bluuebunny/crossref_metadata_2025 huggingface dataset:
Response of mouse lung to crocidolite asbestos. 1. Minimal fibrotic reaction to short fibres
Authors: Adamson Ian Y. R. , Bowden Drummond H.
Published: June 2005

To determine the relationship between the development of pulmonary fibrosis and the size of deposited asbestos, we prepared a pure sample of short crocidolite fibres and instilled 0.5 mg of 0.1 mg to the lungs of mice. Animals were killed up to 20 weeks later with 3H thymidine injected 1 h before death. By bronchoalveolar lavage, there was a rapid transient increase in polymorph neutrophils (PMN) and in glucosaminidase levels; alveolar macrophage (AM) numbers were elevated in the 0.5 mg group for eight weeks. Most fibres were phagocytized by AM, many of which were heavily laden and cleared from the lung over the 20 week period. Some fibres were seen in type 1 epithelial cells, frequently associated with cell injury. From cell kinetic studies, a very brief proliferative response was seen in bronchiolar epithelial and Type 2 alveolar epithelial cells. A greater response was seen in interstitial fibroblasts which showed increased labelling up to two weeks after 0.5 mg asbestos. However no granulomas were seen and very little fibrosis was found by morphology or by biochemistry at any time after 0.5 mg; no fibrosis was seen after instilling 0.1 mg. The results show that a high dose of exclusively short asbestos fibres produces minimal lung injury and fibrosis in spite of long standing macrophage‐fibre interaction in the alveoli.
Response of mouse lung to crocidolite asbestos. 2. Pulmonary fibrosis after long fibres
Authors: Adamson Ian Y. R. , Bowden Drummond H.
Published: June 2005

To determine the cellular and fibrogenic responses of the lung to long asbestos fibres, mice were instilled intratracheally with 0.1 mg of a sample of long crocidolite fibres. Animals were killed at intervals to 20 weeks with 3H thymidine injected one h before death. Following bronchoalveolar lavage, an increase in polymorph neutrophils (PMN) and alveolar macrophages (AM) was found during the first week, accompanied by elevated glucosaminidase and alveolar protein levels. Although the PMN number dropped, some were always recovered by lavage to 20 weeks. Early multifocal necrosis of bronchiolar epithelium was followed by a large increase in labelling of epithelial cells and underlying fibroblasts. Epithelial overgrowth of luminal long fibres and inflammatory exudates was followed by giant cell and granuloma formation in the interstitium. After four weeks collagen levels were significantly increased and fibrosis was seen in these peribronchiolar locations. A few small fibres were observed in AM but no evidence of fibrosis was seen in alveolar walls. These findings suggest that injury to bronchial and bronchiolar epithelium allows long fibres to reach the interstitium where subsequent macrophage‐fibroblast interactions result in a severe fibrotic reaction that resembles the bronchiolar component of human asbestosis.
Epithelial‐cell architecture during involution of the human thymus
Authors: Henry L. , Anderson G.
Published: June 2005

One hundred thymus glands were assessed histologically as to their degree of involution. Epithelial cells were demonstrated by an immunoperoxidase method using a monoclonal antibody against cytokeratin. The distribution of these cells was studied in the medulla, the cortico‐medullary junction, the cortical parenchyma and the subcapsular cortex. As involution proceeds, the loss of cells from the thymus is almost totally confined to the lymphoid‐cell elements. The architecture of the epithelial‐cell network remains largely intact although there is extensive collapse of the structure due to the loss of the intervening lymphocytes. Even when involution is apparently complete; sheets of epithelial cells can be demonstrated in the thymic remnant.
Pulmonary vascular disease in ventricular septal defect: Structural and functional correlations in lung biopsies from 85 patients, with outcome of intra‐cardiac repair
Authors: Haworth Sheila G.
Published: June 2005

Pulmonary vascular structure was analysed using morphometric techniques, and arterial wall abnormalities in lung biopsy specimens taken from 85 cases of ventricular septal defect, aged 3 weeks to 30 years were described. The defect was closed in 53 patients, 12 died at operation and 11 survivors were recatheterized. Structural examination revealed a characteristic pathological picture which appeared to precede classical grade IV pulmonary vascular disease. This predilatation phase was identified by finding pre‐acinar obstructive intimal proliferation or fibrosis, associated with only a slight increase in intra‐acinar arterial muscularity, in the absence of stigmata of grade IV disease in patients with a pulmonary resistance greater than 6 units m2. Predilatation features occurred in 62 per cent of patients who either died at repair or who had post‐operative pulmonary hypertension. These findings help identify a high risk group in whom resistance is higher than expected in the absence of classical grade IV changes. In addition, a marked increase in muscularity without intimal obstruction can also be associated with a pre‐operative resistance of more than 6 units m2. The presence of medial hypertrophy only does not ensure either survival or a normal postoperative pulmonary arterial pressure. Early intra‐cardiac repair is recommended before obstructive intimal fibrosis develops during the second year.
Pancreatic venous stasis and endotoxaemia as aetiologic factors in acute haemorrhagic pancreatitis
Authors: Shibayama Yuro
Published: June 2005

The present study was undertaken to assess the possible significance of endotoxaemia and venous stasis of the pancreas in the pathogenesis of acute haemorrhagic pancreatitis. Complete obstruction of the venous drainage of the pancreas in rats induced acute haemorrhagic pancreatic necrosis. Partial venous obstruction caused only oedema and haemorrhage in the interstitium. Systemic endotoxaemia produced slight superficial pancreatic necrosis and fat necrosis, but not oedema or haemorrhage. The administration of endotoxin to the rats with partial obstruction of pancreatic venous outflow caused severe haemorrhagic pancreatic necrosis and a large number of fibrin thrombi in the capillaries and venules in and around the necrotic areas, although the severity of the lesions was less severe when compared with those induced by complete obstruction of pancreatic venous drainage. These findings suggest that acute haemorrhagic pancreatitis can be induced by the coexistence of endotoxaemia and partial venous obstruction of the pancreas. The mechanism may be that the endotoxin‐induced capillary and venous fibrin thrombi superimposed upon the venous stasis lead to obstruction of venous drainage of the pancreas severe enough to produce haemorrhagic pancreatic necrosis.
Intermediate filaments cytokeratin and vimentin in ovarian sex cord–stromal tumours with correlative studies in adult and fetal ovaries
Authors: Benjamin Elizabeth , Law Sharon , Bobrow Lynda G.
Published: June 2005

The expression of the intermediate filaments cytokeratin and vimentin were studied immunohistochemically in a series of ovarian sex cord–stromal tumours (26 adult and juvenile granulosa cell tumours, 11 thecomas, six fibromas, three Sertoli‐Leydig cell tumours and 1 sex cord tumour with annular tubules). Contrary to previous reports, granulosa cell tumours expressed cytokeratins as well as vimentin. Thecomas and fibromas expressed vimentin only. In Sertoli‐Leydig cell tumours and the sex cord tumour with annular tubules, both cytokeratins and vimentin were detected. Correlative studies in adult ovaries showed that patterns of expression in non‐neoplastic granulosa, thecal and stromal cells correspond to their neoplastic counterparts. Investigation of fetal ovaries demonstrated that these patterns of intermediate filament expression exist from relatively early stages of development. Ovarian surface epithelium and rete ovarii, like granulosa cells, co‐expressed cytokeratin and vimentin. The demonstration of cytokeratins in granulosa cells and the reported presence of desmosomes and tonofilaments, suggests the epithelial nature of these cells although not clarifying their histogenesis. The presence of both these intermediate filaments in granulosa and Sertoli‐Leydig cell tumours as well as in some ovarian carcinomas which may mimic them, limits their value in differential diagnosis between these tumour groups.
Identification of cells of the human mononuclear phagocyte system with rat monoclonal antibodies
Authors: Aqel N. M. , Clark M. , Jones D. B. , Arno J. , Waldmann H.
Published: June 2005

Five rat monoclonal antibodies (McAbs) to human macrophages are described: YTH 8.18, YTH 25.7, YTH 51.1, YTH 85.12.1, and YHB 65.5. These McAbs are divided into three groups, since YTH 8.18, YTH 51.1, and YHB 65.5 are thought to identify the same antigen.

These McAbs react with some bone marrow blast cells, granulocytes, and different percentages of peripheral blood monocytes. When studied on different body tissues, they were found to identify all members of the mononuclear phagocyte system (MPS), except Langerhans cells of skin and epithelium and in the case of one group (YTH 8.18/YTH 51.1/YHB 65.5) osteoclasts. In nine reactive lymph nodes the anti macrophage McAbs identified germinal centre macrophages sinus macrophages, and interdigitating cells, but not dendritic reticulum cells. They also identified epithelioid macrophages and Langhans‐type multi‐nucleated giant cells in lymph nodes involved in granulomatous lesions (sarcoidosis and toxoplasmosis). In 24 cases of non‐Hodgkin's lymphoma, the antimacrophage McAbs identified reactive macrophages in cases of B‐ or T‐lymphocyte origin, whereas in three selected cases of true histiocytic lymphoma all the McAbs were found to be reactive with the vast majority of neoplastic macrophages as they were with the cells of a neoplastic macrophage line (U937). The possible use of these McAbs in the identification of benign and malignant macrophages in different systems is discussed.
Proliferative index in breast carcinoma determined in situ by Ki67 immunostaining and its relationship to clinical and pathological variables
Authors: Barnard Nicola J. , Hall P. A. , Lemoine N. R. , Kadar N.
Published: June 2005

Sixty cases of primary breast carcinoma have been studied using a monoclonal antibody, Ki67, which recognizes an antigen expressed by cells in G1, S, G2, and M phases of the cell cycle but not Go. A Ki67 score (positive cells/total tumour cells) was determined, and possible relationships between this index of cellular proliferation and a number of clinical and pathological parameters were investigated. There was a strong positive correlation between the Ki67 score and mitotic index (p < 0.001), a weak negative correlation with age (p < 0.02), and weak positive correlations with histological tumour grade (p < 0.03), tumour necrosis (p < 0.01), and cellular reaction (p < 0.01). No relationship was noted between the Ki67 score and tumour size, nodal status, tumour oestrogen receptor levels, or menopausal status. The Ki67 score may prove to be an objective indicator of biological behaviour and thus be of clinical significance, particularly since it is not strongly related to other clinical and pathological parameters used in predicting outcome in breast carcinoma.
Hepatocellular carcinoma: Expression of basement membrane glycoproteins. An immunohistochemical approach
Authors: Grigioni Walter F. , D'Errico Antonia , Mancini Antonio M. , Biagini Graziella , Gozzetti Giuseppe , Mazziotti Alighieri , Garbisa Spiridione
Published: June 2005

The identification and characterization of collagenous and non‐collagenous glycoproteins have made it possible to use specific antibodies as tools for the topographical localization of the various connective tissue components, and thus to follow the progression of parenchymal–stromal interactions. This investigation is an approach to the study of in vivo relationships between basement membrane components (type IV collagen, laminin) and neoplastic cells of hepatocellular carcinoma. Ten cases of hepatic carcinomas were analysed and paraffin–embedded sections were immunostained with anti‐laminin and anti‐type IV collagen antibodies. The avidin–biotin–peroxidase complex technique was used. In well differentiated neoplasms with hepatic tumour cells organized in a trabecular pattern lined by sinusoid structures, type IV collagen was always detected at the sinusoidal level. Laminin was evident only in two cases with a prominent intraparenchymal vascular bed. In less differentiated neoplasms, sinusoids were almost absent and only large tumour vessels were positive for both laminin and type IV collagen. At the interface between tumour tissue and the surrounding stroma, some carcinomatous elements were surrounded by laminin and type IV collagen. Our data further support the hypothesis that basement membrane phenotypic expression may be influenced both by the degree of tumour differentiation and by the characteristics of the micro‐environment.
Electron microscopic identification of aberrant melanosomes using a combined DOPA/Warthin–Starry technique
Authors: Rennison Alexander , Duff Carol , McPhie James L
Published: June 2005

A method combining the DOPA and Warthin–Starry techniques is described in order to positively establish the nature of pleomorphic granules observed in the cytoplasm of cells of putative amelanotic melanoma. The technique identifies these granules as aberrant melanosomes by discretely depositing electron dense silver on suitably prepared sections of DOPA‐treated tissue blocks.
The assessment of in vitro modulation of milk fat globule membrane expression by human breast carcinomas
Authors: Jones J. Louise , Walker Rosemary A.
Published: June 2005

Although knowledge of functional differentiation and tumour‐associated changes of breast carcinomas can be gained by the application of antibodies directed against the milk fat globule membrane, more significant information may be obtained by assessment of the potential of breast carcinomas to modulate their antigenic phenotype. In this study, the extend to which primary tumours can undergo modulation in vitro has been investigated, with consideration of the suitability of organ culture in combination with the immunohistochemical detection of two milk fat globule membrane epitopes, HMFG1 and HMFG2, as methods for detecting this.

The preservation of three of the 30 carcinomas assessed, all poorly differentiated, was poor after 3 days of culture. The viability of the other 27 was variable, and was greater in the better differentiated tumours and with the addition of insulin. Expression of the milk fat globule membrane epitopes was generally well maintained. Six of the carcinomas showed a significant change in antigen expression, with this being more frequent in tissues incubated with insulin. Hence, a small group of carcinomas have been identified which appear to have a greater capacity to undergo functional differentiation.

Organ culture is considered to be a suitable method for maintaining the tissues in vitro for such evaluation, but the problems encountered in quantifying the immunohistochemical staining, because of antigenic heterogeneity, were such that it is suggested that other approaches be employed.
Immunohistochemical markers of small cell carcinoma and related neuroendocrine tumours of the lung
Authors: Addis Bruce J. , Hamid Qutayba , Ibrahim Nassif B. N. , Fahey Mary , Bloom Stephen R. , Polak Julia M.
Published: June 2005

A selected group of 263 pulmonary neuroendocrine tumours comprised 156 small cell carcinomas, five combined cell carcinomas, nine atypical carcinoid/small cell carcinomas, 32 atypical carcinoids, ten large cell/small cell carcinomas, and 51 carcinoid tumours. These were compared with a group of 109 non‐small cell carcinomas, using four markers of neuroendocrine differentiation to determine differences in reactivity between the two groups and among the variants of neuroendocrine tumour. The antibodies used were neuron‐specific enolase (NSE), protein gene product (PGP) 9·5, human bombesin, and the C‐terminal flanking peptide of human bombesin (CTP). Most small cell carcinomas, carcinoid tumours, and atypical carcinoid variants showed immunoreactivity for both NSE and PGP 9·5 but a significant number of non‐small cell carcinomas, mainly squamous cell carcinomas, were also positive (11 and 35 per cent, respectively). Bombesin was specific for neuroendocrine tumours, being demonstrable in 35 per cent carcinoids and 24 per cent small cell carcinomas, but staining was focal and often confined to scattered cells. Diffuse strongly positive immunoreactivity for CTP was seen in the majority of malignant neuroendocrine tumours, but only 12 per cent of carcinoid tumours were positive and non‐small cell carcinomas were negative. CTP is therefore of potential value as a specific marker of malignant neuroendocrine tumours, particularly if the amount of biopsy material is limited and the tumour is an unusual variant, such as atypical carcinoid or large cell‐small cell carcinoma.
Leu‐M1 antigen expression in acute leukaemias
Authors: De Mascarel Antoine , Coindre Jean Michel , De Mascarel Isabelle , David Bernard , Trojani Monique , Broustet Antoine
Published: June 2005

Leu‐M1 is a differentiation antigen present in human myelomonocytic cells. Seventy‐seven acute leukaemias were retrospectively stained with anti‐Leu‐M1 using the immunoperoxidase technique on Bouin‐fixed paraffin‐embedded sections. The subjects were 44 acute lymphoblastic leukaemias (ALL) and 33 acute myeloid leukaemias (AML) previously characterized by cytochemical and immunologic (cell suspension) methods. Leu‐M1 was positive in all the AML and in half of the ALL cases. These results suggest that Leu‐M1 does not allow differentiation between AML and ALL. For the ALL cases Leu‐M1 was positive in 15/28 B‐cell types, 4/12 T‐cell type and 3/4 ‘null’‐cell type cases. Thus, this antibody is of no assistance in defining types B, T, or ‘null’ in ALL. Leu‐M1 was also studied on paraffin sections of 34 high grade malignant lymphomas. The antibody was negative in all 13 B‐cell lymphomas (lymphoblastic: 6; immunoblastic: 7) and in all 4 ‘null’ cell lymphomas. It was positive in 4/9 peripheral T‐cell type, the other T‐cell lymphomas (lymphoblastic: 5; immunoblastic:3) remaining negative. Thus, Leu‐M1 may be positive in T‐cell lymphomas but it is negative in B‐cell lymphomas and is always negative in B or T lymphoblastic types. It seems that lymphoblasts are Leu‐M1 negative in non‐Hodgkin's lymphoma and may be Leu‐M1 positive in leukaemias.
Demonstration of human papillomavirus types 6 and 11 in juvenile laryngeal papillomatosis by in‐situ DNA hybridization
Authors: Terry R. M. , Lewis F. A. , Griffiths S. , Wells M. , Bird C. C.
Published: June 2005

A study is reported in which an in situ hybridization technique for the demonstration of human papillomavirus (HPV) employing a biotin–streptavidin polyalkaline phosphatase complex has been successfully applied to formalin‐fixed paraffin‐processed tissue obtained from ten patients with juvenile laryngeal papillomatosis. In all cases, positive results were obtained for either HPV type 6 or 11. Normal vocal cord epithelium was negative.
Fine structural changes in idiopathic pulmonary haemosiderosis
Authors: Corrin B. , Jagusch M. , Dewar A. , Tungekar M. F. , Davies D. R. , Warner J. O. , Turner‐Warwick M. , Empey D.
Published: June 2005

Lung biopsies from four children and two adults with idiopathic pulmonary haemosiderosis have been examined by transmission electron microscopy. No qualitative differences were identified between the children and the adults but the changes were more severe in the children. In each case the major damage involved the capillary endothelium and its basement membrane. Capillary endothelial swelling was very noticeable and in one case the endothelium was attenuated but gaps between endothelial cells were very difficult to find. Capillary narrowing and platelet aggregation were common. The capillary endothelial basement membrane showed focal thickening, particularly on the thick side of the air/blood barrier, but no electron dense deposits were identified. Degenerative changes in the alveolar epithelium were not so marked as those in the capillary endothelium and the epithelial basement membrane was normal except for haemosiderin deposition. Haemosiderin was also noted on elastin and within intra‐alveolar macrophages. Other secondary changes included mild interstitial oedema and fibrosis. These findings indicate that the major site of damage is the alveolar capillary, but provide no evidence of the cause of the disease.
Immunocytochemical evidence that endometrial stromal granulocytes are granulated lymphocytes
Authors: Bulmer Judith N. , Hollings Debra , Ritson Anne
Published: June 2005

Endometrial stromal granulocytes (EGs) are prominent in late luteal phase human endometrium and in early pregnancy decidua. They have been believed to develop from endometrial stromal cells and to secrete relaxin. Recent immunohistochemical studies have suggested that EGs are derived from bone marrow but this has been difficult to prove, mainly because the characteristic cytoplasmic granules are not preserved in frozen tissues. Two separate approaches have now been employed to investigate the cellular lineage of EGs. Formalin‐fixed paraffin‐embedded sections of first trimester decidua were labelled by an immunoperoxidase method with four monoclonal antibodies (mAbs) reactive with routinely fixed and processed tissues. In addition, acetone‐fixed smears of decidual cell suspensions were labelled with a panel of mAbs. Sections and smears were counterstained to demonstrate the charateristic cytoplasmic granules of EGs. Endometrial granulocytes were LCA+, CD2+, MT1+, and UCHL1+, which provides evidence that they are leucocytes. EGs are probably members of the large granular lymphocyte series and may have an essential role in normal implantation and placentation.
Morphometry of bladder carcinoma: I. The automatic delineation of urothelial nuclei in tissue sections using an ibas II image array processor
Authors: Sowter C. , Slavin G. , Rosen D.
Published: June 2005

Semi‐automatic methods of morphometry require the boundaries of the objects under study to be drawn by hand. This is slow, tedious and does not guarantee accuracy. Complete automation, with recognition, detection and verification by computer is not yet feasible. Automatic detection of nuclear boundaries with observer verification provides a means of obtaining large amounts of data for analysis, quickly and with similar accuracy to manual tracing.
Elastosis in breast carcinoma: II. Association of protease inhibitors with immature elastic fibres
Authors: Davies J. D. , Mera S. L.
Published: June 2005

The elastosis of 11 invasive ductal and infiltrative lobular carcinomas of the breast was specifically immunostained for the plasma protease inhibitors alpha‐1 antitrypsin, alpha‐1 antichymotrypsin, alpha‐2 macroglobulin, inter alpha trypsin inhibitor and C1 esterase inhibitor. None of these components was detected in the elastic fibres of normal ducts or blood vessels in the breast. The elastosis in breast carcinomas was also stained by Concanavalin A and Triticum vulgaris lectins. Such lectin staining probably represents binding to the microfibrillar component of elastic fibres, which is increased in immature elastic fibres, thus suggesting that the elastotic fibres of breast carcinoma are recently synthesised. It is suggested that the presence of protease inhibitors may influence the metabolism of elastic fibres, facilitating elastic fibre proliferation by the inhibition of elastinolytic enzymes.
An ultrastructural study of spontaneous cell death in a mouse mastocytoma with particular reference to dark cells
Authors: Harmon Brian V.
Published: June 2005

The morphology and frequency of the various types of cell death occurring spontaneously in a mouse mastocytoma growing as intramuscular nodules were investigated. In addition to necrosis and apoptosis, which have been well documented in malignant neoplasms in the past, a third morphological pattern of cell death, the formation of dark cells, was observed. Necrosis first appeared in confluent patches about 5 days after tumour inoculation, and these increased in size as the tumours grew. Apoptosis, on the other hand, was present at all stages of tumour growth, and remained at a reasonably constant level. Dark cells were first observed at about 6 days, and increased in numbers thereafter. Dark cells were characterised by overall cellular condensation and gross swelling of mitochondria. Their cytoplasm became squeezed out between adjacent cells and then fragmented. Remnants of dark cells were eventually phagocytosed and degraded by macrophages. The distribution of dark cells in the tumours suggested that crowding and compression may contribute to their development.
Monoclonal antibody to desmosomal glycoprotein 1—A new epithelial marker for diagnostic pathology
Authors: Vilela Marcelo J. , Parrish Elaine P. , Wright Dennis H. , Garrod David R.
Published: June 2005

Desmosomes are intercellular adhesive junctions that occur in almost all epithelia and should therefore be useful as epithelial markers in tumour diagnosis. Here, we describe a monoclonal antibody, 32‐2B, to a major desmosomal glycoprotein (dg1) which reacts with human tissues in paraffin sections. This antibody was tested for its ability to stain epithelia and tumours. It reacted with all epithelia tested and with every specimen of a wide range of carcinomas. It also stained meningiomas, another desmosome‐containing tumour. It did not stain other types of tumours including lymphomas, melanomas, and various sarcomas, or normal tissues which lack desmosomes.

These characteristics demonstrate that 32‐2B is a reliable epithelial marker that may have a useful role in diagnostic histopathology.
NCL‐5D3: A new monoclonal antibody recognizing low molecular weight cytokeratins effective for immunohistochemistry using fixed paraffin‐embedded tissue
Authors: Angus B. , Purvis J. , Stock D. , Westley B. R. , Samson A. C. R. , Routledge E. G. , Carpenter F. H. , Horne C. H. W.
Published: June 2005

Production of a new monoclonal antibody designated NCL‐5D3 is described. The antibody recognizes several low molecular weight cytokeratins, in particular cytokeratin Moll number 8 as determined by immunoblotting studies, and is highly effective for immunocytochemistry using routinely processed paraffin‐embedded material. Staining is enhanced by prior treatment of the sections with trypsin. Assessment using a wide variety of normal and neoplastic tissue indicates reactivity with all tissues of simple or glandular epithelial origin, and in addition with many squamous carcinomas. Thus the antibody should prove of value in diagnostic histopathology.
The prevalence of isolated atrial amyloid
Authors: Steiner Ivo
Published: June 2005

The frequency of isolated atrial amyloid (IAA), a form of ‘senile’ cardiac amyloidosis, was determined in younger age groups. For the detection of amyloid the Sirius red staining technique was used.

IAA first appears in the fourth decade; its prevalence increases roughly linearly by 15–20 per cent with each subsequent decade, reaching 95 per cent in the 81–90 years age group. The prevalence is higher in females than in males.
A quantitative study of glomerular basement membrane changes in IgA nephropathy
Authors: Morita Miyako , Sakaguchi Hiroshi
Published: June 2005

A quantitative study of glomerular basement membrane (GBM) changes in 16 cases of IgA nephropathy was carried out on two whole glomeruli per case using a wide‐field electron microscope. We found that GBM changes are observed more frequently than previously reported, although some changes are small and uneven in distribution. Changes include (a) attenuation, (b) lytic attenuation, (c) garland‐shaped widening of the GBM, (d) dome‐shaped widening of the GBM, and (e) disruption of the GBM. There was some correlation between the severity of light microscopic findings and the percentage of GBM affected by complicated changes ((b)–(e)). The percentage of complicated GBM changes correlated with the amount of proteinuria at biopsy. The frequent occurrence of GBM changes in IgA nephropathy suggests that they might be playing a role in the pathogenesis of IgA nephropathy.
Lymphocytic gastritis—relationship to Campylobacter pylori infection
Authors: Dixon Michael F. , Wyatt Judith I. , Burke Denis A. , Rathbone Barrie J.
Published: June 2005

The existence of a distinctive form of chronic gastritis characterized by marked infiltration of the surface and pitlining epithelium by mature T lymphocytes has been confirmed. Seventeen cases were identified amongst 382 patients with active chronic gastritis (4·5 per cent). The cases with lymphocytic gastritis had significantly higher counts of intra‐epithelial lymphocytes than sex and age‐matched controls drawn from a series of patients with the usual form of active Type B chronic gastritis. Furthermore, the lymphocytic gastritis group exhibited unusual endoscopic findings, namely erosions and ‘raised lesions’, in the body of the stomach. Such appearances have been previously described as ‘varioliform’ gastritis. Only seven of the patients (41 per cent) had C.pylori‐positive biopsies, compared with over 90 per cent in the generality of active chronic gastritis, but all but two of the eleven cases tested had serological evidence of C. pylori infection. While the pathogenesis of this condition is unclear, the histological resemblance to coeliac disease suggests that lymphocytic gastritis might also represent an abnormal response to a local antigen to which the patient has become sensitized. It is possible that this antigen is C. pylori.
Expression of Leu‐8 surface antigen in B‐cell lymphomas. Correlation with other B‐cell markers
Authors: Carbone A. , Manconi R. , Poletti A. , Gloghini A. , de Paoli P. , Volpe R.
Published: June 2005

Using in situ immunohistological analysis, expression of Leu‐8 and its correlation with other B‐cell markers were investigated in 21 selected lymphomas of different categories, each one expressing its own typical immunophenotype. These categories included eight follicular centroblastic/centrocytic (CB/CC) lymphomas, eight intermediately differentiated lymphocytic lymphomas (ILL)/mantle zone lymphomas (MZL), and five lymphocytic lymphomas (LL) associated with chronic lymphocytic leukaemia (CLL). Four reactive lymph nodes and three tonsils were also studied using double immunolabelling procedures. Cell suspensions were also performed in three CB/CC and four ILL/MZL cases. Leu‐8 was consistently expressed in ILL/MZL and LL but it was absent in most (7/8) CB/CC lymphomas. In reactive tissues, the Leu‐8‐positive B cells were strictly confined to the mantle zones. A close association emerged between Leu‐1 (CD5) and Leu‐8, both being present in ILL/MZL and LL but absent in CB/CC. A consistent lack of association was found between Leu‐8 or CD5 antigens and common acute lymphoblastic leukaemia antigen (CD10) and BA‐2 (CD9) antigen, whereas Leu‐8 and CD5 were strictly associated with surface IgD. Reactivity with Leu‐8 provides a means of distinguishing between CB/CC and ILL/MZL. Furthermore, shared immunoreactivity for Leu‐8 in ILL/MZL and LL may represent a potential clue to the still uncertain cellular derivation of LL/B‐CLL.
Immunocytochemical investigation of intermediate filament proteins and epithelial membrane antigen in spindle cell tumours of the breast
Authors: Ellis Ian O. , Bell Jane , Ronan John E. , Elston Christopher W. , Blamey Roger W.
Published: June 2005

Seven consecutive cases of primary spindle celled tumours of the breast have been studied immunohistologically using antisera to the intermediate filament proteins (IFP) vimentin, cytokeratin, and desmin, and with an antibody to epithelial membrane antigen. Representative paraffin sections were examined using a peroxidase–antiperoxidase method. In three cases, very occasional foci of epithelial differentiation were apparent by conventional microscopy, and in one case, adjacent ductal carcinoma in situ was present. The remaining three cases were composed of spindle cell elements entirely, with no evidence of epithelial differentiation morphologically. Immunoreactivity of spindle cell elements for vimentin was found in all seven cases, and for cytokeratin in six cases. One case showed immunoreactivity for vimentin, cytokeratin, and desmin, and one case only for vimentin. Epithelial membrane antigen was not identified in the spindle cell elements of any tumour, but was present in the invasive epithelial component of three cases and the in situ component of one case. We conclude that many spindle cell tumours of breast show immunohistological evidence of epithelial differentiation and can be regarded as spindle cell carcinomas. However, in some cases IFP expression may be complex and histogenesis cannot be determined. This technique can aid histological diagnosis in some cases.
Control of excisional margins by conventional histopathological techniques in the treatment of skin tumours. An alternative to Mohs' technique
Authors: Breuninger Helmut , Schaumburg‐Lever Gundula
Published: June 2005

For histological control of excisional margins, routinely fixed tumour specimens or, under certain conditions, specimens fixed immediately in warm formalin are processed in the histology laboratory. Strips are then cut from the undersurface, edge, and cross‐section of the remainder of the specimen and processed further by routine paraffin techniques until H&E‐stained sections of the entire periphery and midsection are available. We suggest that the method is simple, easy to apply, and suitable for the assessment of excisional margins of a variety of skin tumours. Extremely low recurrence rates over a relatively long follow‐up period substantiate the effectiveness of the method.
The morphological effects of dexamethasone on the pituitary–adrenal axis of the rat—a quantitative study
Authors: McNicol Anne M. , Kubba M. A. , Stewart C. J. R.
Published: June 2005

Adult Sprague–Dawley rats received a daily intraperitoneal injection of dexamethasone (100 or 200 μg/kg) for 2 or 6 weeks. Quantitative assessment of the anterior pituitary corticotroph population was performed using the stereological measurement of volume density (Vv). An indirect assessment of corticotroph function was also made, based on adrenal weight and histology. Adrenal changes were consistent with dose‐related inhibition of corticotroph function in all dexamethasone‐treated animals. Immunopositive corticotrophs were easily identified and in no treatment group was corticotroph Vv significantly less than in the appropriate vehicle‐injected control group. In male animals, there was a significant increase (P<0·05) in Vv with 100 μg/kg at both 2 and 6 weeks. These results suggest that it is possible to produce inhibition of corticotroph function by the administration of such doses of dexamethasone without causing a significant reduction in the anterior pituitary corticotroph population. This may be related to the mode of negative feedback of such a regime.
Activation and differentiation antigen expression in B‐cell non‐Hodgkin's lymphoma
Authors: Salter Donald M. , Krajewski Andrew S. , Cunningham Scott
Published: June 2005

In an attempt to establish whether extended immuno‐phenotyping allows more accurate definition of subgroups of B‐cell non‐Hodgkin's lymphoma (NHL) we have stained a series of 145 cases with a large panel of monoclonal antibodies that recognize B‐cell differentiation and activation antigens. No antigen was expressed by all cases. The B‐cell histogenesis in many cases could be confirmed only by using a panel of immunoglobulin and pan B‐cell markers. There was marked phenotypic heterogeneity within and between major groups of B‐cell NHL as delineated by the Kiel classification although the differentiation antigens CD5 (lymphocytic and centrocytic NHL) and OKT10 (plasma cell tumours) were more often expressed by certain morphological groups. The activation antigens 4F2 and transferrin receptor were expressed more strongly and more often by high grade NHL but other activation antigens (CD23 and CD25) were not more frequently associated with these tumours. Extended phenotyping may be of value in improving the understanding of biological abnormalities and processes involved in B‐cell NHL, but we conclude that a limited panel of markers (CD3, CD5, CD22, CD45, IgM, kappa, and lambda) should be sufficient for routine diagnosis and classification of most cases.
Diagnostic value of DNA flow cytometry combined with fine needle aspiration biopsy in lymphomas
Authors: Joensuu Heikki , Klemi Pekka J. , Eerola Erkki
Published: June 2005

The nuclear DNA content of cells from 45 malignant lymphomas and from 60 benign lymph nodes obtained by fine needle aspiration was analysed to investigate the diagnostic value of DNA flow cytometry combined with routine diagnostic cytology in lymphomas.

DNA aneuploidy was found in 43 per cent of lymphomas of high grade malignancy (NCI Working Formulation) but only rarely in lymphomas of intermediate‐ or low‐grade malignancy or in Hodgkin's disease, and never in benign lymph nodes. The median percentage of proliferative cells (S+G2/M) was 22·6 per cent in diploid high‐grade lymphomas, 15·3 per cent in intermediate‐, and 8·1 per cent in low‐grade lymphomas, as compared with 4·9 per cent in benign lymph nodes (P<0·0001). If the presence of DNA aneuploidy or more than 12 per cent of proliferative cells is used as a criterion for malignancy, the diagnostic accuracy of DNA flow cytometry in detecting lymphoma is 81 per cent. DNA flow cytometry suggested correct diagnosis in 10 of the 19 false positive, false negative, or indeterminate cytological findings encountered during the study. It is concluded that DNA flow cytometry combined with fine needle aspiration biopsy has diagnostic value in lymphomas, but false negative results are common especially in low‐grade lymphomas; the method should therefore be used in conjunction with light microscopy.
Nucleolar organizer regions in cutaneous tumours
Authors: Egan M. J. , Crocker J.
Published: June 2005

A silver colloid technique to identify nucleolar organizer region associated protein (AgNOR) has been applied to 68 cutaneous tumours. Basal cell carcinomas, eccrine tumours, apocrine tumours, and hair follicle tumours had differences in their numbers of AgNORs; these appeared as small black dots in their nuclei. Dermatofibromas and squamous cell carcinomas showed a degree of variability in the number of AgNORs depending on the cellularity of the former and differentiation of the latter. Basal cell carcinomas possessed significantly many more AgNORs per nucleus than the other neoplasms. It is suggested that this technique, previously the province of the cytogeneticist, may be of use in the diagnosis of cutaneous neoplasms.
Southern blot analysis of DNA extracted from formol–saline fixed and paraffin wax embedded tissue
Authors: Warford A. , Pringle J. H. , Hay J. , Henderson Susan D. , Lauder I.
Published: June 2005

Model experiments were designed to assess whether DNA could be recovered from formol–saline fixed peripheral blood lymphocytes and tonsil tissue for use in Southern blot gene analysis. Lymphocytes were fixed for 30 min and tonsil for 6 and 24 h, then paraffin embedded. High molecular weight DNA was extracted by prolonged digestion (2–7 days) with proteinase K or protease XXIV in the presence of 1 per cent sodium dodecyl sulphate. Restriction, transfer and hydridization were possible without modification of standard procedures. Multiple copy sequences were demonstrated using Mspl and Bst Nl restriction and hybridization for the Y chromosome (pHY 2·1 probe), single copy genes using EcoRI and BamHl restriction for the T‐cell receptor β chain (Tβ probe), and Bgl II and Hind III for the immunoglobulin heavy chain (JH probe). Identical banding to unfixed tissue was achieved except when 24 h fixed extracts were used. With these, demonstration of the 24 KB Bam Hl/Tβ and 9·2 KB Hind III/JH bands was not obtained. These findings suggest that as the fixation time is extended, alterations to DNA will limit the available range of restriction enzyme/probe combinations. However, with careful choice of these the extraction of DNA from formalin fixed and paraffin embedded pathological tissue for Southern blotting should be profitable.
Adenomatous hyperplasia of the rete testis
Authors: Nistal M. , Paniagua R.
Published: June 2005

A gland‐like cellular proliferation was observed in the deepest portion of the rete testis in both testes from a 55‐year‐old man who died from metastasis of breast carcinoma to the brain. The gland‐like proliferations consisted of columnar epithelial cells supported by a thin lamina propria. These cells displayed irregularly outlined nuclei with deep indentations. Atypias and mitoses were infrequent. The term ‘adenomatous hyperplasia of the rete testis’ is proposed to designate the benign lesion reported here.
Extraglomerular distribution of immunoreactive Goodpasture antigen
Authors: Cashman S. J. , Pusey C. D. , Evans D. J.
Published: June 2005

The distribution of Goodpasture antigen (GA) was studied in a range of human tissues using indirect immuno‐fluorescence and immunoperoxidase techniques. Frozen sections were stained using (1) a mouse monoclonal antibody (P1) raised against the autoantigenic component of human glomerular basement membrane, (2) autoantibodies eluted from the kidneys of patients with Goodpasture's syndrome, (3) antibodies eluted from the kidneys of a sheep with Steblay nephritis, and (4) mouse monoclonal and guinea pig polyclonal antibodies to human type IV collagen. The same pattern of staining was demonstrated using the eluted antibodies and monoclonal antibody P1. The presence of GA was confirmed in the lung and choroid plexus. GA was also detected in basement membranes at a number of previously unreported sites in the eye, thyroid, pituitary, adrenal, breast, and liver. GA was absent from other sites at which type IV collagen could be demonstrated. Direct immunofluorescence studies of tissue from a patient with Goodpasture's syndrome revealed deposition of IgG in the choroid plexus and eye, as well as in the kidney and lung.
Cytokeratins in cervical dysplasia and neoplasia: A comparative study of immunohistochemical staining using monoclonai antibodies NCL‐5D3, CAM 5·2, and PKK1
Authors: Angus Brian , Kiberu Sam , Purvis James , Wilkinson Linda , Horne Charles H. W.
Published: June 2005

The expression of low molecular weight cytokeratins (normally expressed only in simple epithelia) in intraepithelial neoplasia of grade CIN III or greater in cervical biopsies has recently been described by Bobrow et al. Our study of 127 cases confirms this finding and in addition we compare the use of three monoclonal antibodies, namely NCL‐5D3, CAM 5.2, and PKK1, in demonstrating the phenomenon. Both NCL‐5D3 and CAM 5.2 give consistently negative results for non‐neoplastic stratified squamous epithelium, as well as CIN I and CIN II lesions, whilst staining about 30 per cent of CIN III biopsies and most carcinomas. PKK1, on the other hand, stained 50 per cent of non‐neoplastic epithelia and thus did not serve as a marker of severe dysplasia. The possible implications of these observations are discussed.
Class II MHC expression in normal adrenal cortex and cortical cells in autoimmune Addison's disease
Authors: Jackson Robert , McNicol Anne Marie , Farquharson Maura , Foulis Alan K.
Published: June 2005

It has been proposed that aberrant expression of class II major histocompatibility complex (MHC) molecules by target cells may be an initiating factor in some forms of organ specific autoimmunity. This hypothesis was tested in relation to the autoimmune form of Addison's disease by studying autopsy‐adrenal glands from eight patients who had died of recent onset idiopathic Addison's disease. Using an immunohistochemical technique, class II MHC expression was found in a minority of adrenal cortical cells in the zona reticularis in 25 normal and four hyperplastic glands, while in Addison's disease almost all residual cortical cells expressed class II MHC. Three tuberculous adrenals showed increased staining of cortical cells around areas of chronic inflammation. It is concluded that since adrenal cortical cells of the normal gland express class II MHC, aberrant expression of this product cannot be invoked as an initiating mechanism in autoimmune adrenalitis. The increased cortical expression of class II MHC seen in idiopathic Addison's disease and tuberculosis may be due to local release of lymphokines by inflammatory cells.
Immunohistochemical study of rhabdomyosarcoma. Unexpected staining with S100 protein and cytokeratin
Authors: Coindre Jean‐Michel , De Mascarel Antoine , Trojani Monique , De Mascarel Isabelle , Pages André
Published: June 2005

The immunohistochemical study of 60 cases of rhabdomyosarcomas made it possible to test eight different antibodies currently used in tumour pathology: i.e., antisera to vimentin, desmin, myoglobin, cytokeratin, epithelial membrane antigen, S100 protein, neurofilaments, and leukocyte common antigen. Vimentin was found in 58 cases (97 per cent), desmin in 49 cases (82 per cent), myoglobin in 23 cases (38 per cent), S100 protein in 7 cases (12 percent), and cytokeratin in 3 cases (5 per cent). Other markers were negative. S100 protein was present in large round tumour cells with abundant eosinophilic cytoplasm (round rhabdomyoblasts), whereas cytokeratin was present in small tumour cells similar to those observed in rhabdoid sarcoma. This unexpected staining should become common knowledge for the correct interpretation of the immunohistochemical study of small cell tumours in the young.
Subacute infantile mountain sickness
Authors: Sui G. J. , Liu Y. H. , Cheng X. S. , Anand I. S. , Harris E. , Harris P. , Heath D.
Published: June 2005

A description is given of a disease of infants occurring in Lhasa, Tibet at an altitude of 3600m. Typically it affects infants who have been born at low altitude and subsequently brought to reside in Lhasa, and it is usually fatal within a few weeks or months. There is extreme medial hypertrophy of muscular pulmonary arteries and muscularization of pulmonary arterioles, together with dilatation of the pulmonary trunk and massive hypertrophy and dilatation of the right ventricle. The disease is distinct from acute or chronic mountain sickness and appears to be the human counterpart of ‘brisket disease’ in cattle.
Solid cell nests of the thyroid
Authors: Harach H. Rubén
Published: June 2005

The ultimobranchial thyroid solid cell nests (SCN), irregular structures of about 1 mm in maximal diameter, are usually found in the middle third of the thyroid lateral lobes. SCN are basically composed of non‐keratinizing epidermoid cells which lack intercellular bridges and are immunohistochemically positive for a panel of high and low molecular weight keratin proteins, as well as for carcinoembryonic antigen. In addition, SCN display isolated or grouped peripheral calcitonin‐immunoreactive ‘clear’ (C) cells in up to 54 per cent of cases. The SCN central lumen, when present, is usually surrounded by mucinous cells; in addition, it may contain desquamated cells, cell debris, acid mucosubstances, characteristic PAS‐positive granular material after diastase treatment, and colloid‐like material. The so‐called mixed follicles, structures lined by epidermoid cells of SCN and follicular epithelium, are often found as an additional component of the ultimobranchial remnants.

The relationship of SCN to thyroid parenchymal cells and the probable implications of the thyroid ‘ultimobranchial system’ to tumour histogenesis are analysed. Pitfalls that may emerge with regard to SCN in practical pathological approaohes are emphasized.