bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional and biosynthetic changes in endothelial cells of vessels in chronically inflamed tissues: Evidence for endothelial control of lymphocyte entry into diseased tissues
Authors: Freemont Anthony J.
Published: June 2005

In vitro lymphocyte adhesion to, and selective radiosulphate uptake by, endothelial cells has been demonstrated in chronically inflamed tissues of patients with peptic ulceration, rheumatoid disease, pilonidal sinus, autoimmune thyroiditis, polymyositis, primary biliary cirrhosis, and pyelonephritis. These characteristics have been described previously in endothelial cells functionally specialized for promoting lymphocyte traffic from blood to lymph node parenchyma. It is suggested that these observations indicate that some vessels in inflamed tissues may be, at least in part, responsible for the selective accumulation of lymphocytes within the tissue. Manipulating the development of this type of vessel may offer a novel way of influencing the progress of inflammatory disorders.
Giant cell carcinoma of the lung—immunohistochemical and ultrastructural evidence of dedifferentiation
Authors: Addis Bruce J. , Dewar Ann , Thurlow Nicola P.
Published: June 2005

Ten examples of giant cell carcinoma of the lung were examined by immunohistochemistry for expression of keratin and vimentin intermediate filaments and for epithelial membrane antigen (EM A). Six cases were also examined electron microscopically. Keratin expression and, to a lesser extent, EMA immunoreactivity were reduced in comparison with better differentiated forms of lung carcinoma. Vimentin expression was increased, often taking the form of strong paranuclear staining. This may correspond to dense paranuclear aggregates of intermediate filaments seen ultrastructurally. Desmosomes were absent or sparse in most tumours. We propose that giant cell carcinoma arises by a process of dedifferentiation. The resulting loss of epithelial features gives rise to neoplastic cells which have features in common with some forms of sarcoma.
Pulmonary endothelial and alveolar epithelial lesions induced by O,O,S‐trimethyl phosphorothioate in rats
Authors: Durham Stephen K. , Mezza Lawrence E. , Imamura Toshiko
Published: June 2005

The morphogenesis of pulmonary injury induced by an impurity present in a commercially important organophosphorus insecticide, O, O, S‐trimethyl phosphorothioate (OOS‐TMP), was studied by combined light and transmission electron microscopy. Weanling female WAG/Rij rats received OOS‐TMP dissolved in corn oil by gavage and were studied at intervals from 6 to 168 h after treatment. Sequestration of neutrophils was initially observed at 12 h after treatment and was accompanied by interstitial oedema. Plasmalemma alterations in endothelium lining capillaries and small arteries and veins were observed from 12 to 120 h after treatment and were accompanied by endothelial cell detachment and separation from the basal lamina. Abundant aggregates of fibrin were sequentially observed in intravascular, interstitial, and alveolar spaces. Platelet aggregation and degranulation were occasionally observed in capillaries as early as 12 h after treatment, and frequently observed in capillaries and small vessels from 24 to 96 h after treatment. Significant increases in wet lung weight and lung water content occurred at the same time that morphologic changes were observed in pulmonary endothelium. Alterations in type I alveolar epithelial cells were initially observed at 24 h after treatment. Cell swelling, fragmentation, and necrosis were observed in both type I and type II cells and resulted in a bare basal lamina. Marked attenuation, hypertrophy, and proliferation of type II epithelial cells followed alveolar epithelial cell injury and loss. Minimal changes were observed in non‐ciliated bronchiolar epithelial (Clara) cells; predominant changes included the loss of surface microvilli and apical cytoplasmic bulge. The results of this study indicate that the endothelium and alveolar epithelium are the predominant cell types in the rat lung injured following OOS‐TMP administration. It is further concluded that the endothelial cell is the initial pulmonary cell type injured following OOS‐TMP treatment in this strain and that this cell population plays an important role in the development of OOS‐TMP‐induced pulmonary injury.
Plasmacytoid T cells in a case of lymphocytic infiltration of skin. A component of the skin‐associated lymphoid tissue?
Authors: Facchetti Fabio , De Wolf‐Peeters Chris , Van Den Oord Joost J. , Desmet Valeer J.
Published: June 2005

A case of cutaneous lymphocytic infiltration with large numbers of plasmacytoid T cells (PTC) is reported. Lectin staining and immunohistological analysis revealed that PTC and cutaneous dendritic cells showed a similar expression of concanavalin A, LN2, and MT1. Moreover, differences in TAL 1B5 and S‐100 expression were noted. From these findings we suggest that PTC may occur in the skin as a component of the skin‐associated lymphoid tissue.
Lectin binding and desmin staining during bupivicaine‐induced necrosis and regeneration in rat skeletal muscle
Authors: Helliwell Timothy R.
Published: June 2005

The processes of bupivicaine‐induced necrosis and regeneration in rat skeletal muscle have been studied with a panel of biotinylated lectins and by immunohistochemical staining for desmin. The results indicate that the binding of lectins to the periphery of muscle fibres is not altered in necrotic and regenerating fibres at the light microscopic level although abnormal cytoplasmic staining by lectins occurs early in necrosis and is also present during regeneration. Desmin staining is lost at an early stage of necrosis and is present at an early stage of regeneration. Desmin staining in combination with morphometrical assessment of the rate of fusion and growth of regenerating fibres provides a powerful method for evaluating the processes of muscle regeneration in experimental situations.
The autopsy: A useful tool or an old relic?
Authors: Peacock Sharon J. , Machin David , Duboulay Clair E. H. , Kirkham Nigel
Published: June 2005

In a combined retrospective and prospective study, clinical and autopsy data were collected to assess the changes in autopsy rate in recent years, the attitudes of clinicians and pathologists to the autopsy, and the accuracy of ante‐mortem diagnosis when compared with autopsy findings. Between 1962 and 1986, the total autopsy rate for hospital patients remained relatively constant, with an increase in Coroner's and a decrease in the hospital autopsy rate. Analysis of 5064 deaths over a 6‐year period showed a significantly greater number of males than females coming to autopsy and a decrease in autopsy rate with age for both sexes.

Attitudes to the autopsy were assessed using a questionnaire. The majority of clinicians considered the autopsy to be an important investigation despite new diagnostic techniques and confirmed its value in teaching and research. Seventyseven per cent agreed that autopsy findings occasionally led to modification of the treatment of subsequent patients with the same condition. Pathologists disagreed that the autopsy is outdated in its present form and considered that not enough hospital autopsies are being requested. They also upheld its use and value in education. The cause of death as given by clinicians for a group of 60 patients was inaccurate in 12 cases.
Synergism between ethanol and carbon tetrachloride in the generation of liver fibrosis
Authors: Bosma Anne , Brouwer Adriaan , Seifert Wilfried F. , Knook Dick L.
Published: June 2005

In this study, alcohol‐induced histological lesions in a short‐term experimental rat model were compared with those characteristic of human alcoholic liver disease. In the rat model used, pretreatment with carbon tetrachloride (CCl4) for 6 weeks was employed possibly to sensitize the liver for the effects of alcohol and shorten the time of induction of alcoholic liver disease. After 6 weeks of CCl4 treatment, subsequent maintenance on drinking water containing up to 10 per cent alcohol for 7 weeks potentiated liver fibroplasia as compared with non‐alcohol‐treated rats. However, steatosis and alcoholic hepatitis, as histological evidence for alcoholic liver disease as seen in humans, were not observed. In non‐CCl4‐pretreated control animals, alcohol administration had no effect on liver histology.

It can be concluded that in the model used, CCl4 pretreatment sensitizes the liver to increase collagen deposition following alcohol administration, but not to steatosis or alcoholic hepatitis as seen in human alcoholic liver disease. In this experimental set‐up, direct metabolic interaction of CCl4 with alcohol as a cause of the increased fibroplasia can be excluded.
An analysis of spontaneous and chemotherapy‐associated changes in skeletal osteosarcomas
Authors: Misdorp W. , Hart G. , Delemarre J. F. M. , Voŭcte P. A. , Van Der Eijken J. W.
Published: June 2005

Microscopically assessed changes observed in large sections of osteosarcomas from patients who had undergone pre‐operative chemotherapy (PCT) (n=22), or no chemotherapy (n=22), were examined either quantitatively, semi‐quantitatively, or qualitatively. Eight tumour characteristics were associated with the treatment mode by way of a stepwise logistic analysis. Minimal amount of viable tumour tissue (< 10 per cent) and strong fibroblastic proliferation were each proved to be associated with PCT. These two variables in combination indicated a good response to PCT. The discrimination between PCT and non‐PCT patients based on statistical analysis was superior to discrimination based on ‘overall impression’.
The pathology of diabetic hepatitis
Authors: Nagore Norma , Scheuer Peter J.
Published: June 2005

Liver biopsies from nine patients with maturity‐onset diabetes and fatty liver hepatitis were semiquantitively assessed, and the findings compared with those in alcoholic hepatitis. Overall appearances were similar, but the lesion in some diabetics was periportal rather than perivenular in location, and nuclear vacuolation of hepatocyte nuclei was alway present. The inflammatory infiltrate often included neutrophil leucocytes, as in the alcoholic. In three patients with multiple biopsies, progression appeared to be slow, but one patient developed cirrhosis.
CD1c antigens are present in normal and neoplastic B‐cells
Authors: Smith Mark E. F. , Thomas J. Alero , Bodmer Walter F.
Published: June 2005

The immunohistochemical detection of CD1c antigen is described in mantle zone B‐cells of the tonsil, lymph node, and spleen, and also in the marginal zone B‐cells of the spleen. CD1c expression was observed in most cases of low‐grade, but in only a single case of high‐grade, B‐cell non‐Hodgkin's lymphoma. It was not detected in germinal centre cells, nor in Epstein—Barr virus‐transformed or Burkitt's lymphoma B‐cell lines. This distribution suggests that CD1c expression may occur preferentially in slowly proliferating B‐cell populations and does not support previous suggestions that CD1c is a human equivalent of the mouse thymus leukamiea antigens.
The histopathology of the upper airway in the neonate following mechanical ventilation
Authors: Hwang W. S. , Boras V. , Trevenen C. L. , McMillan D. D. , Gargey P.
Published: June 2005

Laryngotracheobronchial lesions were carefully documented in 26 neonatal autopsies and were classified into two main types. Type I lesions were focal desquamative or ulcerative, asynchronous, and variable in severity involving areas exposed to contact with endotracheal tube or suction catheter. These lesions are most likely due to trauma of artificial ventilation. Type II lesions were diffuse, necrotizing, more synchronous and uniform in severity involving tissues distal to the endotracheal tube and extending to second or third generation bronchi. The early or mild type II lesions consisted of coagulative necrosis of epithelial cells and mucosal oedema. The late or severe type II lesions showed features similar to those of necrotizing tracheobronchitis described by Metley et al. All the cases with type II lesions had been ventilated with 100 per cent oxygen continuously for at least 3 h during life. The use of pure oxygen may be an important factor leading to necrotizing tracheobronchitis.
Host—parasite relationship in the brains of mice with congenital toxoplasmosis
Authors: Sims T. A. , Hay J. , Talbot I. C.
Published: June 2005

The wall of intact tissue cysts in the brains of mice with congenital toxoplasmosis was investigated using light and electron microscopy. Impregnation of the wall with reduced silver salts and protargol silver suggested that it was composed, at least in part, of components derived from the neuronal cytoskeleton. Electron microscopy extended these observations and revealed that intact cysts were separated from the extracellular compartment by a layer of neurofibrillae enclosed within the host cell membrane. It is suggested that this may be a means whereby intact Toxoplasma tissue cysts are protected from the host's immune response.
Epithelial cell markers and proliferating cells in odontogenic jaw cysts
Authors: Matthews John B. , Mason Gillian I. , Browne Roger M.
Published: June 2005

The expression of keratins, CEA, EMA, and rat liver antigen (RLA) and the presence of Ki67+ proliferating cells were studied in the epithelial linings of 50 odontogenic cysts using an indirect immunoperoxidase method on acetone‐fixed frozen sections. All cysts were positive with monoclonal antibodies of broad keratin specificty (CK1, AE1‐3), and between 40 and 100 per cent of epithelial cells expressed keratins 13 and 19. Keratins 7, 8, and 18 were rarely expressed although surface cells in areas of mucous metaplasia often expressed keratins 7 and 18. Expression of keratin 10/11 was related to the presence of a well‐ordered epithelial lining and was detected in isolated cells in 4/32 non‐keratinizing cysts and in the upper suprabasal cell layers of 17/18 keratocysts. Although CEA, EMA, and RLA were detected in the epithelium of all specimens, the pattern of expression of CEA and EMA differed between cyst types. Ki67+ proliferating cells were most prevalent in keratocyst epithelia, where they were usually found within lower suprabasal layers which were negative or weakly positive for keratins 10/11 and 13. These results indicate differences in keratin, CEA, and EMA expression between cyst types which appear to be dependent on epithelial differentiation/structure rather than cyst type or histogenesis. Although these differences may not be of diagnostic significance, the consistent expression of both keratins 13 and 19 may provide a useful marker of odontogenic epithelium in general.
Changes at the glomerulo‐tubular junction in renal transplants
Authors: Lee S. J. , Howie A. J.
Published: June 2005

We studied by microscopy 377 biopsies, nephrectomies, and necropsy kidneys from 123 human renal transplants. We discovered two common abnormalities of the renal corpuscle, both affecting the glomerulo‐tubular junction. Adhesion of the tip of the glomerular tuft to the origin of the tubule, as reported in various non‐transplant glomerulopathies, was seen in 197 specimens (52 per cent). This change was common in material showing acute or chronic vascular rejection and glomerulopathy, and was almost universal in transplants that had been in place for over 1 year. Another change at the glomerulo‐tubular junction, not previously highlighted, consisted of an infiltrate of lymphocytes or neutrophil polymorphs into the epithelium at the tubular origin. This change was seen in 145 specimens (38 per cent) and was associated with cellular rejection and ascending infection. These changes are of importance because they show two responses of the kidney to injury that involve the glomerulo‐tubular junction and thus suggest that this part of the kidney has some specific properties that have been largely neglected up to now.
Oncogenes and onco‐suppressor genes: Their involvement in cancer
Authors: Spandidos Demetrios A. , Anderson Margaret L. M.
Published: June 2005

We review the involvement of two groups of genes, oncogenes and onco‐suppressor genes, in malignant transformation. Approximately 40 oncogenes have been described mainly through studies on retroviruses and by in vitro functional analyses such as transfection of transforming genes into ‘normal’ cells. Because they are more difficult to identify, only a handful of onco‐suppressor genes have been described so far, but potentially they could number as many as oncogenes. Where these genes have been isolated and sequenced, they have been shown to be highly conserved among species, suggesting that these genes play an essential role in the normal cell. Although some properties of oncogenes have been identified, we do not know in detail the role these genes play in normal cells or how genetic damage contributes to malignancy. The effect of oncogene expression on a cell depends both on the cell type and on the oncogene, and in some circumstances oncogenes act as onco‐suppressor genes and vice versa. The elucidation of the mechanism of action of oncogenes and onco‐suppressor genes will not only increase our understanding of these important genes but might also provide the framework for a biological approach to the treatment of cancer.
Mast cells in human lungs
Authors: Heard Brian E. , Nunn Andrew J. , Kay A. B.
Published: June 2005

Mast cells were stained deeply in human lung tissue with acidic toluidine blue to obtain maximum numbers possible in paraffin sections. One hundred high‐power fields were counted per section, and mean and median values summarized as mast cells per mm2.

Immersion‐fixed samples of fresh lung tissue (not bronchi) were taken as controls from seven patients after surgery, and showed mean values of 44.7 mast cells per mm2 after formalin fixation, and 51.9 per mm2 after Carnoy's fixative. Mast cell heterogeneity may explain these differences, but so could random variation between counts.

In two patients with extrinsic allergic alveolitis (hypersensitivity pneumonitis), fresh lung tissue from open lung biopsies showed raised values of 90.8 and 101.9 mast cells per mm2, matching the high mast cell counts reported in bronchopulmonary lavage fluid in the condition.

Control post‐mortem lung tissue from two patients dying of non‐pulmonary diseases showed mean values of 26.1 and 50.6 mast cells per mm2. Post‐mortem lung tissue from three patients dying of asthma showed very low mean values of 4.7, 5.7, and 5.9 mast cells per mm2. Low mast cell counts due to severe degranulation have been reported before in the bronchi in asthma deaths, but not, to our knowledge, in the lung parenchyma. This finding implies a wider area of mediator release, and helps to explain the severity of the acute attack, and the fatal outcome.
Macroscopic and microscopic early effects of tumour necrosis factor on murine Meth A sarcoma, and relation to curative activity
Authors: van de Wiel Paul A. , Bloksma Nanne , Kuper C. Frieke , Hofhuis Frans M. , Willers Jan. M.
Published: June 2005

Mice with solid Meth A sarcoma in the skin received an intravenous or intralesional injection of graded doses of recombinant human tumour necrosis factor (rTNF). Local treatment caused red discolouration and necrosis of the central portion of the tumour within 24 h over a larger range of doses than intravenous treatment. Effects showed a limited dose dependence and no significant correlation with subsequent cures, which were far more frequent after local treatment. A dose of rTNF that induced about equal macroscopic necrosis by both routes caused much more pronounced microscopic effects after local administration. Effects included mitotic arrest, granulocyte margination, endothelial damage, hyperaemia, congestion, oedema, and tumour cell necrosis. rTNF did not affect the Meth A cells in vitro. Locally injected skins showed moderate vascular effects which were more marked in tumour‐bearing mice, but skin necrosis was absent.

Data show that quantitative histology rather than macroscopically visible necrosis correlates with cure rates. A broad interference of rTNF with tumour blood supply seems to be a major cause of the induced necrosis. Granulocytes may be involved in vascular damage. The different effects of rTNF on skin and tumour indicate that tumour vasculature has enhanced susceptibility to rTNF and probably lesser repair capacity.
Different types of segmental sclerosing glomerular lesions in six experimental models of proteinuria
Authors: Howie A. J. , Kizaki T. , Beaman M. , Morland C. M. , Birtwistle R. J. , Adu D. , Michael J. , Williams A. J. , Walls J. , Matsuyama M. , Shimizu F.
Published: June 2005

From 133 to 615 glomeruli were examined in sections of kidneys from each of 60 animals, representing six rodent models of proteinuria. Particular attention was paid to the position of segmental lesions. Lewis rats given sheep anti‐rat glomerular basement membrane antibodies had lesions almost exclusively at the glomerulo‐tubular junction. Wistar rats on a diet of 24 per cent casein or with subtotal nephrectomy and a diet of 24 per cent soya had lesions mainly at the hilum. Wistar rats given bovine serum albumin had global lesions but virtually no segmental lesions. Wistar rats given puromycin aminonucleoside had lesions at the glomerulo‐tubular junction and global mesangial abnormalities shortly after the treatment but later developed segmental lesions at all parts of the glomerulus. Untreated BUF/Mna rats had lesions at the glomerulo‐tubular junction early in life but later had lesions at all parts of the glomerulus. Untreated NZB/NZW hybrid mice had various types of glomerulonephritis and also had lesions at the glomerulo‐tubular junction. These findings showed that (1) segmental lesions at the glomerulo‐tubular junction, or glomerular tip, occur in experimental animals, a fact not previously reported, and these tip changes are a common feature in several different models of proteinuria; (2) hilar segmental lesions are seen in conditions with hyperfiltration of protein; and (3) segmental lesions at various parts of the glomerulus are seen in some models of proteinuria and probably indicate late effects of random toxic damage to the glomerulus. Thus, there are at least three different types of segmental glomerular lesions in experimental animals—tip, hilar, and random—with different morphology and pathogenesis. It is likely that these findings can be extended to human renal diseases with segmental glomerular lesions. This will help to clarify the controversial and unsatisfactory term focal segmental glomerulosclerosis.
Expression of the nuclear oncogene p53 in colon tumours
Authors: Van Den Berg F. M. , Tigges A. J. , Schipper M. E. I. , Den Hartog‐Jager F. C. A. , Kroes W. G. M. , Walboomers J. M. M.
Published: June 2005

The nuclear tumour antigen p53 is expressed by a gene localized on the p‐arm of human chromosome 17, a region frequently deleted in colon carcinomas. Using a monoclonal antibody to p53 antigen, immunohistochemical analysis of carcinomas and dysplastic tubular adenomas of the colon has been performed to study the relation between p53 expression and dysplasia or malignancy. With this methods p53 was detectable in 55 per cent of colon carcinomas (n = 29).

In 8 per cent of adenomas (n = 74), focal nuclear p53 expression was found in dysplastic epithelial cells. In general, these p53‐positive regions of the polyps were histologically indistinguishable from the neighbouring tubuli. Sometimes the p53‐positive nuclei were found in a focus of more highly dysplastic epithelium. The results suggest that expression of the p53 gene may be part of the process of malignant transformation of dysplastic colon polyps.
Immunohistological determination of oestrogen receptor, progesterone receptor, and intermediate filaments in Leydig cell tumours, Leydig cell hyperplasia, and normal Leydig cells of the human testis
Authors: Düe Wolfgang , Dieckmann Klaus‐Peter , Loy Volker , Stein Harald
Published: June 2005

Testicular Leydig cell tumours are able to produce oestrogens and can be induced by exogeneous oestrogen administration. Oestrogen and progestrone receptors, cytokeratin, vimentin, and proliferative activity were determined immunohistologically in human testes in six Leydig cell tumours, 14cases of Leydig cell hyperplasia, and 13 cases with normal Leydig cells. While both steroid receptors were detected in about 70 per cent of the tumour cells in cryostat sections, no reaction was observed in normal Leydig cells. This supports the hypothesis of an enhanced receptor state in a Leydig cell subpopulation as a basic pathophysiological factor in the development of Leydig cell tumours. On cryostat sections, all tumours co‐express cytokeratin and vimentin. Neither the receptors nor the intermediate filaments could be detected reliably in paraffin sections. The low proliferative activity of Leydig cell tumours corresponds to their benign clinical course.
Vascular volume in B16 allografts and human melanoma xenografts estimated by means of Hoechst 33342
Authors: Fallowfield Mary E.
Published: June 2005

The vasculature of B16, a murine melanoma and Mel‐mo, a human melanoma, was studied using intravital staining of patent capillaries by the fluorescent bisbenzamine dy Hoechst 33342. Capillaries were numerous at the edge of tumours in both the lines studied, but were scarcer within the nodules. Vascular volume as a proportion of total tumour volume was estimated by means of point counting. In both B16 and Mel‐mo, the percentage vascular volume was inversely related to log tumour weight.

Tumour necrosis, which increased with tumour size, was inversely correlated with percentage vascular volume, emphasizing the central under‐perfusion of these experimental tumour nodules. This pattern of perfusion, with greater density of functioning capillaries at the periphery of tumour nodules, was seen in both the tumour lines examined despite differences in the degree and pattern of necrosis.
Detection of latent virus mRNA in tissues using the polymerase chain reaction
Authors: Lynas Caroline , Cook Stuart D. , Laycock Keith A. , Bradfield John W. B. , Maitland Norman J.
Published: June 2005

The polymerase chain reaction (PCR) has been adapted for use in gene expression studies. Using this technique, we have been able to specifically detect Herpes simplex virus gene expression in the amount of RNA equivalent to that present in a single mouse ganglion. We have also detected specific transcription of the ras oncogene in biopsies of hepatocellular carcinoma tissue. The single tube RNA PCR reaction should be readily adaptable for use as a rapid screening tool in virus diagnosis; it is capable of detecting several virus infections simultaneously using extremely small tissue biopsies.
Silver‐binding nucleolar organizer regions (AgNORs) in benign and malignant breast lesions: Correlations with ploidy and growth phase by DNA flow cytometry
Authors: Giri D. D. , Nottingham J. F. , Lawry J. , Dundas S. A. C. , Underwood J. C. E.
Published: June 2005

Silver‐binding nucleolar organizer regions (AgNORs) have been counted in sections of routinely processed paraffin‐embedded tissue blocks and have been shown to assist in the distinction between benign and malignant lesions. We have examined 214 benign and malignant breast lesions by this method. The AgNOR counts were fibroadenomas 1.87 + 0.20 (mean + SD; n = 39), papillomas 1.92 + 0.21 (n = 28), sclerosing adenosis 1.96 + 0.24 (n = 23), epitheliosis 2.21 + 0.30 (n = 38), lobular carcinoma in situ 2.67 + 0.54 (n =9), intraduct carcinoma 3.75 + 1.33 (n = 37), and invasive carcinoma 4.22 + 1.18 (n = 40). However, the counts in 25–30 per cent of epitheliosis lesions and intraduct carcinomas overlapped in the region of 2–3 AgNOR dots per nuclear profile. The AgNOR counts in carcinomas were also compared with ploidy and growth phase fractions (S + G2 + M%) by flow cytometry. Thirty‐three of the 46 cancers with counts over 3 AgNOR dots per nuclear profile contained aneuploid cells (> 10 per cent of the total), whereas 8 of the 12 with counts below 3 comprised diploid cells only (P <0.05). Similar trends were noted with regard to growth phase fractions which were 19.15 per cent + 12.31 and 13.98 per cent + 5.55, respectively, for the two groups (P>0.10). We conclude that this method alone does not offer a reliable histological discriminant for malignancy in the breast. However, AgNOR counting may provide information on breast cancer prognosis supplementary to that obtained from DNA flow cytometric analyses.
IgA nephropathy associated with chronic hepatitis B virus infection in adults: The pathogenetic role of HBsAG
Authors: Lai Kar Neng , Lai Fernand Mac‐Moune , Tam John S.
Published: June 2005

Five adult cases of IgA nephropathy associated with chronic hepatitis B virus infection were studied. Serum HBsAg and anti‐HBc were present in five patients and HBeAg in four patients. Glomerular changes were typical of primary IgA nephropathy in four patients, and a mixed picture of IgA and membranous nephropathy was demonstrated in one patient. Immunofluorescence microscopy using polyclonal and monoclonal antibodies against HBsAg, HBcAg, and HBcAg revealed mesangial deposits of HBsAg in renal biopsies from four patients. One renal biopsy showed only mesangial and capillary HBcAg by polyclonal antiserum, and virus‐like particles were demonstrated in the intramembranous electron‐dense deposits on ultrastructural examination. Mesangial HBeAg was not detected in the renal biopsies from these patients with IgA nephropathy. As for the single patient with a mixed picture of IgA and membranous nephropathy, granular deposits of HBeAg with a distribution similar to IgG were detected in the glomerular capillary walls in addition to the mesangial deposition of HBsAg. These findings suggest that HBsAg rather than HBeAg may play a role of the pathogenesis in some of the adult patients with IgA nephropathy associated with chronic hepatitis B virus infection.
Primary liver neoplasms: Evaluation of proliferative index using MoAb Ki 67
Authors: Grigioni W. F. , D'Errico A. , Bacci F. , Gaudio M. , Mazziotti A. , Gozzetti G. , Mancini A. M.
Published: June 2005

Thirty‐two cases of primary liver neoplasms comprising 12 benign, 15 malignant, and 5 cases with equivocal histopathological features between benign and malignant have been investigated using monoclonal antibody (MoAb) Ki 67, which reacts with a nuclear protein expressed in the G1, G2, S, and M phases of the cell cycle.

The Ki67 score (positive cells/total neoplastic cells) seems to correlate to the classes of lesions tested. In the hepatocellular carcinoma (HCC) group, the percentage of labelled nuclei, ranging from 15 to 50 per cent, showed a good correlation with Edmondson‐Steiner's histological tumour grade.

A percentage of positive cells similar to that of the proved low‐grade HCCs was detected in the five neoplastic lesions in which the routine histopathological criteria of malignancy were not fulfilled. The benign neoplasms showed a very low growth fraction, similar to that of normal or cirrhotic tissues.

The use of the Ki 67 score seems to offer useful information about the biological behaviour of some liver masses and may help in the differential diagnosis of hepatocellular adenoma versus carcinoma.
Pleural mesothelioma of connective tissue type, localized fibrous tumour of the pleura, and reactive submesothelial hyperplasia. An immunohistochemical comparison
Authors: Al‐Izzi Moutaiz , Thurlow Nicola P. , Corrin Bryan
Published: June 2005

Ten diffuse pleural mesotheliomas of connective tissue type have been compared with 14 examples of pleural granulation tissue and 7 localized fibrous tumours of the pleura, using immunohistochemistry to identify cytokeralins oflow and high molecular weight and vimentin. Low molecular weight cytokeratin and vimentin were both delected in 8 of the 10 mesotheliomas and in 12 of the 14 reactive iesions. High molecular weight cylokeratin was rarely detected in either lesion. The seven localized fibrous tumours of the pleura were all positive for virnentin and negative for both cytokeratins. These findings support an origin of connective tissue type mesotheliomas from multipotential submesothelial spindle cells and of localized fibrous tumours of the pleura from either conventional fibroblasts or resting submesothelial spindle cells. Antibodies to cytokeratin help distinguish these two neoplasms but provide no assistance in the more difficult diagnostic problem of distinguishing mesotheliomas of connective tissue type from pleural reactions characterized by abundant granulation tissue.
In situ evaluation of the stimulatory state of hepatic macrophages based on their ability to produce superoxide anions in rats
Authors: Mochida Satoshi , Ogata Itsuro , Ohta Yasuhiko , Yamada Shinwa , Fujiwara Kenji
Published: June 2005

When a liver perfusion with nitro blue tetrazolium (NBT) and phorbol myristate acetate (PMA) was performed in carbon tetrachloridc (CCl4)‐intoxicated rats, formazan deposition was remarkable in macrophages in the necrotic areas of the liver, its intensity varying with the extent of injury. The deposits almost disappeared after addition of Cu(Lys)2 a scavenger of intra‐ and extracellular superoxide, but were not affected by superoxide dismutase (SOD), which acts extracellularly. The formazan content after incubation with NBT and PMA was higher in macrophages isolated from CCl4‐intoxicated liver than in those from normal liver, though their PMA‐induced chemiluminescence did not differ. In Corynebacteriun parvum‐treated liver, both Cu(Lys)2 and SOD reduced the deposits. This method cn estimate in situ the ability of hepatic macrophages to produce superoxide and the cellular sites of its production.
An immunohistochemical and in situ hybridization study of c‐myc and c‐erbB‐2 expression in primary human breast carcinomas
Authors: Walker Rosemary A. , Senior P. V. , Jones J. Louise , Critchley D. R. , Varley Jennifer M.
Published: June 2005

In previous studies of the expression and organization of proto‐oncogenes in human breast a significant correlation has been found between amplification of c‐myc and c‐erbB‐2 genes in carcinomas and poor short‐term prognosis. Gene expression was estimated by analysis of total RNA from tissues, and similarly assessment of gene organization relied upon extraction of DNA from tissues. The present study has compared the expression of c‐myc and c‐erbB‐2 mRNA as determined by in situ hybridization, and c‐myc and c‐erbB‐2 protein expression detected by immunohistochemistry in a group of carcinomas for which there was knowledge of genomic organization and/or expression.

Formalin‐fixed, paraffin‐embedded tissues of 38 carcinomas were assessed for the presence of c‐myc protein, and 13 of these were examined for c‐myc mRNA by in situ hybridization. Similarly processed tissue from 14 tumours was tested for c‐erbB‐2 protein using the antiserum21N and ten of these carcinomas studied for c‐erbB‐2 mRN A localization.

There was a good correlation between gene amplification, the presence of c‐erbB‐2 protein and mRNA: both the latter were detected in six of the seven carcinomas with an amplification but in none without. For some carcinomas there was a good correlation between c‐myc protein and mRNA levels. Three carcinomas with gene amplification had a lower percentage of cells with detectable protein than showed hybridization for mRNA. Other carcinomas had a lower level of mRNA expression than protein. Neither approach could predict which carcinomas had amplification of the c‐myc gene. The subcellular localization of the c‐myc protein was affected by fixation.

Localization of c‐erbB‐2 protein and mRNA in routinely processed tissues could provide information of clinical value but the same cannot be said for expression of c‐myc.
Cell death by apoptosis in acute leukaemia
Authors: Baxter Glenn D. , Collins Russell J. , Harmon Brian V. , Kumar Sharad , Prentice Roger L. , Smith Peter J. , Lavin Martin F.
Published: June 2005

We have previously demonstrated that when freshly isolated childhood T‐cetl acute lymphoblastic leukaemia cells are incubated in growth medium after isolation from blood, chromatin is rapidly cleaved into nucleosomal sized fragments that are multiples of 200 bp. The fragmentation is similar to that observed in other types of cells undergoing apoptosis or programmed cell death. In this study we describe a more comprehensive approach to the study of DNA fragmentation in leukaemia. Fragmentation was observed in freshly isolated cells from patients with T‐cell acute lymphoblastic leukaemia and in one with common acute lymphoblastic leukaemia. Frozen samples of T‐cell acute lymphoblastic leukaemia, common acute lymphoblastic leukaemia, and acute myeloid leukaemia cells also showed fragmentation of DNA. However, no fragmentation was evident in normal leukocytes treated under the same conditions. Ultrastructural studies on the isolated leukaemia cells demonstrate that the chromatin cleavage observed biochemically is associated with morphological changes characteristic of apoptosis.
Metallothionein and copper in liver disease with copper retention—a histopathological study
Authors: Elmes Margaret E. , Clarkson Johanna P. , Mahy Nicolas J. , Jasant Bharat
Published: June 2005

We have examined the relationship between (a) histochemically demonstrable copper using rubeanic add, (b) copper‐associated protein (CAP) using orcein, and (c) immunoreactive metallothionein (MT) using DNP hapten sandwich staining and have correlated these with histological lesions in 95 liver biopsies from patients with conditions associated with hepatic copper retention, 4 fetal livers, and 25 historically normal adult controls.

No copper or CAP was present in normal adult liver but periportal CAP was present in fetal liver. MT was present in hepatocytes of normal livers with a predominantly perivenular (centrilobular) cytoplasmic distribution varying in staining intensify; all fetal hepatocytes stained strongly for MT.

Fifty‐two of 95 (55 per cent) abnormal livers contained CAP and 42 (44 per cent) contained both CAP and copper. In CAP‐positive livers, the commonest histological lesions were piecemeal necrosis and cholestasis.

CAP was present in (a) 15/15 cases of primary biliary cirrhosis including early cases with minimal pathology; and (b) 5/5 cases of Wilson's disease, 6/6 cases of biliary atresia, and 3/9 cases of sclerosing cholangitis. In other conditions, it was present in 25–50 per cent of cases.

MT distribution was abnormal in most CAP‐positive livers. Necrotic hepatocytes were intensely MT‐positive and in Wilson's disease had a characteristic appearance.
Hepatic sinusoidal cell destruction in the development of intravascular coagulation in acute liver failure of rats
Authors: Hirata Keiichi , Ogata Itsuro , Ohta Yasuhiko , Fujiwara Kenji
Published: June 2005

Rats received a dose of dimethylnitrosamine (DMN) or carbon tetrachlonde (CCl4). In the liver of rats given DMN, apoptosis of fat‐storing cells occurred at 7.5 h, and sinusoidal endothelial cell degeneration followed, with parenchymal cell necrosis after 9 h. Fibrin thrombi appeared in the sinusoids as well as in these necrotic areas after 12h. In contrast, in the liver of rats given CCl4, parenchymal cell degeneration was seen after 6 h and necrosis with fibrin thrombi developed after 9 h. Fat‐storing cells and endothelial cells were almost intact, and fibrin thrombi were not present in the sinusoids. SGPT values increased with decreased plasma levels of fibrinogen and antithrombin III and prolonged prothrombin time after 3 and 6 h, in the CC14 and DMN models, respectively. An extensive reduction in plasma factor VIIIC levels and peripheral platelets was seen after 18 and 24 h, respectively, only in the DMN model. These results suggest that endothelial cells destruction can cause fibrin formation in the hepatic sinusoids in acute liver injury. Fatstoring cell injury may contribute to the destruction.
The utility of Ki67 immunostaining, nuclear organizer region counting, and morphology in the assessment of follicular lymphomas
Authors: Cibull M. L. , Heryet A. , Gatter K. C. , Mason D. Y.
Published: June 2005

Three methods, the enumeration of large non‐cleaved cells (LNCC), the enumeration of nucleolar organizer regions (AgNORs), and the estimation of the percentage of Ki67‐positive cells, have been compared on a series of 36 follicular lymphomas for their utility in subclassificalion. All three methods produced similar subdivisions io those obtained using the histological classification of the Working Formulation for clinical usage. Twenty cases have been followed clinically to assess any relationship between these parameters and short‐term (less than 4 years) survival. Each technique showed a trend towards identifying patients with a poor short‐term prognosis with no one method being superior to any other. Unless larger series with longer follow‐up suggest otherwise, there is no indication to use either the AgNOR or Ki67 methods which offer no advantage over the simple and inexpensive Working Formulation or Berard's LNCC counting.
Functional activity of intestinal epithelium demonstrated by mRNA in situ hybridization
Authors: Talbot Ian C. , Primrose Lindsay , Pringle James H.
Published: June 2005

To elucidate the synthetic activity in relation to the morphology of the epithelial cells of the small and large intestine, in situ hybridization with a poly‐deoxyribothymidine (poly d(T)) probe was applied to paraffin sections of formalin fixed blocks. This effectively displays poly‐adenylated RNA and, by implication, messenger RNA (mRNA). By minimizing proteinase K pretreatment, the relative concentrations of cellular mRNA were visualized. This revealed minimal mRNA in crypt columnar cells, and maximal mRNA in proliferating cells and in cells showing terminal differentiation. The latter include surface epithelial cells, endocrine cells, Paneth cells, and maturing, but not mature, goblet cells. The goblet cells showing positive hybridization can be regarded as active cells and show characteristic morphology. Such cells are particularly evident in untreated coeliac disease, remitting ulcerative colitis, and transitional mucosa. The proliferating cells showing increased hybridization include normal mitotically active crypt epithelium, regenerating epithelium in ulcerative colitis, adenomatous epithelium, and adenocarcinomatous epithelium. The similarity of hybridization between metaplastic polyp epithelium and surface colonocytes is consistent with the concept that metaplastic polyps are formed of cells showing premature terminal differentiation.
Expression of parathyroid hormone related protein in normal skin and in tumours of skin and skin appendages
Authors: Hayman J. A. , Danks J. A. , Ebeling P. R. , Moseley J. M. , Kemp B. E. , Martin T. J.
Published: June 2005

Parathyroid hormone related protein (PTHrP) has been demonstrated in the tumour cells of squamous cell carcinomas originating in a variety of organs, in undifferentiated small cell tumours of the bronchus, and in carcinoma of the kidney. The protein hormone is thought to produce the hypercalcaemia which may complicate some of these malignan cies. By using an antibody raised in rabbits against the N‐terminal portion of the molecule, the polypeptide may be demonstrated in cells of the prickle cell layer of normal skin and in the cells of hair follicles. Skin tumours showing squamous or hair follicle differentiation are shown to contain the protein antigen, while basal cell carcinomas and tumours with sweat gland differentiation do not The hormone may be primordial in origin and the progenitor of parathyroid hormone.
Superficial gastritis and Campylobacter pylori in dyspeptic patients—a quantitative study using computer‐linked image analysis
Authors: Collins J. S. A. , Hamilton P. W. , Watt P. C. H. , Sloan J. M. , Love A. H. G.
Published: June 2005

The purpose of this study was the quantitative assessment of mucosal inflammation and its relationship to Campylobacter pylori in gastric antral and body biopsies from patients with dyspepsia and controls. The study groups comprised patients with duodenal ulcer (DU; n = 20), duodenitis (DUN;n = 20), non‐ulcer dyspepsia (NUD; n = 20), Using a semiautomatic, computer‐linked image analyser (Kontron: MOP Videoplan), mucosal acute and chronic inflammatory cell densities were measured in defined gastric sites for each patient group and expressed as number per mm2 of lamina propria and number per mm length of epithelium. Measurements were also made on a group of asymptomatic controls (n = 9) who fulfilled strict exclusion criteria. All biopsies were analysed for the presence of Camplyobacter pylori (CP) with a Giemsa stain. Data between groups were compared using the Mann‐Whitney U‐test. In the antrum and body, the mononuclear cell count was significantly higher in lamina propria in DU patients than in DUN, NUD and controls. In the body, DU laminia propria mononuclear cell counts were higher than those of DUN and controls. Prevalence rates for CP for DU, DUN, and NUD were 94, 89, and 50 per cent for antral and 88, 83, and 56 per cent for body biopsies. Significant differences were present between CP‐positive and negative subjects in the NUD group. Antral and body inflammation within these clinical groups shows a wide variation. Higher inflammatory cell counts in the DU group may reflect the prevalence of CP colonization.
Antigenic heterogeneity of renal endothelium
Authors: Fleming S. , Jones D. B.
Published: June 2005

We have identified several antibodies which in immunocytochemical experiments reveal antigenic heterogeneity in renal vascular endothelium. In the renal vascular endothelium, blood group antigen H type II was carried in a sialylated form on an endogalactosidase resistant molecule. The glomerular reactivity was sensitive to digestion by this enzyme. Monoclonal antibodies of the CD 39, CD 14, and CD 11C leucocyte differentiation clusters bind to renal vascular endothelium but not to glomerular capillaries. In fetal kidney, the developing glomerular endothelium has the same phenotype as the remainder of the vascular tree with respect to these markers. There are therefore antigenic differences among renal endothelial cells and these arise during renal organogenesis.
Transfer of anti‐glomerular basement membrane antibody‐induced glomerulonephritis in inbred rats with isologous antibodies from the urine of nephritic rats
Authors: Sado Yoshikazu , Naito Ichiro , Okigaki Tohru
Published: June 2005

Anti‐glomerular basement membrane antibody‐induced glomerulonephritis (anti‐GBM nephritis) was transferred from nephritic rats to normal recipient rats with isologous antibodies obtained from the urine of the nephritic rats. The original actively‐immunized anti‐GBM nephritis was induced in inbred WKY/NCrj rats by injecting the nephritogenic antigen from bovine renal basement membranes. Excreted urinary antibodies were collected, purified, and then injected into recipient rats of the same strain, Haematuria and proteinuria appeared on day 2 and day 3, respectively; both became heavier and reached a plateau by day 5. Endocapillary hypercellularity of mononuclear cells in glomeruli was the first histological change, which was observed from day 2, and later extracapillary changes such as fibrin deposition, capsular adhesion, and crescent formation were observed. These histological changes were the same as those seen in the actively‐immunized nephritis. The results demonstrate that anti‐GBM nephritis is clearly induced by autoantibodies. This new passively‐immunized model of anti‐GBM nephritis makes it possible and easier to analyse further the mechanism of anti‐GBM nephritis because only isologous antibodies are used. This study also indicates that the urine of the nephritic rat is a good source of autoantibodies.