bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery and development of anticancer agents from plants
Authors: Valeriote Fred , Grieshaber Charles K. , Media Joseph , Pietraszkewicz Halina , Hoffmann Joseph , Pan Meide , McLaughlin Steve
Published: March 2003

A novel in vitro assay for the discovery of anticancer agents was used to examine aqueous and organic extracts from 1847 plants collected mainly in the U.S. Southwest and West. The assay results were separated into 5 categories: inactive (62%), equally active (36%), equally active and potent (0.5%), solid tumor selective (1.4%), and human selective (0.8%). Extracts from the latter three categories were fractionated using the in vitro assay to biodirect each step. Psorothamnus emoryi extracts were solid tumor selective and yielded two active compounds upon fractionation: dalrubone and 5‐methoxydalrubone. Calocedrus decurrens was equally active and potent and yielded deoxypodophyllotoxin as the active compound. Linanthus floribundus was human selective and yielded strophanthidin as the active compound. The potential of this assay to discover novel anticancer agents from the active extracts is discussed.
Domain switching between hrpR and hrpS affects the regulatory function of the hybrid genes in Pseudomonas syringae pv. phaseolicola
Authors: Schuster Martina , Grimm Charlotte
Published: March 2003

In prokaryotes, a diverse set of physiological processes is regulated by transcription factors which belong to the well‐conserved, enhancer‐binding protein (EBP) family. These regulatory proteins function together with the alternate sigma factor (σ54). Structurally, the EBPs are characterized by a central activator domain, containing the recognition motif for the RNA polymerase/σ54 complex (Eσ54), and the C‐terminal domain, containing a DNA‐binding helix–turn–helix motif. A regulatory system of the EBP type also exists in Pseudomonas syringae, where it controls the expression of genes required for the induction of disease symptoms and resistance responses in plants. The system consists of the two genes, hrpR and hrpS, which belong to the hrp (hypersensitive response and pathogenicity) gene cluster. The two genes show a high degree of structural and sequence similarities, but function at different positions in the hrp regulatory cascade of the bean pathogen Pseudomonas syringae pv. phaseolicola.

In this paper, we were interested in the basis of the difference in specificity between hrpR and hrpS. The functional specificities of the two domains of hrpS and hrpR were analysed by domain switching. Complementation analyses with the hybrid genes and retardation experiments with the protein products showed significant differences between the respective domains of hrpS and hrpR.
Pseudomonas syringae pv. tomato: the right pathogen, of the right plant, at the right time
Authors: Preston Gail M.
Published: March 2003

Pseudomonas syringae pv. tomato and the closely related pathovar P. s. pv. maculicola have been the focus of intensive research in recent years, not only because of the diseases they cause on tomato and crucifers, but because strains such as P. s. pv. tomato DC3000 and P. s. pv. maculicola ES4326 are pathogens of the model plant Arabidopsis thaliana. Consequently, both P. s. pv. tomato and P. s. pv. maculicola have been widely used to study the molecular mechanisms of host responses to infection. Analyses of the molecular basis of pathogenesis in P. s. pv. tomato reveal a complex and intimate interaction between bacteria and plant cells that depends on the coordinated expression of multiple pathogenicity and virulence factors. These include toxins, extracellular proteins and polysaccharides, and the translocation of proteins into plant cells by the type III (Hrp) secretion system. The contribution of individual virulence factors to parasitism and disease development varies significantly between strains. Application of functional genomics and cell biology to both pathogen and host within the P. s. pv. tomato/A. thaliana pathosystem provides a unique opportunity to unravel the molecular interactions underlying plant pathogenesis.

Taxonomic relationship: Bacteria; Proteobacteria; gamma subdivision; Pseudomonadaceae/Moraxellaceae group; Pseudomonadaceae family; Pseudomonas genus; Pseudomonas syringae species; tomato pathovar.

Microbiological properties: Gram‐negative, aerobic, motile, rod‐shaped, polar flagella, oxidase negative, arginine dihydrolase negative, DNA 58–60 mol% GC, elicits the hypersensitive response on tobacco.

Host range: Primarily studied as the causal agent of bacterial speck of tomato and as a model pathogen of A. thaliana, although it has been isolated from a wide range of crop and weed species.

Disease symptoms: Tomato (Lycopersicon esculentum): Brown‐black leaf spots sometimes surrounded by chlorotic margin; dark superficial specks on green fruit; specks on ripe fruit may become sunken, and are surrounded by a zone of delayed ripening. Stunting and yield loss, particularly if young plants are infected. Reduced market value of speckled fruit. A. thaliana: Water‐soaked, spreading lesions, sometimes surrounded by chlorotic margin.

Epidemiology: Seed borne. Survives as a saprophyte in plant debris, soil and on leaf surfaces. Dispersed by aerosols and rain splash. Development of disease symptoms favoured by leaf wetness and cool temperatures (55–77 °F/13–25 °C).

Disease control: Pathogen‐free seed and transplants. Resistant and tolerant cultivars. Sanitation, rotation, and drip irrigation to reduce leaf wetness. Some measure of control with bactericides (copper, streptomycin).
Variation in structure and activity among elicitins from Phytophthora sojae
Authors: Qutob Dinah , Huitema Edgar , Gijzen Mark , Kamoun Sophien
Published: March 2003

Transcripts encoding elicitin‐like protein domains were identified from similarity searches of Phytophthora sojae expressed sequence tags and were characterized with regard to molecular structure and elicitor activity. The P. sojae elicitin family consists of at least nine genes with products similar to previously described elicitins (SOJA‐2, SOJB, SOJ2, SOJ3, SOJ5, SOJ6 and SOJ7) or highly diverged from known sequences (SOJX and SOJY). The predicted structural features of seven (SOJA‐2, SOJB, SOJ2, SOJ3, SOJ6, SOJX and SOJY) of the elicitin preproteins were compared. All of the predicted elicitins possess a leader signal sequence and a core elicitin domain. Five (SOJ2, SOJ3, SOJ6, SOJX and SOJY) of the characterized elicitins also contain a variable C‐terminal region. In addition, SOJX and SOJY contain a C‐terminal hydrophobic membrane‐spanning domain. An analysis of expression patterns of the elicitin transcripts showed that SOJA‐2, SOJB, SOJ2, SOJ3 and SOJ6 were expressed in axenically grown mycelia and during infection, but not in zoospores. In contrast, SOJX and SOJY were predominantly and specifically expressed in zoospores. Selected elicitin domains were also tested for the induction of the hypersensitive response (HR) in Nicotiana spp. All of the elicitin protein domains tested induced the HR, except for SOJX and SOJY. Overall, the results show that the P. sojae elicitin gene family is large and diverse, with varying patterns of expression and HR‐inducing activity.
Launching a library service for the blind in Trafford*
Authors: LUCCOCK GRAHAM
Published: March 2003

An outside questionnaire acted as a catalyst in indicating that library provision for blind people in Trafford was limited. The process of investigating needs, deciding on and launching a locally organized books‐on‐tape service is described. Few problems have been encountered and the operation of the service to date is outlined.
Dutch library services to disadvantaged persons
Authors: WAGENAAR HELEN
Published: March 2003

Hospital libraries in the Netherlands provide a variety of services. In this paper two well‐equipped hospital libraries, staffed by professionally qualified librarians, are described. Some hospital libraries rely on volunteers, supervised by professional librarians, while in others volunteers work completely on their own.

Special services for elderly people are focused on persons who cannot visit the library by themselves. These services vary from visiting house‐bound people to placing a small library in residential homes. Of special interest is the library work for aphasics in the Netherlands.

The Section of Library Work for the Elderly, Sick and Handicapped Persons, a section of the Dutch Centre for Public Libraries and Literature (NBLC) is described.
Unmet needs for health information: a literature review
Authors: BUCKLAND SARAH
Published: March 2003

This paper explores the recent literature on unmet needs for health information, giving an overview of some of the research that has been carried out since Kempson's review and study in 1987.1 Many of the studies looking at health information needs have been approached from a narrow focus of individual information needs for specific services, with limited research into the views of the general public. The greatest demand for health information appears to be in the area of specific diseases and medical conditions with limited demand for information on the availability and quality of care. These findings may be a reflection of the narrow focus of much previous research and/or the limited availability of health information on access and quality. The paper argues for the need to look widely at the health information needs of households and families at all stages of health and illness, taking into account the interrelationship of needs and the social context in which such needs are, or are not perceived.
A library for problem‐based learning (PBL)
Authors: TAYLOR SOLVEIG I. , LANDE RAGNHILD E.
Published: March 2003

Developing a traditional medical library into a resource suitable to support a problem‐based learning (PBL) curriculum is a major undertaking. Experience at the Medical Library and Information Center in Trondheim, Norway, is described. Key issues have been: developing the basic physical infrastructure and facilities, upgrading librarians’ skills to offer new services and meet new demands, and working closely along side the faculty as curriculum developers. The importance of adequate space to accommodate new facilities and greatly increased use by students is emphasized. The experience has been received very positively by library staff who are continuing to work with the process of change.
The ‘market’ for medical and health information in transition: the case of the Hong Kong Hospital Authority libraries
Authors: CHENG GRACE
Published: March 2003

The last few years have been a period of transition not only for hospitals and their governance but also for post‐graduate medical education in Hong Kong. Both trends have a direct impact on the information market place. This article starts by studying the provision of medical and health‐related information in Hong Kong. The two university medical and dental libraries, together with the hospital and health sciences libraries in government hospitals and the Department of Health, house the major collections on medicine and health care. The demand for medical and health care information is increasingly felt with the takeover of 39 hospitals by the statutory Hong Kong Hospital Authority in 1991. The major problems and issues in planning for library information services are the historically uneven development of libraries, discrepancies in funding, the changes in organizational and management structure, and the competition with higher development priorities within the organization. In view of current technology and the availability of rich external resources, the adopted strategies tend towards the formation of 10 library service networks, development of integrated library information systems on the Health Authority‐wide area network, and the devolution of management responsibilities. The future challenges in store for the information professional are examined.
Library services to Australians with disabilities
Authors: MURRAY JANET , WALLIS LINLEY
Published: March 2003

An overview is presented of the historical development of library services to people with disabilities in Australia and the current services now being offered by libraries in all sectors. Federal legislation in the disability area and its impact on libraries and disability agencies is discussed, as is the work of the National Library of Australia in this area.
Nordic cooperation—expanding to the Baltic countries
Authors: Shaw Jean , Petrak Jelka , SALMI LIISA , AKRE ELISABETH
Published: March 2003

The paper describes the establishment in 1995 of the Nordic Association for Medical and Health Information, bringing together the five national associations from Denmark, Norway, Sweden, Iceland and Finland. Many forms of good and informal cooperation between these countries have always existed, but an association is needed to be able to officially act as a unified medical library community. Since the opening up of Eastern Europe to the West in the early 1990s, their need for professional updating and literature was paramount, and one of the current concerns of the Nordic Association is cooperation with the Baltic countries.
Restoring the Tower of Babel: building a multilingual thesaurus on health promotion
Authors: Shaw Jean , Petrak Jelka , DORST LAURA
Published: March 2003

In 1994 the International Union for Health Promotion and Health Education, Regional Office for Europe (IUHPE/EURO), began a thesaurus project in the field of health promotion and health education, in collaboration with terminologists and health promotion specialists from various European countries. This article describes the different phases of the international project. Special attention is paid to the origin of the project and the international cooperative imperative needed to bring such a project to fruition.
Information support for general practice in the new NHS
Authors: Gillies Alan
Published: March 2003

Surveys of GP computing suggest that over 95% of practices now have computers. Unfortunately, many of these practices are making little effective use of this technology. Recent White Papers, The New NHS and Information for Health place an even greater emphasis upon the effective use of information and its associated technology.

This paper describes a model for the assessment and managed change of information management maturity within general practice. The model, known as GPIMM (General Practice Information Maturity Model), which has been developed from related models in fields such as software quality and diffusion of innovation, provides a framework for the assessment of the maturity of information processes within general practice. The model can also be used to define key tasks in terms of training and information strategies to facilitate practice development.

The model and its antecedents are described, and it is shown how this model can be used to assess and improve information processes within case study practices. This paper then goes on to examine the health librarians’ role in the process of change and discuss the metaphor of a ‘virtual library’ as a means to shift the agenda from information technology to information itself.
Histone mRNA in‐situ hybridization in astrocytomas: a comparison with PCNA, MIB‐1 and mitoses in paraffin‐embedded material
Authors: Rautiainen  , Haapasalo  , Sallinen  , Rantala  , Helen  , Helin
Published: March 2003

Aims:

Non‐isotopic histone mRNA in‐situ hybridization (HmRNA NISH) allows detection of cells in the S phase of the cell cycle in paraffin‐embedded tissue. The aim of this study was to evaluate the technique in measuring the proliferative activity of astrocytic neoplasms, and to compare the results with other proliferation estimates and patient survival.

Methods and results:

The proliferative activity of 71 routinely fixed and paraffin‐embedded astrocytomas was studied by light microscopic HmRNA NISH, proliferating cell nuclear antigen (PCNA), Ki67MIB‐1 and mitoses. A significant correlation was found between the labelling indices of histone mRNA (the percentage of histone‐positive tumour cells; HmRNA‐LI), immunohistochemical proliferation marker labelling indices (PCNA‐LI: r = 0.64 and Ki67MIB‐1‐LI: r = 0.44) and mitotic indices (r = 0.45). The results were reproducible as judged by intra‐ and interobserver agreement (HmRNA/10 HPF (high power fields): r = 0.91 and r = 0.75, respectively, and HmRNA‐LI: r = 0.61 and r = 0.62, respectively). The fraction of the cells in the most active cell cycle phases, as suggested by the HmRNA/Ki67 and mitotic index/Ki67 ratios, increased significantly with malignancy grade. In the univariate analysis the association of HmRNA‐LI with survival was highly significant (P < 0.0001). Multivariate survival analysis showed that HmRNA‐LI was an independent prognostic marker.

Conclusions:

Non‐isotopic histone mRNA in‐situ hybridization assay offers an alternative and reproducible method for measuring proliferative activity (S phase) in tumours under morphological control.
Vascular density does not predict future metastatic disease in clinical stage 1 non‐seminomatous germ cell tumours of the testis
Authors: Maher  , Lee
Published: March 2003

Aim:

This study aimed to determine whether patients with stage 1 testicular non seminomatous germ cell tumours (NSGCT) with high vascular density have a greater risk of disease recurrence than those with a low vascular density.

Methods and results:

Orchidectomy specimens from 42 patients with stage 1 NSGCT, treated by orchidectomy and surveillance alone, were studied. Vessel density was counted in tumour sections immunohistochemically stained for CD34. The mean of the three highest counts (× 250, field size 0.67 mm2) for each tumour was used. Tumour vessel density was very similar for relapsing and non relapsing patients. Vascular invasion was the only variable significantly predictive of disease recurrence at 2 years post‐orchidectomy (P = 0.025). There was wide variation of vessel counts between different blocks of a tumour, compared with interobserver variation. The tumour tissue type in the area of highest vessel density was embryonal carcinoma in 50% and teratoma (mature or immature) in 38%.

Conclusions:

We confirmed the value of vascular invasion as a prognostic marker in stage 1 NSGCT. Tumour vessel density was of no prognostic value. Two factors may contribute to this. First, there was wide variation of vessel density between different blocks of a tumour. Second, the most vascular area in a tumour was frequently in low‐grade tumour.
Scalloped cell xanthogranuloma
Authors: Zelger  , Orchard  , Rudolph  , Zelger
Published: March 2003

Aims:

We describe nine cases of scalloped cell xanthogranuloma, a distinct solitary variant of non‐Langerhans cell histiocytoses.

Methods and results:

In this retrospective clinicopathological study scalloped cell xanthogranuloma mostly occurred on the back or head and neck of young adult males diagnosed as a xanthogranuloma, naevus, or basal cell carcinoma. Histology characteristically revealed a sheet‐like infiltrate of predominantly scalloped histiocytes (> 75% of all cell types) in the upper dermis. Other mononuclear (vacuolated, xanthomatized, spindle‐shaped, oncocytic) and multinucleate (foreign body, ground glass and Touton) histiocytes were also regularly seen. Immunohistochemically, all cases exhibited a macrophage/dendritic cell lineage positive with KP1 (CD68), KiM1p, HAM 56 and factor XIIIa. Ultrastructurally, numerous intracytoplasmic dense, occasionally also myeloid bodies were present. No associated systemic disease, hyperlipidaemia or recurrence were seen during follow‐up.

Conclusions:

These findings are similar to those of early lesions of xanthoma disseminatum; thus, scalloped cell xanthogranuloma could be regarded as a solitary counterpart of xanthoma disseminatum, and, moreover, fits neatly into a unifying concept of non‐Langerhans cell histiocytoses.
Spindle epithelial tumour with thymus‐like element (SETTLE): the predominantly monophasic variant
Authors: Chetty R , Goetsch S , Nayler S , Cooper K
Published: March 2003

Aims

To describe two cases of spindle epithelial tumour with thymus‐like element (SETTLE) which are composed predominantly of spindle cells. In addition, to highlight some unusual histological features in SETTLE and discuss its separation from histological mimics.

Methods and results

The thyroid masses were in a 4‐year‐old boy and a 25‐year‐old male. Both patients were euthyroid and were well except for thyromegaly. The specimens were formalin fixed, and immunohistochemistry was performed on this material using a panel of antibodies following microwave antigen retrieval. Morphologically, the dominant pattern was of sheets of spindle cells arranged in several patterns. There was mild pleomorphism and occasional mitoses. There were very small foci of squamous epithelium and occasional ductular structures. The stroma was composed of fibrous tissue and isolated areas of calcification were noted. The spindle cells showed strong and diffuse immunoreactivity with AE1/3, CAM5.2 and vimentin.

Conclusion

We describe two cases of SETTLE that are composed mainly of spindle cells and only a very focal ductular component. In addition, calcification was noted within the stroma in one of the cases. These predominantly spindle examples of SETTLE must be separated from synovial sarcoma, which is a more mitotically active, aggressive tumour displaying only patchy immunopositivity with epithelial markers.
Altered expression of membrane inhibitors of complement in human gastric epithelium during Helicobacter‐associated gastritis
Authors: Sasaki  , Joh  , Tada  , Okada  , Yokoyama  , Itoh
Published: March 2003

Aims: Membrane inhibitors of complement are thought to protect bystander cells from complement mediated damage. Expression of these proteins is enhanced in the colonic mucosa of patients with ulcerative colitis. Our aim was to investigate the regulation of complement activity in Helicobacter‐associated chronic gastritis.

Methods and results

We immunohistochemically assayed expression of three membrane inhibitors of complement, decay accelerating factor (DAF; CD55), 20 kDa homologous restriction factor (HRF20; CD59) and membrane cofactor protein (MCP; CD46), in 55 biopsy specimens of the human gastric mucosa. DAF, expressed in 33 (60%) of biopsy specimens, and HRF20, expressed in 45 (82%) of the samples, were located mainly on the apical surface of the epithelial cells, whereas MCP, expressed in 48 (87%) of the biopsies, was found on the basolateral surface. We found strong correlation between expression of DAF on gastric mucosal epithelium and the severity of mucosal infiltration of neutrophils (rs = 0.875, P < 0.0001) and mononuclear cells (rs = 0.773, P < 0.0001). No significant correlation was observed between HRF20 expression and neutrophil or mononuclear cell infiltration, while there was a weak negative correlation between MCP expression and these cellular infiltrations. When we assayed immunostaining of Helicobacter pylori (H. pylori) in these biopsy specimens, strong correlation with the degree of neutrophil (P < 0.0001) and mononuclear cell (P < 0.0001) infiltration were observed. The expression of DAF and H. pylori infection in these biopsies were also significantly (P < 0.0001) correlated. No correlation between HRF20 expression and H. pylori infection was observed, but we did find a significant negative correlation (P < 0.005) between the expression of MCP and H. pylori infection.

Conclusions

Our results, demonstrating altered expression of membrane inhibitors of complement in gastric mucosa during inflammation and/or H. pylori infection, suggest that complement may significantly participate in the pathology of gastric inflammation. Moreover, DAF and MCP may play an important role in the regulation of complement activation in the alimentary tract.
Pigmented atypical fibroxanthoma
Authors: Diaz‐Cascajo  , Borghi  , Bonczkowitz
Published: March 2003

Aim: The purpose of this report is to call attention to a pigmented variant of atypical fibroxanthoma that resembles malignant melanoma, both clinically and histopathologically.

Methods and results

Thirty‐eight cases of atypical fibroxanthoma were examined for the presence of pigmented areas. Four such cases were found. Neoplastic cells showed erythrophagocytosis and accumulation of haemosiderin pigment in the cytoplasm. In three cases, immunohistochemical studies using a battery of antibodies were performed. Neoplastic cells were strongly positive for vimentin and weakly positive for CD68, whereas they were negative for melanocytic markers, including S100 protein, HMB45, and the monoclonal antibody NK1‐C3 to melanoma‐associated antigen.

Conclusions

Pigmented atypical fibroxanthoma represents a poorly recognized variant of the neoplasm that may be easily misinterpreted as malignant melanoma. To the best of our knowledge, this is the first report of erythrophagocytosis in atypical fibroxanthoma.
Coronary artery remodelling and the assessment of stenosis by pathologists
Authors: Davies
Published: March 2003

When atherosclerotic plaques develop, the cross‐ sectional area of the artery at that point often increases to accommodate the plaque without any reduction in lumen size. In consequence the angiogram does not detect a high proportion of atherosclerotic plaques. The increase in size of the artery (compensatory dilatation − arterial remodelling) varies widely in degree between different plaques even in the same artery. Dilatation of a degree to prevent any loss of lumen size is regarded as adequate compensatory dilatation. In contrast, other plaques are associated with no or minimal increase in the vessel cross‐sectional area and a reduction in lumen size is present (inadequate compensation). High‐grade stenosis is in particular associated with a total failure of remodelling. Such plaques may have had a rapid growth phase, out‐pacing the ability of the medial smooth muscle cells to undergo a rearrangement.

The phenomenon of remodelling has important consequences for pathologists who use the traditional method of comparing the lumen size relative to the cross‐sectional area of the vessel at the site of a plaque to measure stenosis. The area of the vessel at this point may be anything up to 60% above its size before the plaque developed. An error is introduced which on average overestimates diameter stenosis by 30% when compared to an angiographic equivalent method in which the lumen size at the lesion is compared to the lumen size at an adjacent segment of artery without a plaque.
Angiofibroblastoma of the skin: a histological, immunohistochemical and ultrastructural report of two cases of an undescribed fibrous tumour
Authors: Diaz‐Cascajo C , Metze D
Published: March 2003

Aims

The aim of this report is to present two cases of a distinct mesenchymal tumour of the skin that does not fit into one of the established entities.

Methods and results

All cases of fibromyxoid tumours from the files of two dermatopathology centres, together with clinical data and histopathological records, were reviewed. Two cases of a lesion composed of stellate and spindle‐shaped cells with the phenotype of fibroblasts embedded in a fibromyxoid to dense fibrous stroma were identified. Because of the large number of capillary‐sized blood vessels and their peculiar distribution within the stroma, the name angiofibroblastoma of the skin is proposed for this peculiar neoplasm. In both cases, the tumour appeared as an indolent and slowly growing nodule on the extremities of adults. Immunohistochemical and, in one case, ultrastructural studies were performed.

Conclusions

The lack of recurrences during a follow‐up period of 9 and 3 years, respectively, after complete excision together with the bland histopathological appearance supports the benign character of the tumour.
Immunohistochemical analysis of pleomorphic lobular carcinoma: higher expression of p53 and chromogranin and lower expression of ER and PgR
Authors: Radhi
Published: March 2003

Aims

Pleomorphic lobular carcinoma of the breast is a histological variant of infiltrating lobular carcinoma with a poor prognosis. The aim of this study is to investigate the immunohistochemical profile of this distinctive breast carcinoma in comparison with the classical type. The expression of cytokeratin, epithelial membrane antigen, gross cystic disease fluid protein‐15, chromogranin, oestrogen and progesterone receptors and p53 oncoprotein was investigated to examine whether the expression of these markers correlates with the aggressiveness of this variant.

Methods and results

Sections from 10 cases of pleomorphic lobular carcinomas were reviewed and examined for the expression of cytokeratin of high and low molecular weight, epithelial membrane antigen (EMA), gross cystic disease fluid protein‐15 (GCDFP‐15), chromogranin, oestrogen (ER) and progesterone receptors (PgR), and p53 oncoprotein. Immunohistochemical staining was performed on paraffin wax embedded sections. Ten cases of classical lobular carcinomas were used for comparison. A semiquantitative count of the percentage of positive tumour cells was recorded. Pleomorphic lobular carcinomas have most of the characteristic histological features of the classical type but have nuclear anaplasia and abundant granular cytoplasm. Clinically they exhibited poor prognosis and a high frequency of nodal metastases. All of the pleomorphic lobular carcinomas expressed low and high molecular weight keratin, EMA, and GCDFP‐15, eight cases expressed nuclear p53 at a range between 10% and 45%. All cases expressed chromogranin (3–5%). ER and PgR were weakly positive in two cases and negative in eight cases. Classical infiltrating lobular carcinomas were all positive for cytokeratin, EMA, ER and PgR and negative for GCDFP‐15. Only five cases of classical lobular carcinoma expressed p53 positivity with up to 5% nuclear staining while chromogranin showed less expression (1–2%).

Conclusion

Pleomorphic lobular carcinoma exhibits distinct cellular features with apocrine differentiation, higher expression of chromogranin and p53 protein and lower ER and PgR in comparison with classical lobular carcinomas. Determination of p53 overexpression and reduced or absent expression of ER and PgR may help predict the behaviour of this variant of lobular carcinoma.
Mandibular pseudocarcinomatous hyperplasia
Authors: Warter A , Walter P , Meyer C , Barrière P , Galatir L , Wilk A
Published: March 2003

Aims:

Three unusual cases of pseudocarcinomatous (pseudoepitheliomatous) hyperplasia (PH) affecting chronic osteomyelitic mandibular sequestra are reported to highlight the differences with the various squamous neoplasms which occur in that site.

Methods and results:

In two patients carrying a mandibular graft following the excision of an ameloblastoma, mucosal ulcers resulted in chronic osteomyelitis. In a third patient, an apical dental infection was associated with fistulated osteomyelitis. Histology of the three sequestra showed an intraosseous squamous proliferation. It was characterized by a peripheral involvement of medullary spaces, the more mature epithelial layer covering the bone trabeculae without intervening stroma, and the basal type epithelial layer surrounding a central fibrovascular core. There were no histological or cytological signs of malignancy.

Conclusions: 

PH shows an inverted pattern when compared with the centro‐medullary tumoural islands seen in the various oral or odontogenic squamous neoplasms which occur in the jaws. The lack of signs of malignancy distinguish PH from common squamous cell carcinomas. A short clinical course is an important feature in the distinction of PH from the well differentiated squamous cell carcinomas which may develop in fistulated chronic osteomyelitis.
Uncommon histopathological findings in fatal measles infection: pancreatitis, sialoadenitis and thyroiditis
Authors: Vargas P A , Bernardi F D C , Alves V A F , Gianotti M A , Almeida O P , Saldiva P H N , Mauad T
Published: March 2003

Aims

: We report uncommon histopathological findings in fatal measles infection.

Methods and results

: We describe the autopsies of four patients who died during a measles outbreak in São Paulo, Brazil, in 1997. Two of the patients were children receiving chemotherapy for non‐Hodgkin's lymphoma, one was an adult with acquired immunodeficiency syndrome (AIDS) and the fourth was an apparently healthy woman. All patients had their deaths attributed to measles pneumonia. The autopsies revealed extensive giant cell pneumonia and diffuse alveolar damage, severe acute pancreatitis, necrotizing sialoadenitis and thyroiditis due to measles. Measles antigen was detected in lung tissue using a monoclonal anti‐measles antibody.

Conclusions

: Pancreatitis, thyroiditis and sialoadenitis are not previously reported histopathological findings in measles infection. Pancreatitis is a potentially severe complication and should be considered when treating patients with atypical measles.
A study of four cases of extra‐orbital giant cell angiofibroma with documentation of some unusual features
Authors: Thomas R , Banerjee S S , Eyden B P , Shanks J H , Bisset D L , Hunt R , Byers R J , Oogarah P , Harris M
Published: March 2003

A study of four cases of extra‐orbital giant cell angiofibroma with documentation of some unusual features

Aims: To document the clinical, light microscopic, immunohistochemical and ultrastructural features of four cases of extra‐orbital giant cell angiofibromas.

Methods and results: Sections of formalin‐fixed paraffin‐embedded specimens were studied by haematoxylin and eosin, reticulin and immunohistochemical stains. Electron microscopy was carried out in two cases on tissue fixed in formalin. The age of the patients ranged from 30 to 41 years. Two patients presented with a soft tissue swelling in the left groin, one patient had a left axillary soft tissue lump and one patient presented with a parotid lump. All lesions were well circumscribed and contained variably cellular and vascularized tissue composed of round to spindle cells with a patternless arrangement, scattered multinucleate giant cells and pseudovascular spaces conforming to the description of giant cell angiofibroma. Mononuclear and multinucleate tumour cells were both positive for vimentin and CD34; one tumour exhibited focal S100 protein and GFAP positivity. Both of the tumours examined by electron microscopy showed fibroblastic features, but in addition one contained cells having Schwannian features. All four patients were well without recurrent disease on follow‐up (average 25 months).

Conclusion: Giant cell angiofibroma shares many features with solitary fibrous tumour and giant cell fibroblastoma and shows a wider distribution than initially recognized. Rarely, Schwannian differentiation may be observed in these tumours.
Ordered array of dendritic cells and CD8+ lymphocytes in portal infiltrates in chronic hepatitis C
Authors: Gallè M B , DeFranco R M S , Kerjaschki D , Romanelli R G , Montalto P , Gentilini P , Pinzani M , Romagnoli P
Published: March 2003

Ordered array of dendritic cells and CD8+ lymphocytes in portal infiltrates in chronic hepatitis C

Aims: Despite the importance of dendritic cells in stimulating primary and secondary immune responses by presenting antigens to T‐lymphocytes in draining lymph nodes and peripheral tissues, respectively, very limited information is available on the presence and localization of these cells in hepatitis C virus (HCV)‐related chronic active hepatitis. Therefore, we addressed the ultrastructure, immunophenotype, distribution and relationships to lymphatics of dendritic cells in portal infiltrates of this disease.

Methods and results: Part of percutaneous diagnostic liver biopsies (Knodell’s histological assessment index: 9–13) was processed for electron microscopy and for immunohistochemical detection of immune system cell membrane antigens and of the lymphatic endothelium marker podoplanin. In portal infiltrates, cells with electron microscopical and cell marker features of dendritic cells and expressing the activation markers CD54, CD80, CD83 and CD86 were organized in a discontinuous network, that embedded CD8+ lymphocytes in close contact with dendritic cells and came in contact with hepatocytes, sometimes infiltrating beyond the limiting plate. Also, dendritic cells were found within newly formed lymphatic capillaries in thin, infiltrated septa among hepatocytes.

Conclusions: This evidence strongly suggests a critical role of dendritic cells and newly formed lymphatics in the pathogenesis and organization of the immune infiltrate that characterizes HCV‐related chronic active hepatitis.
Histological and immunohistochemical characterization of extranodal diffuse large‐cell lymphomas with prominent spindle cell features
Authors: Wang J , Sun N C J , Nozawa Y , Arber D A , Chu P , Chang K L , Weiss L M
Published: March 2003

Histological and immunohistochemical characterization of extranodal diffuse large‐cell lymphomas with prominent spindle cell features

Aims: To describe five cases of diffuse large‐cell lymphoma with prominent spindle cell components involving skin, nasal‐ocular mucosa, and soft tissue. Because of the spindle cell morphology, such cases must be differentiated from true sarcomas arising in or metastasizing to soft tissue, skin, bone, lymph node, or other organs and sites.

Methods and results: Formalin‐fixed paraffin‐embedded archival tissue from five consultation cases of diffuse large‐cell lymphoma with prominent spindle cell features involving the skin, nasal‐ocular mucosa, and soft tissue in three male and two female patients was studied by histology and immunohistochemistry. Clinicopathological findings were also reviewed for all the patients. By morphology, initial evaluation of the cases suggested spindle cell sarcoma in two cases, inflammatory pseudotumour in one case, large‐cell lymphoma in another case, and one case was considered suspicious for malignant lymphoma. Immunohistochemistry demonstrated a B‐cell lineage in four of the spindle cell lesions, with a diagnosis of primary cutaneous CD30+ anaplastic large cell lymphoma made for the fifth case. Four of five cases also showed actin reactivity.

Conclusions: Although extremely rare, lymphomas with prominent spindle cell morphology can be encountered in daily surgical pathology practice, and should be included in the differential diagnosis of spindle cell lesions in skin and soft tissue. The observed actin reactivity in four of the five spindle cell lymphomas may lead to a misdiagnosis of leiomyosarcoma if lymphoid markers are not included in the immunohistochemical panel.
Review. Histopathology and the ‘third great lie’. When is an image not a scientifically authentic image?
Authors: Suvarna S K , Ansary M A
Published: March 2003

Histopathology and the ‘third great lie’. When is an image not a scientifically authentic image?

This article considers the issues of image manipulation within the context of electronic/digital images. The possibility for such alterations has occurred with the increasing availability of simple and cheap computer software, permitting modification of digitized images as a whole, or in part. The concepts of acceptable, through to unacceptable, manipulations are discussed using macroscopic and histological illustration examples. The legal and editorial problems that this poses for medical and scientific publishing are also discussed, alongside examples of previous fraudulent image publications and the historical context of valid scientific images.
Mucinous metaplasia of the penis
Authors: Fang A W , Whittaker M A , Theaker J M
Published: March 2003

Mucinous metaplasia of the penis

Aims: To determine the incidence of mucinous metaplasia occurring in the foreskin or glans penis and any associated clinical or histopathological features.

Methods and results: Following the recognition of two index cases, 100 other foreskin specimens were retrieved from the histopathology archives at Southampton General Hospital. The haematoxylin and eosin‐stained slides were examined by a single observer to detect the presence of mucin‐producing cells in the surface epithelium. The absence of mucinous metaplasia in negative cases was confirmed with mucin histochemistry. In total, four cases of mucinous metaplasia were identified, three involving the foreskin and one involving the glans penis. The age range was 51–80 years. Three cases were associated with Zoon's balanitis and the fourth showed mild non‐specific balanitis. All four cases showed positive staining with both diastase periodic acid–Schiff and alcian blue. No mucin‐producing cells were identified in non‐inflamed or minimally inflamed specimens.

Conclusions: Mucinous metaplasia of the penis is an uncommon but under‐recognized condition. It is seen in the elderly and appears to be a metaplastic change associated with severe chronic inflammation, and possibly more specifically with Zoon's balanitis. Our study identified a case affecting the glans penis, a site not previously recorded.
Tumour `budding' as an index to estimate the potential of aggressiveness in rectal cancer
Authors: Ueno H , Murphy J , Jass J R , Mochizuki H , Talbot I C
Published: March 2003

Tumour `budding' as an index to estimate the potential of aggressiveness in rectal cancer

Aims: Although the characteristic of invasive pattern which contributes to Jass's classification is a sensitive prognostic marker in rectal cancer, reproducibility of its assessment has been shown to be problematic. As another histological parameter of invasive margin, we examined the prognostic significance of tumour ‘budding’ and attempted to establish its appropriate criteria.

Methods and results: A total of 638 rectal cancer specimens was examined. We defined tumour `budding' as an isolated single cancer cell or a cluster composed of fewer than five cancer cells. We divided these into two groups by their intensity, i.e. the number of `budding' foci within a microscopic field of × 250. Rectal cancer with high‐grade `budding' (≥ 10 foci in a field) was observed in 30.1% of patients, and was associated with lower 5‐year survival rates (40.7%) than patients with low‐grade `budding' (84.0%) (P < 0.0001). Based on multivariate analysis, tumour `budding' was selected as the significant independent variable, together with the number of nodes involved, extramural spread, lymphocytic infiltration, apical nodal involvement and tumour differentiation. Kappa coefficient of two‐graded tumour `budding' in the intraobserver study was 0.84.

Conclusions: Because of its value as a prognostic indicator and its reproducibility, tumour `budding' would be a good index to estimate the aggressiveness of rectal cancer.
Expression of metallothionein in lung carcinoma: correlation with histological type and grade
Authors: Theocharis S , Karkantaris C , Philipides T , Agapitos E , Gika A , Margeli A , Kittas C , Koutselinis A
Published: March 2003

Expression of metallothionein in lung carcinoma: correlation with histological type and grade

Aims: Over‐expression of cellular metallothionein occurs frequently in human tumours but the underlying mechanism remains unknown. The aim of this study was to assess metallothionein expression in cases of lung carcinoma and to correlate it with histopathological parameters.

Methods and results: Tumour tissue samples from 89 patients with lung carcinoma were immunostained by the streptavidin–biotin–peroxidase technique, using a monoclonal antibody against both metallothionein‐1 and ‐2 isoforms. Positive matallothionein immunostaining was prominent in 44 out of 89 (49%) and negative in 45 out of 89 (51%) cases of lung carcinoma examined. Metallothionein positivity was prominent in 32 out of 43 (74%) cases of squamous cell lung carcinoma, and in 12 out of 35 (34%) cases of adenocarcinoma, while it was negative in all 11 cases of small‐cell lung carcinoma examined, presenting a statistically significant difference between the different histological types. The intensity of metallothionein staining revealed a statistically significant difference between the squamous cell and adenocarcinoma cases examined. The pattern and extent of metallothionein staining in tumour cells and the expression of metallothionein in stromal cells were not correlated with histopathological parameters (type and grade) in metallothionein‐positive cases of lung carcinoma examined. No association was found between metallothionein expression and lymph node status in the examined cases of lung carcinoma.

Conclusions: Our findings indicate that expression of metallothionein was evident in squamous cell lung carcinoma and adenocarcinoma, but absent in small‐cell lung carcinoma, supporting evidence for participation of this protein in the biological mechanisms underlying the carcinogenic evolution in the lung.
Immunohistochemical detection of CD30 remains negative in nodular lymphocyte‐predominant Hodgkin's disease using enhanced antigen retrieval
Authors: Roberts C , Jack F , Angus B , Reid A , Thompson W D
Published: March 2003

Immunohistochemical detection of CD30 remains negative in nodular lymphocyte‐predominant Hodgkin's disease using enhanced antigen retrieval

Aims: The aims of this study were to confirm that CD30 is reproducibly negative in cases of nodular lymphocyte‐predominant Hodgkin's disease (nLPHD), and its relationship to further antibody targets for the distinction of L&H cells from classical Hodgkin's and Reed–Sternberg cells.

Methods and results: We examined 16 cases of nLPHD from two centres in the UK to characterize immunohistochemically L&H cells for CD30, EMA, J‐chain and Oct2, using different methods of antigen retrieval, antigen amplification and antigen detection systems. Two cases could not be stained with J‐chain and Oct2. All cases were negative for CD30 following manual and automated staining. Only one case became positive for EMA after manual staining using tyramide amplification. J‐chain and Oct2 were negative in all cases following manual staining. J‐chain showed a positive result of variable degree in all but one case using automated Dako ChemMateTM amplification system staining. Oct2 demonstrated a positive, albeit variable, staining pattern in all cases following automated staining.

Conclusions: CD30 remains negative in L&H cells of nLPHD using enhanced antigen retrieval and can therefore reliably be used to distinguish nLPHD from classical Hodgkin's disease. The value of EMA in the diagnosis of nLPHD remains uncertain, as it does not reproducibly mark L&H cells, even after the use of enhanced antigen retrieval. J‐chain and Oct2 appear to be useful markers in the diagnosis of nLPHD using enhanced immunostaining and should therefore be included in lymphoma panels. Automated enhanced staining, using standardized protocols, precoated slides and the full system of prepared reagents, further diminishes the occurrence of errors associated with manual staining, and thereby improves confidence and reliability in diagnosing nLPHD.