bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinicopathological significance of intratumoural variations in elastosis grades and the oestrogen receptor status of human breast carcinomas
Authors: Giri D. D. , Lonsdale R. N. , Dangerfield V. J. M. , Harris S. C. , Parsons M. A. , Underwood J. C. E.
Published: June 2005

Cryostat sections from seventy‐eight female breast carcinomas were assayed for oestrogen receptors by isoelectric focusing. Adjacent cryostat sections stained by Miller's elastic/van Gieson's method were graded for elastosis. Elastosis was similarly graded on near‐equatorial paraffin sections from the same tumours. A positive correlation was obtained between elastosis in the near equatorial sections and oestrogen receptor positivity (p<0·0005), menstrual status (p<0·05) and parity (p<0·01) but no correlation was found between these factors and elastosis graded on cryostat sections from the more peripheral areas which had been selected for oestrogen receptor assay. These observations suggest that the central region of breast carcinomas, where connective tissue responses are fully developed, exhibits grades of elastosis with greater clinical significance. This may explain the conflicting published observations on the correlations between elastosis and oestrogen receptor status, which we believe are due to the lack of uniformity in tissue sampling. The possible implications of the absence of significant correlation between elastosis grades and tumour size, nodal status and disease‐free interval are discussed.
Sinusoidal circulatory disturbance by microthrombosis as a cause of endotoxin‐induced hepatic injury
Authors: Shibayama Yuro
Published: June 2005

The present study was undertaken in rats to examine the significance of sinusoidal circulatory disturbance by microthrombosis in the pathogenesis of hepatic damage and dysfunction due to endotoxin. Administration of endo‐toxin induced fibrin deposits and infiltration of polymorphonuclear leukocytes in the sinusoids, focal random coagulative hepatocellular necrosis and elevation of serum transaminase activities. When heparin was given simultaneously with endotoxin, the formation of fibrin thrombus in the sinusoids was prevented, and the endotoxin‐induced morphological and functional changes in the liver were markedly inhibited. Infusion of thrombin into the portal vein induced a large amount of fibrin thrombi in the sinusoids, focal random necrotic foci resembling the lesions produced by endotoxin and elevation of levels of serum transaminases. These experimental data suggest that disturbance of hepatic microcirculation by sinusoidal thrombosis is the necessary and sufficient condition for the development of endotoxin‐induced hepatic injury.
Primary B‐cell gastric lymphoma—a reassessment of its histogenesis
Authors: Myhre Michael J. , Isaacson Peter G.
Published: June 2005

Primary gastric lymphoma, (PGL), is thought to be a tumour of follicle centre cell origin containing centrocyte‐like (CCL) cells, and plasma cell components. The advent of novel leucocyte antibodies reactive in paraffin sections and improved techniques for the demonstration of immunoglobulin (Ig) in tissues has permitted a reassessment of the histogenesis of PGL. Our results have shown that PGL is a tumour of CCL cells with plasma cell differentiation in a minority of cases. Follicles were reactive, as defined by polytypic expression of Ig, in each case but selective invasion of reactive follicles by neoplastic CCL cells often led to a misleading appearance of malignancy. CCL cells bear close similarities to marginal zone cells which have been defined as a distinct non‐circulating B‐cell lineage. This could account for the favourable clinical behaviour of PGL.
Use of the monoclonal antibody WR17, identifying the CD37 gp40–45 Kd antigen complex, in the diagnosis of B‐lymphoid malignancy
Authors: Moore K. , Cooper S. A. , Jones D. B.
Published: June 2005

The distribution of the gp40–45 Kd antigen bound by the WR17 monoclonal antibody of IgG2 subclass in normal lymphoid tissue was characterized by immunohistochemistry and immunofluorescence staining with flow cytometric analysis. The predominant staining pattern observed was characteristic of an anti‐pan‐B‐lymphocyte reagent. Weak reactions were observed by immunofluorescence staining of viable cell suspensions with all neutrophils and T‐lymphocytes in some normal donors. In tissue sections, B‐lymphocytes were stained and no cross reactions were observed with T‐lymphocytes, although macrophages stained in some sections.

A range of T‐ and B‐cell malignancies were stained with WR17 and the reactivity compared to that observed with other monoclonal antibodies in the CD 19, CD21 and CD22 clusters. All B‐non‐Hodgkin's lymphomas, B‐chronic lymphocytic, prolymphocytic and hairy cell leukaemia cells examined were stained by WR17 in indirect immunofluorescence assays, whilst the T‐cell tumours were negative. The same pattern was observed in cryostat sections of malignant tissue and in addition some tissue macrophages expressed the CD37 antigen cytoplasmically. Intra‐tumour heterogeneity of staining was observed with all the monoclonal antibodies tested, although overall WR17 consistently stained B‐cell tumours even when expression of the CD 19 pan‐B‐lymphocyte antigen could not be detected with some monoclonals.

Monoclonal antibodies, such as WR17, within the CD37 cluster and binding to the gp 40–45 Kd molecule, bind to mature B‐lymphocytes and identify the majority of B‐cell malignancies.
Fucose‐containing antigens in normal and neoplastic human gastric mucosa: A comparative study using lectin histochemistry and blood group immunohistochemistry
Authors: Macartney J. C.
Published: June 2005

The histochemical binding to normal and neoplastic human gastric mucosa of two lectin‐peroxidase conjugates which are specific for fucose‐containing glycoconjugates is described. The lectins are Ulex europaeus (UEA1) and Lotus tetragonolobus (LTA). Results are compared with ABO and secretor status and the immunohistochemical demonstration of a Type 1 antigen (Lewisa) and two Type 2 antigens (X and H) using monoclonal antibodies. Binding of UEA 1 and LTA to surface mucus cells in normal gastric mucosa is only seen in secretors but is independent of ABO status. In gastric carcinomas lectin binding is reduced. There is a relationship between UEA1 binding and the immunohistochemical demonstration of H Type 2 antigen and secretor activity. In contrast LTA staining is associated with both H Type 2 and Lea antigen but not with secretor status. X antigen is only demonstrable in small amounts. Despite subtle differences in the binding patterns of the two lectins, immunohistochemical studies with monoclonal antibodies against defined oligosaccharides provide greater information. The results of the study are consistent with the hypothesis that competitive interaction between fucosyl and sialyl transferases occurs in gastric malignancy and leads to the expression of abnormal blood group‐related antigens.
Pathogenicity of HIV in lymphatic organs of patients with AIDS
Authors: Pekovic Drasko D. , Gornitsky Mervyn , Ajdukovic Djordje , Dupuy Jean‐Marie , Chausseau Jean‐Paul , Michaud Jean , Lapointe Normand , Gilmore Norbert , Tsoukas Chris , Zwadlo Gabriela , Popovic Miculas
Published: June 2005

HIV antigens were searched for in the thymus, lymph nodes, bone marrow, and spleen of AIDS patients, by means of immunofluorescence technique. Human IgG against HIV and monoclonal antibodies against viral gag P24 protein yielded strong cytoplasmic fluorescence of cells in sections of the thymus, lymph nodes and spleen. Some cells containing HIV antigens were morphologically multinucleated giant cells. They reacted with monoclonal antibodies against helper/inducer T‐cells (OKT4+), and were complexed with antibody or with complement as demonstrated by double‐staining immunofluorescence technique. A large number of inflammatory cells infiltrated the thymus in areas containing cells expressing HIV antigens. These studies demonstrated an association of HIV virus with cytopathic and immunopathogenic reactions in lymphatic organs of AIDS patients, and are consistent with previous results, as well as indicative of a primary aetiologic role for the virus.
A demonstration of a strain related restriction effect in the formation of experimental metastases
Authors: Jack A. S. , McVeigh Karen L.
Published: June 2005

In view of the role of histocompatibility proteins in mediating many types of cell interaction it was decided to investigate their role in the formation of experimental metastatic deposits using the B16 mouse melanoma cell line. The expression of both major histocompatibility complex (MHC) Class I and Class II proteins was studied in vitro. Expression of both MHC Class I and Class II proteins was greater in the highly metastatic F10 cell line as compared with the poorly metastatic F1 line. Intravenous injection of cells into syngeneic and semi‐allogeneic animals revealed a strain related restriction effect on tumour growth following intravenous injection. However, this was mediated by a locus other than H‐2. No restriction of lung trapping of radiolabelled cells or local growth following intraperitoneal injection was found. It is suggested that non‐H‐2 Class I proteins may mediate some of the stages of metastatic tumour growth independent of the immune system.
T‐cell lymphomas in adults: A clinicopathological study of eighteen cases
Authors: Ramsay Alan D. , Smith Wendy J. , Earl Helena M. , Souhami Robert L. , Isaacson Peter G.
Published: June 2005

Eighteen cases of adult T‐cell lymphoma have been studied with respect to clinical presentation, response to treatment, histology, enzyme histochemistry, immunocytochemistry, and gene rearrangement. Seven cases (39 per cent) presented at extra‐nodal sites, and the age range was from 18 to 79. Treatment was with combination chemotherapy in most cases, and 11 of the 18 patients died within the three year follow‐up period. The lymphomas were classified morphologically into six types; T‐lymphoblastic lymphoma (TLL), angioimmunoblastic lymphadenopathy (AIL)‐like T‐cell lymphoma, T‐zone lymphoma, pleomorphic mixed medium and large cell T‐cell lymphoma (PMMLC), pleomorphic large cell T‐cell lymphoma (PLC), and monomorphic large cell T‐cell lymphoma (MLC). Enzyme histochemistry was found to be of limited value in the identification of T‐cell lymphomas. Immunocytochemistry showed a degree of correlation between the immunological profile and morphology, with cases in the PLC and MLC groups showing limited expression of T‐cell antigens. Re‐arrangement of the β chain of the T‐cell receptor gene was detected in 12 of the 14 cases studied, and all showed germ‐line immunoglobulin genes. The study emphasizes the varied morphological and clinical appearances of adult T‐cell lymphoma.
Morphological observations on the gallbladder of ground squirrels fed a lithogenic diet
Authors: Pemsingh Ramjeet S. , Macpherson Brian R. , Scott Gerald W.
Published: June 2005

Richardson's ground squirrels (Spermophilus richardsonii) of both sexes were fed a 2 per cent cholesterol‐enriched rat chow diet for intervals of 1, 2, 10 and 20 weeks. Light microscopy and 3H‐thymidine autoradiography revealed an increase in cell proliferation prior to the occurrence of macroscopically visible stones, but in the presence of crystals and microliths. Transmission electron microscopy studies showed that columnar epithelial cells undergo mitosis rather than basal cells and that oedematous cells were extruded from the epithelial sheet. Transmission and scanning electron microscopy studies on gallbladders of animals fed the lithogenic diet for 10 and 20 weeks revealed damaged epithelial cells either singly or in groups. Neighbouring cells often slide under the basal aspects of cells being extruded. Hypertrophy, hyperplasia, Rokitansky‐Aschoff sinuses, thickening of the lamina propria around the muscle bundles and inflammatory cells in the lamina propria began to occur about the time macroscopically visible stones were present. The epithelium of the Richardson's ground squirrel gallbladder is damaged more slowly than that of other animal models by a cholesterol‐enriched, lithogenic diet and may more accurately reflect changes occurring in human cholecystitis.
The pathogenesis of beta cell destruction in type I (insulin‐dependent) diabetes mellitus
Authors: Foulis Alan K.
Published: June 2005

In a study of pancreases from 75 patients who died at presentation of Type I diabetes there was selective destruction of beta cells associated with islet inflammation (insulitis). According to a recent hypothesis, aberrant expression of Class II major histocompatibility complex (MHC) products on a target cell may allow presentation of organ specific surface antigen(s) to potentially autoreactive T helper lymphocytes and thus lead to autoimmunity. Aberrant expression of Class II MHC was demonstrated immunohistochemically on beta cells in 21 out of 23 patients with recent onset diabetes. No such expression was seen on the other pancreatic endocrine cells. Ninety‐four per cent of insulin‐containing islets in these patients had marked hyperexpressions of Class I MHC affecting all endocrine cells in these islets. Insulin deficient islets were not thus affected. Both these abnormalities of MHC expression appeared to precede insulitis within a given islet and appeared to be unique to Type I diabetes, being absent in pancreases of patients with Type II diabetes, chronic pancreatitis, cystic fibrosis, graft‐versus‐host disease and Coxackie B viral pancreatitis. The development of autoimmunity to beta cells in Type I diabetes may be a ‘multistep’ process in which abnormalities of MHC expression are crucial events.
Immunohistochemical analysis of HLA antigens and mononuclear infiltrates of benign and malignant breast
Authors: Zuk John A. , Walker Rosemary A.
Published: June 2005

Using immunohistochemistry, the epithelial expression of HLA Class I and II antigens (and β2 microglobulin) was compared in benign and malignant breast, and the stromal lympho‐histiocytic infiltrate of these tissues quantified. The findings were compared with certain characteristics of the carcinomas. In contrast to other studies, malignancy was found to be associated with a far greater infiltrate of both lymphocytes and macrophages. In carcinomas, lymphocyte but not macrophage numbers showed a positive correlation with epithelial HLA ABC and HLA DR expression. This was particularly striking for T lymphocytes and especially for the T4 subset. The histological grade of carcinoma is closely related to the degree of HLA ABC and β2 microglobulin expression, but no such relationship was found for HLA DR. There were greater numbers of mononuclear cells in the poorer differentiated tumours compared with other grades. Those carcinomas with evidence of lymph node metastasis contained greater numbers of macrophages identified by the antibody Y1/82A, but none of the other parameters studied was found to be associated with local lymph node status. The use of a large panel of monoclonal antibodies against various cellular subtypes has allowed a more detailed analysis of the interaction between breast epithelium and the host response.
Epidermal growth factor receptors in lung tumours
Authors: Berger Mark S. , Gullick William J. , Greenfield Charles , Evans Stuart , Addis Bruce J. , Waterfield Michael D.
Published: June 2005

Immunocytochemical analysis of epidermal growth factor (EGF) receptor expression was carried out on frozen sections of 109 primary lung tumours resected at the Brompton Hospital from February 1984 to May 1985. Tumours with detectable levels of this proto‐oncogene protein were significantly more frequent among squamous cell carcinomas than among other types of lung tumour. No truncated EGF receptors were detected in the tumours using two monoclonal antibodies (Mabs) directed against different portions of the receptor (EGFR1 and F4). Mab F4 is the first antibody to the EGF receptor to show reactivity in paraffin sections. Southern blot analysis of a subset of the tumours detected amplification of the EGF receptor gene in squamous cell carcinomas but not in adenocarcinomas. The one carcinosarcoma examined had a re‐arranged and amplified EGF receptor gene. Measurement of EGF receptor expression in lung tumours can be of diagnostic value and may prove to be useful in the development of antibody‐directed therapy.
Pleural mesothelioma of epithelial type and pulmonary adenocarcinoma: An ultrastructural and cytochemical comparison
Authors: Dewar A. , Valente M. , Ring N. P. , Corrin B.
Published: June 2005

Twelve diffuse pleural mesotheliomas of epithelial type have been compared with 20 intrapulmonary adenocarcinomas. All mesotheliomas were negative for epithelial mucin by diastase periodic acid Schiff staining and for carcinoembryonic antigen by immunoperoxidase staining, whereas 17/20 carcinomas stained for epithelial mucin and 15/20 for carcinoembryonic antigen. Hyaluronidase‐sensitive alcian blue positive material was present in 6/10 mesotheliomas and 0/20 carcinomas. Previously described electron microscopic differences were validated, including one which has so far received insufficient emphasis: microvilli making direct contact through basement membrane deficiences with collagen fibres on the abluminal side of tumour cells were identified in 10/12 mesotheliomas and in 0/20 carcinomas.
Three‐dimensional reconstruction of biliary pathways in primary biliary cirrhosis: A computer‐assisted study
Authors: Yamada Shoji , Howe Stephen , Scheuer Peter J.
Published: June 2005

Bile ducts and ductules were traced by means of computerized three‐dimensional reconstruction in seven patients with primary biliary cirrhosis, three of them in the early asymptomatic stage and four of them with late disease. A patient with cryptogenic cirrhosis was also studied. Loss of bile ducts was confirmed, and was greater in the late stages as expected. Reconstruction demonstrated amputation of bile ducts of various sizes ranging from less than 40 μm to more than 80 μm in external diameter. Amputation was sometimes seen in relation to granuloma formation. The main or side branches of ducts could be traced to zones of proliferated ductules which, in turn, often communicated with liver‐cell plates. Clusters of atypical ductules could be seen to communicate with liver‐cell plates but not with ductules and ducts.

We concluded that proliferation of ‘typical’ ductules with well‐defined lumens, characteristically seen in primary biliary cirrhosis, probably represents a means whereby bile continues to be drained from the liver in spite of interruption of ducts. Computerized three‐dimensional reconstruction proved to be a rapid and accurate way of accumulating the necessary data.
Immunohistochemical localization of apolipoproteins A–I and B in human carotid arteries
Authors: Carter Richard S. , Siegel Robert J. , Chai Andrew U. , Fishbein Michael C.
Published: June 2005

Decreased plasma levels of apolipoprotein A–I (apo A–I) and increased plasma levels of apolipoprotein B (apo B) have been shown to correlate with increased risk of atherosclerosis. While many studies have investigated the plasma levels of these apolipoproteins with regard to their value as predictors of cardiovascular disease, comparatively little is known about their precise tissue localization in atherosclerotic plaques. The purpose of this study was to determine the tissue localization of apo A–I and apo B in atherosclerotic segments of human carotid arteries through the use of immunohistochemical techniques. With tissue samples obtained from surgery and autopsy, apo A–I and apo B were found to be present in atherosclerotic plaques and absent in normal arterial tissue. In the plaques, both apo A–I and apo B were found extracellularly, primarily in the lipid core, but also in connective tissue. In addition, both apo A–I and apo B were found intracellularly in foam cells. This similar intracellular and extracellular distribution of apo A–I and apo B was unexpected, in view of their differing associations with atherosclerosis.
Demonstration of cytokeratins and an epithelial membrane antigen in chondroid chordoma
Authors: Salisbury Jonathan R.
Published: June 2005

Chondroid chordomas are shown to possess cytokeratins and to stain with HMFG‐2 as do ordinary chordomas. These findings support the concepts that these neoplasma are a variant of chordoma and that they are unrelated to myxoid chondrosarcoma.
Gastric submucosal tumours of neurogenic origin with neuroaxonal and schwann cell elements
Authors: Yagihashi Soroku , Kimura Masamichi , Kurotaki Hidekachi , Fukuda Masami , Mikami Yasunori , Ozawa Masanori , Nagai Kazunori
Published: June 2005

Twelve cases of gastric submucosal tumours, originally diagnosed as leiomyoma and leiomyosarcoma, were investigated by staining with the neurogenic markers S‐100 and neuron specific enolase (NSE). Three cases were, in addition, studied by electron microscopy. The tumours stained negatively for desmin, indicating that they were not of smooth muscle origin. All stained positively for S‐100 and NSE. The ultrastructural features in the cases examined by electron microscopy were reminiscent of autonomic nerve structures normally present in the gastric wall. These included fine cytoplasmic processes of Schwann cells, wrapped with complete or incomplete basement membranes, and structures analogous to post‐ganglionic neuroaxonal components. These tumours appear to represent a distinct type of gastric neoplasm originating from autonomic nerve elements in the stomach wall. They are different from previously described schwannomas or neurofibromas. In some of the tumours, identifiably neural elements are relatively a minor component, and the majority of the tumour cells are of undetermined origin. It is suggested that these cells may be poorly differentiated, lacking their antigenic determinants specific to neural differentiation.
Phagocytosis of necrotic muscle in muscle isografts is influenced by the strain, age, and sex of host mice
Authors: Grounds Miranda D.
Published: June 2005

In grafts of skeletal muscle the implanted muscle becomes necrotic, is phagocytosed and replaced by new muscle cells. This study investigates the hypothesis that removal (phagocytosis) of necrotic implanted muscle is impaired in grafts made into old Swiss mice. Isografts (154) of minced muscle were made between young (20 day) and old (140 day) mice of the strains Swiss, AKR, BALBc, C3H and C57BL. Grafts were examined histologically after 7 days. A relationship between impaired phagocytosis and increasing host age was confirmed for male Swiss mice but was not seen with female Swiss mice or the other four strains. The proposal that ageing of bone marrow was responsible for diminished phagocytosis in old Swiss mice was investigated by replacing the marrow of 33 lethally irradiated male Swiss mice with marrow cells from mice of different ages (20 and 140 day), before isografting minced muscle. The results clearly show that macrophage stem cell function is unimpaired with age. Testosterone levels might account for the impaired phagocytosis seen in many sexually mature male Swiss mice. Support for this proposal came from experiments in which 15 mice were castrated before implanting muscle isografts. This study shows that genetic factors rather than the age of mice influenced phagocytosis and muscle formation in grafts.
Changes in autopsy profile—1975 and 1984
Authors: Hartveit F. , Karwinski B. , Giertsen J. Chr.
Published: June 2005

In 1975 diseases of the circulatory system were the major cause of death in our hospital autopsies, with neoplasia a poor second. In 1984 the situation was the reverse. The reduction in diseases of the circulatory system was due mainly to that in cerebrovascular cases, deaths from coronary artery disease being unchanged. The increase in neoplasia affected older women in particular, who died from less common types of cancer. It is suggested that these patients may have escaped death from cerebrovascular disease and avoided cancers that usually kill in middle age, to die later of other age‐related types that were less common in 1975. The present findings emphasize the importance of recognizing and adjusting to a changing spectrum of disease that is developing in the ageing population found in a West European country.
Prevalence of HPV DNA and viral copy numbers in cervical scrapes from women with normal and abnormal cervices
Authors: Wickenden C. , Malcolm A. D. B. , Byrne M. , Smith C. , Anderson M. C. , Coleman D. V.
Published: June 2005

Cervical scrapes were obtained from 215 women with cytologically normal cervices and 74 women with cervical intraepithelial neoplasia (CIN) and probed for HPV 6, 11, 16, and 18 by dot‐blot hybridization. Viral copy numbers were determined by densitometric scanning of autoradiographs.

The prevalence of HPV DNA in women with normal smears was as follows: 23 per cent of women attending a Family Planning Clinic (FPC), 16 per cent of women attending a Sexually Transmitted Diseases (STD) clinic, and 48 per cent of women attending a laser follow‐up clinic after treatment of CIN. Ten per cent of women with normal cervices harboured HPV 16. Viral copy numbers ranged from 1300 to 52 800 genome equivalents per cell. Twenty‐seven HPV‐positive women with normal smears (including four patients infected with HPV 16) were followed for up to 3 years. None developed CIN irrespective of copy number.

Our results show that HPV is present in normal cervices in the absence of CIN. Copy number has no relation to the development of CIN and factors other than the amount of HPV DNA may trigger the neoplastic process.
Stromal changes in invasive breast carcinoma: An ultrastructural study
Authors: Tamimi Salah O. , Ahmed Ali
Published: June 2005

The stroma in infiltrating breast carcinomas, with particular reference to stromal spindle cells, has been studied by electron microscopy. A mixture of cells including resting fibroblasts, active fibroblasts, early myofibroblasts, and mature myofibroblasts has been identified. In loose stroma, myofibroblasts possessed prominent organelles and showed secretory products along the cell surface, whereas in dense stroma, there was relative proinence of cytoplasmic filaments as well as other features consistent with a contractile state of myofibroblasts. The degree of myofibroblastic proliferation was related to the growth pattern of the tumour. It is suggested that the infiltrating process of cancer cells is analogous to wound production and healing with continuous granulation tissue and scar formation resulting in the characteristic desmoplastic reaction seen in certain breast carcinomas.
DMSO potentiates aminonucleoside of puromycin nephrosis in rats
Authors: Spear Gerald S. , Nguyen Diep , Conklin Suzanne , Wikle John S. , Fan Joseph , Lan Yuhuan , Allen James , Reineck Scott
Published: June 2005

Dimethyl sulphoxide (DMSO), 3 g/kg body weight, administered daily by the intraperitoneal route, potentiated the proteinuria and formation of tubular casts in aminonucleoside of puromycin (PA) induced nephrosis in Sprague‐Dawley rats. The effect was evident at 4 as well as 8–9 days following PA administration. In the absence of PA, DMSO did not induce proteinuria or cast formation. The mechanism by which DMSO enhanced proteinuria and cast formation is not known.
Immunohistochemical staining of non‐Hodgkin's lymphoma in paraffin sections using the MB1 and MT1 monoclonal antibodies
Authors: Dobson C. M. , Myskow M. W. , Krajewski A. S. , Carpenter F. H. , Horne C. H. W.
Published: June 2005

We have performed a single blind trial to assess the value of the monoclonal antibodies MB1 and MT1 in lymphoma classification. Sixty cases of non‐Hodgkin's lymphoma (NHL) were stained with MB1 and MT1 using an indirect immunoperoxidase technique in paraffin sections. The majority of B tumours (27/33) stained with MB1, and most of the T tumours (24/27) stained with MT1. The MB1 antibody often produced rather weak staining but it was apparently highly specific for B cells, with only three (3/27) of the T tumours (two cases of ‘malignant histiocytosis’ of the intestine (MHI) and one pleomorphic T‐cell lymphoma) displaying ‘false’ positivity. The MT1 antibody generally produced very strong staining, but it was not very selective, with 14/33 of the B lymphomas displaying ‘false’ positivity.

The cross‐reactivity observed in 17 cases led to only three misdiagnoses, two B tumours being designated as T lymphomas and one T tumour being designated as a B lymphoma. In a few cases (7/17), dual staining with both antibodies precluded firm diagnosis. In other cases (6/17), classification was possible despite some of the tumour cells showing dual staining. The seventeenth case was a plasmacytoma displaying MT1 positivity only.

While the monoclonal antibodies MB1 and MT1 are of use in classifying lymphomas in paraffin section, they are not entirely lineage‐specific, and the uncritical use of these two reagents alone may give rise to misdiagnosis; the use of a panel of monoclonal antibodies may yield more accurate results. As with any immunohistochemical marker, their limitations should be recognized; interpretation must be judicious and always in the context of the histological appearances.
Lymphoplasmacytoid lymphoma: An immunohistological study
Authors: Hall P. A. , D'Ardenne A. J. , Richards M. A. , Stansfeld A. G.
Published: June 2005

Eighteen cases of lymphoplasmacytoid lymphoma (LPL) have been immunophenotypically characterized with a panel of 26 monoclonal antibodies. All cases expressed leucocyte common antigen, class II MHC and stained with B cell markers (CD19, CD20, CD22) although a variable proportion of tumour cells were noticed to have lost some B cell marker expression. There was some phenotypic heterogeneity with variable immunostaining with KB61, CD21, and CD5. A variable proportion of cells in all cases contained cytoplasmic immunoglobulin. Surface immunoglobulin light chain restriction was demonstrated in 11 cases and heavy chain predominance in 16 cases. Few tumour cells were proliferating as indicated by Ki67 immunostaining. A wide variation in number of macrophages and T lymphocytes were present in association with the tumours. A significant association between the expression of CD5 and the presence of peripheral blood lymphocytosis was noticed (p<0·003) but there was no association between CD5 and co‐expression of IgM and IgD. This data supports an origin from non‐germinal centre cells for LPL and suggests that CD5 expression by B cells may be related to lymphocyte migration. LPL shows some immunological heterogeneity and can present diagnostic difficulties, but its poor prognosis makes it an important category of lymphoma to recognise.
Immunocytochemical demonstration of the association between Legionella pneumophila, its tissue‐destructive protease, and pulmonary lesions in experimental Legionnaires' disease
Authors: Williams Ann , Baskerville A. , Dowsett A. B. , Conlan J. W.
Published: June 2005

Using immunocytochemical techniques at the light and electron microscope levels, Legionella pneumophila and one of its extracellular proteases were located in the lungs of guinea pigs with experimental Legionnaires' disease (LD). L. pneumophila was immunostained by several peroxidase‐ and gold‐labelling methods for light and electron microscopy. The protease was immunolabelled in tissue fixed in Carnoy's fluid at the light microscopical level and on broth‐grown organisms at the ultrastructural level. It was not labelled in either formalin‐ or glutaraldehyde‐fixed tissue.

Using double‐labelling techniques, L. pneumophila and protease were located in the same section and were shown to be intimately associated with pulmonary lesions, providing strong evidence for the role of this protease in LD pneumonia.
Antidesmosomal monoclonal antibody in the diagnosis of intracranial tumours
Authors: Parrish Elaine P. , Steart Philip V. , Garrod David R. , Weller Roy O.
Published: June 2005

Immunocytochemistry has been applied extensively to the diagnosis of intracranial tumours, but meningiomas still present a diagnostic problem. However, desmosomes have been shown by electron microscopy to be present in meningiomas, and this distinguishes them from gliomas. This paper describes a new monoclonal antibody, 11‐5F, against desmosomal proteins 1 and 2 (desmoplakins) and assesses its usefulness in the diagnosis of meningiomas and other intracranial tumours. A total of 74 surgically removed intracranial tumours were examined by fluorescent antibody staining with 11‐5F on frozen sections. In addition, a panel of antibodies against cytokeratin, vimentin, glial fibrillary acidic protein, and S100 protein was used. 11‐5F stained 30/30 meningiomas and 14/14 metastatic carcinomas but 0/30 gliomas, thus distinguishing meningiomas and metastatic carcinomas from gliomas. The distinction between meningiomas and metastatic carcinomas on the basis of intermediate filaments staining was more difficult because neither the anticytokeratin nor the antivimentin antibody was specific for either tumour type. This study emphasizes the value of antidesmosomal antibodies as an important adjunct to the diagnosis of intracranial tumours.
Cell death and cell proliferation during atrophy of the rat parotid gland induced by duct obstruction
Authors: Walker Neal I. , Gobé Glenda C.
Published: June 2005

Rat parotid gland atrophy after unilateral duct ligation was studied by light and electron microscopy. Death of secretory acinar cells, which took the form of apoptosis, resulted in their complete disappearance within 5 days. The remnants of the dying cells were mostly phagocytosed and degraded by macrophages within the glandular epithelium; a few were taken up by adjoining epithelial cells. The acinar cell deletion was accompanied by increased mitosis of striated and intercalated duct epithelial cells. However, over many weeks, there was enhanced apoptosis of duct cells, which eventually led to marked shortening of intercalated ducts. Apoptosis of capillary endothelial cells was observed and may account for the reduction in the capillary bed known to accompany gland atrophy. The end‐stage lesion comprised small numbers of ducts in a condensed stroma. Compensatory hyperplasia, involving proliferation of duct and acinar cells, was demonstrated in the contralateral glands.
Immunohistochemical studies on the distribution and frequency of fatty‐acid‐binding protein positive cells in human fetal, newborn and adult liver tissues
Authors: Suzuki Toshimitsu , Ono Teruo
Published: June 2005

Human tissues from adult, newborn/infant, and fetal livers, and gall bladders were immunostained with rabbit antibodies against fatty‐acid‐binding protein (FABP) isolated from rat liver. These antibodies cross‐reacted with FABP from human liver by a double immunodiffusion method. The antigenicity of FABP of human liver is well preserved in various fixatives including 10 per cent formaldehyde, 4 per cent paraformaldehyde, and Zamboni's and Bouin's solution. FABP immunoreactivities, moreover, could be detected similarly in both crvostat and paraffin sections.

FABP of hepatic type was found in hepatocytes most frequently in the fetus (as early as the 7th week of gestation), moderately in the newborn/infant, and infrequently in adult liver tissues.

The distribution pattern of the positive hepatocytes was uniform throughout the acini in fetuses, but periportal in adults. No immunoreactive cells were found in the gall bladder or in the extra‐ and intra‐hepatic bile ducts. In this study, FABP was found in human hepatocytes in both fetal and postnatal livers. FABP, therefore, might be a useful marker substance in the investigation of the physiology and pathology of the human liver.
Tamm–Horsfall protein outside the kidney
Authors: Howie A. J.
Published: June 2005

Tamm–Horsfall protein is the main protein in normal urine and readily precipitates. Previously there has been little study of the protein outside the kidney. An antiserum to the protein was used in an immunohistological investigation of human tissues. No Tamm–Horsfall protein was detected in normal organs other than the kidney. The protein was detected outside the kidney in abnormal organs in three general sites: (i) in ulcers of epithelial surfaces exposed to urine, (ii) deep in the wall of a bladder that had had previous surgery and (iii) in lymph nodes at the hilum of kidneys that had been obstructed or contained extra‐tubular deposits of the protein. There was little evidence of a cellular response to the deposits of Tamm–Horsfall protein. The antiserum to Tamm–Horsfall protein is a good immunohistological marker of extravasated urine and is useful in the study of such conditions as fistulas of the urinary tract, operations on the urinary tract and reflux of urine into lymphatics and lymph nodes.
Postnatal development of the innervation and paraganglia in the porcine pulmonary arterial bed
Authors: Wharton John , Haworth Sheila G. , Polak Julia M.
Published: June 2005

The innervation of the pulmonary trunk and pulmonary arterial bed was studied in 17 pigs from birth to 6 months of age. After birth, the pulmonary trunk and extra‐and intra‐pulmonary arteries contained neurofilament and protein gene‐product‐immunoreactive nerve fibres in both the adventitia and media. The density of nerve fibres increased from birth to 2 months, this being most marked during the first 2 weeks of life. Most of the fibres in the media were presumed to be sympathetic in origin as they contained both neuropeptide tyrosine and tyrosine hydroxylase immunoreactivity. Fibres were associated with the vasa‐vasorum and vascular smooth muscle running around the vessel, between the elastic laminae and smooth muscle cells, in the outer two‐thirds of the media. Vasoactive intestinal polypeptide and calcitonin gene‐related peptide‐immunoreactive nerve fibres were found to be associated with the pulmonary trunk and extra‐pulmonary artery, but generally not with the intra‐pulmonary arteries. Tyrosine hydroxylase immunoreactivity was detected in the glomus cells at birth, but peptide immunoreactivity (enkephalin) was not demonstrated in paraganglia until 14 days of age. Adaptation to extra‐uterine life is associated with rapid development changes in the innervation of the pig pulmonary trunk, extra‐and intra‐pulmonary arteries and in the expression of peptide immunoreactivity in both nerve fibres and glomus cells. These changes may have a role in the postnatal adaptation of the pulmonary circulation.
Correlation between DNA flow cytometric and nucleolar organizer region data in non‐Hodgkin's lymphomas
Authors: Crocker J. , Macartney J. C. , Smith P. J.
Published: June 2005

The argyrophilic staining (AgNOR) technique, novel in histopathology, was applied to a series of 20 non‐Hodgkin's lymphomas (NHL) of established Kiel subtype. The method demonstrates nucleolar organizer regions (NORs) by virtue of sulphydryl groups on their associated proteins and the enumeration of AgNOR foci has been previously shown to discriminate between NHL of low‐ and high‐grade histological types. This finding was confirmed and the results were compared with those obtained by means of DNA flow cytometry performed on paraffin wax‐embedded tissue from the same lymphomas. There was a very good linear correlation between the mean numbers of AgNOR sites per nucleus and the percentage of S‐phase cells for each case, both values being high in high‐grade NHL and low in low‐grade lesions. Conversely there was no significant correlation between the DNA index, representing DNA aneuploidy, and AgNOR counts. It is suggested that the numbers of AgNORs in a lymphoma may be related to the dividing fraction of cells rather than, as might be expected, to ploidy alone. It is also proposed that the AgNOR technique, which is rapid, simple, and inexpensive, may provide, at least, an adjunct to DNA flow cytometry in the assessment of neoplasm in histopathology.
The glomerular tip lesion: A distinct entity or not?
Authors: Huppes Willem , Hené Ronald J. , Kooiker Cornnelis J.
Published: June 2005

Howie and Brewer1 recently described a novel glomerulopathy: the glomerular tip lesion (GTL). The characteristic feature of this entity is a collection of intracapillary foam cells and marked vacuolization of the epithelial cells of the glomerular segment adjacent to the origin of the proximal tubule. Although this lesion resembles focal segmental glomerulosclerosis (FSGS), Howie and Brewer suggested that it constitutes a distinct entity, differing also clinically from FSGS, in that it would have a better response to steroid treatment. We treated five patients fulfilling the criteria of Howie and Brewer. However, neither corticosteroids (1·5 mg/kg/day for 1 month in five patients) nor cyclosporin‐A (5 mg/kg/day for three months in four patients) caused a decrease in proteinuria to below 4 g/day. In two patients, renal function deteriorated and in one of them, recurrence of classical FSGS was found in the renal transplant. A sixth patient was observed in whose biopsy a combination of GTL with membranous glomerulopathy was present. We conclude that GTL is not a distinct entity and that in the clinical course and response to treatment it does not differ from FSGS.
The prognostic value of Ki67 immunostaining in non‐Hodgkin's lymphoma
Authors: Hall P. A. , Richards M. A. , Gregory W. M. , D'Ardenne A. J. , Lister T. A. , Stansfeld A. G.
Published: June 2005

The monoclonal antibody Ki67 recognizes an antigen expressed in all phases of the cell cycle except Go. It has been used in 141 biopsies from 138 patients with non‐Hodgkin's lymphoma to identify proliferating cells in histological sections. A Ki67 index (the number of Ki67 positive tumour cells divided by the sum of Ki67 positive and negative tumour cells) has been derived by counting 1000 cells in each case. A correction for the presence of non‐tumour cells has been incorporated by counting non‐tumour cells in serial sections stained with a panel of other antibodies. A very strong correlation between a low Ki67 index (<20 per cent) and low grade histology and a high Ki67 index (>20 per cent) and high grade histology was found (Chi2 = 98·0). Ninety‐one patients could be analysed for survival and those with low grade lymphoma (n = 38) who had a relatively high Ki67 index (>5 per cent) had a worse survival than those with an index of <5 per cent (p<0·05). In contrast, there was a trend for those patients with high grade disease with a very high Ki67 index (>80 per cent) to have a better survival than those with a lower index (<80 per cent). The patients with high grade disease who achieved complete remission or good partial remission and had a Ki67 index of less than 80 per cent were more likely to relapse than those with an index of greater than 80 per cent (p<0·04). These findings could not be explained by the effect of other prognostic factors such as age, stage, or serum albumin. While the use of Ki67 immunostaining has potential drawbacks, it appears to be a simple and reproducible method of determining a tumour proliferative index which provides relevant clinical data.
Flash labelling of S‐phase cells in short‐term organ culture of normal and pathological human endometrium using bromodeoxyuridine and tritiated thymidine
Authors: Thornton James G. , Wells Michael , Hume William J.
Published: June 2005

Normal hyperplastic and malignant endometrial specimens were labelled in vitro with bromodeoxyuridine (BrdU). S‐phase cells were stained after DNA denaturation, using a monoclonal antibody to BrdU and an indirect immuno‐peroxidase method. Various conditions for BrdU uptake, DNA denaturation, and staining were tested. BrdU labelling was compared with autoradiography using tritiated thymidine, with good correlation. Glandular labelling indices of proliferative endometrium were significantly higher than both secretory and hyperplastic endometrium but were similar to carcinoma. Stromal labelling showed the same trend but the differences were not statistically significant.
Architectural and nuclear morphometrical features together are more important prognosticators in endometrial hyperplasias than nuclear morphometrical features alone
Authors: Baak Jan. P. A. , Nauta J. J. P. , Wisse‐Brekelmans E. C. M. , Bezemer P. D.
Published: June 2005

Previous studies have shown that 80–90 per cent of cases of atypical hyperplasia of the endometrium do not progress to cancer. Criteria to predict the outcome in an individual patient with hyperplasia are lacking, and hysterectomy is the usual (over)treatment in order to avoid a 10–20 per cent chance of confrontation with cancer later on in the course of the disease. A recent study has shown that using a nuclear morphometric classification rule, 15 per cent of patients without progression can be accurately separated from patients with progression. However, as it is unlikely that nuclear morphometrical features are the only morphological factors reflecting the outcome of the disease, other quantitative parameters describing the architecture of the glands have also been studied for their potential value in selecting patients who will progress to cancer. In total, 10 nuclear features and 12 glandular architectural features were studied in 39 cases of atypical endometrial hyperplasia. Among these cases, seven (18 per cent) progressed to cancer.

Using linear stepwise regression analysis and discriminant analysis, the volume percentage stroma and the standard deviation of the shortest nuclear axis are the best discriminators, although the outer surface density of the glands also adds to the discriminating power. The volume percentage stroma is the best single prognosticator; this feature is highly reproducible. In total, using these combined architectural and nuclear morphometrical features, 20 of the 32 cases without progression were separated from those who subsequently progressed (62·5 per cent). This is a considerable improvement over nuclear morphometrical features alone (15 per cent separated).
Mast cell numbers in appendices with threadworm infestation
Authors: Crow Julie , Howe S.
Published: June 2005

A study has been made of mast cells (MC) in surgically resected appendices using a long toluidine blue (LTB) staining method. The numbers of MC in measured areas of both mucosa and submucosa/muscularis were counted and comparisons made between 22 appendices containing threadworms and 22 which were histologically normal. There was considerable variation in MC numbers from case to case and the patients aged under 15 as a group had a higher mean number of mucosal MC than the older patients. The reasons for the high individual variation could not be identified from the histological sections, and no correlation was found between MC numbers and the presence of threadworms.
Observations favouring Pneumocystis carinii pneumonia as a primary infection: a monoclonal antibody study on paraffin sections
Authors: Millard Peter R. , Heryet Andrew R.
Published: June 2005

Pneumocystis carinii pneumonia is characteristic of immunodeficiency and the organism is probably acquired during early childhood. Since infection is only manifest in the lungs, it has been presumed that the organism lies dormant in these tissues following the primary infection. Conventional staining procedures have, however, failed in the absence of pneumonia to demonstrate consistently any forms of Pneumocystis carinii. To study this problem further, lung sections and hilar lymph nodes from immunodepressed adults with and without Pneumocystis carinii pneumonia as well as lung sections from presumed immunocompetent patients were examined for the cyst and trophozoite forms of Pneumocystis carinii using a monoclonal antibody. The organism was only identified in areas of pneumonia, and the source of the organism in these patients may therefore be a new infection with a different human subtype and not, as previously thought, reactivation of a primary infection.