bluuebunny/crossref_metadata_2025 huggingface dataset:
Intra‐ocular transplantation of carcinoid tumours from Mastomys and humans
Authors: Nilsson Ola , Bilchik Anton J. , Adrian Thomas E. , Modlin Irvin M.
Published: June 2005

Carcinoid tumours from man and Mastomys (Praomys) natalensis produce a variety of peptide hormones. The study of these peptide‐secreting tumours has been difficult because of the small amount of tissue available and because of limitations with present cell culture systems. The aim of this study was to establish an experimental model where carcinoid tumours could be maintained and their hormone secretion studied. The intra‐ocular transplantation technique was chosen for its simplicity and high rate of success. Gastric carcinoid tumours from mastomys (n=4) and human carcinoids (n = 2) (one bronchial and one ileal) were transplanted to the anterior eye chamber of SpragueDawley rats. Pieces of fresh tumour tissue were injected into the anterior eye chamber of rats and allowed to grow for 4–8 weeks. Rats transplanted with human tissue were immunosuppressed by daily injections with cyclosporin A (20 mg/kg). Eye chambers were inspected regularly and plasma from transplanted rats was collected for assay of peptide YY (PYY) and glucagon. Vascularization of transplants occurred within 1–2 days after transplantation in 70–80 per cent of all experiments. Microscopic analysis of transplants demonstrated a rich supply of blood vessels to tumour cells which contained characteristic neurosecretory granules. Transplanted rats had significantly (P<0.05) elevated levels of PYY (44–165 pmol/1) and glucagon (67–162 pmol/l) in plasma as compared with sham‐operated rats (PYY 28–40 pmol/1, glucagon 33–40 pmol/l), indicating that hormone secretion by tumour cells in oculo was maintained. Thus, carcinoid tumours from mastomys and humans can be grown in the anterior eye chamber of rats with preserved endocrine activity. The transplantation model may prove to be useful in the study of tumour cell bioactivity and prediction of therapeutic efficacy.
Adhesions, focal sclerosis, protein crescents, and capsular lesions in membranous nephropathy
Authors: Van Damme B. , Tardanico R. , Vanrenterghem Y. , Desmet V.
Published: June 2005

All biopsies of membranous glomerulopathy collected between 1965 and 1988 (n=198) were examined for the presence of adhesions, focal sclerosis, protein crescents, capsular drops, and other capsular lesions. These were observed with a frequency related to the number of glomeruli in the biopsy and the number of sections examined. A peculiar interrelation between these lesions was found. In the 63 cases with sufficient clinical follow‐up, the capsular lesions were associated with a lower incidence of remission of the disease, and with more proteinuria and a higher serum creatinine at the last follow‐up. It is hypothesized that focal detachment of podocytes may result in the formation of a protein crescent if a plasma‐like filtrate is ‘injected’ between the epithelium of Bowman's capsule and its basement membrane. The detachment of the epithelium may lead to focal sclerosis and the formation of adhesions. The capsular drop is thought to be a final stage of inspissation of the protein crescent.
Age‐related changes in metallothionein, copper, copper‐associated protein, and lipofuscin in human liver: A histochemical and immunohistochemical study
Authors: Fuller Clare E. , Elmes Margaret E. , Jasani Bharat
Published: June 2005

The relationship between immunohistochemically demonstrable hepatic metallothionein (MT) and age was studied in histologically normal livers from 12 fetuses (13–28 weeks' gestation) and 19 children (birth‐4 years). In addition, the relationships between copper (rubeanic acid‐positive), copper‐associated protein (orcein‐positive), lipofuscin (periodic acid Schiff after diastase digestion and Schmorls‐positive), and MT (immunostaining) were studied. The fetal livers showed periportal and patchy mid‐zone copper‐associated protein and lipofuscin granules, together with strong diffuse cytoplasmic and nuclear MT immunostaining. On the other hand, the livers of the children over 6 months of age showed no copper‐associated protein or lipofuscin granules, and minimal or no cytoplasmic MT immunostaining (one case showed nuclear MT immunostaining). The DPAS and Schmorls‐positive lipofuscin granules appeared to be identical to the orcein‐positive copper‐associated protein granules which were consistently negative on MT immunostaining. The demonstration of cytoplasmic granular orcein positivity or diffuse non‐granular MT immunostaining in liver above the age of 6 months would appear to be of pathological significance.
Ribosome‐lamella complexes observed in an epstein‐barr virus‐producing B‐cell line, infected with human T‐lymphotropic virus type I
Authors: Ohtsuki Yuji , Yano Shoki , Kubonishi Ichiro , Hayashi Kazuhiko , Sonobe Hiroshi , Iwata Jun , Furihata Mutsuo , Hikita Tomonori , Wakiguchi Hiroshi , Kurashige Takanobu , Miyoshi Isao
Published: June 2005

Co‐cultivation of peripheral blood mononuclear cells, from a 4‐year‐old boy with infectious mononucleosis, with a human T lymphotrophic virus type I (HTLV‐I)‐producing T‐cell line resulted in the establishment of an HTLV‐I infected Epstein‐Barr virus (EBV)‐producing B‐cell line. Ultrastructural examination revealed the presence of ribosome‐lamella complexes (RLCs), in a small proportion of long‐term cultured cells. Evidence is presented of continuity between RLC and the rough endoplasmic reticulum, and in some instances there was also an intimate relationship with tubuloreticular structures. The findings support the view that RLC is derived from the rough endoplasmic reticulum and also provide further evidence of the non‐specific nature of RLC in relation to cell type.
Identification and distribution of atrial natriuretic polypeptide in ventricular myocardium of humans with myocardial infarction
Authors: Takemura Genzou , Fujiwara Hisayoshi , Yoshida Hirotsugu , Mukoyama Masashi , Saito Yoshihiko , Nakao Kazuwa , Fujiwara Takako , Uegaito Takashi , Imura Hiroo , Kawai Chuichi
Published: June 2005

The expression of atrial natriuretic polypeptide (ANP) in the ventricles of human hearts with myocardial infarction (MI) was studied immunohistochemically. Immunoreactive myocytes were identified in the ventricular tissues of all of 16 hearts with old MI (both with and without heart failure) and in all five hearts with subacute MI, but not in any of the eight hearts without MI nor in the five with acute MI. In the nonfailing hearts with MI, ANP positive myocytes surrounded the areas of infarction, and were also seen in the subendocardium of the infarcted segment. In the failing hearts with MI, ANP expression was noted in the whole ventricular subendocardial region, in addition to the border of infarcts. The sites of ANP expression corresponded well to those of marked stress attributable to tissue shrinkage or fibrosis due to MI, haemodynamic overload, or both. It thus appears that ANP expression is augmented in human hearts with MI regardless of the presence or absence of heart failure, and it is suggested that regional mechanical stress on the ventricular myocardium, as well as haemodynamic overload, may be very closely associated with ventricular ANP expression.
Malignant haemangiopericytoma of lung: A cell culture and ultrastructural study
Authors: Yang Hang , Liu Hung Chang
Published: June 2005

Malignant haemangiopericytoma was grown in vitro to assess the histogenesis of the tumour. Disaggregated tumour cells maintained in serum‐supplemented Waymouth's MB 752/1 medium showed monolayers of homogeneous spindle cells. Post‐confluent cultures exhibited hillocks or plaques of multilayer growth within which considerable amount of basal lamina‐like material and fibrillar matrix were present between cells. Delicate basal laminae were also expressed on cell surfaces facing matrix material. Other consistent features were attenuated cytoplasmic processes, desmosome‐like junctions, abnormal mitochondria and a paucity of intracellular filaments. The three‐dimensional organization of tumour cells with concomitant expression of differentiated phenotype in vitro has significant implications on the cell of origin and differentiation process of haemangiopericytoma.
DNA analysis by flow cytometry in malignant pleural mesothelioma: Relationship to histology and survival
Authors: Dazzi H. , Thatcher N. , Hasleton P. S. , Chatterjee A. K. , Lawson R. A. M.
Published: June 2005

In a retrospective study of 70 patients with malignant pleural mesothelioma, 168 formalin‐fixed, paraffin‐embedded tumour specimens were examined for DNA content by flow cytometry. In 20 patients where two or more blocks of the same tumour were available, there was considerable agreement between ploidy status and S‐phase percentage in the different specimens.

There were no significant differences for survival for patients who had been exposed to asbestos and those in whom no exposure could be elicited, nor for aneuploid and diploid tumours. The S‐phase content was examined for different areas of the same tumour and the percentages were largely in agreement. However, those patients who had tumours with an S‐phase percentage greater than the median (6 per cent) had a significantly shorter survival than those with tumours of lower S‐phase percentage. Differences in DNA content and other cell cycle parameters were not associated with the histological subtypes.
Histopathological changes in simian immunodeficiency virus infection
Authors: Baskerville A. , Ramsay A. , Cranage M. P. , Cook N. , Cook R. W. , Dennis M. J. , Greenaway P. J. , Kitchin P. A. , Stott E. J.
Published: June 2005

The histological lesions were studied in seven rhesus and three cynomolgus monkeys infected with simian immunodeficiency virus for periods ranging from nine weeks to 18 months. Lymphoreticular changes included hyperplasia, follicular involution and depletion, and one animal had amyloidosis of the spleen. Hyperplastic changes also took place in mucosa‐associated lymphoid tissue and infiltrations occurred in the vaginal mucosa of one animal, which could be significant in sexual transmission of the infection. The range of opportunistic infections was small compared with that in human AIDS patients, although two monkeys had Pneumocystis carinii pneumonia. Enterocolitis was a common finding and brown adipose tissue was transformed into a large vacuolated type. Lesions of the central nervous system were found in five of nine monkeys, and consisted of foci of glial activity and perivascular and meningeal lymphocytic infiltration. A lymphoma involving the lumbar spinal cord developed in one animal.
Silicone plastinated pathology specimens and their teaching potential
Authors: Dawson Timothy P. , James Ryk S. , Williams Geraint T.
Published: June 2005

Plastination is a process of tissue preservation by impregnation with silicone polymers or epoxy resins. The resulting specimens are dry, odourless, durable, life‐like, non‐hazardous, maintenance‐free, and do not deteriorate with time. The technique may be easily mastered by those with a basic knowledge of histology laboratory practice. A small‐scale system is relatively inexpensive to establish and specimens are comparable in cost to traditional ‘pots’.

Plastinated specimens are a useful adjunct to the teaching of pathology, anatomy, radiology, and surgery, and are particularly suited to use in small groups. They are much preferred to conventional ‘pots’ by both students and teachers owing to their accessibility, superior illustrative powers, and comparative ease of interpretation.
In situ and slot hybridization analysis of RNA in colorectal tumours and normal colon shows distinct distributions of mitochondrial sequences
Authors: Chester K. A. , Robson L. , Begent R. H. J. , Pringle H. , Primrose L. , Talbot I. C. , Macpherson A. J. S. , Owen S. L. , Boxer G. , Malcolm A. D. B.
Published: June 2005

cDNA clones of mRNAs with an abnormal abundance in familial adenomatous polyposis were used to examine the levels and distribution of the mRNAs in tissues from 15 patients with colorectal cancer. Of 12 cloned sequences studied by slot hybridization, one was substantially reduced in tumours compared with normal tissue. Sequence analysis showed this to code for IgA. In situ hybridization was consistent with slot hybridization and immunohistochemistry. Two mitochondrially encoded sequences had distinct distributions detected by in situ hybridization but did not have detectable quantitative differences in whole tumour or mucosa extracts.
Determinants of glomerular cross‐sectional area
Authors: Newbold K. M. , Howie A. J.
Published: June 2005

A method of measurement of glomerular cross‐sectional area was applied to 267 renal biopsies from 19 groups of patients with well‐defined pathological and clinical conditions. There was a correlation between the mean glomerular area for each group and the percentage of global sclerosis in each group. A few groups had glomeruli that were larger than would be expected from their percentage of global sclerosis, probably due to cellular proliferation and/or infiltration. A few groups had glomeruli that were smaller than would be expected from their percentage of global sclerosis, probably due to ischaemic shrinkage. These observations indicate that as well as the known influence of body size on the glomerular area, the number of functioning glomeruli in the body has an important effect on the glomerular area.
Grading of superficial antral gastritis: Comparison of cell‐counting and photographic‐based methods
Authors: Collins J. S. A. , Watt P. C. H. , Hamilton P. W. , Sloan J. M. , Love A. H. G.
Published: June 2005

A cell‐counting technique and a photographic‐based scoring system for assessing inflammatory cell infiltration were compared for agreement in 275 endoscopic gastric antral biopsies from 55 dyspeptic patients. Each biopsy was independently scored 0–5 for polymorphs and mononuclear cells using both methods, and a mean score was derived for each patient. There was a highly significant correlation between the mean patient scores obtained using each method (P < 0·001). Agreement statistics showed that the mean score difference (cell‐counting minus photographic score) was negative for polymorphonuclear and mononuclear cells, indicating that the photographic method yielded higher mean patient scores. Scatterplots of difference versus mean by the two methods showed that only 3·6 per cent of scores fell outside ±2 SD of the mean difference. The use of standard photomicrographs to grade superficial antral gastritis therefore provides accurate results, comparable to those obtained by cell counting, yet is a faster and much cheaper technique.
Monoclonal antibodies to cultured human glomerular mesangial cells. I. Reactivity with haematopoietic cells and normal kidney sections
Authors: Stewart Keith N. , Roy‐Chaudhury Prabir , Lumsden Lynne , Jones Michael C. , Brown Paul A. J. , Macleod Alison M. , Haites Neva E. , Simpson John G. , Power David A.
Published: June 2005

The aim of this study was to produce monoclonal antibodies to cultured human glomerular mesangial cells in order to obtain specific markers for these cells and to aid the study of their function. Using standard monoclonal antibody techniques, 29 hybridomas producing antibodies directed to cultured mesangial cells were obtained. Most of these antibodies were not reactive with normal or neoplastic haematopoietic cell lines by flow cytometry. Fourteen of the 29 culture supernatants bound to various components of normal human kidney sections stained by the alkaline phosphatase/anti‐alkaline phosphatase (APAAP) method. Ten of these supernatants reacted with components within the glomerulus, with six binding to the mesangium. These studies suggest that (1) mesangial cells in culture may show significant de‐differentiation, because most supernatants which reacted with mesangial cells in culture did not do so in tissue sections: (2) antibodies reactive with haematopoietic cells may not detect the majority of immunogenic surface antigens on cells in tissues; and (3) some of the antibodies which we have produced may prove to be useful markers for mesangial cells in glomerular disease.
Expression of chromogranin a mRNA in small cell carcinoma of the lung
Authors: Hamid Q. , Corrin B. , Sheppard M. N. , Huttner W. B. , Polak J. M.
Published: June 2005

Chromogranin A (CgA) is the most specific neuroendocrine marker but in small cell carcinoma of the lung (SCCL) CgA immunoreactivity cannot always be detected, possibly owing to poor granularity. The localization of CgA mRNA could be a more useful indicator of CgA synthesis in SCCL. We have therefore studied the expression of CgA mRNA in SCCL, using in situ hybridization and Northern blot analysis, comparing it with CgA immunoreactivity. The expression of CgA mRNA and immunoreactivity in other types of lung tumours was also investigated. Freshly fixed, surgically resected SCCL (n = 5), adenocarcinoma (n = 10), squamous cell carcinoma (n = 10), large cell carcinoma (n = 5), and primary lymphoma (n = 2) were examined. Weak immunoreactivity to CgA was seen in one SCCL but all five strongly expressed CgA mRNA. The specificity of the in situ hybridization signal and the probe was confirmed by the use of a sense probe and Northern blot analysis. Non‐SCCLs were negative for both CgA mRNA and immunoreactivity. This study provides evidence for CgA synthesis in SCCL and confirms the specificity of CgA for neuroendocrine differentiation. In situ hybridization appears to be a very useful tool for investigating the nature of tumour cells, especially in the absence of the end product of the gene transcript.
Detection of Epstein–Barr virus antigens and DNA in major and minor salivary glands using immunocytochemistry and polymerase chain reaction: Possible relationship with Sjogren's syndrome
Authors: Deacon E. M. , Matthews J. B. , Potts A. J. C. , Hamburger J. , Bevan I. S. , Young L. S.
Published: June 2005

This study has investigated the presence of Epstein–Barr virus (EBV) in parotid (n = 12), submandibular (n = 15), and minor salivary glands (n = 25) using immunohistochemical methods for detection of EBV‐encoded antigens and the polymerase chain reaction (PCR) for detection of viral DNA. Major salivary glands were from patients without connective tissue disease. Labial glands were from patients with primary Sjogren's syndrome (n = 10), rheumatoid arthritis (n = 8), or from normal individuals (n = 7). None of the glands exhibited specific reactivity for lytic (EA‐D, EA‐R, VCA) or latent (EBNA‐2, LMP) viral antigens. Antibodies to EA‐D, when used at 20–50 times their optimal concentration, gave lumenal staining of ducts and acini of all the specimens tested (n = 14), irrespective of the presence (n = 8) or absence (n = 6) of EBV‐DNA by PCR. Ductal immunoreactivity for the EBV/C3d (CR2, CD21) receptor was found in 40 per cent of specimens. PCR detected EBV‐DNA in 64 per cent submandibular, 46 per cent parotid, and 80 per cent of minor glands. There were no significant differences in the detection of EBV‐DNA between specimen/patient groups. Only type A EBV was detected by strain typing PCR. These results indicate that EBV (type A), undetected immunocytochemically, is commonly present at low copy numbers within salivary glands irrespective of a clinical diagnosis of Sjogren's syndrome.
Cell adhesion and epithelial differentiation
Authors: Fleming Stewart
Published: June 2005

The differentiated function of epithelial tissues is dependent on the molecules which mediate the cohesion and polarization of the epithelium. Separate molecular families are responsible for the adhesion between adjacent cells and the adhesion beween cells and the substratum. Using the kidney as a model of epithelial differentiation it has been shown that the assembly of a basal lamina containing the glycoprotein laminin and cadherin mediated intercellular adhesion are key events. The Wilms' tumour anti‐oncogene plays a regulatory role in renal epithelial differentiation. Tissue modelling and tumour formation are both accompanied by reduced cell adhesion molecule function.
Potential antigen‐presenting cells in normal extraocular muscles demonstrated with double immunoenzyme staining
Authors: Schmidt E. D. , Das P. K. , van Der Gaag R. , Tigges A. J. , van Der Loos C. M. , Koornneef L.
Published: June 2005

Antigen‐presenting cells are of crucial importance for the initiation and regulation of regional immune responses. In a previous study, indirect morphological evidence that morphologically normal human orbital tissues contain HLA‐DR‐positive macrophages, which may represent antigen‐presenting cells, has ben obtained. In the present study, these cells were characterized in detail using double immunoenzyme staining techniques with monoclonal antibodies directed against several well‐characterized monocyte/macrophage markers and against HLA‐DR gene products. The orbital muscular tissues appear to contain numerous HLA‐DR, monocyte/macrophage marker double‐stained cells, which are considered to be potential antigen‐presenting cells. The cells are widely distributed in the connective tissue of all the orbital muscular tissues studied and consist of several subsets with different phenotypes. Furthermore, site‐specific differences were shown between recti muscles and the levator/Müller's muscles with respect to the distribution of HLA‐DR and one monocyte/macrophage marker (OKM5). Many of the orbital antigen‐presenting cells appear to be of the dendritic type and are considered to be of major importance in regulating local orbital immunity.
Expression of different cytokeratin subclasses in human chordoma
Authors: Heikinheimo Kristina , Persson Stellan , Kindblom Lars‐Gunnar , Morgan Peter R. , Virtanen Ismo
Published: June 2005

A detailed immunohistochemical characterization of different cytokeratin subclasses was performed on frozen tumour tissue from three classical chordomas. Simple epithelium cytokeratins Nos 8, 18, and 19 were detected in all tumour cells while cytokeratin No. 7 was not found. Cytokeratins characteristic of squamous differentiation, including keratinization, were generally lacking, with the exception of the varying expression of cytokeratin No. 4. Vimentin was found in all the tumours, while they lacked desmin immunoreactivity. The present study indicates the co‐expression of vimentin and cytokeratins, predominantly of the simple epithelium type. In addition, chordoma cells have the ability to express cytokeratins characteristic of squamous differentiation. This finding corresponds well to the electron microscopic findings of tonofilament bundles ending in well‐developed desmosomes.
Pneumocystis carinii pneumonia in simian immunodeficiency virus infection: Immunohistological and scanning and transmission electron microscopical studies
Authors: Ville A. Basker , Dowsett A. B. , Cook R. W. , Dennis M. J. , Cranage M. P. , Greenaway P. J.
Published: June 2005

Pneumocystis carinii pneumonia occurred in 6 of 17 rhesus monkeys infected with simian immunodeficiency virus and was studied by immunohistochemistry and by scanning and transmission electron microscopy. A monoclonal antibody/streptavidin‐biotin‐peroxidase staining method was highly sensitive for detecting the organisms in small, early lesions and was much more sensitive and specific than traditional silver impregnation methods. Reprocessing of paraffin wax‐embedded lung tissue for scanning electron microscopy and use of a video printer to produce a photographic montage of light microscopic lesions allowed the same areas of tissue to be examined and compared by both methods. The ultrastructural morphology of P. carinii in the rhesus monkey was identical to that in man, as were the histological and electron microscopic lesions, including pulmonary fibrosis. Trophozoites were seen attached to alveolar type I epithelium mainiy by intimate apposition to the plasma membrane, but scanning electron microscopy also showed attachement by elongated filopodia. Few macrophages were present in infected alveoli, and though phagocytosis followed by digestion of P. carinii trophozoites was observed, it appeared to occur at a very low level.
The topographical and age distributions of neuroendocrine cells in the normal human appendix
Authors: Shaw Paul A. V.
Published: June 2005

In order to clarify the histogenesis of appendiceal carcinoid tumours, epithelial (ENC) and subepithelial (SNC) neuroendocrine cells were counted at four sites in 50 normal appendices stained by standard argyrophil and argentaffin techniques. In general, ENC were present in similar number at all sites within the appendix, whereas SNC were more numerous at the tip than at the base. The number of ENC was similar throughout life, apart from an increase in one neonate and some elderly patients, whereas SNC were maximal in young adults. Thus, the topographical and age distributions of SNC, but not those of ENC, parallels the topographical and age incidence of appendiceal carcinoid tamours, suggesting that most appendiceal carcinoid tumours arise from SNC rather than ENC.
Image analysis quantification of peptide‐immunoreactive nerves in the skin of patients with Raynaud's phenomenon and systemic sclerosis
Authors: Terenghi Giorgio , Bunker Christopher B. , Liu Yu‐Fei , Springall David R. , Cowen Tim , Dowd Pauline M. , Polak Julia M.
Published: June 2005

Image analysis quantification was used to assess the results of immunocytochemistry for a neuronal marker and neuropeptides in digital skin biopsies from Raynaud's phenomenon (RP) and systemic sclerosis (SS) patients, to verify the possibility of a selective quantitative abnormality of immunoreactive nerves. The field area of specific immunostaining and nerve counts were evaluated on coded specimens, and the data compared by statistical analysis. Nerves immunoreactive for protein gene product 9.5 (PGP), a marker for neuronal elements, were decreased significantly in epidermal and subepidermal layers of digital skin in RP patients (P < 0.0001). This change was paralleled by a decrease of calcitonin gene‐related peptide (CGRP) immunoreactive nerves in the epidermis and around capillaries in the dermal papillae (P=0.005). In the skin of RP patients, these changes were readily demonstrated by image analysis, although they were not always apparent on visual screening. In digital skin of SS patients, there was a generalized and very significant decrease of PGP, CGRP, and VIP immunoreactivities in all areas (P<0.0001). These results demonstrate that neuropeptide‐containing nerves are involved in the digital pathology of RP and SS, and that image analysis quantification is an accurate and sensitive method for assessing morphological changes in pathological samples.
Necrotizing myopathy in critically‐ill patients
Authors: Helliwell Timothy R. , Coakley John H. , Wagenmakers Anton J. M. , Griffiths Richard D. , Campbell Iain T. , Green Ceri J. , McClelland Peter , Bone John M.
Published: June 2005

Skeletal muscle wasting is commonly observed in critically‐ill patients and has been attributed to catabolic fibre atrophy and to neuropathy. This study describes the occurrence of a necrotizing myopathy in 15 out of 31 critically‐ill patients who had percutaneous biopsies taken from the tibialis anterior muscles. While most cases showed necrosis of isolated fibres, 5 of the 12 patients who had serial biopsies showed progressive necrosis of up to 95 per cent of the fibres. One other case showed infarction and one case had staphylococcal vasculitis. Atrophy of type 1 and/or type 2 fibres was documented by morphometry in 12 cases. Myoglobin‐containing casts were demonstrated immunohistochemically in renal tubules on either biopsy or necropsy material in 5 out of 7 cases.

The presence of muscle necrosis was a clinically unexpected finding which may contribute to weakness, complicate the interpretation of tissue biochemistry and energy balance studies, and potentiate renal failure. The necrosis is probably multifactorial in origin, with ischaemia and sepsis contributing factors.
Infantile desmoid‐type fibromatosis. Morphological features correlate with biological behaviour
Authors: Schmidt Dietmar , Klinge Petra , Leuschner Ivo , Harms Dieter
Published: June 2005

It is generally agreed that the biological behaviour of infantile desmoid‐type fibromatosis is unpredictable in terms of the likelihood of local recurrence. We evaluated the prognostic importance of the number of slit‐like blood vessels with a mean diameter of less than 20 μm and of the quantity of undifferentiated mesenchymal cells. In addition, we studied the immunophenotypic characteristics of the proliferating cells and their nucleolar organizer region (AgNOR) numbers and distribution. Statistical analysis showed that the tendency to recur locally was correlated with larger numbers of slit‐like blood vessels and undifferentiated mesenchymal cells. The proliferating cells were identified by immunohistochemistry as myofibroblasts. No correlation was found between AgNOR numbers and clinical course of the disease. We conclude that histological features easily evaluated by conventional light microscopy provide useful information on the possible course of infantile desmold type fibromatosis.
Dermatopathology
Authors: Slater D. N.
Published: June 2005

Recent advances in dermatopathology such as epidermal cytokines, adhesion molecules, DNA analysis, and the application of the polymerase chain reaction are of undoubted scientific importance. However, most laboratories have limited access to these techniques and in many instances the diagnostic role in skin disease remains uncertain. Accordingly, the summaries have been selected because of their diagnostic relevance to general histopathologists reporting dermatopathology. They have been chosen from journals not usually perused by general histopathologists, and cutaneous lymphoproliferative disorders have been purposely omitted in view of recent personal coverage (Slater DN. J Pathol 1987; 153: 5–19; J Pathol 1990; 162: 1–4; Br J Dermatol 1991; 124: 309–323).
Variations in the occurrence of silver‐staining nucleolar organizer regions (AgNORs) in non‐proliferating and proliferating tissues
Authors: Leek Russell D. , Alison Malcolm R. , Sarraf Catherine E.
Published: June 2005

Previous studies on the subject of silver‐staining nucleolar organizer regions (AgNORs) as indicators of precise proliferative status of tissues have sometimes resulted in ambiguity. The studies, however, have most frequently addressed themselves to the prognosis of neoplasias, with the aim of using AgNORs principally to distinguish between benign and malignant tumours. This investigation was to determine a base‐line relationship of AgNOR clusters to proliferation and thus concentrated on normally proliferative tissues and conditionally renewing tissues after appropriate stimulation. Two murine transplantable tumours were also examined as examples of frank malignancy. As an example of the former, variations in AgNOR clusters were noted in the small intestine of man, mouse, and rat. The conditionally renewing systems of liver, prostate, and salivary glands were stimulated into proliferation by two‐thirds partial hepatectomy, castration followed by treatment with testosterone, and isoproterenol treatment, respectively, in rat models; the murine sarccma SaF and carclnoma CaNT provided relatively simple malignant tumours for AgNOR investigation. Proliferation was monitored by noting labelling indices after injection with bromodeoxyuridine (BrdUrd) in vivo followed by immunocytochemical visualization of S‐phase cells. In all tissues, an increase in the size of AgNOR clusters rather than their number correlated positively with elevated labelling, particularly with the emergence of silver‐staining regions of 2–3 μm visible diameter. Thus, increased AgNOR cluster size (diameter) as representative of AgNOR cluster/nucleolus volume was found to be dependent on proliferative activity in a range of normal and neoplastic tissues.
Re‐evaluating silver‐stained nucleolar organizer regions (AgNORs) in problematic cutaneous melanocytic lesions: A study with quantitation and pattern analysis
Authors: Evans A. T. , Orrell J. M. , Grant A.
Published: June 2005

Previous studies enumerating AgNORs in cutaneous melanocytic lesions have produced inconsistent results. It is probable that such inconsistencies arise from differences in fixation, staining technique, and counting strategies. Our group, having demonstrated an improved method of silver staining and having optimized counting, is now able to reconsider the role of AgNORs in evaluating borderline melanocytic lesions. Diagnostic problems similar to those encountered in routine practice have been examined. It is shown that only by counting intra‐ and extranucleolar AgNORs in combination with assessing the pattern of AgNOR dispersal is it possible to (1) discriminate dysplastic naevi from melanoma and (2) distinguish Spitz naevi and pigmented spindle cell naevi from melanoma. An analysis of AgNOR numbers alone results in considerable overlap between the groups studied. The value of assessing patterns of AgNOR dispersal within and outside clustered nucleolar structures is emphasized.

Lesions labelled as minimal deviation melanoma (by experts in dermatopathology) were also investigated. The majority of these specimens form a distinct group lying apart from control naevi and melanomas. This finding, whilst of interest, is difficult to evaluate because of poorly defined diagnostic criteria.
Helicobacter pylori in gastric biopsy specimens. Comparison of culture, modified Giemsa stain, and immunohistochemistry. A retrospective study
Authors: Loffeld R. J. L. F. , Stobberingh E. , Flendrig J. A. , Arends J. W.
Published: June 2005

Antral biopsy specimens of 302 different endoscopic Investigations of 200 patients with non‐ulcer dyspepsia were studied for the presence of Helicobacter pylori in order to determine the most sensitive detection method. Part of the biopsy was cultured, and part stained using a modification of the Giemsa stain, and with an immunoperoxidase technique using a polyclonal rabbit anti‐H. pylori antiserum. Cross‐reactivity of this antiserum with other Campylobacter species was minimal.

Material from 244 investigations was studied using all three detection methods. Culture was positive in 44 per cent, Giemsa in 78 per cent, and immunoperoxidase in 89 per cent of these biopsy specimens. Only five positive Giemsa stains with negative immunoperoxidase stain were found, whereas in 32 cases a negative Giemsa stain with a positive immunoperoxidase stain was seen. In the latter cases, the bacterial load was very low. The specimens revealed bacteria only sporadically, always confined to the deep layers of the gastric pits. Culture results correlated significantly with the bacterial load observed in the Giemsa stain. It is concluded that culture of H. pylori is the least sensitive detection method, whereas immunoperoxidase staining is the most sensitive. For daily practice the modified Giemsa stain, however, appears to be sufficient to diagnose the presence of the micro‐organism.
Immunocytochemical characterization of large granular lymphocytes in normal cervix and HPV associated disease
Authors: McKenzie Jolenta , King Ashley , Hare John , Fulford Tony , Wilson Beverley , Stanley Margaret
Published: June 2005

A quantitative immunocytochemical study of large granular lymphocytes (LGLs) in the normal cervix and in human papillomavirus (HPV) associated disease was performed using a panel of monoclonal antibodies which included those for LGL surface markers CD56, CD16, and CD57. Only CD56‐positive cells were found within the ectocervical epithelium and these cells increased in number in cervical intraepithelial neoplasia (CIN) in comparison with normal cervix. Examination of serial sections and double labelling suggests that these cells are CD3+, CD8+, CD56+, CD16+. The observed increase in number of this subset was not associated specifically with HPV infection but was related to CIN. Lymphocytes expressing all three LGL markers were found in the stroma and CD16+‐positive cells clustered around endocervical glands with occasional cells extending into the endocervical epithelium. These results indicate that a small subset of LGLs which express T‐cell markers is increased in number in CIN. Cells expressing classical NK markers are restricted to the stroma and are not found within the ectocervical epithelium.
Recovery from hepatic necrosis following acute portal vein embolism with special reference to reconstruction of occluded vessels
Authors: Shibayama Yuro , Hashimoto Kazuaki , Nakata Katsuji
Published: June 2005

We examined the morphological and haemodynamic changes in the livers of rats following acute obstruction of portal vein branches by the injection of agar into the portal vein. Histological and angiographic examinations of the liver were performed after measurements of portal vein pressure in vivo and portal vascular resistance by an isolated liver perfusion method. Portal vein embolism induced hepatic necrosis in the centrilobular and midzonal areas, which was rapidly resorbed and replaced by regenerated liver cells leaving no trace. This recovery from hepatic necrosis was closely related to recanalization of obstructed portal vein branches, which led to falls in both the elevated portal vein pressure and the increased portal vascular resistance following embolization.
Alpha‐1 antichymotrypsin is increased in human alveolar macrophages by phorbol myristate acetate or lipopolysaccharide and released from these activated macrophages by glucocorticoid
Authors: Nagareda Tomofumi , Takeda Masashi , Kojima Kayo , Tanaka Akira , Terada Nobuyuki , Yamasaki Tomoyosi , Nagareda Teako , Ueno Hirosi , Kotoh Kiyoshi
Published: June 2005

Alveolar macrophages were obtained from 23 patients and the effects of phorbol myristate acetate (PMA), lipopoly‐saccharide (LPS), and dexamethasone (DEX) on the proportion of cells with intracellular alpha‐1 antichymotrypsin (ACT), and concentrations of ACT in the culture medium were studied in vitro. The alveolar macrophages were obtained by bronchoalveolar lavage at autopsy or from resected lungs at operation and were cultured in suspension for 3 days in medium containing PMA, LPS, DEX, PMA + DEX, or LPS + DEX. Both PMA and LPS significantly increased the percentage of macrophages with intracellular ACT. Dexamethasome did not increase the number of ACT‐positive cells and significantly suppressed the increase induced by PMA or LPS, releasing ACT into the culture medium. The release of ACT from macrophages may contribute to anti‐inflammatory effects of corticoids.
Video image analysis of AgNOR distribution in the normal and adenomatous colorectum
Authors: Weeks Sandy C. , Beroukas Dimitra , Jarvis Lynn R. , Whitehead Richard
Published: June 2005

The nucleolar organizer regions (AgNORs) have been studied by video image analysis in the normal colorectum and in adenomas arising there. Total AgNOR area was measured in conjunction with the total area of nuclei and expressed as a ratio. AgNORs are found to predominate in the proliferative regions of the normal mucosal crypt, and the ratio of AgNOR to nuclear area proved significantly greater in the normal colon than in the rectum and far greater in colorectal adenomas. Further, there is a significant difference between the ration in tubular as opposed to villous patterns of adenomatous growth in the colon but not in the rectum. When classified according to their degree of dysplasia, adenomas in the rectum exhibit a significantly higher ratio of AgNOR to nuclear area as the degree of dysplasia increases in severity. This correlation is not shown in the colon.
Nucleolar organizer regions in benign and malignant glandular lesions of the cervix
Authors: Allen J. P. , Gallimore A. P.
Published: June 2005

The argyrophil technique for nucleolar organizer regions was applied to cases of normal cervix (n = 6), microglandular hyperplasia (n = 6), adenocarcinoma in situ (n = 15), and invasive adenocarcinoma of the cervix (n = 19). A rigorous staining technique was employed which facilitated the enumeration of individual AgNORs even when they were aggregated as tight clusters within the nucleolus (AgNUs). Two methods of counting AgNORs were used: a simple enumeration of dispersed AgNORs and AgNUs, and the more time‐consuming counting of all individual AgNORs, including those within AgNUs. With both techniques, there was no significant difference in counts between in situ and invasive adenocarcinoma, but cases of microglandular hyperplasia showed significantly fewer AgNORs than either of these. This suggests that AgNORs may be useful in differentiating difficult cases of microglandular hyperplasia from adenocarcinoma and that the simplified counting technique is adequate for this purpose. AgNOR counts are of no use in discriminating between invasive and in situ adenocarcinoma.
Comparative study of the prognostic value of nuclear grade and silver‐binding nucleolar organizer region in renal cell carcinomas
Authors: Yang An Hang , Wang Tao Yeuan , Liu Hung Chang
Published: June 2005

Silver‐binding nucleolar organizer region (AgNOR) and nuclear grade were histologically assessed in 112 renal cell carcinomas. Nuclear grade was better capable of stratification than AgNOR in terms of survival prediction. It also had prognostic significance when total metastatic rates were evaluated. Although higher mean AgNOR numbers were constantly associated with higher nuclear grades, two arbitrary classifications of AgNOR (<1.5, 1.5–3.5, >3.5; <2, 2–3, >3) failed to resolve the survival difference.
Lymphocytes in pseudomembranes of late prosthetic joint failure
Authors: Salter D. M. , Krajewski A. S. , Robertson S.
Published: June 2005

The pseudomembrane formed in association with late aseptic prosthesis failure contains a mixed giant cell and histiocytic infiltrate with variable numbers of lymphocytes. Immunolabelling with a panel of antibodies on paraffin sections was undertaken to define the nature of the lymphoid infiltrate in 19 cases. In all cases, the predominant lymphoid cell was a memory (CD45RO +, CD45RA‐) T‐cell. B‐cells were rare. Tissue from patients with rheumatoid arthritis (RA) contained greater numbers of T‐cells when compared with patients with osteoarthritis (OA), suggesting that the intensity of the lymphoid infiltrates reflects the underlying joint disease rather than necessarily being part of a hypersensitivity response to wear debris.
An immunohistological study of cartilage and synovium in primary synovial chondromatosis
Authors: Apte Suneel S. , Athanasou N. A.
Published: June 2005

The antigenic phenotype of cartilage and synovial cells from six cases of primary synovial chondromatosis (PSC) was determined. This was compared with profiles similarly obtained for adult and fetal cartilage cells. The Ki‐67 (proliferation‐associated) antigen was present on 40–50 per cent of chondrocytes in the proliferative zone of fetal epiphyseal cartilage but absent in chondrocytes of adult articular cartilage and PSC cartilage nodules. The absence of Ki‐67 antigen suggests that there were no proliferating cells in the synovium or cartilage in these cases of PSC. In PSC alone, some chondrocytes in the cartilage nodules and mononuclear subintimal cells around the nodules also reacted for CD68, suggesting that growth of the cartilage nodules may occur by a metaplastic process. All synoviocytes in PSC were positive for leucocyte common antigen, HLA‐DR, and CD68, a pattern typical of reactive rather than normal synovium.
Tissue‐type plasminogen activator and its inhibitor in human glomerulonephritis
Authors: Aya Naofumi , Yoshioka Kazuo , Murakami Katsumi , Hino Satoshi , Okada Kiyotaka , Matsuo Osamu , Maki Sunao
Published: June 2005

We carried out an immunohistochemical study of tissue‐type plasminogen activator (PA) and urokinase‐type PA, and their inhibitors, PA inhibitor‐1 and PA inhibitor‐2, using renal biopsy specimens obtained from 86 patients with various forms of glomerulonephritis. The controls were four normal renal tissue specimens.

On immunofluorescent observation, granular staining for tissue‐type PA was found to be distributed along the glomerular capillary walls. The fluorescence was weak in the normal renal tissue and occasionally intense in the tissues of patients with IgA nephritis, minimal change nephrotic syndrome, and lupus nephritis. PA inhibitor‐1 was abundant in the glomerular epithelial cells and scarce in the mesangial area and glomerular capillary lumens of the normal renal tissues. This was confirmed by immunoelectron micrscopy using gold staining. The fluorescence of PA inhibitor‐1 was weaker in some specimens of nephritic tissues than in the normal renal tissues. Urokinase‐type PA and PA inhibitor‐2 were negative within the glomeruli in all the specimens. In the glomerulonephritic tissues which were fibrin deposition‐positive, tissue‐type PA expression in the glomeruli tended to be strong. An association between fibrin deposition and PA inhibitor‐1 staining was not clear. These data suggest that expression of tissue‐type PA in the glomeruli increases in association with fibrin deposition.
Image analysis in the discrimination of verrucous carcinoma and squamous papilloma
Authors: Cooper John R. , Hellquist Henrik B. , Michaels Leslie
Published: June 2005

Verrucous carcinoma is a differentiated variant of squamous cell carcinoma and may present diagnostic difficulties as it may be erroneously diagnosed as squamous papilloma. In this study, the sizes of the intermediate cells in thes two conditions were measured by means of morphometric analysis. Biopsies from 28 patients with verrucous carcinoma, 25 patients with squamous papilloma, and ten squamous cell carcinomas were analysed. A significant difference was shown (P < 0.001) by an uncorrelated t‐test between verrucous carcinoma and squamous papilloma. The former had a mean cell area of 373 μm2 and the latter 184 μm2. Squamous cell carcinomas differed from the other two neoplasms by thier large range of cell areas both within and between cases. Thus, image analysis can be of diagnostic help in cases where no firm initial histopathological diagnosis can be obtained. The diagnosis should be made on morphological grounds, but a mean cell area greater than 300 μm2 supports a diagnosis of verrucous carcinoma whereas an area less than 250 μm2 supports a diagnosis of squamous papilloma.
Fabry's disease without angiokeratomas showing unusual eccrine gland vacuolation
Authors: Idoate Miguel A. , Pardo‐mindan Francisco J. , Alamillo Carlos Gonzalez
Published: June 2005

An unusual case of Anderson—Fabry's disease with renal (damage and bilateral) corneal deposits but without angiokeratomas is presented. Diagnosis was made by renal biopsy. Typical foamy transformation of endothelium, mesangium, tubular epithelial cells, vascular smooth muscle, and fibroblasts of kidney biopsy and similar changes of myoepithelial, perineural, and endothelial cells on the skin biopsy were observed. At electron microscopy, ‘fingerprint‐like’ myelin figures were seen. The epithelial cells of eccrine sweat glands showed striking vacuolation but myelin figures were not seen. We suggest that electron microscopic study of skin biopsies is indicated in the evaluation of patients clinically suspected of having Fabry's disease.
A neuroendocrine cause of oncogenic osteomalacia
Authors: Stone Michael D. , Quincey Caroline , Hosking David J.
Published: June 2005

All definite cases of oncogenic osteomalacia have, until now, been classified as mesenchymal tumours. We report here a case of oncogenic osteomalacia caused by a spinal tumour. Microscopically, it resembled the mixed connective tissue variant of previously described phosphaturic tumours. Immunohistochemical studies, however, showed the tumour cells to be positive for low molecular weight cytokeratin (CAM 5.2), S100 protein, PGP 9.5, and synaptophysin. Electron microscopy demonstrated neurosecretory granules. The histopathological findings strongly suggest that this is a neuroendocrine tumour.