bluuebunny/crossref_metadata_2025 huggingface dataset:
Calgranulin expression in inflammatory dermatoses
Authors: Kelly Susan E. , Jones David B. , Fleming Stewart
Published: June 2005

We have used monoclonal antibodies to study the expression of calgranulins by keratinocytes in inflammatory dermatoses. Calgranulins are intracellular calcium binding proteins which have inflammatory cytokine activity and are composed of at least two different chains, calgranulin A and B. Antibody CF 145 and CF 557 identify calgranulin A and B, respectively. MAC 387 recognizes a molecule probably containing both calgranulins. Keratinocytes in normal skin did not contain these molecules. The keratinocytes in 52 cases of different inflammatory dermatoses showed expression of both calgranulin chains in lesional but not in non‐lesional skin. Keratinocytes in inflammatory dermatoses therefore express an intracellular calcium binding protein which has cytokine activity.
Ploidy as a prognostic indicator in oesophageal squamous carcinoma and its relationship to various histological criteria
Authors: Edwards J. M. , Jones D. J. , Wilkes S. J. L. , Hillier V. F. , Hasleton P. S.
Published: June 2005

One hundred surgically resected squamous cell carcinomas of the oesophagus were studied retrospectively to assess the significance of DNA aneuploidy as determined by flow cytometry using paraffin‐embedded tissue. DNA aneuploidy was not an independent prognostic indicator but was found to be associated with tumour necrosis and host/tumour interface fibrosis. When tumours confined to submucosa or muscle wall were assessed, diploid tumours had a poorer survival rate than DNA aneuploid tumours. Other histological variables studied were tumour differentiation, depth of infiltration, glandular and small cell differentiation, lymphatic and vascular spread and host inflammatory response. These failed to show any significant association with ploidy.
Studies on the mechanisms of mucous cell depletion in experimental colitis
Authors: Kaftan Safa M. , Wright Nicholas A.
Published: June 2005

Mucous cell depletion is an important histological discriminator in favour of ulcerative colitis. The mechanism of this change was investigated in guinea pigs with experimental colitis induced by intrarectal instillation of acetic acid or dinitrochlorobenzene (DNCB) in sensitized animals. Both models showed mucous cell depletion. Increased numbers of mucous cells were flash‐labelled with tritiated thymidine (3HTdR), indicating an increased pool of proliferating (oligo‐) mucous cells; mucous cell production was in fact increased absolutely compared with control animals, and there was a marked increase in the rate of turnover of mucous cells.

The results indicate that in colitis there is (i) increased mucous cell production and (ii) an increased rate of mucous cell turnover due to increased loss of older mucous cells. It is concluded that the disease process in experimental colitis leads to premature discharge of mucin, so that mucous cells are no longer recognizable by light microscopy. This explains the increase in mucin production in ulcerative colitis, which occurs even in the presence of significant mucous cell depletion.
The ultimobranchial gland and congenital thyroid abnormalities in man
Authors: Williams E. D. , Toyn C. E. , Harach H. R.
Published: June 2005

This study was carried out to investigate the fate of the ultimobranchial contribution to the thyroid in man when the thyroid lobe is not fully descended. Thyroid abnormalities were recorded in 41 of 29000 autopsies at the London Hospital—a prevalence of 1·41/1000. The 18 major abnormalities included four cases of lingual thyroid, in two of which cystic structures were noted in the neck in the region of the upper parathyroid. Three further cases of lingual thyroid with upper parathyroid cysts were collected from other sources.

The multilobulated cystic structures were up to 1·5 cm in diameter and showed a variety of histologic features. In four cases there were glandular nodules of up to 1 mm across lying in the intercystic connective tissue. These nodules showed solid areas of irregularly distributed cells that stained positively for calcitonin and calcitonin gene‐related peptide, intermingled with, and sometimes apposed to, follicular structures that showed follicular cells and colloid that stained for thyroglobulin.

This study has provided conclusive evidence that the ultimobranchial body contributes both C cells and follicular cells to the thyroid in man, has documented the prevalence of congenital defects of thyroid development, and has described the human ultimobranchial gland as showing a wide developmental potential which may have implications in the histogenesis of thyroid neoplasia.
Sequential demonstration of antigens and AgNORs in frozen and paraffin sections
Authors: Murray Paul G. , Boldy David A. R. , Crocker John , Ayres Jon G.
Published: June 2005

A technique has been designed which enables the sequential demonstration of nucleolar organizer regions (NORs) and various antigens, in both frozen and paraffin wax‐embedded sections. The NORs were demonstrated by the standard argyrophil (AgNOR) method and the antigens were shown by either immunoperoxidase (PAP) or immunoalkaline phosphatase (alkaline phosphatase–anti‐alkaline phosphatase or avidin–biotin–alkaline phosphatase) methodology. Clear, reproducible results were obtained and AgNOR sites were enumerated with ease. It is suggested that the sequential method may be of great use in the evaluation of AgNOR numbers in neoplasms, where cell populations are heterogeneous. Cell populations may be demarcated with accuracy prior to the counting the AgNORs.
Prognostic significance of activation and differentiation antigen expression in B‐cell non‐Hodgkin's lymphoma
Authors: Salter D. M. , Krajewski A. S. , Sheehan T. , Turner G. , Cuthbert R. J. G. , McLean A.
Published: June 2005

Immunophenotyping shows heterogeneity of expression of activation and differentiation antigens in B‐cell non‐Hodgkin's lymphoma (NHL). To investigate whether antigen expression correlates with clinical behaviour we have studied the clinical presentation and follow‐up of a series of 111 B‐cell lymphomas previously phenotyped for a panel of antigens including CD groups 5, 9, 10, 21, 23, 25, 30, 38, 4F2 antigen, and transferrin receptor. CD antigens 5, 10, and 23 were expressed significantly more often by low grade lymphomas whereas CD38, 4F2 antigen, and transferrin receptor were more often expressed by high grade lymphomas. There was a significant correlation with survival and age, stage at presentation, histological grade, and expression of 4F2 antigen and transferrin receptor but not with the other antigens studied. 4F2 antigen and transferrin receptor may identify a poor prognostic group of cases in low grade lymphoma but we conclude that phenotyping B‐cell NHL for many of the antigens expressed at various stages of B‐cell differentiation and activation does not provide clinically useful information in addition to that obtained from standard histological classifications.
Tenascin distribution in basal cell carcinomas
Authors: Stamp Gordon W. H.
Published: June 2005

The distribution of tenascin, an extracellular matrix protein highly expressed in the stroma around sites of epithelial‐mesenchymal interaction during morphogenesis and in malignant neoplasms, was assessed in cryostat sections of 17 basal cell carcinomas using a polyclonal antibody. There was marked staining of the vascularized stroma around neoplastic islands, usually as an intense, well‐defined band, but being more widespread and diffuse in sclerosing, infiltrative areas. Apparently enhanced staining was seen in tumours showing retraction artefact, which may be related to the observation that tenascin interferes with the cell binding function of fibronectin. Reduced staining was seen in areas showing evidence of tumour regression. Tenascin is an important component of the epithelial‐mesenchymal interactive process and further studies on its distribution in benign and malignant skin tumours are required.
Abnormal alveolar epithelial repair associated with failure of resolution in experimental streptococcal pneumonia
Authors: Rhodes Gregory C. , Lykke Athol W. J. , Tapsall John W. , Smith Lance W.
Published: June 2005

We describe an experimental model in Wistar rats of non‐resolving bronchopneumonia evoked by Streptococcus pneumoniae type 25. In contrast to a model of resolving streptococcal pneumonia that we have previously described, morphological studies reveal that in this model, there is significant early damage to type 1 pneumocytes which progresses to necrosis, leaving isolated areas of denuded alveolar basement membrane. Furthermore, there is accompanying degeneration and necrosis of a proportion of the type 2 pneumocytes, and alveolar epithelial repair by proliferation and differentiation of these cells appears to be retarded. Isolated, hypertrophic, and hyperplastic foci of type 2 pneumocytes persist as the acute inflammatory response subsides, and organization progresses with proliferation and emigration of fibroblasts into the lumina of alveoli and terminal bronchioles. The resultant lesion is morphologically indistinguishable from bronchiolitis obliterans organizing pneumonia. We hypothesize that the abnormal outcome in this model of pneumonia is a consequence of the failure of proliferating type 2 pneumocytes to transform into type 1 pneumocytes and thus maintain the integrity of the alveolar epithelial surface.
Bronchial nerves in chronic obstructive airways disease: A preliminary report
Authors: Edwards Christopher
Published: June 2005

The nerves lying within 300 μm of the basement membrane were studied in the named bronchi of five normal subjects and nine patients with chronic obstructive airways disease (COAD), using S‐100 protein as a marker. Two types of change were found. Firstly, there was patchy proliferation of fine nerve twigs, associated with focal increase in fibroelastic tissue. This proliferation was present to a minor degree in two normal subjects, and to a much greater extent in all patients with COAD. The second type of change was most marked in the main and lobar bronchi of the patients with COAD and cor pulmonale, and consisted of enlargement of nerves to a maximum of 150 μm in diameter. The overall mean nerve diameter in these latter patients was 22·3 μm, significantly greater than the mean diameter, 15·8 μm, in the normal subjects (P<0·001).
Histometric studies on biopsies of tuberculin skin tests showing evidence of ischaemia and necrosis
Authors: Beck J. Swanson , Gibbs J. H. , Potts R. C. , Kardjito T. , Grange J. M. , Jawad Emtithal S. , Spence V. A.
Published: June 2005

In a study of tuberculin skin tests in 216 consecutive untreated pulmonary tuberculosis patients, one showed central necrosis at 48 h: there was no effective blood flow at the centre of this lesion, but the periphery was markedly hyperaemic. Many dermal capillaries and venules contained deposits of fibrin, but none was occluded completely: the surviving cells in the dermal infiltrate were almost all macrophages.

Five patients with strongly positive reactions at 48 h showed slower blood flow at the centre of the reaction than at the periphery (central relative slowing, CRS), possibly indicating central ischaemia short of necrosis: no fibrin deposits were seen in the dermal vessels of these skin test sites. The cellular infiltrate in the dermis was similar in distribution, but more abundant than that seen in uncomplicated positive reactions of comparable clinical size and with blood flow velocity maximal at the centre. At 48 h, lymphocytes were more numerous than macrophages in both groups, CD8 lymphocytes were more abundant in CRS reactions, but CD4 and CD25 (activated) T‐lymphocytes and macrophages had a similar density in both groups. Epidermal CD1 cells were less frequent in CRS reactions than in uncomplicated positive reactions. Although CRS reactions showed more intense inflammation than the uncomplicated controls, none of the histometric measurements correlated with the extent of CRS.

Follow‐up studies showed that CRS reactions reverted to a normal hyperaemic blood flow pattern 5 days after antigen injection. Thus, relative ischaemia may arise temporarily in intense delayed hypersensitivity reactions during the early developing phase when compensatory hyperaemia is unable to match metabolic demand, but the tissue will survive for a few days provided the vessels are not occluded by fibrin.
Localization of endothelin‐like immunoreactivity in airway epithelium of rats and mice
Authors: Rozengurt Nora , Springall David R. , Polak Julia M.
Published: June 2005

We have examined lungs from adult Wistar rats (n = 6) and four different strains of juvenile and adult mice (n = 40) to localize endothelin‐like immunoreactivity. Paraffin sections of lung tissue fixed by distension in Bouin's fluid were stained by the peroxidase–antiperoxidase (PAP) method using 10 different rabbit antisera to endothelin. Immunoreactivity was detected in the majority of epithelial cells of conducting airways from the hilum to the periphery and was similar in rats and all four strains of mice studied. Intense immunostaining was detected in mucous, serous and Clara cells and in occasional alveolar pneumocytes type II. Basal cells and most ciliated cells did not immunostain. From these results it is concluded that endothelin‐like immunoreactivity is present in bronchiolar epithelial cells in vivo in rats and mice.
Morphometric evaluation of intracytoplasmic lipid in normal and pathological parathyroid glands
Authors: Cinti Saverio , Sbarbati Andrea , Zancanaro Carlo , Morroni Manrico , Franceschini Fiorella , Carboni Vittorio , Cascio Vincenzo Lo
Published: June 2005

The chief morphological criterion for classifying parathyroid glands as “normal”, ‘suppressed’, or ‘activated’ is the lipid content of the cytoplasm. In particular, cytoplasm lipid deposit is scanty in the active parathyroid cell, according to many authors. In this paper we present the results of a morphometrical study of ten normal parathyroid glands from patients undergoing thyroidectomy, 20 enlarged ‘adenomatous’ glands from patients with primary hyperparathyroidism, and 20 glands of normal size from the same hyperparathyroid patients. We aimed at assessing the content of intracytoplasmic lipid of secretory cells in all these conditions. The results show that secretory cells of adenomatous glands have less lipid than those from normal glands; however, there was considerable overlapping of the data in the two groups. The mean lipid content of cells in glands of normal size taken from hyperparathyroid patients was not significantly different from the mean value of normal cells, even when ultrastructural evidence of activation was present in the former. These data suggest that caution has to be exercised in assessing the functional status of parathyroid glands on the basis of lipid content of secretory cells, mainly when differentiating between adenoma and hyperplasia.
Expression of the VLA family of integrins in human intestine
Authors: Choy M.‐Y. , Richman P. I. , Horton M. A. , Macdonald T. T.
Published: June 2005

The distribution of cells expressing the integrins VLA‐1 to 6 in human intestine was examined by alkaline phosphatase immunohistochemistry using monoclonal antibodies specific for the individual α‐chains of the VLA heterodimer. VLA‐2,3, and 6 were expressed on all epithelial cells in the small and large bowel. VLA‐1 was expressed on crypt cells in the small and large bowel, but was only weakly expressed or was absent on villus epithelial cells in the small bowel and colonic surface epithelial cells. All epithelia were negative for VLA‐4 and VLA‐5. Intraepithelial lymphocytes were VLA‐l+ and VLA‐4+.

VLA‐1, 3, and 5 were expressed uniformly by muscularis propria, muscularis mucosae, pericrypt cells, and smooth muscle fibres within the villi. By contrast, VLA‐2 and 4 were present only in pericrypt cells and fibres within the villi; they were absent from the muscularis mucosae. VLA‐1, 3, 5, and 6 were expressed by endothelium.

Staining of muscle fibres and endothelium in the lamina propria made it difficult to determine the extent of VLA expression on lamina propria lymphocytes. However, VLA‐ 1 + cells with lymphoid morphology were only rarely seen. All mononuclear cells in the lamina propria were VLA‐4 +.
Microdissection: A novel method for the study of intracellular inclusion bodies
Authors: Martin J. E. , Swash M. , Mather K. , Garofalo O. , Dale G. E. , Leigh P. N. , Anderton B. H.
Published: June 2005

The purification of many intracellular and extracellular inclusions is often difficult to achieve due to the low concentration of the abnormalities in the tissue under study, or due to the degradation of components during extraction. We describe the use of microdissection for the isolation of neurons and intraneuronal inclusion bodies. The resulting suspension may be used for biochemical, immunological or ultraslructural studies. The technique is applicable to the study of a wide range of cellular abnormalities.
Histochemical detection of the messenger RNAs coding for calcitonin and calcitonin gene‐related peptide in medullary thyroid carcinomas with radioactive and biotinylated oligonucleotide probes
Authors: Mougin C. , Guitteny A. F. , Fouque B. , Viennet G. , Teoule R. , Bloch B.
Published: June 2005

Ths present study has been undertaken to investigate the efficiency of biotinylated synthetic oligonucleotide probes in detection by in situ hybridization of the mRNAs coding for calcitonin (CT) or calcitonin gene‐related peptide (CGRP) in human medullary thyroid carcinomas (MTCs). Tissue sections fixed with formaldehyde were hybridized with 45‐base long oligonucleotides, specific for CT or CGRP mRNA. Recombinant DNA probe or synthetic oligonucleotides radioactively labelled with 32P or 35S were used as controls to detect by autoradiography the corresponding mRNAs in the tumour cells. Oligonucleotide probes labelled by fixation of one biotin molecule at their 5′‐end, or by incorporation of a tail of biotin‐11‐dUTP at their 3′ ‐end, were used and were revealed by incubation with streptavidinalkaline phosphatase associated with the corresponding substrate. Each biotinylated probe stained exclusively the cytoplasm of the tumour cells, the CT probe giving a much higher level of staining than the CGRP probe. The same cells were found to contain CT and CGRP mRNAs. Controls performed with either radioactive or biotinylated probes confirmed the specificity of the staining. These results demonstrate that biotinylated synthetic oligonucleotides can be used as efficient tools to investigate gene expression in tissue sections, thus avoiding the various inconveniences connected with the use of radioactive probes, especially bio‐hazards, the use of autoradiography, the limited histological resolution, and the delay in obtaining results.
Adenosine deaminase complexing protein (ADCP) expression and metastatic potential in prostatic adenocarcinomas
Authors: Dinjens Winand N. M. , Kate Joop Ten , Kirch Jan A. J. M. , Tanke Hans J. , van der Linden Edith P. M. , van den Ingh Harry F. G. M. , van Steenbrugge Gert Jan , Khan P. Meera , Bosman Fred T.
Published: June 2005

The expression of the adenosine deaminase complexing protein (ADCP) was Investigated by immunohistochemistry in the normal and hyperplastic human prostate, in 30 prostatic adenocarcinomas, and in seven human prostatic adenocarcinoma cell lines grown as xenografts in athymic nude mice. In the normal and hyperplastic prostate, ADCP was localized exclusively in the apical membrane and the apical cytoplasm of the glandular epithelial cells. In prostatic adenocarcinomas, four distinct ADCP expression patterns were observed: diffuse cytoplasmic, membranous, both cytoplasmic and membranous, and no ADCP expression. The expression patterns were compared with the presence of metastases. We found an inverse correlation between membranous ADCP immunoreactivity and metastatic propensity. Exclusively membranous ADCP immunoreactivity occurred only in non‐metastatic tumours. In contrast, the metastatic tumours showed no or diffuse cytoplasmic ADCP immunoreactivity. This suggests that immunohistochemical detection of ADCP might predict the biological behaviour of prostatic cancer. However, the occurrence of membranous ADCP immunoreactivity in the xenograft of a cell line (PC‐EW), derived from a prostatic carcinoma metastasis, indicates that not only the tendency to metastasize modulates ADCP expression.
Identification of primary tumour site by immunolocalization of progastricsin in metastatic adenocarcinoma
Authors: Reid William A. , Branch Timothy , Gorman Christopher , Kay John
Published: June 2005

The aspartic proteinase zymogen, progastricsin, which occurs in normal gastroduodenal mucosa and prostate has been localized by the immunogold‐silver method in formalin‐fixed, paraffin‐embedded sections of metastatic adenocarinoma in lymph nodes and liver, the primary site being known in each case. Progastricsin was demonstrated in 16 of 84 lymph node metastases, including 7 of 17 from stomach, 2 of 2 from prostate, and 7 of 65 from other sites Progastricsin was also found in 19 of 98 hepatic metastases, including 8 of 22 from stomach, 6 of 24 from pancreas, and 5 of 52 from other sites. The presence of progastricsin in a metastasis correlated well with a primary tumour in the stomach or prostate or, less significantly, pancreas. Immunolocalization of progastricsin in a histological section of metastatic adenocarcinoma may help to locate the primary site.
A study of the properties of a low‐grade mucosal B‐cell lymphoma using a monoclonal antibody specific for the tumour immunoglobulin
Authors: Spencer J. O. , Diss Tim C. , Isaacson Peter G.
Published: June 2005

Primary low‐grade B‐cel1 lymphomas of mucosa‐associated lymphoid tissue (MALT) are tumours with distinctive clinico‐pathological characteristics, two of which are studied in this paper, namely the tendency of the tumours to remain localized and the morphologic and phenotypic resemblance of the malignant cells to splenic marginal zone B cells. We have made a detailed study of a small intestinal lymphoma and a gastric lymphoma, which together with the spleen were resected from the same patient. Using a monoclonal antibody (7G3) raised against a unique determinant on the small intestinal tumour, we were able to detect disseminated small intestinal tumour cells in the stomach and spleen. The tumour in the stomach was genetically related, but non‐identical to that in the small intestine, and was not recognized by 7G3. Lymphocytes expressing the marker of the small intestinal tumour (7G3) were present in lymphoid nodules in the stomach, and 7G3+ plasma cells were present beneath the gastric epithelium. In the speen, cells expressing 7G3 were present in the marginal zone and plasma cells expressing the same marker were present in the red pulp. These findings suggest that low‐grade MALT lymphomas may migrate beyond the primary tumour site, but that tumour cells distant to the primary site may differentiate into mature, non‐dividing plasma cells. The localization of small intestinal tumour cells in the splenic marginal zones reinforces the suggestion of lineage homology between these populations of cells.
Morphometric correlates of renal excretory function
Authors: Howie A. J. , Gunson B. K. , Sparke J.
Published: June 2005

There is often thought to be little or no correlation between renal excretory function and histological changes in the kidney, especially in acute renal failure and in the kidney examined post‐mortem. We studied the relationship between renal function and structure in 28 patients at necropsy and in 41 patients who had had a renal biopsy. A point‐counting method was used on kidney stained by an immunoperoxidase method using an antiserum to proximal tubule brush border an antiserum to Tamm–Horsfall protein, which is a marker of thick limbs of the loop of Henle: and a monoclonal antibody to epithelial membrane antigen, normally a marker of all parts of the tubule except proximal tubule. There was a correlation between the reciprocal of plasma creatinine concentration, which is a measure of renal, function, and the ratio of brush border positive tubules to negative tubules. There was also a less strong correlation between renal function and ratios of Tamm–Horsfall positive tubules to negative tubules and of cast‐containing tubules to others. There was no correlation between renal function and the ratio of tubules expressing epithelial membrane antigen to those not expressing it. The method of point‐counting tubules stained by the brush border antiserum was a useful, practical way of correlating renal function and structure which could be used even on post‐mortem kidney.
Assessment of glomerular size in renal biopsies including minimal change nephropathy and single kidneys
Authors: Newbold K. M. , Howie A. J. , Koram A. , Adu D. , Michael J.
Published: June 2005

A method of assessing glomerular size on sections of post‐mortem kidney was adapted for use on needle biopsies of kidney. A semi‐automatic image analyser was used to measure the cross‐sectional area of the outline of Bowman's capsule on all glomeruli in renal biopsies. The mean of approximately the largest 25 per cent of areas was calculated. The method was used to compare glomeruli in 13 control patients without obvious structural abnormalities with those in 10 patients with a single kidney, 22 with minimal change nephropathy, and 20 with membranous nephropathy. Patients were at least 14 years old. Glomeruli in minimal change nephropathy were significantly smaller than those in all other groups. Glomeruli in single kidneys were significantly larger than those in all other groups. Glomeruli in membranous nephropathy were the same size as controls. Any differences between groups could not be explained by differences in body build. It is possible that in adults glomeruli in minimal change nephropathy are abnormally small. The method of assessing glomerular size can be used on renal biopsies as well as on sections of whole kidney.
The behaviour of human oral squamous cell carcinoma in cell culture
Authors: Prime Stephen S. , Nixon Sally V. R. , Crane Isabel J. , Stone Andrea , Matthews John B. , Maitland Norman J. , Remnant Lucy , Powell Susan K. , Game Stephen M. , Scully Crispian
Published: June 2005

This study examined the initial behaviour of 48 human oral squamous cell carcinomas (SCC) in cell culture. The early outcome of these cultures (contamination, absence of cell growth, epithelial cell senescence/fibroblast overgrowth, extended keratinocyte growth) did not reflect the clinical characteristics of the tumours of origin. Four new human oral SCC cell lines were characterized more extensively. Each cell line was immortal, 3T3‐independent, and expressed low degrees of anchorage independence (CFE < 4 percent). Two of the four cell lines were tumorigenic in athymic mice. All of the cell lines expressed keratin intermediate filaments and two showed weak co‐expression of vimentin. A wide range of keratins were expressed by the tumour xenografts; cornified keratins(Kl, K10) were only expressed in the absence of K19 and vimentin, and vice versa. The nuclear: cytoplasmic ratio and the degree of serum independence correlated with each other and with the STNMP clinical grading of the tumours of origin.
Oestrogen receptor staining of paraffin‐embedded breast carcinomas following short fixation in formalin: A comparison with cytosolic and frozen section receptor analyses
Authors: Raymond Wendy A. , Leong Anthony S.‐Y.
Published: June 2005

This paper describes an improved immunohistochemical method for demonstrating oestrogen receptor (OR) protein in paraffin‐embedded sections of tissue fixed for 1.5h in formalin. Thirty‐two cases of infiltrating ductal breast carcinoma were stained with a monoclonal anti‐OR antibody (H222), using a standard streptavidin–biotin method, following pretreatment with pronase. OR counts in paraffin sections were compared with those of frozen sections and with cytosolic values detcrmined by a dextran‐coated charcoal method. Twenty‐seven of the carcinomas were OR‐positive in paraffin sections. There was concordance between the paraffin section and the frozen section‐determined receptor status in 30 cases (94 per cent) and a strong correlation was observed (r = 0.76: P< 0.0001). Similarly, OR counts in paraffin sections correlated with cytosolic OR values (r = 0‐60; P < 0.001) and there was concordance in 97 per cent of cases. The percentage of positively‐stained tumour cells in paraffin sections ranged from 0 to 94 percent with staining intensities comparable to those seen in frozen sections. Staining of paraffin sections identified more OR‐positive tumours than either frozen section staining or cylosolic assay. This study validates immunohistochemical OR analysis in formalin‐fixed, paraffin‐embedded breast carcinomas using a commercial ami‐OR antibody.
Time‐related decrease of substance P and CGRP in central and peripheral projections of sensory neurones in Mycobacterium leprae infected nude mice: A model for lepromatous leprosy in man
Authors: Karanth S. S. , Springall D. R. , Kar S. , Gibson S. J. , Royston J. P. , Banerjee D. K. , Polak J. M.
Published: June 2005

We have previously shown the depletion of cutaneous calcitonin gene‐related peptide (CGRP)‐ and substance P‐comaining nerves in human leprosy. The aims of this study were to investigate the temporal effects of leprosy on nerves in skin and spinal cord. Tissues were taken from nude mice, 6 and 12 months after inoculation of Mycobacterium leprae into the hind footpads, and from age‐matched controls. Sections were immunostained with antisera to substance P or CGRP. After 6 months of infection, substance P‐ and CGRP‐immunoreactive nerves were reduced in skin from all body areas; by 12 months, the reduction was substantially greater. In the spinal cord, sensory fibres immunoreactive for substance P had decreased compared with controls at 6 and 12 months [by 60 per cent (0.022 mm2) and 80 per cent (0.048 mm2), respectively, P<0.001], as with CGRP [30 per cent (0.018 mm2) (P<0.02) and 40 percent (0.028 mm2) (P<0.01), respectively]. CGRP immunoreactivity was completely absent in motor neurones after 12 months of infection. Loss of CGRP‐ and substance P‐immunoreactive fibres in skin and spinal cord, and CGRP in motor neurones is in accord with impaired pain sensation and muscle weakness in leprosy.
NCL‐CB11, a new monoclonal antibody recognizing the internal domain of the c‐erbB‐2 oncogene protein effective for use on formalin‐fixed, paraffin‐embedded tissue
Authors: Corbett Ian P. , Henry James A. , Angus Brian , Watchorn Caroline J. , Wilkinson Linda , Hennessy Colm , Gullick William J. , Tuzi Nadia L. , May Felicity E. B. , Westley Bruce R. , Horne Charles H. W.
Published: June 2005

The c‐erbB‐2 proto‐oncogene encodes a 190 k Mr protein representing a putative growth factor receptor with considerable homology to the EGF receptor. Gene amplification and overexpression of the oncogene protein have been demonstrated in a variety of tumours including breast cancer, where it is associated with a poor prognosis.

In this study we have produced and characterized a mouse monoclonal antibody, designated NCL‐CB11, to the c‐erbB‐2 protein. NCL‐CB11 was generated to a synthetic peptide sequence corresponding to a site of predicted antigenicity near the C‐terminus of the internal domain of the protein. NCL‐CB11 produces intense membrane‐associated immunohistochemical staining in a proportion of human cancer cells. The specificity of the antibody is supported by Western blotting and immunoprecipitation studies. Reactivity with an internal site of the protein is confirmed by the necessity of cell permeabilization for reactivity in fluorescence‐activated cell sorter(FACS) analysis. A high degree of correlation between immunohistochemical staining using NCL‐CB11, and c‐erbB‐2 gene amplification has been observed.

NCL‐CB11 should prove to be a valuable reagent for investigations into the pathological significance of c‐erbB‐2 protein expression.
Immunohistochemical localization of parathyroid hormone‐related protein in parathyroid adenoma and hyperplasia
Authors: Danks Janine A. , Ebeling Peter R. , Hayman John A. , Diefenbach‐jagger Hannelore , Collier Fiona Mcl , Grill Vivian , Southby Justine , Moseley Jane M. , Chou S. T. , Martin T. John
Published: June 2005

Parathyroid hormone‐related protein (PTHrP) is invoked as the cause of humoral hypercalcaemia of malignancy (HHM); it is contained in the keratinocyte layer of normal skin; and there is evidence that is is produced by fetal parathyroids. Antibodies against synthetic PTHrP peptides have been raised in rabbits and sheep. This immunohisto‐chemical study has found that primary parathyroid adenomata and hyperplastic glands from patients with chronic renal failure stain positively with antisera against PTHrP(1–34) and PTHrP(50–69). Primary hyperplastic glands are negative. No staining with anti‐PTHrP(106–141) antiserum could be detected immunohistochemically in any of the parathyroid adenomata or hyperplasia.
S100 protein, neurone specific enolase, and nuclear DNA content in Spitz naevus
Authors: Rode J. , Williams R. A. , Jarvis L. R. , Dhillon A. P. , Jamal O.
Published: June 2005

The differentiation between Spitz naevus and melanoma is at times difficult. The present study was undertaken to define means to positively identify such melanocytic tumours of doubtful malignancy. Immunohistochemical staining intensity for S100 protein and neurone specific enolase (NSE) was measured in sections of 35 Spitz naevi using a microcomputer image analysis system. The data were compared with results previously obtained from 19 cases of malignant melanoma and 16 benign compound naevi. Disaggregated cells from paraffin‐embedded material were stained by the Feulgen technique for DNA estimation. The nuclear DNA content distributions were measured using the same image analysis system. Compared with the malignant cases, the Spitz naevi showed significantly lower staining intensity for both S100 protein (P<0.0001) and NSE (P<0.0001). When compared with the benign compound naevi, the staining intensity was significantly lower for S100 protein (P=0.003). The nuclear DNA distribution in Spitz naevi proved to be a normal diploid pattern in 31 cases. Four cases showed a small proportion of hyperdiploid nuclei. The results show that Spitz naevi can be significantly distinguished from malignant melanoma by staining intensity for S100 protein and NSE. A normal diploid DNA content distribution appears to be typical for Spitz naevi. Spitz and benign compound naevi show dissimilar expression of S100 protein which may indicate different patterns of differentiation in these two types of lesion. The image analysis equipment used in this study is accurate, simple to use, produces results rapidly, and is economic. Therefore, it is clinically practicable.
Immunohistochemical demonstration of liver fatty acid‐binding protein in human hepatocellular malignancies
Authors: Suzuki Toshimitsu , Watanabe Kazuo , Ono Teruo
Published: June 2005

Twenty‐three hepatoblastomas of childhood, sixty‐two adult hepatocellular carcinomas, and two hepatic sarcomas were examined immunohistochemically with the use of a polyclonal antibody against rat liver fatty acid‐binding protein (L‐FABP), which cross‐reacts to human L‐FABP. All the hepatoblastomas and half of the hepatic cell carcinomas contained L‐FABP immunoreactive tumour cells, whereas two hepatic sarcomas were negative. The overall frequency of immunostained tumour cells was 43.5 per cent in hepatoblastomas and 18.6 per cent in hepatocellular carcinomas, respectively. Histologically well‐differentiated areas contained more numerous immunopositive cells than undifferentiated or immature ones. These results indicate that L‐FABP immunoreactivity is a new candidate for a tumour cell marker in hepatic cell malignancies, although its biological role has not been elucidated.
Ultrastructure of the jejunal mucosa in human immunodeficiency virus infection
Authors: Mathan Minnie M. , Griffin G. E. , Miller A. , Batman P. , Forster S. , Pinching A. , Harris W.
Published: June 2005

The ultrastructural changes in the jejunal muscosa of 11 male patients, three with clinical AIDS, five with AIDS related complex‐progressive generalized lymphadenopathy (ARC‐PGL), and three who were only HIV antibody positive, were studied. In the enterocytes, major abnormalities were proliferation of smooth endoplasmic reticulum mitochondrial changes, vacuolization of cells, and fat hold up. In the lamina propria, degeneration of enteric nerve axons and smooth muscle were seen. Microvasculature showed both endothelial cell degeneration and hyperplasia. The presence of tubuloreticular inclusions in endothelial cells paralleled the stage of the disease. Since none of the 11 patients had any opportunistic infection, these changes are likely to be the effect of HIV infection.
The c‐erbB‐2 proto‐oncogene in human pancreatic cancer
Authors: Hall P. A. , Hughes C. M. , Staddon S. L. , Richman P. I. , Gullick W. J. , Lemoine N. R.
Published: June 2005

The c‐erbB‐2 oncogene encodes a 190 kD transmembrane growth factor receptor which is closely related to the EGF receptor and has been found to be amplified and overexpressed in a number of human adenocarcinomas, particularly of the breast. We have analysed, by immunocytochemistry using the 21N antibody, expression of c‐erbB‐2 in a retrospective series of pancreatic adenocarcinoma, chronic pancreatitis, and examples of histologically normal pancreas. In three cases (21 per cent) of chronic pancreatitis, there were focal areas of cytoplasmic immunoreactivity in regenerating epithelium. In 15 cases (17 per cent) of pancreatic adenocarcinoma, cytoplasmic immunoreactivity was seen, while in two cases (2 per cent) strong membrane staining of tumour cells was seen which could be blocked by peptide controls. c‐erbB‐2 immunoreactivity was also demonstrated using a second antibody, 20N, which recognizes another peptide sequence of the c‐erbB‐2 protein. There was no relationship between immunoreactivity and histological subtype or grade, but there was absolute concordance between staining in primary and metastatic deposits. Since the rat homologue (neu) of the c‐erbB‐2 oncogene may be activated by a specific point mutation in its transmembrane region, we have analysed 23 cases from this series for mutations by polymerase chain reaction amplification and sequence‐specific oligonucleotide hybridization. We were unable to identify activity mutations in this series. These data suggest that there is abnormal expression of c‐erbB‐2 oncogene in nearly 20 per cent of cases although mutational activation of this gene is not seen in human pancreatic adenocarcinoma.
Morphometric definition and grading of gastric intestinal metaplasia
Authors: Tosi P. , Filipe M. I. , Baak J. P. A. , Luzi P. , Santopietro R. , Miracco C. , Sforza V. , Megha T.
Published: June 2005

Type I and type III intestinal metaplasia in gastric mucosa have been examined using morphometric methods. Tissue (volume per cent gland, lumen, epithelium, goblet cell vacuoles) and nuclear parameters (area, with related standard deviation, and form factors) were used as indicators of gland crowding, nuclear‐cytoplasmic ratio, nuclear atypia, and pleomorphism. In type III intestinal metaplasia, there is significantly (i) greater nuclear pleomorphism, (ii) a higher nuclear‐cytoplasmic ratio, and (iii) smaller and less numerous goblet cell vacuoles in both the upper and the lower parts of the crypts. These two parameters have significantly higher values in the lower than in the upper part of individual crypts. No cell population with large pleomorphic nuclei characterized type III metaplasia, though there was more variation in nuclear size.
Myopathy of internal anal sphincter with polyglucosan inclusions
Authors: Martin J. E. , Swash M. , Kamm M. A. , Mather K. , Cox E. L. , Gray A.
Published: June 2005

In two members of an affected family with a hereditary syndrome of proctalgia fugax and constipation, a hypertro‐phied internal anal sphincter was found with histological features suggesting a myopathy of this muscle. In these two patients, and in an unrelated patient with a similar clinical syndrome, smooth muscle fibres of the internal anal sphincter showed numerous vacuoles, many of which contained ovoid inclusion bodies. The structural features and histochemical reactions of the inclusion bodies were consistent with a polyglucosan composition. Histological examination of the internal anal sphincter may reveal smooth muscle abnormalities in functional bowel disorders.
The expression of Lewisa and Lewisb antigens reflects changes in fucosylation between normal and neoplastic cervical squamous epithelium
Authors: Sanders D. S. A. , Milne D. M. , Kerr M. A.
Published: June 2005

Antibodies against the carbohydrate antigens Lewisa (Lea) and Lewisb (Leb) allow further investigation into the changes in fucosylation of the glycocalyx occurring during the normal and neoplastic development of cervical squamous epithelium. Lea and Leb are expressed on a broad zone of suprabasal cells in normal cervical squamous mucosa often independent of individual Lewis gene and secretor status. A proportion of Lea is expressed in sialylated form. In cervical intraepithelial neoplasia, the progressive dedifferentiation of the squamous mucosa is mirrored by loss of both Lea and Leb expression. In invasive squamous carcinomas, Lea and Leb expression is seen only on cells in areas of differentiation.

The expression of Lea and Leb in normal and neoplastic cervical squamous epithelium resembles that of the Lex antigen described by us previously. The structural similarity betweenthese antigens is highlighted and evidence for a common functional role in maintaining the integrity of squamous mucosae is discussed.
Role of sinusoidal pressure in the development of vacuolation in liver cells
Authors: Shibayama Yuro , Hashimoto Kazuaki , Nakata Katsuji
Published: June 2005

Vacuolation of liver cells, which is often seen in patients with right‐sided heart failure, is sometimes confused with fatty change, but the contents are components of blood. This study was undertaken using an isolated rat liver perfusion model to clarify the pathogenesis of vacuolation of liver cells. It has been demonstrated that (1) hypoxia alone cannot cause vacuolation; (2) elevation of the sinusoidal pressure leads to vacuoles in liver cells, irrespective of the oxygen content of the perfusate; and (3) the number and size of vacuoles are proportional to the height of the sinusoidal pressure, but not to the oxygen content of the perfusate. The reason why vacuolation generally appears in the pericentral area in patients with right‐sided heart failure may be that the sinusoidal pressure in this area rises in parallel with the inferior vena cava pressure.
Analysis of the position of segmental lesions in glomeruliin vasculitic‐type glomerulonephritis and other disorders
Authors: Newbold K. M. , Howie A. J.
Published: June 2005

A method was developed of plotting the position of segmetal lesions in glomeruli on histological sections of kidney. Using a Leitz Imagan semi‐automatic image analyser, the outline of lesions was traced, as was the outline of Bowman's capsule. The centre of gravity of a lesion, computed by the image analyser, was plotted with reference to the line through the hilum and the centre of gravity of the glomerulus, by taking its angle to that line and its proportional distance between that line and Bowman's capsule. Points representing all lesions were transferred onto a circle graphically representing a glomerulus. Lesions in 11 renal biopsies with the glomerular tip lesion were clustered at the tubular origin. Lesions four necropsy kidneys from patients with one kidney were clustered at both the vascular pole and the tubular origin. Lesions in 13 renal biopsies with acute vasculitic‐type glomerulonephritis were shown to be randomly scattered by nearest‐neighbour analysis, after allowance had been made for an edge effect due to the method of plotting lesions and for an area where the arterioles passed through Bowman's capsule. Scientific analysis of the position of segmental lesions is possible and has confirmed previous suggestions that there are at least three general sites in which these lesions can be distributed in glomeruli: at the tip, at the vascular pole, and randomly.
Reduction of major histocompatibility complex class I antigens on invasive and high‐grade transitional cell carcinoma
Authors: Tomita Yoshihiko , Matsumoto Yoh , Nishiyama Tsutomu , Fujiwara Michio
Published: June 2005

We examined immunohistologically the expression of major histocompatibility complex (MHC) class I and II antigens, which play important roles in immune reactions, on transitional cell carcinoma (TCC). When stained with monoclonal antibody W6/32 against class I antigens, reduced staining was observed in 34 of 46 TCCs and was virtually absent in 15 of these. The cases showing reduced staining were much more frequent (29 of 34) in high‐ to moderategrade than in low‐grade TCC. Furthermore, class I antigens were reduced in 18 of 19 invasive TCCs, but in 16 of 27 superficial TCCs. Thus, the reduction of class I antigens was correlated significantly with a decreased degree of tumour cell differentiation and the presence of invasion. Class II antigens on TCC showed variable expression and were not related to tumour grade or stage.
Changes in the expression of major histocompatibility complex class II antigens in liver allograft rejection
Authors: Hubscher S. G. , Adams D. H. , Elias E.
Published: June 2005

The expression of major histocompatibility complex (MHC) class II antigens was studied in human liver grafts by immunohistochemical staining with monoclonal antibodies to HLA‐DR, HLA‐DP, and HLA‐DQ antigens. Staining was carried out on frozen sections from 13 normal livers, used as controls, and 85 post‐transplant specimens in six histological categories: acute rejection (n= 25); chronic rejection (n= 21); massive haemorrhagic necrosis (n= 2); resolving acute rejection (n=10); non‐rejection complications—pure cholestasis, ischaemia, biliary obstruction (n= 23); and stable graft function > 1 year post‐transplantation (n= 4). Staining was graded semi‐quantitatively on a scale of 0‐3+ in bile ducts, hepatocytes, and vascular endothelium. Expression of class II antigens was increased in bile ducts, hepatocytes, and vascular endothelium in all of the post‐transplant groups compared with controls. The degree of expression of HLA‐DR and HLA‐DP in bile ducts and vascular endothelium was significantly greater in cases of rejection than in the non‐rejection groups. These observations suggest that increased class II antigen expression may be important in the pathogenesis of immune‐mediated bile duct and endothelial damage in liver allografts. Immunohisto‐chemical staining for class II antigens in post‐transplant biopsies may also be useful as an adjunct to conventional histological diagnosis.