bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatal legionnaires' pneumonia: Frequency of legionellosis in autopsied patients with pneumonia from 1969 to 1985
Authors: Schürmann D. , Ruf B. , Fehrenbach Franz J. , Jautzke G. , Pohle Hans D.
Published: June 2005

In 89 of 3027 (2·9 per cent) patients in whom pneumonia was found at autopsy during the period from 1969 to 1985. legionella pneumonia was diagnosed. Legionellae were demonstrated through the direct fluorescent antibody test by screening lung tissue sections. All 89 cases were caused by Legionella pneumophila. Suspicious typical rod‐shaped organisms were demonstrated in all cases by the modified Dieterle stain whereas conventional histological stains failed to detect causative bacteria. The frequency per year of legionellosis in patients with pneumonia at autopsy ranged from 1·4 per cent (3/212 cases) to 6·8 per cent (12/177 cases). In patients who have died of unexplained pneumonia, examinations for the demonstration of legionellae should be carried out.
Endodermal sinus (yolk sac) tumour of the liver. A case report and review of the literature
Authors: Narita Takeo , Moriyama Yuzo , Ito Yasuo
Published: June 2005

A primary endodermal sinus tumour of the liver which developed in a 27‐year‐old woman is reported. The dimensions of the tumour were 11 × 11 × 9·5 cm. Most parts were friable, haemorrhagic, and necrotic. No metastasis was found, but one part of the tumour was invading the diaphragm directly. Histologically, the tumour had mainly a reticular pattern, and partly a solid pattern, and was characterized by the presence of Schiller–Duval bodies and intra‐and extracellular hyaline globules. A small part of the tumour showed a polyvesicular vitelline pattern and glandular structures with enteric differentiation. Serum alpha‐fetoprotein was very high (28 500 ng/ml), but carcinoembryonic antigen was within the normal range. Immunohistochemically, most of the tumour cells contained alpha‐fetoprotein and alpha‐1‐antitrypsin. Carcinoembryonic antigen and glutathione S‐transferase, which was recently proved to be a useful marker for colonic carcinoma, were detected only in the glandular part. Four previously reported cases of primary endodermal sinus tumour of the liver are reviewed.
The demonstration of tissue clonality by X‐linked enzyme histochemistry
Authors: Thomas Geraldine A. , Williams Don , Williams E. Dillwyn
Published: June 2005

We report here the first demonstration in normal, as opposed to chimaeric mice, of the clonal architecture of the small intestine, oesophagus, breast, and thyroid, using polymorphism of the X‐linked enzyme glucose‐6‐phosphate dehydrogenase (G6PD, EC 1.1.1.49) as a clonal marker.

Reproducible results using X‐linked histochemistry were found to depend upon the simultaneous study of tissue from normal mice, mice homozygous for abnormal enzyme levels, and heterozygous mice. In tissues from homozygous animals where levels of enzyme activity normally vary, the use of a physiological stimulus to reduce this metabolic heterogeneity allowed interpretation of clonality in the heterozygotes. The details of the histochemical technique used require modification for each of the different tissues studied.

A dual population of cells was seen in the heterozygous animals in all tissues studied. Oesophageal epithelium showed sharply separated alternating patches of positive and negative cells. Small intestinal crypts were always monophenotypic, while villi were polyphenotypic, indicating that crypts are monoclonal and villi derive from more than one crypt, confirming work in allophenic animals. In contrast, thyroid follicles and breast acini showed a mixture of mono‐ and polyphenotypia, consistent with a polyclonal origin. These results, which have important implications for the study of the clonal origins of normal and neoplastic growth, require the direct in situ demonstration of the cellular phenotype.
The effect of a series of fixatives on the agnor technique
Authors: Smith Paul J. , Skilbeck Nick , Harrison Adrian , Crocker John
Published: June 2005

With increasing interest being shown in nucleolar organizer regions (NORs) in pathology, it was considered of great importance to evaluate the effect of some of the more commonly used and more specialized fixatives on the demonstration of these moieties.

NORs can be demonstrated in paraffin sections by a silver technique (AgNOR method) which was developed from a method used by cytogeneticists for the demonstration of NORs in chromosome spreads. The degree of staining is dependent on the fixation regime employed and results may vary greatly from one fixative to another. The fixative schedules and post‐treatments used in this study were based on standard sequences from the literature. We have shown that, in general, alcohol‐based fixatives give optimal results, Carnoy's fluid being especially recommended. Mercurial and dichromate‐containing fixatives were found to have highly detrimental effects on NOR staining. ‘Routine’ 10 per cent formol saline fixation gave adequate results whereas 10 per cent neutral buffered formalin gave optimal staining, similar to alcohol‐based fixation.
The immunohistology of synovial lining cells in normal and inflamed synovium
Authors: Athanasou N. A. , Quinn J. , Heryet A. , Puddle B. , Woods C. G. , McGee J. O'D
Published: June 2005

The immunohistology of synovial lining cells (SLCs) in normal and inflamed hyperplastic synovium was investigated using monoclonal antibodies directed against leucocyte common antigen (LCA) HLA‐DR and other macrophage components. We found that some SLCs in normal synovium express LCA, HLA‐DR, and monocyte/macrophage‐associated antigens. The number of SLCs expressing these antigens is increased in hyperplastic osteoarthritic (OA) and rheumatoid (RA) synovium. Some SLCs which did not react for LCA or other macrophage markers but were positive for HLA‐DR were also noted in normal synovium and some segments of hyperplastic OA synovium. SLCs which are positive for LCA, HLA‐DR, and macrophage markers contribute to the intimal hyperplasia in RA where they account for the majority of SLCs in the synovial intima. In OA synovium, the distribution of SLCs showing this pattern of reactivity was less uniform with numerous SLCs which were positive for HLA‐DR but negative for LCA and other macrophage markers also present in the synovial intima. These findings indicate that there are some SLCs of bone marrow origin in normal and hyperplastic synovium. They also suggest that recruitment of SLCs of marrow origin is important in the production of intimal hyperplasia in both RA and OA and that there is also a significant local proliferation of non‐marrow derived SLCs in OA.
Relationships between oestrogen receptor, epidermal growth factor receptor, ER‐D5, and P24 oestrogen regulated protein in human breast cancer
Authors: Horne Glenda M. , Angus Brian , Wright Christopher , Needham Geoffrey , Nicholson Stewart , Harris Adrian L. , Innes Barbara , Horne Charles H. W.
Published: June 2005

Proteins regulated by or related to the oestrogen receptor (ER) may prove to be more reliable indicators of prognosis and hormone sensitivity then expression of the receptor itself. It has been shown recently that expression of epidermal growth factor receptor (EGFR) is associated with a poor prognosis in breast cancer. In a series of 60 breast cancers, we have studied relationships between ER, ER‐D5 oestrogen receptor related protein, P24 oestrogen regulated protein, and EGFR using an immunohistochemical technique employing monoclonal antibodies in each case. In addition, radioligand binding assays for ER and EGFR were carried out and tumour histological grade was determined. Seventy‐one per cent and forty‐three per cent of tumours stained for ER‐D5 and P24, respectively, but there was no relationship between staining for these and ER or EGFR status. There was a significant correlation between staining for ER and EGFR, and the respective biochemical assays. Relating ER to EGFR, very few ER‐positive cases expressed EGFR, but this relationship fell short of significance. The prognostic significance of expression of the epitopes recognized by the ERD5 and P24 antibodies must await assessment of clinical outcome.
Expression of the CD 15 antigen is a marker of cellular differentiation in cervical intra‐epithelial neoplasia (CIN)
Authors: Sanders D. S. A , Kerr M. A. , Hopwood D. , Coghill G.
Published: June 2005

The CD 15 antigen (3‐fucosyl N‐acetyllactosamine), present on the outer cell membrane of cervical squamous epithelial cells, is recognized by the monoclonal antibody MC2, which is similar to several commercially available antibodies. Staining sections of cervical biopsies with MC2 clearly demonstrates the zone of supra‐basal differentiated cells in the normal squamous epithelium. Staining with MC2 also demonstrates the diminished proportion of this zone occurring with grades of CIN, reflecting progressive de‐differentiation of the epithelium. In immature squamous metaplastic epithelium, absence of cytoplasmic differentiation is reflected by lack of staining.

As expression of the CD 15, antigen by cervical squamous cells mirrors cytoplasmic maturity and is a marker of cellular differentiation, staining colposcopic biopsies with MC2 may aid the routine histopathological grading of CIN. A comparison is made between the staining pattern observed using MC2 with that of two commercially available antibodies (Leu M1 and Dako M1), and a possible role for the CD 15 antigen in cellular adhesion in squamous mucosae is discussed.
Ki‐67 derived proliferative activity in colorectal adenocarcinoma with prognostic correlations
Authors: Shepherd N. A. , Richman P. I. , England Janet
Published: June 2005

Cryostat sections from samples of 108 colorectal carcinomas were stained with the murine monoclonal antibody Ki‐67, which is expressed in proliferating cells. Ki‐67 immunoreactivity was assessed independently by two pathologists using a semi‐quantitative method. There was excellent correlation between the two observers. Ten cases were assessed quantitatively by counting at least 2000 cells and there was a very good correlation between this method and the semiquantitative method. The carcinomas showed a wide range of Ki‐67 labelling, reflecting a variation in proliferative activity. The tumour labelling index ranged from 1 to 80 per cent positivity: there was also heterogeneity of labelling within many of the tumours. There was no correlation between Ki‐67 derived proliferative score and known prognostic parameters, including Dukes stage, New Prognostic Classification grade, lymph node status, tumour differentiation, venous spread, invasive margin, lymphocytic infiltrate, and curative versus palliative surgery. Nevertheless, it is concluded that Ki‐67 immunohistochemistry provides a reliable and reproducible method of assessment of proliferative activity in colorectal cancer. Ki‐67 immunohistochemistry may have a clinical application in the selection of patients with colorectal cancers who might benefit from radiotherapy and/or chemotherapy, particularly those with unresectable or locally recurrent tumours.
HLA class II sublocus expression in benign and malignant breast epithelium
Authors: Zuk John A. , Walker Rosemary A.
Published: June 2005

Using immunohistochemistry and a panel of five monoclonal antibodies, the epithelial expression of HLA class II sublocus products by benign and malignant breast has been studied. The magnitude of the stromal mononuclear inflammatory cell infiltrate was assessed. There was expression of HLA class II by 75 per cent of epithelial cells in the benign tissues, with little variation in intensity and between antibodies. There was coordinate expression of DR and DQW1. Epithelial expression by carcinomas was more complex and variable. Most (61 per cent) carcinomas exhibited variable loss of epithelial expression of class II products, as detected by three antibodies recognizing epitopes on DP, DQ, and DR together. Thirteen (28 per cent) carcinomas were completely negative or had very occasional positive cells. The extent of this loss was unrelated to the magnitude of the inflammatory infiltrate and axillary lymph node status. No well‐differentiated carcinomas exhibited complete loss. Furthermore, non‐coordinate expression of DR and DQW1 was present in 8 out of 40 carcinomas, with the proportion of DQW1 positive epithelium always being less than that of DR. Carcinomas exhibiting non‐coordinate expression were never well differentiated; there was no relationship with the extent of the inflammatory infiltrate. This is the first study to detail HLA class II expression in breast, and our results suggest that alterations in expression of these products may modify or reflect tumour behaviour.
Undifferentiated columnar cells on the gastric interfoveolar crest: A previously undescribed observation
Authors: Newbold K. Mark , Macdonald Fiona , Allum William H.
Published: June 2005

We have observed and defined morphometrically and histochemically an entity composed of groups of undifferentiated columnar cells on the interfoveolar crest of gastric mucosa. These cells are clearly distinct from either normal foveolar cells or regenerative epithelial cells associated with ulcer healing. They show a close association with atrophic gastritis, particularly in the presence of type 3 sulphomucin‐secreting intestinal metaplasia. We have termed this the gastric tip lesion since it is observed only on the tips of the mucosal folds.

This has not been described previously. We propose that these cells are the precursors of type 3 intestinal metaplasia and may also provide a link between this type of intestinal metaplasia and the intestinal variant of gastric adeno‐carcinoma.
Response of cerebral microvasculature to brain injury
Authors: Maxwell William L. , Irvine Alyson , Adams J. Hume , Graham David I. , Gennarelli Thomas A.
Published: June 2005

There is increasing evidence that there is a direct response of the cerebral microvasculature to head injury. We have investigated using SEM and TEM the response of microvessels within the white matter of the baboon brain to lateral head acceleration. There is rapid endothelial disruption and swelling of perivascular astrocytes near the sites of petechial haemorrhage. The formation of microvilli in all vessels reaches a peak at 6 h and extends at least 5 mm from the site of haemorrhage. The astrocyte response suggests a partial recovery by 6 h. The endothelial response is most marked in arterioles and venules and is maintained for 6 days after injury. We suggest there is a biphasic cerebrovascular response to brain injury. First there is rapid astrocytic swelling possibly correlated with transient disruption of the blood‐brain barrier. This is followed by morphological changes in the endothelium of all vessels which are most marked in arterioles and venules and extend considerable distances throughout the neuropile. This response is discussed in the light of disruption of the blood–brain barrier.
Application of a monoclonal antibody for the detection of Trichosporon beigelii in paraffin‐embedded tissue sections
Authors: Takeuchi Tamotsu , Kobayashi Makoto , Moriki Toshiaki , Miyoshi Isao
Published: June 2005

Trichosporon beigelii is a normal inhabitant of soil and is occasionally found as normal flora of the skin and mouth. Opportunistic infection by this fungus has been increasingly reported in immunocompromised patients. The diagnosis of this infection depends on positive cultures or histological evidence. However, it is sometimes difficult to distinguish this fungus from Candida species in tissue section. We have generated two monoclonal antibodies that can distinguish T. beigelii from other fungi including several species of Candida. One of these antibodies (K‐16) reacts with T. beigelii in formalin‐fixed, paraffin‐embedded tissue sections and will be useful as an aid to the accurate diagnosis of trichosporonosis.
Lectin binding in the male breast
Authors: Raju Gangaraju C. , Lee Yoke‐Sun
Published: June 2005

Twenty‐four male breast lesions including ten normal, ten gynaecomastia, and four infiltrating carcinomas were studied for the presence and distribution of lectin binding carbohydrates. For comparison, tissue sections of five normal female breast lesions, ten each of fibrocystic disease, fibroadenoma, and carcinoma, were also included in this study. Formalin‐fixed, paraffin‐embedded tissues were tested with Glycine maximus (SBA), Dolichos biflorus (DBA), Triticum vulgaris (WGA), Concanavalia ensiformis (Con A), Lotus tetragonolobus (LTA), Arachis hypogaea (PNA), and Bandeiraea simplicifolia (BSAI). The lectin‐binding patterns were similar in normal, gynaecomastia, and carcinoma, and were not pathognomonic to any male breast lesion. These lectin reactive patterns in the male breast appear to be similar to those reported for the female breast lesions.
Emphysema in the blotchy mouse: A morphometric study
Authors: McCartney Alison C. E. , Fox Bernard , Partridge Terence A. , Macrae Kenneth D. , Tetley Teresa D. , Phillips Gary J. , Guz Abraham
Published: June 2005

Inheritance of the Blotchy allele at the X‐chromosomal Mottled locus of mice results in changes in the lung which resemble emphysema. Previous studies using measurements of mean linear intercept have recognized emphysema in the hemizygous, Blo/Y, male and homozygous, Blo/Blo, female, but not in the heterozygous, Blo/+, female.

The aim of this study was to develop a rapid, accurate method for analysis of emphysema and to establish whether it would identify emphysema in the heterozygote.

Lungs from wild type and outbred Blo mice were inflated with fixative at a pressure of 25 cm and then sectioned and stained Transect lengths across air spaces were measured using computerized image analysis and the results were plotted as histograms. Data were also expressed as cumulative frequencies (ogives) and subjected to statistical analysis by the non‐parametric Kolmogorov—Smirnov test.

Emphysema was shown by significantly increased (P<0.001) transect lengths in the Blo/Blo female and Blo/Y male compared with the wild type controls. The heterozygous Blo/+ mice form an intermediate group significantly different (P<0.001) from the wild and blotchy mice. The sensitivity of the method is illustrated by the fact that the Blo/+ female formed an intermediate group between wild type and the Blo/Y male and Blo/Blo female.
The laser videodisc and computer‐assisted learning
Authors: Mercer Jane , Pringle James H. , Rae Malcolm J. L. , Harkin Patrick J. R. , Lauder Ian
Published: June 2005

A laser videodisc, holding 54 000 still frames per side, can be used to provide visual material of excellent quality for pathology teaching. In a collaborative project between ten pathology departments, the first pathology videodisc has recently been completed and the production of the disc is described. When used as illustrative material for computer‐assisted learning programs, the videodisc offers accurate random access of still frames and allows the overlay of computer‐generated graphics onto the video picture. This can be used to pre‐identify every individual feature of a particular frame, and an example tutorial program is described to show how this may be used to improve the students' understanding of what they see. Details and costs are given for a workstation suitable for this application and potential future developments for this teaching method are discussed. Although objective assessment of the cost‐effectiveness of interactive video in teaching pathology has yet to be undertaken, one suitably designed program can give individual tuition to many students, making this a most efficient use of teaching time.
Basal cell carcinoma xenografts in nude mice: Studies on epithelial differentiation and stromal relationships
Authors: Stamp G. W. H. , Quaba A. , Braithwaite A. , Wright N. A.
Published: June 2005

Thirty‐three basal cell carcinomas (BCC) were transplanted into athymic mice, and foci of tumour were identified in 17 grafts recovered after intervals of 2–5 months. Fifteen of these xenografts contained apparently normal differentiated epithelia, considered to derive from elements within the original tumours. The level of differentiation was very close in original and corresponding xenograft BCC. Morphologically recognizable ‘specialized’ stroma was present in some but not all xenografted BCC, and was also present in some grafts containing only differentiated elements. A monoclonal antibody specific to human type IV collagen showed intact epithelial and also vascular basement membranes within the graft. Surprisingly, mouse cells were found to line these vessels, and the stroma around normal and neoplastic epithelial islands was a mixture of mouse and human cells, with no consistent composition. These observations question the proposed dependence of BCC on its ‘specialized’ stroma.
Correlation between nor sizes and numbers in non‐Hodgkin's lymphomas
Authors: Crocker John , Egan Mark J.
Published: June 2005

A series of 36 cases of non‐Hodgkin's lymphomas (NHL) has been studied by means of the argyrophil (AgNOR) method for nuclear organizer regions (NORs). Morphometric analysis of highly magnified photographic images of light microscope preparations of the AgNORs was performed by means of an interactive image analysis system. It was observed that in the low‐grade specimens (where NORs are less frequent than in those of high‐grade histology), the AgNOR sites were highly significantly (P<0·001) larger than in high‐grade NHL. In the low‐grade lymphomas, the AgNOR maximum diameter (Dmax) ranged from 0·7 to 1·7 μm2 (mean 1·11μm2) and area ranged from 0·48 to 1·99 μm2 (mean 1·11 μm2). In contrast, in the high‐grade specimens, Dmax was from 0·33 to 0·51 μm (mean 0·41μm) and the area ranged from 0·082 to 0·19 μm2 (mean 0·13 μm2). Thus, a well‐defined inverse relationship was observed between AgNOR numbers and their sizes. There was total separation between low‐ and high‐grade values in this series. This light microscope technique offers some advantages over ultrastructural morphometry of interphase NORs (fibrillar centres).
Electron microscopic observations in in situ and microinvasive bronchogenic squamous cell carcinoma
Authors: Imai Tadashi , Saito Yasuki , Nagamoto Noriyoshi , Usuda Katuo , Takahashi Satomi , Sagawa Motoyasu , Sato Masami , Kanma Keiji , Suda Shuichi , Hashimoto Kunihisa , Nakata Tasuku , Tagusagawat Kimihiko , Aso Noboru , Sato Toshio , Sato Hirotoshi
Published: June 2005

Seventeen cases of resected in situ and microinvasive bronchogenic squamous cell carcinoma were studied by light and electron microscopy. No definite secretory differentiation was found in any case. Examination of the tumour cells in the basal layer for electron density of cytoplasm, intercellular spaces, and degree of development of cytoplasmic processes showed a variety of cells ranging from type I, where the cytoplasm was dark, development of cytoplasmic processes was good, and the intercellular spaces were large, to type III, where cytoplasmic processes and intercellular spaces were less well developed and the cells were mostly of clear cell type. The tendency to invasion was greater in type III than type I and there was also more marked cellular atypia, more extensive dissolution of basement membrane, a larger number of mitotic figures per 3000 cells in the basal layer, and greater enlargement of nuclear and cytoplasmic areas. A good rank correlation coefficient was obtained. Small dense‐core granules were observed in some cases. These finding suggest the strong possibility that cell kinetics and cellular morphology are related to the development of squamous cell carcinoma.
Immunohistochemical characterization of osteoclasts and osteoclast‐like cells with monoclonal antibody MB1 on paraffin‐embedded tissues
Authors: Chilosi Marco , Gilioli Eliana , Lestani Maurizio , Menestrina Fabio , Fiore‐Donati Luciano
Published: June 2005

In this study we provide evidence that MB1, a newly developed monoclonal antibody which reacts with B lymphocytes and a proportion of T cells and monocytes, can be successfully used for the direct immunohistochemical identification of osteoclasts on paraffin‐embedded surgical specimens. The antigen(s) recognized by MB1 is present at high density in the cytoplasm of osteoclasts of fetal bone and in the multinucleated cells of human giant cell tumour of bone (osteoclastoma), but is weakly expressed or absent in the giant cells of granulomas. MB1 is thus proposed as a new immunohistochemical marker for osteoclasts on paraffin‐embedded material.
Expressing stereological results ‘PER CM3’, is not enough
Authors: Casley‐Smith J. R.
Published: June 2005

Stereological results are usually expressed as volumes, areas, lengths, or numbers per cm3 of tissue. This has led to wildly incorrect conclusions about tissues when they have been distorted (and effectively ‘diluted’) by oedema. Similar problems occur whenever the reference parameters (volume, area, weight, etc.) differ between one group and another.

In tissues which occur in layers (e.g., the subcutaneous tissue), the mean depth of the tissue superficial to the deep fascia may be used to multiply these estimates, thus giving results expressed per cm2 of deep fascia. Depth measurements incorrect by an angle of 25° to the perpendicular cause only a 10 per cent error. Such results are independent of the effects of oedema.

A similar technique can be used in organs, multiplying the estimates by the volume of the organ, and expressing the results per organ. This presentation can be extended by then dividing these by the animal's body weight and expressing the results per kg. This last is useful for localized disease processes but not for generalized ones, or normal growth.
Antigen preservation in microwave‐irradiated tissues: A comparison with formaldehyde fixation
Authors: Leong Anthony S.‐Y. , Milios Jim , Duncis Craig G.
Published: June 2005

A wide range of immunoreactive antigens commonly investigated in diagnostic pathology were evaluated in tissues subjected to fixation by microwave irradiation in normal saline to 63°C. All of the 23 antigens studied were well preserved and compared with corresponding tissues conventionally fixed by formaldehyde for periods of 16 and 18 h, respectively, immunostaining in microwave‐irradiated tissues was clearly superior, being more intense and also more extensive. Proteolytic digestion was not necessary for irradiated tissues except for the staining of cytokeratins and desmin. It was also possible to stain for Leu‐14 (CD22) and Leu‐1 (CD5), whereas these lymphocyte antigens were lost during formaldehyde fixation. Cytomorphological details were well preserved in the rapidly‐fixed irradiated tissues.
Morphologic changes in the renal glomerulus and the juxtaglomerular apparatus in human preeclampsia
Authors: Hill Prudence A. , Fairley Kenneth F. , Kincaid‐Smith Priscilla , Zimmerman Matthew , Ryan Graeme B.
Published: June 2005

The renal biopsies of ten women with preeclampsia without other underlying renal disease were examined in detail using light and electron microscopy and immunofluorescence. Characteristic preeclamptic glomerular lesions with endocapillary cell swelling, subendothelial and mesangial deposits, and mesangial interposition were detected in each patient. Juxtaglomerular regions were not prominent and were poorly granulated on light microscopy; ultra‐structurally, they showed myoepithelioid cells with sparse renin granulation and considerable heterogeneity of granule size and density in association with relatively meagre granular endoplasmic reticulum and Golgi profiles. These morphologic findings suggest that, in patients with clinical and renal biopsy evidence of preeclampsia, there is no significant stimulation of the renin–angiotensin system.
A monoclonal antibody stains blastemal but not tubular components of Wilms' tumour
Authors: Sarawar S. R. , Schlingemann R. O. , Kelsey A. , Fleming S. , Kumar S.
Published: June 2005

The monoclonal antibody PAL‐E is specific for endothelial cells in a wide variety of normal and tumour tissue. In normal kidney, PAL‐E reacts exclusively with the endothelium of non‐glomerular blood vessels. In Wilms' tumour, binding of PAL‐E was not restricted to the endothelium; staining of blastemal cells was observed in seven out of eight cases examined. Mesenchymal and tubular components, if present in Wilms' tumour, were negative. In contrast, a monoclonal antibody to Factor VIII‐related antigen (RFF‐8‐R‐1) bound only to endothelial cells in these tumours. In fetal kidney, PAL‐E binding showed a wider distribution than in adult kidney and both stromal and glomerular capillaries were stained. Tubules and non‐endothelial stromal cells were negative. These results indicate that the reactivity of the monoclonal antibody, PAL‐E, is not restricted to cells of endothelial origin in all tissues. The implications of these findings for the differentiation of Wilms' tumour are discussed.
Endocrine cell hyperplasia and appendiceal carcinoids
Authors: Cross Simon S. , Hughes Alun D. , Williams Geraint T. , Williams E. Dillwyn
Published: June 2005

As endocrine tumours in a number of organs may arise in a background of hyperplasia, the density of endocrine cells in appendices from ten patients with carcinoid tumours was compared with that in appendices from ten age‐ and sex‐matched control patients. Crypt and lamina propria endocrine cells were quantified separately.

The density of argentaffin endocrine cells in the crypts was significantly higher in appendices with carcinoid tumours when compared with the controls. No difference was found in non‐argentaffin endocrine cells, and no difference was found in either argentaffin or argyrophil endocrine cells in the lamina propria. While it is possible that carcinoid tumours induce an increase in the number of enterochromaffin (EC) cells in the background mucosa, it is considered more likely that EC cell hyperplasia predisposes to the development of carcinoid tumours of the appendix.
A protective effect of sulindac against chemically‐induced primary colonic tumours in mice
Authors: Moorghen M. , Ince P. , Finney Karen J. , Sunter J. P. , Appleton D. R. , Watson A. J.
Published: June 2005

Sulindac, a non‐steroidal anti‐inflammatory drug, has been reported to lead to tumour regression in cases of human polyposis coli. We have investigated the effects of this drug on the growth of 1,2‐dimethylhydrazine (DMH)‐induced mouse colonic tumours. In one experiment, DMH and oral sulindac were administered concurrently to a group of mice for a period of up to 24 weeks, while a control group of animals received DMH only for the same period. Sulindac caused a significant reduction in both the number of mice with colonic tumours and the number of tumours per mouse. In a second experiment, two groups of mice which had already been treated with DMH for 17 weeks received either sulindac or not for 78 days. In this experiment sulindac had no effect. These results demonstrate that sulindac has a protective effect against the chemical induction of colonic tumours in mice, but does not cause the regression of established tumours.
Changes in nerves and neuropeptides in skin from 100 leprosy patients investigated by immunocytochemistry
Authors: Karanth S. S. , Springall D. R. , Lucas S. , Levy D. , Ashby P. , Levene M. M. , Polak J. M.
Published: June 2005

The cutaneous innervation is now known to contain neuropeptides including substance P (SP) and calcitonin generelated peptide (CGRP) in sensory nerves, and vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY), principally in autonomic nerves. Skin biopsies from 100 leprosy patients and equivalent areas from 50 non‐leprosy controls were fixed in p‐benzoquinone solution for immunofluorescence staining, and in Bouin's fluid for classification of leprosy type. Antisera to the neural markers, neurofilaments, and protein gene product 9.5 (PGP 9.5), and to neuropeptides were used. Cutaneous nerves and nerve endings immunoreactive for neuropeptides, neurofilaments, and PGP 9.5 were seen in all non‐leprous control cases. In leprosy, PGP 9.5‐ and neurofilament‐immunoreactive nerve fibres were seen in all 14 cases of the indeterminate (early) type and in the majority (33/43) of lepromatous cases, but in a smaller proportion (15/43) of tuberculoid cases. Neuropeptide immunoreactivity was seen in only 2/14 of the indeterminate leprosy specimens and was completely absent in other types. This early disappearance may be of diagnostic significance. Thus, cutancous sensory and autonomic dysfunctions in leprosy are well reflected by changes in nerve fibres and neuropeptides.
Immunoelectron microscopic studies of immune complex deposits and basement membrane components in IgA nephropathy
Authors: Woodrow David F. , Shore Ian , Moss Jill , Gower Peter , Phillips Malcolm
Published: June 2005

The relationship between the immune complex deposits of mesangial IgA nephropathy and the basement membrane components, type IV collagen and fibronectin, has been investigated by an indirect immunogold technique in four cases of mesangial IgA disease. Using paraformaldehyde‐fixed, Lowicryl K4M resin‐embedded kidney, IgA, IgM and C3 were localized in the mesangial electron‐dense deposits with 10 and 20 nm gold‐labelled secondary antibodies. In the same glomeruli, type IV collagen and fibronectin were rarely present within the electron‐dense deposits, although both were distributed throughout the remainder of the mesangial matrix with the exception of the subepithelial regions. These two components were also present within the glomerular basement membrane and localized mainly on the endothelial aspect. A similar distribution of the basement membrane components was seen in a control kidney processed in the same way.

This technique gives reproducible results and has demonstrated for the first time the relationship between the mesangial immune complex deposits of mesangial IgA nephropathy and the basement membrane components of the matrix in which they are found.
Application of the AgNOR method to cell imprints of lymphoid tissue
Authors: Boldy David A. R. , Crocker John , Ayres Jon G.
Published: June 2005

The argyrophil (AgNOR) staining technique for nucleolar organizer regions was applied to both cell imprint preparations and 3 μm sections of 40 specimens of lymphoid tissue (10 normal tonsil, 10 reactive follicular hyperplasia, and 10 low‐grade and 10 high‐grade non‐Hodgkin's lymphomas). The mean AgNOR count per nucleus was higher for imprint preparations than for 3 μm sections for each group of specimens (P<0.01). The difference was particularly evident for specimens with high AgNOR counts, that is, the high‐grade non‐Hodgkin's lymphomas (pooled mean AgNOR count/cell 16.3 for imprints as opposed to 6.0 for 3 μm sections, P<0.0001). Furthermore, individual AgNOR dots were much more readily discerned in cell imprints than in sections, and this appears to be the method of choice if pathologists wish to at least approach absolute rather than relative AgNOR counts.
Pulmonary endocrine cells in chronic bronchitis and emphysema
Authors: Gosney John R. , Sissons Mark C. J. , Allibone Richard O. , Blakey Andrew F.
Published: June 2005

Pulmonary endocrine cells have been studied according to their immunoreactivity for neuron‐specific enolase, gastrin‐releasing peptide (GRP), calcitonin, leucine‐enkephalin, and serotonin in the lungs of subjects with chronic bronchitis and emphysema. The overall population was significantly greater in comparison with matched controls. The change was most marked in lobes affected by pneumonic consolidation, and did not affect equally the sub‐populations of cells as identified by their content of peptide; the difference was much greater for calcitonin‐containing cells than for those immunoreactive for GRP. This change may be the basis of the hypercalcitoninaemia and hypercalcitoninuria which have been reported in patients with inflammatory pulmonary disease.
The relationship between the distribution of lymphoid cells in the skin and in vitro adhesion to connective tissue
Authors: Jack A. S. , Chapman K. Jane
Published: June 2005

An in vitro assay was used to test whether the patterns of lymphocyte distribution in the mouse skin could be explained by adhesion of lymphoid cells to connective tissue. Using normal skin as a substrate, in vitro adhesion was significantly greater below the panniculus carnosus muscle: when oxazolone sensitized skin was used, binding was seen throughout the skin. This correlated closely with the patterns seen in vivo following injection of lymphocytes into normal skin or sensitization with oxazolone. Adhesion was not affected by divalent cation chelating agents, but was reduced in the presence of some monosaccharides. The property of skin adhesion did not appear to be confined to a small number of cells in the spleen cell preparation. Although only a small proportion of the starting population adhered to the section, transfer of the non‐adherent cells to a fresh skin section produced a similar degree of adhesion.

It is suggested that the variable binding of lymphoid cells by skin connective tissue may be an important factor in determining the retention of cells which have emigrated into the skin from the blood vessels and may explain the distinctive patterns of distribution of lymphocytes in cutaneous inflammatory disorders.
Contact relationships between vascular smooth muscle cells: An in vivo and in vitro study
Authors: Sosa‐Melgarejo J. A. , Berry C. L.
Published: June 2005

Cell/cell contacts in the intact media of the rat thoracic aorta and inferior vena cava, and in cultured smooth muscle cells from these vessels have been quantified in order to determine whether their density and their type can be correlated with the differences in load at these two sites. The type and number of contacts per 100 μm of cell perimeter and per 100 cells were determined with a semi‐automatic image analysis system. In all cases there was a predominance of simple appositions; intermediate junctions, interdigitations, and nexus junctions were less frequently observed. There were more cell contacts of each type in the intact arteries than in the intact veins. In cell cultures, all types of cell contacts were increased but the proportion of load bearing types was reduced.
Type VII collagen antibody LH 7.2 identifies basement membrane characteristics of thin malignant melanomas
Authors: Kirkham Nigel , Price Margaret L. , Gibson Barry , Leigh Irene M. , Coburn Peter , Darley Charles R.
Published: June 2005

A monoclonal antibody (LH 7.2) to the carboxy terminal of type VII collagen has been used in an indirect immunoperoxidase method on frozen sections of biopsies of benign compound and intradermal cellular naevi, dysplastic naevi, and malignant melanomas, to label the epidermal basement membrane. Benign intradermal naevi had an intact membrane with the dermal naevus cell component lying beneath it. Compound naevi showed proliferating junctional nests of naevus cells pushing through the membrane towards the dermis beneath. In contrasts, dysplastic naevi and melanomas showed a progressive displacement of the membrane downwards. Thin lesions were confined above the membrane. With increasing tumour thickness, discontinuities in the membrane were seen and foxi of invasive growth through the line of the membrane were identified. These studies suggest that the good prognosis of thin melanomas is associated with confinement of the tumour within an expanded epidermis above the basement membrane.
Macrophages in bronchoalveolar lavage fluid are not representative of macrophages in granulomas of the lungs of BCG‐infected mice
Authors: Nibbering Peter H. , Van Derheide Annette , Van Furth Ralph
Published: June 2005

To find out whether macrophages obtained by bronchoalveolar lavage (BAL) represent the macrophage population in alveoli, we performed a quantitative study to compare the expression of cell‐surface antigens by macrophages in the lavage fluid as well as in the alveolar spaces of sectioned lung tissue from normal and BCG‐infected mice. The amount of antigen on cells, determined with a quantitative immunocytochemical method, was expressed as the mean specific absorbance per 0–25 μm2 cell‐surface area. In normal mice, BAL and intra‐alveolar macrophages are identical. Macrophages in BAL fluid and intra‐alveolar macrophages, both from BCG‐infected mice, expressed antigen F4/80 and Fc receptor II to about the same extent, but the former showed a significantly higher level of antigen expression as defined by antibodies M1/70, M5/114, 30‐G‐12, and M3/38. In granulomatous lesions, expression of antigens by macrophages, assessed semi‐quantitatively, was considerably less than that by BAL macrophages. Lymphocytes in the BAL fluid resembled those in the granulomas. These findings led to the conclusion that in BCG‐infected mice, the macrophages found in BAL fluid do not resemble those occurring in either the alveoli or the granulomatous lesions of the lungs. On these grounds, the relevance of findings in BAL fluid to lung interstitial lung diseases should be reconsidered.
Induction of soft tissue tumours in F344 rats by subcutaneous, intramuscular, intra‐articular, and retroperitoneal injection of nickel sulphide (Ni3S2)
Authors: Shibata Masashi , Izumi Keisuke , Sano Nobuya , Akagi Akiko , Otsuka Hisashi
Published: June 2005

The carcinogenicity of nickel sulphide (Ni3S2) injected into subcutaneous (s.c.), intramuscular (i.m.), or retroperitoneal intrafat (i.f.) tissue, or the intra‐articular space (i.a.) of male F344 rats was studied. Rats were given a single injection of 0.5 mg of Ni3S2 and were observed for 48 weeks. Malignant soft tissue tumours were induced in 18/19 rats (95 per cent) by s.c. injection, 19/20 rats (95 per cent) by i.m. injection, in 16/19 rats (84 per cent) by i.a. injection, and in 9/20 rats (45 per cent) by i.f. injection of Ni3S2. The i.f. injection of Ni3S2 resulted in a lower tumour incidence and the appearance of tumours 10 weeks later than its injection by other routes. The tumours were examined histologically, ultrastructurally, and immunohistochemically with antibodies against desmin, vimentin, and cytokeratin. The 62 tumours induced by injection of Ni3S2 by different routes were identified as rhabdomyosarcomas (RMS, 35), malignant fibrous histiocytomas (MFH, 18), fibrosarcomas (FS, 5), and unclassified sarcomas (4). All 19 tumours induced by i.m. injection of Ni3S2 were rhabdomyosarcomas; those induced by s.c. or i.f. injection were mainly MFHs. However, a number of RMSs were also found in groups that received i.a., s.c., and i.f. injections; five FSs also developed in these groups. Four sarcomas induced by s.c. and i.a. injections were not classified. No synovial sarcoma developed.
The identification of cells containing JC papovavirus DNA in progressive multifocal leukoencephalopathy by combined in situ hybridization and immunocytochemistry
Authors: Ironside James W. , Lewis Fraser A. , Blythe David , Wakefield Elizabeth A.
Published: June 2005

A double‐labelling technique combining in situ hybridization and immunocytochemistry is described which was used to characterize cells in the central nervous system containing JC virus DNA in formalin‐fixed, paraffin‐embedded tissues from four cases of progressive multifocal leukoencephalopathy. All four cases showed positive nuclear labelling for JC virus in both oligodendrocytes and astrocytes. The latter gave a strongly positive cytoplasmic staining reaction using antibodies to glial fibrillary acidic protein and vimentin. No nuclear labelling of neurones or endothelial cells was noted. The results confirm previous suggestions that glia are the main cells infected by JC virus in this disorder and show that the distribution of viral DNA in the brain is more extensive than suggested by routine microscopy alone. In situ hybridization for JC virus may be useful in confirming the diagnosis of progressive multifocal leukoencephalopathy in both surgical biopsies and post‐mortem brain tissue.
Co‐expression of cytokeratin and vimentin intermediate filament proteins in benign and neoplastic breast epithelium
Authors: Raymond Wendy A. , Leong Anthony S‐Y.
Published: June 2005

This paper identifies another neoplasm of epithelial origin which may express vimentin in addition to cytokeratins, thereby adding to the expanding list of tumours which demonstrate intermediate filaments (IFs) other than those of their reputed cell of origin.

Twenty examples of benign breast disease and 66 carcinomas were examined for vimentin and cytokeratin IFs using an avidin–biotin–peroxidase complex technique. Co‐expression of these IF proteins was found in 35 per cent of cases of benign breast tissue and in 60 per cent of the carcinomas. In 8 (16 per cent) of 50 cases of infiltrating ductal carcinoma, vimentin and cytokeratin immunostaining was observed in more than 60 per cent of the tumour cells. These carcinomas were predominantly of a high histological grade. In benign breast disease and well‐differentiated carcinoma, vimentin was distributed in the basal and perinuclear regions of the cells, with sparing of the apical portions. In those cases in which large numbers of tumour cells expressed vimentin, cytoplasmic staining was diffuse, and often exhibited distinctive perinuclear and subplasmalemmal accentuation.

We propose that a knowledge of the list of carcinomas which may co‐express vimentin and cytokeratin IFs might be helpful in the assessment of undifferentiated tumours and metastatic deposits.
Interleukin‐2 receptor expression in benign and malignant melanocytic skin lesions
Authors: Kernohan N. M. , Sewell H. F.
Published: June 2005

The immunophenotype of the lymphocytic reaction of melanocytic skin lesions (12 cases of cutaneous malignant melanoma (CMM), three of Hutchinson's melanotic freckle (HMF), and eight naevocellular naevi) has been studied using monoclonal antibodies. CMM was associated with the most intense lymphocytic reaction, the lymphocytes being T cells of both CD‐4 T helper/inducer and CD‐8 suppressor/cytotoxic subsets which were present in varying proportions. Although less marked, the lymphocytic reaction to HMF and benign naevi showed similar features. An antibody to the interleukin‐2 receptor (IL‐2R; Tac, CD‐25) was included in the panel and the earlier findings of positively stained cells in association with CMM were confirmed. In addition, the novel finding of these cells in association with HMF and naevocellular naevi is reported. The number of these CD‐25 positive cells was extremely variable but they appeared most prominent in association with CMM. The findings presented here indicate that it is not possible to infer that CD‐25 positive lymphocytes present in the host response to CMM necessarily indicates tumour specific activation of the cells of the host immune system.
Type 4 chain H expression by bile ductules and hepatocytes in cirrhosis
Authors: Okada Yoshio , Colnaghi Maria I. , Tsuji Takao
Published: June 2005

The monoclonal antibody MBrl defines the blood group H determinant with β 1 → 3N‐acetylgalactosamine linkage (Fucα 1 → 2Galβ 1 → 3GalNAc → R) carried by type 3 or 4 backbone. The distribution of the antigen detected by this antibody was studied immunohistochemically in liver tissues. Although bile ducts with a diameter of more than about 100 μm normally expressed the MBrl‐reactive antigen supranuclearly, smaller bile ducts and bile ductules did not express the antigen. In cirrhotic liver, proliferated bile ductules extensively expressed the MBrl‐reactive antigen. In spite of the absence in normal liver cells, the antigen was expressed membranously in some cirrhotic liver cells. Under subcellular fractionation, MBrl reactivity was almost exclusively recovered in the microsomal fraction. By HPTLC immunostaining, the major MBrl‐reactive antigen was shown to be carried by type 4 chain H glycolipid (globo‐H, Fuca 1 → 2Galβ 1 → 3GalNAcβ 1 → 3Galα 1 → 4Galβ 1 → 4Glcβ 1 → 1Cer). MBrl reactive glycoprotein was not found. In conclusion, although type 4 chain H glycolipid is not expressed by normal bile ductules and liver cells, it is actively synthesized and expressed by proliferated bile ductules and some of the liver cells in cirrhosis in the absence of any neoplastic change.