bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of carbohydrate partitioning during the interaction of potato virus Y with tobacco
Authors: Herbers K. , Takahata Y. , Melzer M. , Mock H.‐P. , Hajirezaei M. , Sonnewald U.
Published: March 2003

To test whether carbohydrates may play a signalling function during plant pathogenesis, we investigated the interaction between tobacco and potato virus Y (PVYN). Four days after PVYN infection, leaves started to accumulate soluble sugars and leaf photosynthesis decreased. The accumulation of soluble sugars was accompanied by an induction of cell wall invertase and a gradual decrease in the sucrose‐to‐hexose ratio. In parallel to changes in carbohydrate metabolism and photosynthesis, transcripts encoding PR‐proteins accumulated. Based on this coincidence, it was hypothesized that elevated hexose levels may enhance the expression of defence‐related functions and might possibly explain the phenomenon of high sugar resistance in plants. This notion has been supported by the fact that cell wall invertase‐expressing transgenic tobacco plants were found to be resistant against PVYN (
Herbers et al., 1996b
). To exclude the possibility that salicylate, which accumulates in plants expressing invertase, may be responsible for the observed resistance, these transgenic plants were crossed with salicylate hydroxylase‐expressing plants (nahG). The progeny were selected for high levels of sugar and low levels of salicylate. Necrotic lesions also developed, typically formed on the leaves of plants expressing invertase, and transcripts encoding PR‐Q accumulated in the absence of salicylate. On the other hand, accumulation of PR‐1b transcripts decreased, indicating that sugars are not sufficient for PR‐1b induction. Infection experiments using these plants as hosts revealed resistance towards PVYN. Thus, the mechanism of apoplastic invertase induced virus resistance is salicylate independent and most likely sugar mediated.
Plant signalling and induced defence in insect attack
Authors: Chamberlain Keith , Pickett John A. , Woodcock Christine M.
Published: March 2003

Plants can produce compounds which act as semiochemicals, that is, signals modifying the development or behaviour of other organisms without having direct physiological activity. Among such semiochemicals are plant stress signals associated with the induction of defence systems, and these may include phytopheromones that naturally influence plant development. It is well known that plant‐derived semiochemicals can be exploited by colonizing organisms, particularly pathogens and insect pests. Recently proposed external signals not yet proven as natural phytopheromones are nitric oxide and the volatile methyl esters of jasmonic and salicylic acids. Since it is now possible to use sophisticated electrophysiological techniques to investigate insect interactions with prospective phytopheromones, the detection and characterization of signalling systems has been made much easier and can provide a molecular characterization of signals that are active beyond the insects themselves. In addition to the advances these studies have brought to the understanding of plant/insect and plant/plant interactions, plant signals are potentially valuable in the regulation of gene expression for improved or alternative approaches to crop protection or for other developmental processes in plants.
How the bacterial plant pathogen Xanthomonas campestris pv. vesicatoria conquers the host
Authors: Bonas Ulla , Van den Ackerveken Guido , Büttner Daniela , Hahn Karoline , Marois Eric , Nennstiel Dirk , Noel Laurent , Rossier Ombeline , Szurek Boris
Published: March 2003

Xanthomonas campestris pv. vesicatoria (Xcv) is the causal agent of bacterial spot disease on pepper and tomato. Pathogenicity on susceptible plants and the induction of the hypersensitive reaction (HR) on resistant plants requires a number of genes, designated hrp, most of which are clustered in a 23‐kb chromosomal region. Nine hrp genes encode components of a type III protein secretion apparatus that is conserved in Gram‐negative plant and animal pathogenic bacteria. We have recently demonstrated that Xcv secretes proteins into the culture medium in a hrp‐dependent manner. Substrates of the Hrp secretion machinery are pathogenicity factors and avirulence proteins, e.g. AvrBs3. The AvrBs3 protein governs recognition, i.e. HR induction, when bacteria infect pepper plants carrying the corresponding resistance gene Bs3. Intriguingly, the AvrBs3 protein contains eukaryotic signatures such as nuclear localization signals (NLS), and has been shown to act inside the plant cell. We postulate that AvrBs3 is transferred into the plant cell via the Hrp type III pathway and that recognition of AvrBs3 takes place in the plant cell nucleus.
DNA and protein transfer from bacteria to eukaryotes— the agrobacterium story
Authors: Nester EugenE. W.
Published: March 2003

Agrobacterium is a well‐studied plant pathogen, which has the unique ability to transfer DNA and protein into a number of eukaryotes. The DNA is integrated randomly into the plant genome where it is expressed, thereby leading to the disease crown gall. This system is a paradigm for the interaction of a number of plant and animal pathogens which transfer proteins into their host cells. In Agrobacterium, the tumour inducing (Ti) plasmid codes for the functions specifically required for the transfer process. These genes, termed virulence or vir genes, are activated by plant signal molecules acting through a two component regulatory system. A key structure coded by 11 genes of the vir B operon is a pilus, synthesized at 20 °C, but poorly at 25 °C. How this pilus functions in DNA and protein transfer is unclear, but homologous genes are found in many animal pathogens. In addition to Ti plasmid‐encoded vir genes, chromosomal virulence genes have also been identified. However, these mutations are often pleiotropic because they involve both the normal physiology of Agrobacterium as well as the metabolism of Agrobacterium when it is associated with plant cells. Based on 16S ribosomal RNA sequencing, Agrobacterium is closely related to the intracellular pathogen of animals, Brucella. Several chromosomal mutations of Agrobacterium required for virulence in plants are also required for invasion of animal host cells by Brucella.
Cucumber mosaic virus, a model for RNA virus evolution
Authors: Roossinck Marilyn J.
Published: March 2003

Taxonomic relationships: Cucumber mosaic virus (CMV) is the type member of the Cucumovirus genus, in the family Bromoviridae. Additional members of the genus are Peanut stunt virus (PSV) and Tomato aspermy virus (TAV). The RNAs 3 of all members of the genus can be exchanged and still yield a viable virus, while the RNAs 1 and 2 can only be exchanged within a species.

Physical properties: The virus particles are about 29 nm in diameter, and are composed of 180 subunits (T = 3 icosahedral symmetry). The particles sediment with an s value of approximately 98. The virions contain 18% RNA, and are highly labile, relying on RNA–protein interactions for their integrity. The three genomic RNAs, designated RNA 1 (3.3 kb in length), RNA 2 (3.0 kb) and RNA 3 (2.2 kb) are packaged in individual particles; a subgenomic RNA, RNA 4 (1.0 kb), is packaged with the genomic RNA 3, making all the particles roughly equivalent in composition. In some strains an additional subgenomic RNA, RNA 4A is also encapsidated at low levels. The genomic RNAs are single stranded, plus sense RNAs with 5′ cap structures, and 3′ conserved regions that can be folded into tRNA‐like structures.

Satellite RNAs: CMV can harbour molecular parasites known as satellite RNAs (satRNAs) that can dramatically alter the symptom phenotype induced by the virus. The CMV satRNAs do not encode any proteins but rely on the RNA for their biological activity.

Hosts: CMV infects over 1000 species of hosts, including members of 85 plant families, making it the broadest host range virus known. The virus is transmitted from host to host by aphid vectors, in a nonpersistent manner.

Useful web sites: http://mmtsb.scripps.edu/viper/1f15.html (structure); http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/10040001.htm (general information)
The tobacco mosaic virus resistance gene, N
Authors: Marathe Rajendra , Anandalakshmi Radhamani , Liu Yule , Dinesh‐Kumar S. P.
Published: March 2003

In this mini review we discuss recent advances in the understanding of the N gene‐mediated resistance to tobacco mosaic virus (TMV). The tobacco N gene belongs to toll‐interleukin‐1 receptor homology/nucleotide binding/leucine rich repeat (TIR‐NB‐LRR) class of resistance genes. It encodes two transcripts, NS and NL, by alternative splicing, both of which are required to confer resistance to TMV. The structure–function analysis of the N gene indicates that the TIR, NB and LRR domains are indispensable for its function. The N gene response is elicited by the C‐terminal helicase domain of the 126 kDa TMV replicase protein. Tobacco N gene can also confer resistance to TMV in heterologous plants like tomato and Nicotiana benthamiana. Recent studies on N‐mediated signalling suggest that EDS1, Rar1 and NPR1 genes play an important role in TMV resistance. Finally, we discuss current status of the N‐mediated signal transduction and speculate directions for future work to understand N–TMV interaction.
The phenylpropanoid pathway and plant defence—a genomics perspective
Authors: Dixon Richard A. , Achnine Lahoucine , Kota Parvathi , Liu Chang‐Jun , Reddy M. S. Srinivasa , Wang Liangjiang
Published: March 2003

The functions of phenylpropanoid compounds in plant defence range from preformed or inducible physical and chemical barriers against infection to signal molecules involved in local and systemic signalling for defence gene induction. Defensive functions are not restricted to a particular class of phenylpropanoid compound, but are found in the simple hydroxycinnamic acids and monolignols through to the more complex flavonoids, isoflavonoids, and stilbenes. The enzymatic steps involved in the biosynthesis of the major classes of phenylpropanoid compounds are now well established, and many of the corresponding genes have been cloned. Less is understood about the regulatory genes that orchestrate rapid, coordinated induction of phenylpropanoid defences in response to microbial attack. Many of the biosynthetic pathway enzymes are encoded by gene families, but the specific functions of individual family members remain to be determined. The availability of the complete genome sequence of Arabidopsis thaliana, and the extensive expressed sequence tag (EST) resources in other species, such as rice, soybean, barrel medic, and tomato, allow, for the first time, a full appreciation of the comparative genetic complexity of the phenylpropanoid pathway across species. In addition, gene expression array analysis and metabolic profiling approaches make possible comparative parallel analyses of global changes at the genome and metabolome levels, facilitating an understanding of the relationships between changes in specific transcripts and subsequent alterations in metabolism in response to infection.
A newly identified role for Tomato bushy stunt virus P19 in short distance spread
Authors: Turina Massimo , Omarov Rustem , Murphy John F. , Bazaldua‐Hernandez Cynthia , Desvoyes Bénédicte , Scholthof Herman B.
Published: March 2003

This study identified a role for the Tomato bushy stunt virus (TBSV) p19 protein (P19) in local lesion expansion on cowpea (Vigna unguiculata), and cell‐to‐cell movement in pepper (Capsicum annuum). The contribution to short distance spread in both hosts was strongly influenced by a cluster of charged amino acids between positions 72 and 78 on the 172 amino acid P19. Charged amino acids near this region between positions 43 and 85 were required for long distance spread in pepper. These results indicate that the central domain of P19 plays a key role for its activities in TBSV movement and that additional regions on this protein contribute to virus spread in a host‐specific manner.
Composition and nutritional value of commercial dried whey products from feta cheese manufacture
Authors: Boumba V A , Voutsinas L P , Philippopoulos C D
Published: March 2003

Various commercial dried whey products—WHEYPRO20, WHEYPRO35 and WHEYPRO65 (with approximately 20, 35 and 65% protein, respectively) and LACTINA (a permeate powder)—were studied in terms of chemical composition and nutritional value. These products were produced industrially from the whey of feta cheese manufactured with ovine and caprine milk by ultrafiltration and subsequent evaporation and spray‐drying. As the protein content in these products increased, the nonprotein nitrogen and fat contents increased while the lactose and ash contents decreased. Generally the concentration of minerals (Ca, P, Na, K, Cl) in these products decreased with increasing protein content. With the exception of valine and methionine + cysteine, all essential amino acids were in excess in the whey protein concentrates (WHEYPRO35 and WHEYPRO65) as compared with the Food and Agriculture Organization reference protein and with human milk protein.
What are the Read Codes?
Authors: NHS NICK BOOTH
Published: March 2003

The Read Codes were initially developed by a general practitioner, Dr James Read from Loughborough, in the early 1980s and rapidly gained acceptance by general practitioners as a popular and useful mechanism for storing structured information about patients in individual, patient‐based records, which were beginning to become popular in a few general practices at the time. This short article aims to explain the past and future development of the coding system in the National Health Service as a whole.
Designing a search strategy to identify and retrieve articles on evidence‐based health care using MEDLINE
Authors: HARRISON JANE
Published: March 2003

The practice of evidence‐based health care requires that information on methodology be identified from databases such as MEDLINE. Up until this year there have been no designated medical subject headings (MeSH) for evidence‐based health care. ‘EVIDENCE‐BASED MEDICINE’ appears as a MeSH term from 1997. The absence of designated MeSH for this concept prior to 1997 provides a challenge to the searcher. This paper describes the creation of a MEDLINE search strategy to retrieve articles on the methods of evidence‐based health care published prior to the introduction of the new term, where an optimal combination of free‐text and MeSH terms is required to identify relevant material. The study examines both free‐text and subject heading searching and attempts an optimal balance of sensitivity and specificity. It begins by examining separate free‐text and subject heading searches. Sensitivity of the subject heading search was 33% and specificity 80%, while the free‐text search produced a sensitivity of 50% and a specificity of 67%. The final strategy, combining both approaches, was more successful with sensitivity reaching between 82 and 90% and specificity 83%.

It is therefore possible to devise a search strategy to retrieve articles on the methods of evidence‐based health care with relatively successful rates ofsensitivity and specificity. The limitations of MEDLINE, however, necessitate the use of additional approaches in identifying articles on the methods of evidence‐based health care.
Promoting library services to qualified nurses: towards a market‐led approach
Authors: HERNANDO SALLY
Published: March 2003

This article summarizes a research project carried out with the nursing staff of South Buckingham‐shire NHS Trust. A ‘communityprofde’ looked at nurses’ use of library and information services forpatient care purposes and found that only a small proportion ofall categories of qualified staff were library users.

A postal questionnaire was used to investigate why nurses sought information, what they used it for, where they obtained itfrom and how valuable they perceived it to be. The results show that personal and departmental collections were used quite frequently and the information was widely disseminated by the nurses to patients and their families, to colleagues and to students. The overall messagefrom the survey was that the information obtained is valued highly and is used for various important purposes in health care delivery, such as educating patients and their families and revising treatment plans. However, nurses have diffculty in accessing libraries, which are judged to contain the most accurate, reliable and up‐to‐date information.

The data from the community projle and questionnaire were further analysed using soft systems methodology, in order to identify problems in the traditional model of information delivery to nurses via a conventional library and information service. These were then investigated further and a series of recommendations for action drawn up.
How much should it cost? An introduction to management use of costing information
Authors: COOPER LARRAINE
Published: March 2003

With the introduction of the internal market the health service is changing rapidly and health libraries must change with it. Many libraries are requested to cost their services. The demand comes from external customers and from their own organizations. This paper discusses the various reasons for costing services and how costing information can influence our management decision making.

The paper challenges librarians to move costing processes away from a mechanistic approach, towards a means of demonstrating the worth of a library resources unit in cost and qualitative terms. Using costing information for cost control purposes, comparison of cost with other providers, setting prices or determining future service delivery levels is discussed, as well as considering the question of external provision of library services.

Use of information on fixed and variable costs and assessing break‐even levels of service provision is illustrated as a helpful guide to library survival.
Searching the right database. A comparison of four databases for psychiatry journals
Authors: Mcdonald Steve , Taylor Libby , Adams Clive
Published: March 2003

Journal coverage is one factor that affects the retrieval of relevant information from bibliographic databases. The aims of this study were to investigate the coverage of databases for psychiatry journals, and to assess the overlap between databases. Psychiatry journals were identified using Ulrich’s International Periodicals Directory and then analysed to see which bibliographic databases indexed the most journals. A total of 213 abstracting and indexing services were listed as indexing at least one of the 977 psychiatry journals identified. The four most frequently cited databases (PsycLIT, EMBASE, BIOSIS and MEDLINE) indexed 506 (52%) of the psychiatry journals. Of these 506 journals, PsycLIT indexed 367 (73%), EMBASE 337 (67%), BIOSIS 243 (48%) and MEDLINE 236 (47%). Combining the databases with the highest yields (PsycLIT and EMBASE) increased the number of journals indexed to 461 (91%). The four databases combined accounted for 90% of all psychiatry journals found to be indexed by at least one abstracting and indexing service. More than 400 journals were not indexed at all. Variations in the overlap between PsycLIT, EMBASE, BIOSIS and MEDLINE, and the high proportion (35%) of journals indexed in only one of these four databases emphasize the importance of searching more than one or even two databases to ensure optimal coverage of the literature.
Expression of vascular endothelial growth factor in digestive neuroendocrine tumours
Authors: Terris  , Scoazec  , Rubbia  , Bregeaud  , Pepper  , Ruszniewski  , Belghiti  , FLÉjou  , Degott
Published: March 2003

Aims:

Angiogenesis is a complex multistep process essential for tumour growth. Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen and vascular permeability‐inducing agent. Recent studies have shown that VEGF expression is correlated to microvessel density and tumour progression. The aim of this study was to analyse VEGF expression in a series of gastrointestinal neuroendocrine tumours.

Methods and results:

Surgical specimens from 28 gastrointestinal carcinoids and 20 pancreatic endocrine tumours were examined for VEGF expression by immunohistochemistry. Intense cytoplasmic staining for VEGF was observed in several cells of the islets of Langerhans and in neuroendocrine cells of normal digestive mucosa. All midgut carcinoids showed strong VEGF expression in tumoral cells. Positive VEGF immunostaining was observed in 16 of 20 neuroendocrine pancreatic tumours but it was usually much lower than in midgut carcinoids. Western blotting analysis in eight cases identified a major band at 30–32 kDa. No correlation between VEGF expression and tumour stage was found.

Conclusions:

This study demonstrates that neuroendocrine cells are a major source of VEGF, particularly in midgut carcinoids. This finding suggests that the presence of VEGF may be required to maintain the differentiated state of capillary vessels in these hypervascular tumours. Such secretion, in conjunction with the other growth factors synthesized by these neuroendocrine tumours, may have an important role in tumour growth.
Expression of E‐cadherin, α‐catenin and β‐catenin in normal ovarian surface epithelium and epithelial ovarian cancers
Authors: Davies  , Worsley  , Ponder
Published: March 2003

Aims:

To study the expression of the epithelial adhesion molecule E‐cadherin and its associated proteins α and β catenin in paraffin sections of normal ovaries, benign cystadenomas and ovarian carcinomas, and in immortalized normal ovarian surface epithelial cells and ovarian carcinoma cells in culture.

Methods and results:

Immunocytochemistry was used to to study expression of the proteins in paraffin sections and western blotting was used to determine levels of expression of the proteins in cell extracts. E‐cadherin expression was found to be absent in ovarian surface epithelial cells in culture and infrequently expressed in normal ovarian surface epithelial cells in vivo, although apical punctate staining was occasionally seen. Seven of nine benign cystadenomas and 29/34 epithelial ovarian carcinomas showed some expression of E‐cadherin, but expression was absent in poorly differentiated tumours. Expression of α and β catenin was consistently detected on the lateral membranes of normal ovarian epithelium and benign cystadenomas. α and β catenin expression was lost in 18% and 21% of ovarian carcinomas, respectively; other ovarian carcinomas expressed these proteins at a reduced level. A small number of these tumours showed a diffuse cytoplasmic rather than membranous staining. Reduced staining for α and β catenin appeared to correlate with a more spindly, less adhesive morphology and increased invasive potential in matrigel.

Conclusions:

The results suggest that E‐cadherin expression is generally induced in well differentiated ovarian cancers. In contrast, α and β catenins are consistently expressed in the normal ovarian surface epitheium and benign tumours, but are sometimes reduced or absent in ovarian carcinomas. It is likely that the catenins associate with membrane proteins other than E‐ cadherin in ovarian epithelium, and they may possibly function as tumour suppressors in this epithelium.
Myoepithelial carcinoma (malignant myoepithelioma): first report of an occurrence in the maxillary sinus
Authors: Graadt Van Roggen  , Baatenburg‐De Jong  , Verschuur  , Balhuizen  , Slootweg  , Van Krieken
Published: March 2003

Aim:

We document for the first time the occurrence of a malignant myoepithelioma at a site other than within the major and minor salivary glands.

Methods and results:

A 67‐year‐old male presented with progressive symptoms and signs of a space‐occupying lesion in the right maxillary sinus. An initial biopsy identified a malignant (myo)epithelial lesion and a radical maxillectomy was performed. Histology, supplemented by immunohistochemistry, confirmed the prescence of a malignant myoepithelioma.

Conclusion:

Malignant myoepithelioma is a very rare tumour composed almost exclusively of myoepithelial cells and, to date, has only been described arising in the the major and minor salivary glands. A variety of tumours of salivary tissue have been reported within the head and neck area at sites outside the major and minor salivary glands, probably arising within accessory salivary tissue. We report the first case of a malignant myoepithelioma occurring in the maxillary sinus, also presumably arising in accessory salivary tissue in this location.
Maintenance of polarity and a dual cell population in adenoid cystic carcinoma of the breast: an immunohistochemical study
Authors: Kasami  , Olson  , Simpson  , Page
Published: March 2003

Aims:

Adenoid cystic carcinoma (ACC) of the breast, although quite uncommon, is histologically distinct and has an excellent prognosis. Our purpose was to characterize molecular markers of cellular differentiation and polarity to define better the role that these combined features might play in the excellent prognosis of ACC in this site.

Methods and results:

We performed immunohistochemical stains for expression of vimentin (VM), cytokeratin (CK), smooth muscle actin (SMA), laminin (LAM), E‐cadherin (E‐cad), β‐catenin (β‐cat) and fodrin in 14 examples of ACC. Two types of intercellular lumens and defining lining cells were detected: true epithelial lumens were lined by CK positive cells that maintained the normal glandular luminal cells with an intact polarity and basolateral membrane compartment indicators: fodrin, E‐cad and β‐cat. The second type of intercellular space was a pseudolumen, surrounded by myoepithelial cells that were strongly positive for VM and SMA, and lined by LAM. Double staining for VM and CK, VM and SMA, and CK and SMA detected occasional cytoplasmic co‐expression of these markers in the myoepithelial cell compartment, but VM and SMA did not stain epithelial lumenal cells.

Conclusions:

ACC of the breast is characterized by the presence of two types of intercellular lumens, one conserving basolateral markers of normal polarity (epithelial) with the other containing basement membrane material (abutted by myoepithelial cells). Dominance of VM staining may be a hallmark of ACC, along with maintained epithelial and myoeithelial compartments. This status of advanced, normal differentiation despite local invasion may be responsible for lack of distant metastasis.
A comparative evaluation of immunohistochemical markers for the differential diagnosis of malignant pleural tumours
Authors: Garcia‐Prats  , Ballestin  , Sotelo  , Lopez‐Encuentra  , Mayordomo
Published: March 2003

Aims

To determine the value of immunocytochemistry in differentiation of malignant pleural mesothelioma from carcinoma in a pleural biopsy using commercially available monoclonal antibodies.

Methods and results

A panel of monoclonal antibodies against keratins, epithelial membrane antigen (EMA), epithelial antigen Ber‐EP4, carcinoembryonic antigen (CEA), tumour‐associated glycoprotein (B72.3), Leu‐M1, CD30 (Ber‐H2), vimentin and desmin, was applied to 40 cases of malignant pleural mesothelioma and 23 cases of carcinoma metastatic to the pleura (16 pulmonary and seven extrapulmonary). Positivities for Ber‐EP4, CEA, B72.3 and Leu‐M1 were found to have the highest nosologic sensitivities (87.0%, 65.2%, 52.5% and 43.5%, respectively) and specificities (97.5%, 97.5%, 100% and 95%, respectively) for carcinoma. Positive staining for vimentin had the highest sensitivity (87.5%) with 95.7% specificity for mesothelioma. Positive staining for desmin was found in 45% of mesotheliomas and 0% of carcinomas. Diagnostic sensitivity and diagnostic specificity (P‐values) were calculated for these markers. In respect to the diagnostic power defined by the clinically relevant predictive values of positive and negative tests, we found that a two‐marker panel of antibodies including vimentin and Ber‐EP4 is most useful for the histopathological distinction between carcinoma (pulmonary or extrapulmonary) and malignant pleural mesothelioma.

Conclusions

A combination of Ber‐EP4 and vimentin provides the most sensitive and specific pair of markers for distinguishing between malignant pleural mesothelioma and carcinoma metastatic to the pleura. The prevalence of the tested tumours should be taken into account when evaluating the clinical value of ancillary techniques in pathology.
Nerve sheath tumours with hybrid features of neurofibroma and schwannoma: a conceptual challenge
Authors: Feany  , Anthony  , Fletcher
Published: March 2003

Aims

To characterize and delineate a subset of rare nerve sheath tumours showing hybrid features of neurofibroma and schwannoma.

Methods and results

Nine lesions were identified in the authors' files showing predominant features of neurofibroma with distinct, often nodular regions of classical schwannomatous differentiation. Most patients were adults, eight out of nine were male. Of the nine lesions, two were dermal, two were subcutaneous and five were subfascial. Five lesions had a plexiform architecture and one patient had overt neurofibromatosis. One out of six patients with follow‐up developed local recurrence. Schwannoma‐like regions displayed strong S100 staining, in contrast to more varied and limited S100 reactivity in neurofibromatous areas. The Antoni A areas could be quite cellular with high MIB‐1 proliferation indices. No lesion underwent malignant change.

Conclusions

Our results demonstrate that some nerve sheath tumours may contain histologically clear components of both neurofibroma and schwannoma, suggesting that (despite evident and well‐defined clinicopathological differences) these two lesions may be even more closely related than previously recognized. Whether this phenomenon results from a localized microenvironmental change or from a clonal genetic alteration remains unknown.
Massive lymphocytic infiltration of uterine leiomyomas associated with GnRH agonist treatment
Authors: Bardsley V , Cooper P , Peat D S
Published: March 2003

Aims

To report two unusual cases of massive lymphocytic infiltration of uterine leiomyomas, following GnRH agonist treatment. Previous reports have described a variety of alterations in leiomyoma histology following such therapy.

Methods and results

These cases were studied using haematoxylin and eosin stains, and immunohistochemistry for B and T‐cell markers (CD20/CD79a and CD3/UCHL‐1) was performed. Leiomyomas were heavily infiltrated predominantly by mature lymphocytes of T‐cell phenotype. Associated myocyte degenerative changes were present.

Conclusion

Massive lymphocytic infiltration of leiomyomas may occur as a result of GnRH agonist treatment, although the mechanism is unclear.
Epithelioid sarcoma: presence of vascular‐endothelial cadherin and lack of epithelial cadherin
Authors: Smith M E F , Brown J I , Fisher C
Published: March 2003

Aims

To evaluate the pattern of cadherin expression in epithelioid sarcoma.

Methods and results

Seven epithelioid sarcomas were immunostained by a polyclonal antibody that detects all cadherin subtypes and by monoclonal antibodies that detect epithelial cadherin (E‐cadherin) and vascular‐endothelial cadherin (VE cadherin). In addition, the tumours were immunostained for a variety of epithelial (cytokeratin, EMA, AUA1) and endothelial (Factor VIII‐related antigen, CD34, CD31) markers. Tumour cells of all seven epithelioid sarcomas expressed cadherins. Surprisingly, E‐cadherin was not detected in any of the sarcomas. VE‐cadherin was detected in five of seven cases. All seven tumours expressed cytokeratins and EMA but none expressed AUA1. CD34 was detected in six of seven cases and CD31 was detected in a single case. No case expressed Factor VIII‐related antigen.

Conclusions

Most epithelioid sarcomas strongly express cadherins, a feature which may contribute to their epithelioid appearance. The absence of detectable E‐cadherin suggests that epithelial differentiation in these tumours is, at most, incomplete. The expression of VE‐cadherin by the majority of cases, in the absence of E‐cadherin, is consistent with an element of mesenchymal differentiation, possibly endothelial or perineurial. The additional presence of other markers such as CD34 and CD31 in some cases favours endothelial differentiation.
Expression of c‐erbB‐2 oncoprotein in human thyroid tumours
Authors: Utrilla  , Martín‐Lacave  , San Martín  , Fernández‐Santos  , Galera‐Davidson
Published: March 2003

Aims

c‐erbB‐2 expression has been found to be a potential marker of aggressive biological behaviour in some tumours, but the role played by this oncoprotein in the development and maintenance of thyroid tumours is still controversial. Therefore our objective was to determine whether c‐erbB‐2 was overexpressed in a large retrospective series of human thyroid tumours, including both from follicular and C‐cell differentiation.

Methods and results

We have studied 67 thyroid tumours (10 follicular adenomas, 11 follicular carcinomas, three anaplastic carcinomas, 25 papillary carcinomas and 18 medullary carcinomas and 16 metastases) by immunohistochemistry using an antigen retrieval method for paraffin‐embedded material and a specific polyclonal antibody against the intracytoplasmic part of c‐erbB‐2 oncoprotein. There are marked differences in the pattern of c‐erbB‐2 immunoreactivity depending on the type of thyroid tumour. Thus, no expression of the oncoprotein has been found in follicular adenomas, follicular carcinomas and anaplastic carcinomas, but 52% of papillary carcinomas (membranous and diffuse cytoplasmic patterns) and all medullary carcinomas (granular cytoplasmic pattern) are immunopositive.

Conclusions

Our results indicate that overexpression of c‐erbB‐2 oncoprotein is easily identifiable by immunohistochemistry in paraffin sections of certain thyroid tumours after applying an antigen retrieval method. This study suggests that c‐erbB‐2 oncoprotein may play some role in disease progression in papillary and medullary thyroid carcinomas, but the significance of the different immunohistochemical patterns merits further investigations.
Criteria for grading in the Ljubljana classification of epithelial hyperplastic laryngeal lesions. A study by members of the Working Group on Epithelial Hyperplastic Laryngeal Lesions of the European Society of Pathology
Authors: Hellquist  , Cardesa  , Gale  , Kambic  , Michaels
Published: March 2003

Aims

To validate histological criteria for the grading of epithelial hyperplastic laryngeal lesions (EHHL) (dysplastic laryngeal lesions), we used a system that had been devised and tested in Ljubljana, Slovenia over many years and was felt to be more appropriate to laryngeal pathology than is the commonly‐used model of intraepithelial neoplasia in the cervix.

Methods and results

Vocal cord biopsies of 45 patients with a broad spectrum of EHLL were reviewed. Detailed histological criteria were formulated for each of the four grades of EHLL in the Ljubljana classification, comprising simple hyperplasia (benign spinous layer augmentation), abnormal hyperplasia (benign basal and parabasal layer augmentation), atypical hyperplasia (risky for malignancy) and carcinoma in situ (actually malignant, but without invasion).

Conclusions

Using these criteria a high degree of concordance of histological diagnoses of grading levels for the Ljubljana classification was achieved between the pathologists of the Working Group. The system was found to be more precise for routine diagnostic work than the others in vogue. The different grades of the Ljubljana classification correspond to significantly different levels yielded in each grade by the semi‐objective methods of quantitative morphometry and immunohistochemistry.
Association of Epstein–Barr virus infection with p53 protein accumulation but not bcl‐2 protein in nasopharyngeal carcinoma
Authors: Murono  , Yoshizaki  , Park C‐S , Furukawa
Published: March 2003

Aims

The aim of this study was to investigate the association of Epstein–Barr virus (EBV) infection with status of p53 protein expression in nasopharyngeal carcinoma (NPC). The expression of EBV gene and gene product, p53 protein and bcl‐2 protein in NPC was histopathologically studied.

Methods and results

In‐situ hybridization using oligonucleotide probe to EBV‐encoded small RNAs (EBERs) and immunohistochemistry using monoclonal antibodies against EBV latent membrane protein 1 (LMP1), p53 protein and bcl‐2 proteins were performed in 56 primary NPCs. EBERs were detected in 46 (82%) cases and LMP1 in 17 (30%) cases. While 30 of 32 (94%) cases in differentiated nonkeratinizing carcinoma (NKC, WHO type 2) and 16 of 17 (94%) cases in undifferentiated carcinoma (UC, WHO type 3) showed EBERs expression, neither five cases of keratinizing squamous cell carcinoma (KSCC, WHO type 1) nor two cases of adenocarcinoma showed EBERs. bcl‐2 protein was detected in 50 (89%) cases, but its expression did not depend on expression of LMP1. p53 protein was detected in 31 (55%) cases, and there was a correlation between expression of EBERs and p53 protein (P < 0.05) but not between LMP1 and p53 protein.

Conclusion

In this study, close association of NKC and UC but not KSCC with the latent infection with EBV was demonstrated. The induction of bcl‐2 protein by LMP1, as shown in vitro, was not demonstrated. The association between overexpression of p53 protein and the presence of EBV suggests that some EBV‐encoded protein, which may be different from LMP1, may play a role for nuclear accumulation of p53 protein.
Primary synovial sarcoma of the lung: report of two cases confirmed by molecular detection of SYT‐SSX fusion gene transcripts
Authors: Hisaoka  , Hashimoto  , Iwamasa  , Ishikawa  , Aoki
Published: March 2003

Aims

Primary pulmonary sarcoma is rare, and frequently creates diagnostic challenges. We describe two cases of primary pulmonary spindle cell sarcoma in which a molecular approach using archival paraffin‐embedded tissue was proved to aid diagnosis.

Methods and results

Both patients had huge masses replacing the upper and middle lobes of the lung, respectively, without any primary extrapulmonary neoplastic lesions. Microscopically, the lesions showed a solid hypercellular nodular or lobular growth of atypical short spindle cells in variably intersecting fascicles or in a haphazard fashion, together with focal areas displaying a prominent haemangiopericytoma‐like pattern. Immunohistochemically, a small number of the tumour cells were positive for epithelial markers such as cytokeratin and epithelial membrane antigen. In both cases, a reverse transcription‐polymerase chain reaction using RNA extracted from formalin‐fixed, paraffin‐embedded tissues detected SYT‐SSX fusion gene transcripts, which are characteristic of synovial sarcoma.

Conclusion

On the basis of the morphological and molecular findings, these tumours are considered to be rare examples of monophasic synovial sarcoma of the lung. Our molecular assay detecting the SYT‐SSX fusion transcripts is useful for the final diagnosis of synovial sarcoma arising at such an unusual anatomical site.
bcl‐2 protein expression is associated with better prognosis in colorectal cancer
Authors: Leahy  , Mulcahy  , O'Donoghue  , Parfrey
Published: March 2003

Aims

To investigate the expression of bcl‐2 in colorectal carcinoma and to examine its association with mediators of apoptosis (p53 and mdm‐2), clinicopathological features and long‐term outcome.

Methods and results

We determined by immunohistochemistry the expression of bcl‐2 in 102 colorectal carcinomas with 10‐year follow‐up. In 66 of these cases in which we had previously assessed p53 status, no correlation was seen between bcl‐2 and p53. The mdm‐2 protein was not detected in any of the 66 cases. Cytoplasmic staining of the bcl‐2 gene product was seen in the tumour cells of 22 cases (22%). Using a polymerase chain reaction technique we showed that overexpression of bcl‐2 was not due to rearrangement of the bcl‐2 gene. Expression of bcl‐2 protein was related to tumour grade but was unrelated to patient age, sex, tumour site, tumour size or Dukes' stage. There was a trend towards increased survival in those whose tumours expressed bcl‐2 protein (P = 0.055). When entered into a multivariate analysis, this survival difference was independent of tumour stage (P = 0.05).

Conclusions

These results suggest that bcl‐2 expression in colorectal carcinoma is associated with a better long‐term prognosis.
Sinus histiocytosis with massive lymphadenopathy: evidence for its relationship to macrophages and for a cytokine‐related disorder
Authors: Middel  , Hemmerlein  , Fayyazi  , Kaboth  , Radzun
Published: March 2003

Aims

Sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai–Dorfman disease is a rare histiocytic disorder of unknown origin. Immunophenotypically the histiocytes of SHML express intensively the S100 protein and in addition a panel of macrophage‐associated antigens. Their exact relationship to either monocytes/macrophages or immune accessory dendritic cells is, however, still controversial.

Methods and results

In this report recurrent nodal and extranodal manifestations of SHML of a 70‐year‐old patient were analysed by differential phenotyping using a panel of monoclonal and polyclonal antibodies to macrophage and immune accessory dendritic cell related antigens and by applying nonradioactive in‐situ hybridization.

Conclusions

We conclude that stimulation of monocytes/macrophages via macrophage colony stimulating factor (M‐CSF) leading to immune suppressive macrophages represents a main mechanism for the pathogenesis of SHML. The study further provides evidence for the monocyte/macrophage but not dendritic cell differentiation of SHML histiocytes.
Morphological evidence for field effect as a mechanism for tumour spread in mammary Paget's disease
Authors: Mai
Published: March 2003

Aims

The histogenesis of mammary Paget's disease is controversial. The purpose of this study was to investigate the mechanism of tumour spread in the nipple epidermis by examining 28 cases of mammary Paget's disease associated with underlying intraductal carcinoma.

Methods and results

The atypical cells in the epidermis displayed a spectrum of cytological changes ranging from small‐sized atypical cells located in the basal cell layer to large‐sized atypical cells characteristic of Paget's cells in the upper layer of the epidermis. Serial sectioning revealed the presence of isolated, scattered and small atypical cells in the basal cell layer at the periphery of the epidermal lesion. The atypical cells, including those in the basal cell layer showed positive immunostaining for cytokeratin 7 and Her2/neu oncoprotein. Electron microscopy examination demonstrated the presence of intercellular junctions of desmosomal‐like or desmosomal types between tumour cells and adjacent squamous cells. Furthermore, examination of the intraductal carcinoma of the breast tissue in cases of Paget's disease as well as control cases of intraductal carcinoma also revealed areas of skip lesions of intraductal carcinoma.

Conclusions

In view of these changes, it is unlikely that tumour expansion or tumour cell motility are sufficient explanations to account for the pattern of tumour spread in both the epidermis and the duct epithelium with skip lesions. A ‘field effect’ in the duct system harbouring intraductal carcinoma and the adjacent epidermis may play an important role in the tumour cell spread in the epidermis as well as in the ductal epithelium.
HBME‐1, MOC‐31, WT1 and calretinin: an assessment of recently described markers for mesothelioma and adenocarcinoma
Authors: Oates  , Edwards
Published: March 2003

Aims

To evaluate HBME‐1, WT1, calretinin and MOC‐31 in the differential diagnosis of pleural mesothelioma and adenocarcinoma of the lung.

Methods and results

Paraffin‐embedded formalin‐fixed blocks from six reactive pleuras, 42 mesotheliomas and 40 adenocarcinomas were used. Sections were stained for Leu‐M1, HBME‐1, calretinin, WT1 and MOC‐31. Leu‐M1 was positive or equivocal in 34% of mesotheliomas and in 78% of adenocarcinomas; reactive pleuras were all negative. HBME‐1 was positive or equivocal in 76% of mesotheliomas and in 73% of adenocarcinomas; five reactive pleuras were positive. Calretinin was positive or equivocal in 92% of mesotheliomas and in 73% of adenocarcinomas; two reactive pleura were equivocal and four were positive. WT1 was positive or equivocal in 72% of mesotheliomas (excluding autopsy cases) and in 20% of adenocarcinomas; all reactive pleuras were positive. MOC‐31 was positive or equivocal in 5% of mesotheliomas and in 90% of adenocarcinomas; all reactive pleuras were negative. The reaction with Leu‐M1 was graded as equivocal in 25% of the adenocarcinomas. All 24 of the autopsy cases of mesothelioma were negative for WT1 and in many operative specimens only the periphery was stained.

Conclusions

Neither calretinin nor HBME‐1 are sufficiently discriminatory to be of use, even as members of a panel of antibodies. WT1 shows some promise, but it cannot be used on autopsy material. The utility of MOC‐31 is confirmed, and outperforms Leu‐M1.
Monoclonal antibodies recognizing CD5, CD10 and CD23 in formalin‐fixed, paraffin‐embedded tissue: production and assessment of their value in the diagnosis of small B‐cell lymphoma
Authors: Watson  , Wood  , Lodge  , McIntosh  , Milton  , Piggott  , Proctor  , Taylor  , Smith  , Jack  , Bell  , Steward  , Anderson  , Horne  , Angus
Published: March 2003

Aims

Assessment of the expression of antigens CD5, CD10 and CD23 can be of value in the differential diagnosis of small B‐cell lymphoma. Correct subclassification is important since optimal treatment regimes differ between the subtypes. The aim of this study was to generate monoclonal antibodies recognizing these antigens in paraffin‐embedded tissue and to assess their efficacy using a panel of cases of small B‐cell lymphoma of various subtypes.

Methods and results

For each antibody synthetic recombinant protein and conventional murine hybridoma technology was employed. Monoclonal antibodies effective in formalin‐fixed, paraffin‐embedded tissue were successfully generated, designated NCL‐CD5‐4C7, NCL‐CD10‐270 and NCL‐CD23‐1B12, respectively. A series of 58 cases of small B‐cell lymphoma including examples of each subtype (lymphocytic, follicle centre cell, mantle cell, marginal zone and lymphoplasmacytoid) was assembled and immunostaining for the respective antigens carried out using the monoclonal antibodies produced. Our results indicate that the antibodies are specific for their respective antigens and give the predicted phenotypic profile in the small B‐cell lymphoma subtypes.

Conclusions

These novel monoclonal antibodies may be of value in routine diagnostic practice.
Vulvovaginal soft tissue tumours: update and review
Authors: Nucci  , Fletcher
Published: March 2003

Differences in biological behaviour make familiarity with (and accurate diagnosis of) vulvovaginal soft tissue tumours essential. Since ancillary studies such as immunoperoxidase staining and electron microscopy may not always be helpful in their distinction, one must often rely on morphological features to distinguish between different tumour types. This is particularly pertinent with regard to the relatively site‐specific stromal tumours of this region. The purpose of this review article is to reacquaint the reader with these specific types of vulvovaginal soft tissue tumour, particularly focusing upon the salient morphological features that help in their distinction, as well as to review their clinical aspects and pathogenesis. The following soft tissue lesions are described: fibroepithelial stromal polyp, cellular angiofibroma, angiomyofibroblastoma, superficial angiomyxoma and aggressive angiomyxoma. Because of continued difficulty in predicting their behaviour, a discussion of vulvar smooth muscle tumours is also included, with a particular focus upon a practical approach to their diagnosis.