P. , Taylor C. N. , Chilvers C. E. D. , Sloane J. P.
Published: June 2005

A retrospective histopathological study of 300 women under 36 years of age was carried out to determine whether breast cancers occurring in oral contraceptive users showed any differences in pathological features compared with non‐users. The patients belong to an age group In which an increased risk of cancer development has been reported following oral contraceptive usage. The incidence of non‐neoplastic conditions in the residual breast was also studied in the two groups. There was little difference between breast cancers arising in pill users and non‐users but in the residual non‐neoplastic breast a decreased incidence of cysts and blunt duct adenosis was found in current users of the contraceptive pill. In contrast, lactational foci were found only in the breasts of pill users. The incidence of intraductal hyperplasia was not significantly different in the two groups.
Pathogenesis of pancreatic perilobular necrosis in patients with liver disease
Authors: Shibayama Yuro , Hashimoto Kazuaki , Nakata Katsuji
Published: June 2005

We often see perilobular necrosis of the pancreas in patients with liver disease at autopsy. This study was undertaken to determine the frequency and the mechanism of development of pancreatic perilobular necrosis in patients with liver disease. Pancreatic perilobular necrosis was seen in 21 per cent of 261 autopsied patients: in 41 per cent of 73 autopsied patients with liver disease and in 13 per cent of 188 autopsied patients without liver disease. Moreover, splanchnic congestion was present in 90 per cent of 30 pancreatic perilobular necrosis patients with liver disease. These data indicate that patients with liver disease develop perilobular necrosis of the pancreas more often than patients without liver disease, and that the high frequency may be a sequela of splanchnic congestion; that is, congestion of the pancreas and endotoxaemia due to congestion of the gut.