bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrastructural pathology of experimental ebola haemorrhagic fever virus infection
Authors: Baskerville A. , Fisher‐Hoch S. P. , Neild G. H. , Dowsett A. B.
Published: June 2005

The organs of monkeys infected with Ebola haemorrhagic fever were examined by light and electron microscopy during the acute stage of the disease. The virus caused focal coagulative necrosis in the liver, spleen, kidney, lung and testis and widespread mild vascular damage. In the brain there was intense congestion, with erythrocyte ‘sludging’, but no inflammatory reaction. There was significant injury to the microvasculature in all organs. Virus replicated in endothelial cytoplasm causing focal necrosis, separation of tight junctions and detachment from basement membranes. These changes were associated with oedema and haemorrhage, but though contributing to the hypovolaemic shock were not sufficiently extensive to account for the severity of vascular collapse. Renal involvement was also clinically important. Some renal cellular injury was caused by direct virus invasion ofglomerular endothelium and tubular epithelium, but much tubular damage was probably due to ischaemia resulting from thrombosis in the peritubular capillaries. The virus also replicated in lymphocytes and monocytes and in interstitial cells of the testis. Since particles were not found in seminiferous epithelium, the degeneration of spermatogonia and spermatocytes was probably secondary to ischaemia.
Primary small intestinal lymphoma: A study of 39 cases
Authors: Morgan D. R. , Holgate C. S. , Dixon M. F. , Bird C. C.
Published: June 2005

Thirty‐nine cases of primary small intestinal lymphoma were studied by morphological and immunohistochemical methods. The adjacent uninvolved mucosa was also examined for features suggestive of coeliac disease. Employing the immunogold silver staining (IGSS) technique and polyclonal primary antisera against α‐l‐antitrypsin, lysozyme and κ and λ light chains, 29 cases (74·5 per cent) were found to be B‐cell lymphomas, seven (18 per cent) histiocytic tumours, one (2·5 per cent) Hodgkin's disease and two (5 per cent) remained unclassified. No specific lymphoma subtype was found to be associated with cases having the histological features of coeliac disease in the uninvolved adjacent mucosa. In 35 cases sufficient clinical information was available to assess the significance of histological type and stage in relation to survival. Although the histological type did not correlate with survival, stage did and tumours extending beyond the local lymph nodes were associated with a significantly worse prognosis.
Gastrin releasing peptide in human neuroendocrine tumours
Authors: Bostwick David G. , Bensch Klaus G.
Published: June 2005

Neuroendocrine tumours of the lung and gut are known to possess bombesin‐like immunoreactivity. The recent observation that gastrin releasing peptide (GRP), a 27 amino acid peptide isolated from the porcine intestine, may be the mammalian analogue of bombesin led us to look for this peptide in a variety of human neoplasms. Formalinfixed tissues from 85 tumours were examined by the immunoperoxidase technique, using specific antisera to the GRP molecule (1–27) and the GRP fragment (1–16). Intense cytoplasmic GRP immunoreactivity was seen in thyroid medullary carcinomas (3/3), carcinoids of lung, pancreas, and intestine (22/36), and paragangliomas (2/3). Less frequent staining was present in pulmonary small cell (oat cell) carcinomas (1/8) and pituitary adenomas (1/6). Complete absence of immunoreactivity was observed in three phaeochromocytomas, five Merkel cell tumours, six neuroblastomas and 15 non‐neuroendocrine tumours. Normal neuroendocrine cells of the thyroid (C‐cells) and bronchial mucosa (Kulchitsky cells) exhibited GRP immunoreactivity; nerve fibres from all sites failed to demonstrate staining for GRP. In each positive case, the pattern of staining for GRP (1–27) and GRP (1–16) was identical, although the GRP (1–16) immunostaining was weaker. These findings indicate that bombesin immunoreactivity in human neuroendocrine cells and tumours is attributable to GRP‐like molecules and that GRP is a useful marker of neuroendocrine differentiation in many tumours.
Pulmonary blastoma, carcinosarcoma and spindle‐cell carcinoma: An immunohistochemical study of keratin intermediate filaments
Authors: Addis Bruce J. , Corrin Bryan
Published: June 2005

We have examined 18 primary malignant lung tumours categorized as either carcinosarcoma, blastema or spindle‐cell carcinoma according to accepted criteria. Two monoclonal antibodies to keratins, CAM 5.2 and LP 34, were used to determine whether the non‐epithelial or spindle‐cell components of each tumour showed evidence of keratin expression. By this means the epithelial nature of the five tumours classified as spindle‐cell carcinomas was confirmed. In all four pulmonary blastomas and in five of nine carcinosarcomas, the sarcomatous elements failed to stain for keratin but in the remaining four carcinosarcomas there was focal staining. The histogenesis of these tumours is discussed and it is suggested that the sarcomatous component of a carcinosarcoma may be derived from malignant epithelial cells by a process of mesenchymal metaplasia with a switch in intermediate filament type. It remains uncertain whether blastomas are derived from both endoderm and mesoderm, or from either one of these tissues, with one component representing complete metaplastic transformation.
Effects of ageing on the alveolar pores of Kohn and on the cytoplasmic components of alveolar type II cells in monkey lungs
Authors: Shimura Sanae , Boatman Edwin S. , Martin C. J.
Published: June 2005

The effects of ageing on the numbers of alveolar pores of Kohn and on the cytoplasmic components of alveolar type II cells were studied in monkey lungs by scanning and transmission electron microscopy. Lung tissue from 26 female and three male pigtail macaques whose ages ranged from 1 month to 31 years (life span is 35 years) was analysed. From the age of 1 month to 10 years there was a significant increase in the number of alveolar pores (r = 0·85, p < 0·001); however, between the ages of 14 years to 31 years there was no significant change. In seven animals ranging in age from 1 month to 4 years (mean 2·4 years) the number of pores was 5·8 ± 3·9 (mean · S.D.), whereas in 10 animals aged 16 to 31 years (mean 20·3 years) the number of pores was 32·7 ± 17·5 (mean ± S.D.) per alveolar profile, a significant difference (p < 0·002). In older animals (15–20 years) there was a significant decrease, both in the number of lamellar bodies per alveolar type II cell (p < 0·01) and in the volume density of lamellar bodies to cytoplasmic volume (p < 0·05) compared with young animals (1 month to 4·8 years). In older animals, there was also a significant increase in the volume density of a vacuole‐like dilatation of the endoplasmic reticulum in alveolar type II cells (p < 0·05) compared with young animals. These findings suggest impaired pulmonary surfactant production with aging. Both the increased number of alveolar pores and the postulated decrease of surfactant production could play a role in the pathogenesis of pulmonary emphysema.
Epithelial antigens in malignant mixed Müllerian tumours of endometrium
Authors: Ramadan M. , Goudie R. B.
Published: June 2005

Immunohistochemical staining of formalin fixed paraffin sections with the mouse monoclonal antibodies E29 and CAM 5·2 effectively distinguish epithelium (antigen positive) from stroma (antigen negative) in normal endometrium. These antibodies were used as epithelial markers in the study of eight malignant mixed Müllerian tumours (MMT) of endometrium and gave normal reactions with well differentiated neoplastic glands; in contrast, negative or very weak staining was observed in poorly differentiated epithelial cells, present in large numbers in three cases. Abnormal antigen‐containing cells were observed in the stroma of seven MMT. In some cases these are probably due to stromal invasion by malignant epithelium but in others they may represent an early stage of epithelial differentiation in mesenchymal cells of the malignant stroma.
Electron microscopic localization of cell‐surface markers in tissue sections using monoclonal and gold‐conjugated antibodies
Authors: Rooney N. , Day C. , Gray T. , Underwood J. C. E.
Published: June 2005

We describe a method for the ultrastructural localization of surface markers on cells in intact tissue sections. Using a primary monoclonal antibody to a surface marker followed by a second stage gold‐labelled antibody, surface antigens can be specifically localized. This enables cellular interactions to be studied in solid tissues.
Rheumatoid‐ and osteo‐arthritis: Quantitation of ultrastructural features of capillary endothelial cells
Authors: Sattar A. , Kumar P. , Kumar S.
Published: June 2005

Joint tissues from patients with rheumatoid arthritis (3), osteoarthritis (3) and normal healthy individuals (2) were examined in the transmission electron microscope and the morphological features of capillaries within 2 mm of the synovial membrane were quantified. Weibel‐Palade bodies (WPB) were significantly increased in capillary endothelial cells in rheumatoid and osteoarthritis compared with normal controls, when quantified by three different methods. WPB were positively correlated with both projections of the luminal plasmalemma and pinocytic vesicles in normal joint and some patients with rheumatoid and osteoarthritis. Pinocytic vesicles and projections were also positively correlated.
Evidence that multinucleate giant cells are examples of mononuclear phagocytic differentiation
Authors: Papadmitriou John M. , Van Bruggen Ivonne
Published: June 2005

Murine multinucleate giant cells and mononuclear phagocytes were examined with various quantitative cytochemical and autoradiographic techniques. No evidence was found that multinucleate giant cells were metabolically effete, in fact they compared favourably with mononuclear phagocytes. In addition, rat multinucleate giant cells consistently expressed surface Ia antigens and to a lesser degree fibronectin. It is suggested that multinucleate giant cells are a differentiated derivative of the mononuclear phagocytic system.
An experimental study on the pathogenesis of acute haemorrhagic enteropathy—significance of congestion and endotoxaemia
Authors: Shibayama Y.
Published: June 2005

To clarify the pathogenesis of acute haemorrhagic enteropathy, the present study was undertaken using the ileum of rats. The ligation of marginal veins of the ileum or the injection of endotoxin to the intact rats induced only slight mucosal haemorrhage. On the other hand, the injection of endotoxin into rats with ligation of the marginal veins led to severe mucosal haemorrhage. The severe mucosal haemorrage was markedly inhibited by suppression of the production of bradykinin. These experimental results suggest that some cases of acute haemorrhagic enteropathy may be induced by the co‐existence of endotoxaemia and congestion of the intestine. Thus, the mechanism of severe mucosal haemorrhage may be as follows: bradykinin, induced by endotoxin, acts to dilate capillaries and small veins in the mucosa and markedly increases their permeability.
The validity of negative necropsy reports for metastases in solid organs
Authors: Weiss L. , Harlos J. P.
Published: June 2005

This communication concerns the statistical significance of negative reports, when solid organs are examined for metastases deep to their surfaces, by standard slicing techniques at necropsy. By taking into account factors influencing tumour detection including slice thickness, metastatic tumour size and number, the probabilities of incidence of false negative reports may be calculated and values for the undetected tumour bulk may be obtained. A graph is reproduced which facilitates the assessment.
Adenomatoid tumours: An immunohistochemical and ultrastructural appraisal of their htstogenests
Authors: Stephnson Timothy J. , Mills Patricia M.
Published: June 2005

The histogenesis of adenomatoid tumour has continued to provoke debate since Golden and Ash suggested the term in 1945 for all characteristic benign neoplasm typically found in the uterus, fallopian tube or epidiymis. Hndothelial, epithelial, mesonephric, müllerin and mesothelia histogenesis have been suggested. The balance of evidence suggests mesothclial derivation, but two rcecent studies point to endothelial origin for at least some of these tumours, Twenty‐two histologically typical adenomatoid tumours were studied by electron microscopy, mucin histochemistry and immunohistochemistry. Ultrastructurally, all cases showed vacuolated cells bearing long bushy microvilli and the features were not those of endothelial cells. Glandular spaces contained acid mucopolyscharide consistent with hyaluronic acid. Immunohistochemical double labelling techniques showed the cells lining such spaces to contain cytokeratin in the absence of factor VIII related antigen and receptors for Ulex europapeus I leetin which were expressed in the endothelium of tumour blood vessels. The evidence points !o mesothelial histogenesis in all cases examined.
Puromycin aminonucleoside nephropathy: Ultrastructure, glomerular polyanion, and cell surface markers
Authors: Rossmann P. , Bukovský A. , Matoušovic K. , Holub M. , Král J.
Published: June 2005

Puromycin aminonucleosidc nephropathy with heavy proteinuria and oedema was induced in rats by 10 consecutive daily subcutaneous injections of aminonucleoside (1.67 mg/100 g of body weight). The main ultrastructural lesions were vacuolation of podocytes and total fusion of foot processes with loss of colloidal iron‐reactive polyanion layer on the epithelial surface adjacent to the basement membrane. On the other hand the outer surface of podocytes and intravacuolar granular substance stained with colloidal iron. In scanning electron microscopy of freeze‐fractured tissue the swollen podocytes and the urinary spaces displayed granular and filamentous precipitates. Seven cell surface antigens were examined by indirect enzyme immunohistochemistry with a series of MRC OX monoclonal antibodies. Glomeruli of control rats exhibited rare isolated la‐positive endocapillary cells, possibly monocytes; these elements were significantly reduced in puromycin aminonucleoside nephropathy but there was an increase in la‐positive cells in Ihe cortical interstitium Control kidneys harboured scanty interstitial T lymphocytes. These latter, especially the T8‐positive cytotoxic/suppressor subpopulation, were markedly augmented in puromycin aminonucleoside nephropathy. The expression of class I histocompatibility antigens and of differentiation antigens (Thy I) was not altered by aminonucleosidc.
Collagenous colitis: A disease of pericryptal fibroblast sheath?
Authors: Hwang W. S. , Kelly J. K. , Shaffer E. A. , Hershfield N. B.
Published: June 2005

Mucosal biopsies from four women with collagenous colitis and ten controls were studied. By light microscopy the cells of the pericryptal fibroblast sheath appeared diminished in number but increased in size in collagenous colitis. Electron optically in the controls the pericryptal fibroblasts were in intimate contact with the epithelial basal lamina in the crypts. On the free surface the fibroblasts maintained contact with the epithelial cells by attenuated cell processes. In collagenous colitis, in the middle and upper thirds of the crypts the fibroblasts sheath was separated from the epithelium and the fibroblasts assumed the characteristics of myofibroblasts. The separation was accentuated towards the mouths of the crypts. Beneath the surface epithelium the attenuated fibroblast cell processes seen in normal colon were grossly deficient. The basal lamina was also deficient focally and the surface epithelial cells were resting directly on a thickened collagen table. In collagenous colitis the excess collagen appeared to be secreted by the activated myofibroblasts of the pericryptal sheath.
Changes in lectin binding patterns in the developing pulmonary vasculature of the pig lung
Authors: Mills Adrian N. , Haworth Sheila G.
Published: June 2005

Lectin binding patterns to the developing pulmonary vasculature were studied in 10 Large White pigs aged 1 min to 1 week and in three adult animals. Paraffin‐embedded tissue sections were exposed to eight lectin peroxidase conjugates: Dolichos biflorus, Triticum vulgaris, Concanavalin A, Ricinus communis type 2, Arachis hypogaea, Ricinus communis type 1, Tetragonolobus purpureas and Ulex europeus. Lectin binding patterns to the pulmonary arterial and venous endothelium, to smooth muscle cells (SMCs) and to the arterial connective tissue were age‐related. Changes occurred during the first week of life and between 1 week and adult life. Neither the endothelial binding patterns in the adult nor the SMC patterns in the immature and adult lung conformed to known morphological differences between the different segments of the arterial and venous pathways. Heterogeneity for endothelial binding was seen in the immature lung. These studies indicate biochemical differences in surface structure between the endothelium, SMCs and connective tissue of the immature and mature lung. Ultrastructural localization of the lectins in the vasculature of the developing animal lung ought to help interpret similar data obtained on the vessels of the immature human pulmonary hypertensive lung using lectins which show similar binding patterns in both species.
Variation in the argyrophil cell population of the rectum in ulcerative colitis and adenocarcinoma
Authors: Gledhill Ann , Enticott Michael E. , Howe Stephen
Published: June 2005

Longstanding ulcerative colitis predisposes to carcinoma of the colon. Argyrophil cell hyperplasia has been observed in association with dysplasia and neoplasia in ulcerative colitis. As the argyrophil cell population includes those cells producing enteroglucagon, a hormone thought to stimulate mucosal proliferation, this study was designed to determine whether there was any consistent variation in the argyrophil cell population in longstanding ulcerative colitis. Argyrophil cells were demonstrated by the Grimelius method of silver impregnation in sections of non‐tumour bearing mucosa from the rectosigmoid colon of normal bowel, ulcerative colitics with and without tumour, and mucosa adjacent to, and distant from, carcinoma arising in otherwise normal bowel. Cell numbers were expressed as ratios of argyrophil cells per crypt, per mm of epithelium, and per mm of underlying muscularis mucosae. There was marked individual variation within all groups in all parameters. Between groups, the only significant difference was an increase in argyrophil cells per crypt in ulcerative colitis. The significance of this finding is discussed.
An experimental study into the cause of acute haemorrhagic gastritis in cirrhosis
Authors: Shibayama Yuro
Published: June 2005

To clarify the role of endotoxaemia and congestion of the stomach in the development of acute haemorrhagic gastritis in cirrhotic patients and to investigate the mechanisms of gastric mucosal haemorrhage, the present study was undertaken using rats. Congestion of the stomach was produced by the ligation of gastric veins. Congestion of the stomach or endotoxaemia could not produce gastric mucosal haemorrhage by itself. However, petechial haemorrhage was induced when endotoxin was given to the rats with congestion of the stomach, and the gastric mucosal haemorrhage was largely prevented by administration of gabexate mesilate, an anti‐kallikrein drug. Administration of bromelain, which releases prekallikrein and high molecular weight kininogen, instead of endotoxin, also induced gastric mucosal haemorrhage. These findings suggest that the cause of acute haemorrhagic gastritis may be the coexistence of endotoxaemia and congestion of the stomach due to liver cirrhosis and portal hypertension. The mechanisms of the haemorrhage may be as follows: Endotoxin‐induced bradykinin acts on the dilated capillaries and small veins in the mucosa and markedly increases their permeability.
Desmin‐containing stellate cells in rat liver; distribution in normal animals and response to experimental acute liver injury
Authors: Burt Alastair D. , Robertson James L. , Heir Jane , Macsween Roderick N. M.
Published: June 2005

Using immunhistochemical methods, we have confirmed that the perisinusoidal cells in rat liver express the intermediate filament protein, desmin, and we have used this marker for identification of the cells on light microscopy. The study has been extended to quantify the response of perisinusoidal cells to acute liver injury induced by carbon tetrachloride. A significant increase in desmin‐positive cells was observed in areas of necrosis as early as 48 h following the administration of a single bolus of carbon tetrachloride. This reached a peak at 72 h, with a five‐fold increase in desmin‐positive cells in areas of necrosis. These observations are consistent with the hypothesis that perisinusoidal cells are involved in the response to acute liver injury. Anti‐desmin antibodies are of potential value in further characterizing the functional role of perisinusoidal cells in normal and diseased liver.
DNA flow cytometry of human breast carcinomas and its relationship to transferrin and epidermal growth factor receptors
Authors: Walker Rosemary A. , Camplejohn Richard S.
Published: June 2005

The expression of transferrin and epidermal growth factor receptors in breast carcinomas, as detected by immunohistochemistry, has been compared with DNA ploidy and S‐phase content of the same tumours as determined by DNA flow cytometry of fixed, paraffin embedded tissue, and with tumour differentiation. Good correlations have been found between DNA ploidy, S‐phase content and differentiation. The expression of transferrin receptor appears to relate to DNA ploidy, but only to a limited extent to S‐phase content, indicating that in breast carcinomas immunoreactive transferrin receptor may not be directly related to proliferation. The presence of epidermal growth factor receptor shows a close correlation with high S‐phase content, but only a lesser association with DNA ploidy, and no correlation with tumour differentiation. DNA flow cytometry provides a more reliable method of assessing the relationship of such growth factor receptors in breast carcinomas to cell proliferation, than that obtained from more subjective tumour grading criteria.
Characterization of two cell lines, derived from two malignant fibrous histiocytomas
Authors: Roholl P. J. M. , Kleyne J. , Van Blokland M. , Spies P. L. , Rutgers D. H. , Albus‐Lutter Ch. E. , Van Unnik J. A. M.
Published: June 2005

We have investigated the phenotype and ultrastructure of tumour cells from two cell lines each derived from a malignant fibrous histiocytoma (MFH) as a means of studying the histogenesis of this group of tumours. The first MFH (MFH‐I) was of the pleomorphic subtype, with a predominantly histiocytic appearance, the second was of the pleomorphic subtype associated with myxoid and storiform areas (MFH‐II). In vitro tumour cells from both neoplasms showed aberrant growth properties. Xenografts in nude mice from both neoplasms showed a similar histology to that of the original tumour. Both tumours showed hyaluronidase sensitive alcian blue staining. Phenotypic studies of the two cell lines and of the tumour tissues demonstrated that the cells differed in the presence of collagen types I and III. They did not show evidence of histiocytic, endothelial, leiomyoblastic, rhabdomyoblastic, lipoblastic of schwannian origin. Ultrastructurally, the two cell lines were found to be different. In vitro and in xenografts the cell type of MFH‐I resembled a primitive mesenchymal cell. Whereas that of MFH‐II resembled a fibroblast‐like cell. We concluded that the group of MFH is heterogeneous and is probably derived from more than one progenitor cell.
Lectin histochemistry of galactose and N‐acetyl‐galactosamine glycoconjugates in normal gastric mucosa and gastric cancer and the relationship with ABO and secretor status
Authors: Macartney J. C.
Published: June 2005

The histochemical binding of four lectin‐peroxidase conjugates to normal human gastric mucosa and gastric carcinoma is described. The lectins were peanut agglutinin (PNA) which is specific for galactose residues and soy bean agglutinin (SBA), Dolichos biflorus agglutinin (DBA) and Helix pomatia agglutinin (HPA) which are specific for N‐acetylgalactosamine. Binding of PNA to surface mucous cells or normal gastric mucosa occurred in non‐secretors but not secretors and was independent of ABO blood group at all sites. PNA binding was unrelated to the immunohistochemical demonstration of Thomsen‐Friedenreich (T) antigen. DBA and HPA bound selectively to surface mucous cells in normal gastric mucosa from group A secretors but binding at other sites was independent of ABO status. SBA binding showed no relationship with blood group or secretor status. In gastric cancers the major finding was the occurrence of extensive masking of lectin binding sites by sialic acid which was not seen in normal mucosa. Sialic acid masking was most marked with PNA and least marked with DBA. There was no correlation between lectin binding patterns and the stage or differentiation of tumours. Results are consistent with in vitro studies demonstrating increased sialation of membrane glycoproteins following malignant transformation. Difficulties in interpreting the histochemical demonstration of lectin binding in terms of specific glycoconjugates are discussed.
A study of intermediate lobe differentiation in the human pituitary gland
Authors: McNicol Anne M.
Published: June 2005

The immunohistochemical demonstration of neurofilament (NF) polypeptide was used to identify nerves in a series of 17 pituitary adenomas. NF‐positive fibres were present in two out of five corticotroph adenomas sited deep in the anterior lobe, in one out of five sited in the intermediate zone and in two out of seven non‐corticotroph adenomas. Such nerve fibres were often seen in relation to blood vessels. The distribution of α‐MSH immunoreactive cells was examined in 25 normal pituitaries and in 23 cases of Cushing's disease. Such cells were scattered throughout the normal gland and there was no increase in numbers in pregnancy. α‐MSH was demonstrated in 18 corticotroph adenomas in Cushing's disease. There was no correlation with the site of the tumour or the presence of nerve fibres. α‐MSH cells were distributed normally in the para‐adenomatous gland. Crooke's hyaline change and α‐MSH coexisted in some corticotrophs. These findings support the concept that ‘intermediate lobe’ function, as found in animals, has no discrete anatomical location in man.
The Kupffer cell in experimental extrahepatic cholestasis in the rat—a light microscopy, immunohistochemical and electron microscopy study
Authors: Collier D. St. John , Pain James A. , Wight Derek G. D. , Lovat Penny , Bailey Michael E.
Published: June 2005

Kupffer cell phagocytic function is reduced in the prescence of obstructive jaundice. To investigate possible mechanisms we report a study of the rat liver in extrahepatic cholestasis, using light microscopy, immunohistochemistry and electron microscopy, Immunohistochemistry was performed with monoclonal antibodies specific for rat Kupffer cells ED 1, ED 2 and ED 3 and monoclonal antibodies directed against class II antigens of the rat major histocompatability complex Ox 3 and Ox 6. Extrahepatic cholestasis was produced by bile duct ligation. In bile duct ligated animals light microscopy showed proliferation of bile ductules and an increase in sinusoidal cells. Immunohistochemistry with ED 1, ED 2 and ED 3 demonstrated a marked increase in the number of positive cells, but few of these cells were positive with Ox 3 and Ox 6, whereas the proliferating bile ductules were strongly positive. Electron microscopy revealed two homogenous granular substances within the sinusoidal lumen and loss of the space of Disse. Despite a reduction in Kupffer cell phagocytic function in obstructive jaundice there is an increase in Kupffer cells, but these cells appear to be in an inactivated state as few express class II antigens on their surface. Furthermore the granular substance within the space of Disse may interfere with function.
Haematogenous metastastic patterns in colonic carcinoma: An analysis of 1541 necropsies
Authors: Weiss L. , Grundmann E. , Torhorst J. , Hartveit F. , Moberg I. , Eder M. , Fenoglio‐Preiser C. M. , Napier J. , Horne C. H. W. , Lopez M. J. , Shaw‐Dunn R. I. , Sugar J. , Davies J. D. , Day D. W. , Harlos J. P.
Published: June 2005

The sequence of events in haematogenous metastasis from colonic carcinoma was analysed, using 1541 necropsy reports from 16 centres. The findings are consistent with the cascade hypothesis that metastases develop in discrete steps, first in the liver, next in the lungs and finally, in other sites. Deviations of necropsy findings from the cascade model are largely explained on the basis of false negative reports. In only 216 of 1194 cases was there suggestive evidence that metastatic patterns (excluding lymph nodes) were causally related to lymphatic or non‐haematogenous pathways.

The incidence of metastatic involvement in ‘other’ (quaternary) sites correlated with target organ blood‐flow (ml min‐) per g, only when bone marrow and thyroid were excluded. In the thyroid the incidence was lower than expected on the basis of blood flow per g tissue; this may indicate that the thyroid is an unfavourable site for metastatic growth of colonic carcinoma. In the bone marrow it is higher; the latter may be due to delivery of cancer cells via both arterial blood and the vertebral venous plexus. Recognition of this pattern of metastases in the bone marrow could be important with respect of diagnosis and therapy, in patients with colonic carcinoma.
T‐zone lymphoma with predominance of ‘plasmacytoid T‐cells’ associated with myelomonocytic leukaemia—a distinct clinicopathological entity
Authors: Beiske Klaus , Langholm Ruth , Godal Tore , Marton Per F.
Published: June 2005

In this paper we present a further case of a new clinicopathological entity combining a rare type of non‐Hodgkin lymphoma with a myelomonocytic leukaemia. The characteristic feature of the lymphoma is massive infiltration of the T‐zones of lymph nodes by plasmacytoid cells originally described by Lennert1 in non‐specific lymphadenitis. Two lymphoma cases of this type have recently been published, by Müller‐Hermelink et al.2 who named the cells ‘plasmacytoid T‐cells’ (PTC), and by Prasthofer et al.3 These three cases have similar clinical and pathological features and appear to form a distinct clinicopathological entity. In contrast to the two previously published cases the present lymphoma also contained irregular lymphoid cells accompanying the PTC in the lymph node lesion and focally infiltrating the bone marrow. An accumulation of polytypic IgG positive plasma cells was observed in the remaining lymph node follicles. Immunohistological analysis with a range of monoclonal antibodies showed the PTC of our case to be CD5(T1) +, CD4(T4) +, CD3(T3)‐, CD8(T8)−, CD2(T11)−, and CD25(TAC)−, but HLA‐DR + and transferrin receptor positive. The nature of this peculiar lymphoid lesion and its relationship to myelomonocytic leukaemia are discussed.
The pathogenesis and biochemistry of amyloidosis
Authors: Cohen Alan S. , Connors Lawreen Heller
Published: June 2005

The transformation of serum proteins into Congo red‐sensitive fibrillar material is requisite for the onset and progression of amyloid disease. All the mechanisms which lead to the disease itself have not been elucidated, but our knowledge has increased significantly. It is apparent that in all types of amyloid fibrils, three common features are displayed by the major protein constituents. These are that the fibril protein has (1) a serum precursor, (2) a high degree of anti‐parallel beta‐sheet conformation and (3) a distinctive ultrastructure on electron microscopy. In the AL and AA forms of amyloidosis, the putative precursors appear to undergo limited degradation to form the protein component of amyloid fibrils. It has been suggested that there may be certain primary structural characteristics inherent in precursor molecules which make them amyloidogenic, thus predisposing them to amyloid fibril formation.33 This would include certain subtypes of immunoglobulin light chains, possibly kappa I and lambda VI, in the AL type of amyloidosis and one of the polymorphic SAA species, SAA2, which has been identified as the predominating isotype found in AA amyloid fibrils.32,33,110 In AH amyloidosis, the mechanism of amyloid fibril formation appears to be simply a concentration phenomenon where elevated concentrations of B2‐M are not handled normally and amyloid deposition is the result. Amyloidogenesis in the hereditary form of systemic amyloidosis may involve other factors in addition to the presence of a variant precursor prealbumin as indicated by the delayed onset of the disease. It is evident that the elucidation of the mechanism(s) which governs the onset and progression of the amyloidoses will allow future regulation and treatment of these all too often complex disorders.
Elastosis in breast carcinoma: I. Immunohistochemical characterization of elastic fibres
Authors: Mera S. L. , Davies J. D.
Published: June 2005

Elastosis associated with invasive ductal and lobular carcinomas of the breast was examined by tinctorial and immunohistochemical staining methods, enzyme digestion, and electron microscopy. The elastotic material exhibited the tinctorial staining properties of elastic fibres, and the ultrastructural appearances were those of elastic fibres although there was a higher proportion of microfibrils than in normal mature elastic fibres. The elastosis was immunostained by antisera to human fetal elastin, lysozyme and amyloid P component, as in other sites where elastic fibres are found. These findings indicate that immunohistochemically intact elastic fibres are present in the elastosis of breast cancer. They also demonstrate that lysozyme and amyloid P component are co‐distributed with elastic fibres in elastosis of breast carcinoma, as distinct components with different susceptibilities to enzyme digestion. The cellular origin of elastosis in breast carcinoma remains uncertain.
Nucleolar organizer regions in lymphomas
Authors: Crocker J. , Nar Paramjit
Published: June 2005

Using a silver staining technique, nucleolar organizer region‐associated proteins (Ag‐NORs) have been studied in paraffin sections of 90 non‐Hodgkin's lymphomas, five palatine tonsils and five ‘reactive’ lymph nodes. The method was readily applicable to these preparations and the Ag‐NORs were enumerated with ease. A significant difference was found between the numbers of Ag‐NORs in the nuclei of low‐grade lymphomas (from a mean of 1 to 1·5 per nucleus) and those of high‐grade lymphomas (a mean of 4·4 to 6·8 per nucleus). The Ag‐NOR regions were often observed in nuclei in areas where nucleoli themselves were not visible. It is suggested that this method, previously largely the province of the cytogeneticist, should find widespread applications in the field of tumour histopathology.
Effects of continuous subcutaneous insulin infusion on renal morphology in experimental diabetes. I. Blood glucose levels, body size, kidney weight and glomerulo‐tubular morphometry
Authors: Mayhew Terry M. , Sharma Ashutosh K. , McCallum Kenneth N. C.
Published: June 2005

Observations have been made over a period of 16 weeks on three groups of rats: controls, untreated streptozotocin‐diabetics and diabetics treated with continuous subcutaneous insulin infusion. Good control of circadian and diurnal blood glucose levels was achieved in the insulin‐treated diabetics.

Body weights and tibial lengths were reduced in untreated diabetics and improved, but not normalized, by insulin therapy. Kidney weights were similar in all groups.

Glomerular size and number, tubule volume, glomerular basement membrane volume and surface area were essentially the same in all groups. However, the untreated diabetics possessed tubules of larger diameter and shorter length than those in controls. Both variables were preserved at normal values by insulin infusion therapy.

These results illustrate the value of early blood glucose control for preventing at least some of the structural alterations associated with experimental diabetic nephropathy.
Effects of continuous subcutaneous insulin infusion on renal morphology in experimental diabetes. II. Glomerular basement membrane thickness
Authors: Mayhew Terry M. , Sharma Ashutosh K. , McCallum Kenneth N. C.
Published: June 2005

Stereological studies were performed on renal glomeruli from control rats, untreated streptozotocin‐diabetic rats and diabetics treated by subcutaneous infusion of insulin for 16 weeks. Estimates of glomerular basement membrane thickness were obtained by dividing membrane volume by membrane surface area. In addition, arithmetic and harmonic mean thicknesses were calculated from orthogonal intercept lengths, and used to provide information on the variability of basement membrane thickness.

In untreated diabetics, both arithmetic and harmonic mean thicknesses were significantly greater than values found in control animals. The thickening of the basement membrane appeared to be generalized rather than markedly focal. All thickness variables were normalized by insulin infusion therapy.

These findings underline the importance of good glycaemic control and early intervention in experimental diabetes and one of its main complications.
Role of macrophages in mesothelial healing
Authors: Fotev Z. , Whitaker D. , Papadimitriou J. M.
Published: June 2005

The role of macrophages in rat mesothelial healing was evaluated in vivo and in vitro. In animals whose circulating monocytes were severely depressed, the healing rate was retarded; however, this effect was partly reversed by the introduction of macrophages into the injured site, suggesting that macrophages are of fundamental importance in the healing of mesothelial wounds. Furthermore, it was found that wound exudates stimulated DNA synthesis in normal quiescent mesothelial cells and the component principally responsible for this activity was the macrophage. Cultured macrophage‐conditioned media also induced an increase in mesothelial replication. Moreover, the mitogenic activity present in both wound exudates and macrophage‐conditioned media was increased by dialysis and diminished by heating at 80°C for 1 h. The putative mesothelial mitogenic factor in the supernatant of wound exudates and macrophage cell cultures has a molecular size greater than 7000 dalton and is stable after mild heating (60°C, 1 h). It is postulated that exudate macrophages secrete mitogenic factor(s) which stimulate mesothelial proliferation, and initiate healing.
A useful low temperature method for post‐embedding electron immunocytochemistry in routine histopathology
Authors: McPhail Graham D. , Finn Teresa , Isaacson Peter G.
Published: June 2005

Using a low temperature resin, we have developed a reliable technique for post‐embedding electron immuno‐cytochemistry which is rapid enough to be used in a routine histopathology laboratory.

Glutaraldehyde fixed human tissues were dehydrated and embedded at −25°C in a new acrylic resin called LR‐Gold. Using the immunogold technique, ultra‐thin sections of the tissues were labelled with monoclonal antibodies to cytokeratin, human milk fat globule and HLA‐D region antigen; and with polyclonal antisera to lysozyme, kappa and lambda light chains and immunoglobulin M. The resin was easy to section and the preservation of fine structure was excellent. Immunolabelling procedures gave clean and consistent results, and electron micrographs of examples of this are included. It was felt that the preservation of ultrastructure and antigenicity compared well with the results of other workers using low temperature resins such as Lowicryl K4M, but LR‐Gold was superior to Lowicryl K4M because sectioning was considerably easier and the sections were more stable in the electron beam.
The effect of cimetidine on parathyroid function and histopathology in primary hyperparathyroidism
Authors: Sotsiou F. C. , Singhellakis P. N. , Nikou A. D. , Pappas A. D. , Vambouka Ch. , Sklivagou N. G. , Ikkos D. G.
Published: June 2005

Recent evidence suggests that cimetidine given pre‐operatively in primary hyperparathyroidism (1°HPT) might cause structural changes in parathyroid glands, while its suppressive effects on the disease are disputable.

To determine these possible changes we studied 38 patients with 1°HPT who underwent parathyroidectomy. In 14 of these (group I) cimetidine was given pre‐operatively (1000 mg orally daily for 4 weeks). The remaining 24 patients (group II) did not take any drug. Parathyroid function was estimated by nephrogenous cAMP (NcAMP) and serum immunoreactive parathyroid hormone (iPTH) measurements. Histological examination of the parathyroids was made by conventional techniques.

In group I at the end of cimetidine treatment, the only change observed was a small but significant (p<0·05) decrease of plasma calcium (−0·77 mg/dl). Histologically, the glands of group I—compared with those of group II—showed the following findings: (1) increased gland mass: mean increase 1050 mg (adenomas) and 700 mg (hyperplasias); (2) central oedema in all the cases of group I only; (3) increased (about 50 per cent) cellular size and (4) intranuclear ‘inclusions’ in 10 out of 14 cases of group I only.

It is concluded that treatment with cimetidine in 1°HPT is followed by histopathologic alterations leading to increased size of the diseased parathyroids.
Prognostic significance of DNA aneuploidy and cell proliferation in rectal adenocarcinomas
Authors: Quirke Philip , Dixon Michael F. , Clayden Andrew D. , Durdey Paul , Dyson John E. D. , Williams Norman S. , Bird Colin C.
Published: June 2005

DNA content and cell proliferation were studied retrospectively in 125 patients presenting from 1974–1981 with rectal adenocarcinoma. The presence of DNA aneuploidy or a high level of cell proliferation were associated with a poor prognosis and when combined were the best predictor of survival after Dukes's stage excluding all other pathological assessments investigated. High cell turnover was significantly associated with an infiltrative pattern of growth, an observation that might explain the poorer prognosis of this pattern in rectal adenocarcinomas.
Immunopathological studies on thyroid immunity. IX. Thyroid and renal amyloidosis in thyroglobulin immunized rabbits
Authors: Blumenthal H. T. , Premachandra B. N.
Published: June 2005

In serial studies of immunopathologic changes in an animal model of thyroiditis 52 rabbits were immunized with either bovine, porcine or human thyroglobulin (Tg) in Freund's complete adjuvant, while another 47 animals served as noninjected or adjuvant injected controls. The immunized animals were divided into two groups, one receiving an initial series of only three Tg injections while the other received, in addition, challenging injections over an 8‐week period. The immunized animals were killed over a period of 6–34 months after the last Tg injection, and untreated controls were killed at comparable ages. In Tg immunized animals, lymphocytic thyroiditis was encountered in 25 per cent and thyroid amyloid in 17 per cent; glomerular amyloid was encountered in 44 per cent with diffuse lesions in 8 per cent, nodular lesions in 17 per cent and a mixture of the two in 19 per cent. That the thyroid and glomerular hyaline deposits contained amyloid was shown by various histochemical criteria, as well as by the presence of typical fibrils on electron microscopy. Immunohistochemical studies indicated that the amyloid was predominantly of the AA type. Rabbits receiving challenging Tg injections, in addition to the initial series, showed only thyroiditis and nodular glomerular lesions most of which were amyloid. Whilst the vast majority of rabbits with lymphocytic or amyloidotic responses showed both thyroid and renal lesions, a small percentage of animals showed only a lesion of one or the other of these two organs. It is of interest that the thyroid and renal amyloid lesions, described for the first time with induced thyroglobulin immunity, were not detected in other earlier short term investigations.
Endotoxin induced hepatic necrosis in rats on an alcohol diet
Authors: Bhagwandeen Bramdutt S. , Apte Minoti , Manwarring Lynette , Dickeson John
Published: June 2005

The role of endotoxin in the pathogenesis of progressive liver disease is receiving increasing attention, but remains controversial. Similarly, although alcoholic hepatitis is now recognized as the transitional link between alcoholic fatty liver and advanced alcoholic liver disease, the aetiology of liver cell necrosis in alcoholic hepatitis is not known.

Rats fed a nutritionally adequate liquid alcohol diet according to the formula of Lieber and DeCarli developed fatty livers. Littermates fed an identical diet and challenged with small IV doses (1μg/g body weight) of E. coli lipopolysaccharide endotoxin (LPS) developed focal necrotizing hepatitis. Control littermates fed an identical calorie balanced but alcohol free diet and challenged with identical doses of LPS did not develop any liver lesions.

The hepatocyte necrosis with associated inflammatory changes induced by LPS in fatty livers has some features of early human alcoholic hepatitis and suggests that progressive alcohol induced damage may be multifactorial in origin.
Demonstration of human papilloma virus types in paraffin processed tissue from human anogenital lesions by in‐situ DNA hybridisation
Authors: Wells Michael , Griffiths Sharon , Lewis Fraser , Bird Colin C.
Published: June 2005

A sensitive in situ hybridization technique for the demonstration of human papillomavirus (HPV) employing a biotin‐streptavidin polyalkaline phosphatase complex has been successfully applied to formalin‐fixed, paraffin processed tissue obtained from a selected series of patients with ano‐genital lesions. Benign condylomata from males and females showed the presence of HPV 6 and 11. Two cases of vulval intraepithelial neoplasia showed HPV 16. Four cases of squamous carcinoma of the anal canal also showed HPV 16 in the tumour or in the adjacent pre‐invasive neoplastic epithelium. A case of malignant transformation in a cervical condyloma was associated with HPV 6 and 11. This technique permits the retrospective evaluation of routinely processed material thus widening the investigative spectrum for HPV.
Gastric dysplasia: A stereological and morphometrical assessment
Authors: Tosi Piero , Luzi P. , Baak J. P. A. , Miracco C. , Vindigni C. , Lio R. , Barbini P.
Published: June 2005

The grading systems of gastric dysplasia suffer from the lack of criteria that separate the changes with an acceptable reproducibility. Repeatable and objective grading of the lesion can be obtained by morphometrically measuring histological criteria normally employed in qualitative grading.

In 54 consecutive antrum biopsy specimens in which a blind, independent agreement on the grade of dysplasia had been reached between four independent pathologists, stereological and nuclear morphometrical features have been studied. Single variate, bivariate and multivariate analyses have been performed. Architectural parameters, such as volume and surface densities of glands and epithelium, are especially good discriminators both between mild and moderate, and between moderate and severe dysplasia. Features describing arrangement and shape of nuclei, and nucleolar size are of additional help in improving the objective distinction between moderate and severe dysplasia.