bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene flow on the ice: genetic differentiation among Adélie penguin colonies around Antarctica
Authors: Roeder Amy D. , Marshall Richelle K. , Mitchelson Amanda J. , Visagathilagar Thungar , Ritchie Peter A. , Love Donald R. , Pakai Trevor J. , McPartlan Helen C. , Murray Neil D. , Robinson Nick A. , Kerry Knowles R. , Lambert David M.
Published: March 2003

Each summer Adélie penguins breed in large disjunct colonies on ice‐free areas around the Antarctic continent. Comprising > 10 million birds, this species represents a dominant feature of the Antarctic ecosystem. The patchy distribution within a large geographical range, natal philopatry and a probable history of refugia, suggest that this species is likely to exhibit significant genetic differentiation within and among colonies. We present data from seven microsatellite DNA loci for 442 individuals from 13 locations around the Antarctic continent. With the exception of one locus, there was no significant genic or genotypic heterogeneity across populations. Pairwise FST values were low with no value > 0.02. When all colonies were compared in a single analysis, the overall FST value was 0.0007. Moreover, assignment tests were relatively ineffective at correctly placing individuals into their respective collection sites. These data reveal a lack of genetic differentiation between Adélie penguin colonies around the Antarctic continent, despite substantial levels of genetic variation. We consider this homogeneity in terms of the dispersal of individuals among colonies and the size of breeding groups and discuss our results in terms of the glacial history of Antarctica.
Identification of mycorrhizal fungi from single pelotons of Dactylorhiza majalis (Orchidaceae) using single‐strand conformation polymorphism and mitochondrial ribosomal large subunit DNA sequences
Authors: kristiansen K. A. , taylor D. L. , kjøller R. , rasmussen H. N. , rosendahl S.
Published: March 2003

The mitochondrial ribosomal large subunit (Ls) DNA was used to identify the orchid mycorrhizal fungi found in roots of Dactylorhiza majalis. The gene was amplified using DNA extracted from single pelotons obtained from fresh and silica gel dried roots. Furthermore, sequencing a variety of well‐characterized orchid isolates expanded the fungal database of the mitochondrial ribosomal LsDNA. Polymerase chain reaction product length variants present in D. majalis were sequenced and identified using the expanded database. These analyses revealed two different peloton‐forming fungi in samples from D. majalis, which sometimes occurred together as a single two‐taxa peloton within the same cortex cell. The first taxon belonged to the genus Tulasnella and the second taxon was distantly related to Laccaria.
Microsatellite analysis of female mating behaviour in lek‐breeding sage grouse
Authors: Semple K. , Wayne R. K. , Gibson R. M.
Published: March 2003

We used microsatellite DNA markers to genotype chicks in 10 broods of lek‐breeding sage grouse, Centrocercus urophasianus, whose mothers’ behaviour was studied by radio‐tracking and observing leks. Previous behavioural studies suggested that almost all matings are performed by territorial males on leks and that multiple mating is rare. Two broods (20%) were sired by more than one male. Genetic analyses of the broods of eight females that visited an intensively studied lek were consistent with behavioural observations. Four females observed mating produced singly sired broods and males other than the individual observed copulating were excluded as sires for most or all of their chicks. Territorial males at the study lek were excluded as sires of broods of four other females that visited the lek but were not observed mating there. Radio‐tracking suggested that two of these females mated at other leks. Our results confirm the reliability of mating observations at leks, but do not rule out a possible unseen component of the mating system.
Speciation via introgressive hybridization in East African cichlids?
Authors: Salzburger W. , Baric S. , Sturmbauer C.
Published: March 2003

Speciation caused by introgressive hybridization occurs frequently in plants but its importance remains controversial in animal evolution. Here we report a case of introgressive hybridization between two ancient and genetically distinct species of Lake Tanganyika cichlids that led to the formation of a new species.Neolamprologus marunguensiscontains mtDNA haplotypes from both parental species varying on average by 12.4% in the first section of the control region and by 5.2% in a segment of the cytochromebgene. All individuals have almost identical DNA sequences in the flanking regions of the single‐copy nuclear DNA locus TmoM27, and show a mosaic of alleles derived from both parental lineages in six microsatellite loci. Hence, our finding displays another mode of speciation in cichlid fishes. The increase of genetic and phenotypic diversity due to hybridization may contribute to the uniquely rapid pace of speciation in cichlids.
Single‐nucleotide polymorphism characterization in species with limited available sequence information: high nucleotide diversity revealed in the avian genome
Authors: Primmer C. R. , Borge T. , Lindell J. , Sætre G.‐P.
Published: March 2003

As a case study for single‐nucleotide polymorphism (SNP) identification in species for which little or no sequence information is available, we investigated several approaches to identifying SNPs in two passerine bird species: pied and collared flycatchers (Ficedula hypoleucaandF. albicollis). All approaches were successful in identifying sequence polymorphism and over 50 candidate SNPs per species were identified from ≈ 9.1 kb of sequence. In addition, 17 sites were identified in which the frequency of alternative bases differed by > 50% between species (termed interspecific SNPs). Interestingly, polymorphism of microsatellite/intron loci in the source species appeared to be a positive predictor of nucleotide diversity in homologous flycatcher sequences. The overall nucleotide diversity of flycatchers was 2.3–2.7 × 10−3, which is ≈ 3–6 times higher than observed in recent studies of human SNPs. Higher nucleotide diversity in the avian genome could be due to the relatively older age of flycatcher populations, compared with humans, and/or a higher long‐term effective population size.
Mizoribine in the treatment of rheumatoid arthritis and juvenile idiopathic arthritis
Authors: Takei Syuji
Published: March 2003

Background
: Mizoribine (MZR), isolated from culture medium of the mold, is a novel immunosuppressant developed in Japan. It has been used in patients with renal transplantation, lupus nephritis, nephrotic syndrome and rheumatoid arthritis (RA).

Objectives
: To review MZR in regards to mechanism of action, pharmacokinetics, efficacy and safety in the treatment of rheumatoid RA and juvenile idiopathic arthritis (JIA).

Results
: The drug MZR inhibits both humoral and cellular immunity in RA patients. It is completely excreted in the urine within 24 h, which contributes to the safety of MZR. A series of multicenter studies indicated that MZR was effective and safe in the treatment of RA. In JIA, however, there are only a few case reports reporting its efficacy and safety.

Conclusion
: A double‐blinded multicenter study is needed to establish the efficacy, safety and indication of MZR in the treatment of JIA.
Obstetric and perinatal outcome of women para ≥ 5 including one lower segment cesarean section
Authors: Ali Abdulhai Mohammad , Abu‐Heija Adel T
Published: March 2003

Objective:

To study the prevalence of antenatal, intrapartum and postnatal complications and their perinatal outcome in women who are delivering for the 6th time and have also had one cesarean section.

Methods:

The records of all women para ≥*Τ*5 with one previous cesarean section (n = 238) delivered at King Fahd Hospital of the University between the January 1 1994 and December 31 2000 were reviewed and compared with women who delivered at the hospital in the year 2000 (n = 2470). This data was analyzed for the peripartum and perinatal outcome.

Results:

The incidence of malpresentation was higher in the study group. The incidence of uterine rupture and uterine scar dehiscence was significantly higher in the study group, but there was no perinatal or maternal death associated with this and in all cases the uterus was preserved. More women managed to deliver vaginally after the cesarean section in the grandmultiparous women compared with the women in the control group (81.5%vs 63.0%) P < 0.00006, where the cesarean section rate was significantly higher (P < 0.02). There were no significant differences in the incidences of preterm labor, lethal malformations, stillbirths and neonatal deaths in the two groups of women. There was one case of cesarean hysterectomy in each group due to placenta accreta and atonic postpartum hemorrhage, and one maternal death in the control group.

Conclusion:

Grandmultiparous women with one previous cesarean section have an increased risk of operative delivery, scar dehiscence, but there is no increase in perinatal or maternal mortality.
Severe folate restriction results in depletion of and alteration in the composition of the intracellular folate pool, moderate sensitization to methotrexate and trimetrexate, upregulation of endogenous DHFR activity, and overexpression of metallothionein II and folate receptor alpha that, upon folate repletion, confer drug resistance to CHL cells
Authors: Zhu Wei‐Yong , Bunni M. , Priest D. G. , DiCapua J. L. , Dressler J. M. , Chen Z. , Melera Peter W.
Published: March 2003

DC‐3F/FA3 cells (FA3) were derived from antifolate‐sensitive CHL cells by selection for growth in folate‐free media containing 15 pM [6S]‐5CHOFH4. These cells undergo a 30‐fold decrease in intracellular folates, overexpress folate receptor alpha and metallothionein II, and display increased sensitivity to the dihydrofolate reductase (DHFR) targeted antifolates methotrexate (MTX) and trimetrexate (TMTX), which can be attributed primarily to the folate pool status. Upon folate repletion by growth in 15 nM [6S]‐5CHOFH4, they display a 5‐ and 10‐fold increase in resistance to both drugs, respectively, even though folate pools are restored by only 43%. Enforced overexpression of FRα in transfectants cultured in nanomolar folate did not confer resistance to MTX but did support a modest 2‐fold increase in resistance to TMTX. Enforced overexpression of MTII had a similar effect, but when both were overexpressed together no increase in resistance beyond that conferred by each one separately was noted, suggesting that both confer resistance to TMTX through a common downstream mechanism. Analysis of three independent low folate selected clones, FA3, FA7, and FA14, showed that each had a 5‐ to 6‐fold increase in DHFR activity accompanied by a similar increase in DHFR protein level. However, no differences were detected in the DHFR gene copy number or in the steady‐state amount of DHFR mRNA, suggesting that a posttranscriptional mechanism was responsible for the increase in DHFR expression.
Programmed responses to virus replication in plants
Authors: Maule A. J. , Escaler M. , Aranda M. A.
Published: March 2003

Despite their economic importance, we understand very little about the mechanism leading to symptom formation in compatible virus infections. By applying a spatial analysis to advancing infection fronts, we have been able to relate molecular events in small groups of cells to a sequence of virus‐induced changes. This sequence starts ahead of the main front of virus replication and virus protein accumulation and lasts beyond the time at which virus replication has ceased. The host changes include alterations in gene expression, physiology and cellular ultrastructure. The relationship between these effects has been analysed in comparative studies between different virus infections in different hosts and abiotic stress. The research points to there being common features for different viruses leading to common effects. Also, although many of the consequences of virus infection are similar to the effects of heat shock, there are sufficient differences to suggest that the two inducers use distinct control pathways. The immediate challenge for the future is to establish synchronous infections of tissues so that the complex relationship between the virus and the host can be investigated using temporal rather than spatial analyses.
Expression of theShpx2peroxidase gene ofStylosanthes humilisin transgenic tobacco leads to enhanced resistance toPhytophthora parasiticapv.nicotianaeandCercospora nicotianae
Authors: Way Heather M. , Kazan Kemal , Goulter Kenneth C. , Birch Robert G. , Manners John M.
Published: March 2003

Previous research indicated that the constitutive expression of a pathogen‐inducible peroxidase gene (Shpx6a) fromStylosanthes humilisin transgenic plants resulted in enhanced resistance to fungal pathogens (Kazan,K., Goulter, K.C., Way, H.M. and Manners, J.M. (1998) Expression of a pathogenesis‐related peroxidase ofStylosanthes humilisin transgenic tobacco and canola and its effect on disease development.Plant Sci.136,207–217). We have now investigated another pathogen‐inducible peroxidase gene ofS. humilis, termedShpx2, which is highly divergent fromShpx6a. Constitutive expression of theShpx2cDNA was obtained in tobacco using the 35S CaMV promoter, and up to a 12‐fold increase in total peroxidase activity was observed in the leaves of transgenic plants compared to nontransgenic controls. Disease development was evaluated after inoculations in T1and T2transgenic lines expressingShpx2. Lesion expansion was significantly (P < 0.05) reduced by up to 25% and 50% on leaves and stems, respectively, of transgenic plants expressing high levels of peroxidase compared to nontransgenic controls, following inoculation withPhytophthora parasiticapv.nicotianae, the cause of black shank disease. In addition, plant survival and recovery were greatly enhanced in transgenic plants following stem inoculations of plants with this plant pathogen. A significant (55%,P < 0.05) reduction in lesion number was observed in transgenic plants with high levels of peroxidase activity following inoculation with the fungusCercospora nicotianae, the cause of frog‐eye disease. No significant differences in disease development were observed between the lines expressingShpx2and controls following inoculation with the bacteriumPseudomonas syringaepv.tabaci, the cause of wildfire disease. These results provide evidence for a role for this peroxidase gene in plant defence, and suggest that diverse peroxidase genes may be employed as components of strategies aimed at the engineering of disease resistance.

Map of the T‐DNA region of the binary vector construct for pHW10. The peroxidase gene,Shpx2(striped box), was flanked by the 5′ region of the cauliflower mosaic virus promoter 35S RNA gene (P35S) and the transcription termination region of genes 5 and 7 of pTiA6 (5′ and 7′, respectively). ThenptII gene was flanked by the 5′ (Pnos) and the 3′ ends of the nopaline synthase promoter gene (nos polyA). TheHindIII site used in cloning is shown. LB, T‐DNA left border; RB, T‐DNA right border.

image
Identification of potato genes induced during colonization by Phytophthora infestans
Authors: Beyer Katinka , Binder Andres , Boller Thomas , Collinge Margaret
Published: March 2003

Suppression Subtractive Hybridization (SSH) was applied in a search for genes induced during the compatible interaction between Phytophthora infestans and potato. Using potato leaves that had been treated with benzo(1,2,3)thiadiazole‐7‐carbothioic acid S‐methylester (BTH) as the control tissue, a low redundancy library with a relatively low frequency of the classic plant Pathogenesis‐Related (PR) genes was generated. 288 of the clones were screened for induced sequences using Inverse Northern analysis (hybridizing the arrayed clones with radiolabelled cDNA populations). Of the 75 clones that were detectable by this method, 43 appeared to be induced. Eleven of these clones were then analysed by total RNA blot analysis, and elevation of transcript levels during P. infestans infection was confirmed for 10 of them. Some of the cDNAs analysed by RNA blot analysis have homology to genes already known to be induced during infection, e.g. to β‐1,3‐glucanase. Another group of cDNAs have homology to enzymes involved in detoxification: gamma‐glutamylcysteine synthetase, cytochrome P450, glutathione S‐transferase and an MRP‐type ABC transporter. Other infection induced cDNAs encode putative proteins that have not previously been reported to be induced by infection: e.g. the ER‐located chaperone BiP, and a homologue of Aspergillus nidulans SudD, which was isolated as a suppressor of a mutation in chromosome disjunction. The differential library therefore presents the opportunity to analyse the metabolic changes occurring during infection, and the disease process itself in more detail.
Reduced symptoms of Verticillium wilt in transgenic tomato expressing a bacterial ACC deaminase
Authors: Robison Mary M. , Shah Salehuzzaman , Tamot Bhaju , Pauls K. Peter , Moffatt Barbara A. , Glick Bernard R.
Published: March 2003

Ethylene evolved during compatible or susceptible disease interactions may hasten and/or worsen disease symptom development; if so, the prevention of disease‐response ethylene should reduce disease symptoms. We have examined the effects of reduced ethylene synthesis on Verticillium wilt (causal organism, Verticillium dahliae) of tomato by transforming tomato with ACC deaminase, which cleaves ACC, the immediate biosynthetic precursor of ethylene in plants. Three promoters were used to express ACC deaminase in the plant: (i) CaMV 35S (constitutive expression); (ii) rolD (limits expression specifically to the site of Verticillium infection, i.e. the roots); and (iii) prb‐1b (limits expression to certain environmental cues, e.g. disease infection). Significant reductions in the symptoms of Verticillium wilt were obtained for rolD‐ and prb‐1b‐, but not for 35S‐transformants. The pathogen was detected in stem sections of plants with reduced symptoms, suggesting that reduced ethylene synthesis results in increased disease tolerance. The effective control of formerly recalcitrant diseases such as Verticillium wilt may thus be obtained by preventing disease‐related ethylene production via the tissue‐specific expression of ACC deaminase.
The Potato virus Y MSNR NIb‐replicase is the elicitor of a veinal necrosis‐hypersensitive response in root knot nematode resistant tobacco
Authors: Fellers John P. , Tremblay Douglas , Handest Margaret F. , Lommel Steven A.
Published: March 2003

A root knot nematode resistance gene in Nicotiana tabacum, Rk, providing resistance to the nematode parasite Meloidogyne incognita is tightly linked to, or is a pleiotropic gene with a veinal necrosis systemic hypersensitive response to infection by Potato virus Y (PVY) MsNr. The single PVY MsNr open reading frame was sequenced and found to have 89% protein identity to PVY N. Individual PVY MsNr polypeptides were deduced and the corresponding cDNA were cloned into a Potato virus X (PVX) based expression vector and used as templates for in vitro transcriptions. Infected plant sap, from N. benthamiana inoculated with infectious RNA, was used to inoculate both root knot nematode (RKN) resistant and susceptible tobacco lines. Lines were then evaluated for the induction of the hypersensitive response. The PVY MsNr NIb‐replicase protein was found to induce a hypersensitive response 10 days post inoculation in nematode resistant tobacco. None of the other PVX/PVY MsNr constructs induced a hypersensitive response. The NIb‐replicase of PVY N, which shares 93% identity to PVY MsNr, did not induce a hypersensitive response when expressed from the PVX vector. This confirmed that the PVY MsNr NIb‐replicase is the elicitor of PVY MsNr veinal necrosis on RKN plants and thus the first report of a Potyvirus replicase functioning as an avirulence factor.
Cowpea mosaic virus: effects on host cell processes
Authors: Pouwels Jeroen , Carette Jan E. , Van Lent Jan , Wellink Joan
Published: March 2003

Taxonomy:  Cowpea mosaic virus (CPMV) is the type member of the Comoviridae and bears a strong resemblance to animal picornaviruses, both in gene organization and in the amino acid sequence of replication proteins. Little systematic work has been done to compare isolates of the virus from different parts of the world.

Physical properties:  Purified preparations of virus contain three centrifugal components; empty protein shells without RNA (T) and two nucleoprotein components (M and B), containing 24% and 34% RNA, respectively. The icosahedral particles have with a diameter of 28 nm, consist of 60 copies of two coat proteins, and are heat stable.

Hosts:  CPMV causes one of the most commonly reported virus diseases of cowpea (Vigna unguiculata), in which it produces chlorotic spots with diffuse borders in inoculated primary leaves. Trifoliate leaves develop a bright yellow or light green mosaic of increasing severity in younger leaves. The host range is rather limited, and few hosts are known outside the Leguminosae. The virus is transmitted by various beetles with biting mouthparts. Reported in Africa, the Philippines and Iran. Is apparently absent from North and South America.

Useful website:  http://mmtsb.scripps.edu/viper/1cpmv.html (structure); http://image.fs.uidaho.edu/vide/descr254.htm (general information).
Characterization of oncogene‐silenced transgenic plants: implications for Agrobacterium biology and post‐transcriptional gene silencing
Authors: Escobar M. A. , Civerolo E. L. , Polito V. S. , Pinney K. A. , Dandekar A. M.
Published: March 2003

Agrobacterium tumefaciens
tumorigenesis is initiated by the horizontal transfer of a suite of oncogenes that alter hormone synthesis and sensitivity in infected plant cells. Transgenic plants silenced for the
iaaM
and
ipt
oncogenes are highly recalcitrant to tumorigenesis, and present a unique resource to elucidate fundamental questions related to
Agrobacterium
biology and post‐transcriptional gene silencing (PTGS). The oncogene‐silenced transgenic tomato line 01/6 was used to characterize
A. tumefaciens
growth
in planta
and to screen for
iaaM
and
ipt
sequence variants. Even in the absence of macroscopic and microscopic indications of tumorigenesis,
A. tumefaciens
is capable of long‐term survival in the hypocotyl tissues of the 01/6 line.
A. tumefaciens
growth, however, is significantly reduced in the 01/6 line, with populations decreased by 96% relative to wild‐type at 52 days post‐inoculation. In addition, the 01/6 line displayed suppression of tumorigenesis against all 35 tested strains of
A. tumefaciens
. High target homology is an absolute requirement of PTGS, therefore this result suggests that regions of the
iaaM
and
ipt
oncogenes are very highly conserved across most
A. tumefaciens
strains. Finally, graft transmissibility of oncogene silencing was assessed by grafting various non‐silenced tomato genotypes on to the 01/6 line. Phenotypic and molecular evidence (tumorigenesis and absence of small interfering RNAs, respectively) suggest that oncogene silencing is not graft‐transmissible, at least to wild‐type and antisense
iaaM ‐over‐expressing genotypes.
The sensory characteristics of different types of halloumi cheese as perceived by tasters of different ages
Authors: Papademas P , Robinson R K
Published: March 2003

Three different types of halloumi cheese were assessed immediately after production and after 40 days in brine (~12% NaCl) by two taste panels, using a customized evaluation form based upon a quantitative descriptive analysis schedule. The average ages of the panels were 23 and 45, respectively. The younger panel was more conscious of the overall difference between the fresh and mature cheeses, and specifically with respect to the comparative chewiness and layered appearance of the young cheese. By contrast, the older panel was more sensitive to the salty and minty attributes of the cheeses, as well as differences in crumbliness and colour. Increasing age and/or familiarity with the product did not appear to change the tasters’ perceptions of the cheeses to the extent that might have been anticipated.
Libraries, postgraduate medical education and the management of change*
Authors: BAYLEY T J
Published: March 2003

The changes surrounding the funding of postgraduate medical and dental education are outlined and the funding implications for libraries considered. The management of this period of change is vital if all players are to appreciate the advantages of implementation, not least cost‐effectiveness. In conclusion three problem areas in the post‐reform NHS are identified and briefly discussed:  • the need for access and provision of information to all;  • development of regional librarian role across all regions to ensure effective co‐ordination of resources;  • a national policy which will integrate national, regional and unit structures for the delivery of health‐care information needs to be developed.
Beyond CD‐ROM: wider horizons in the provision of electronic information*
Authors: LAW DEREK
Published: March 2003

The availability of information across the networks is explored and described, along with plans for the navigation and filtering tools which will promote access to them. Issues of funding of datasets, end‐user training, document delivery, the marginalization of the traditional library and the Follett Committee Review of Library Provision in Higher Education are explored. The current level of investment in CD‐ROM is discussed, as well as the possibilities and limits of the technology. The two technologies are compared and contrasted and the particular importance of services free at the point of use stressed.
The 1994 Unified Medical Language System Knowledge Sources
Authors: Humphreys Betsy L.
Published: March 2003

Unified Medical Language System, UMLS, MEDLINE, Metathesaurus, and MeSH are all registered trademarks of the US National Library of Medicine
The legal responsibilities of the health–care librarian
Authors: MUIR ADRIENNE , OPPENHEIM CHARLES
Published: March 2003

This article discusses the legal responsibilities that information intermediaries have towards the users of their services. The areas of law that affect legal liability are contract law, tort and strict liability. The likelihood of health‐care librarians being held liable for the service they provide is assessed, and methods of reducing this risk are discussed. The key issues are: whether the recipient is relying on the information you provide and whether this reliance is reasonable; whether money changed hands; and whether the institution is under a statutory obligation to provide the information. All‐embracing exclusion clauses are often used as an attempt to exclude liability, but their validity in law is doubtful, and they should be replaced by more reasonable ones. Adhering to good professional practice, and avoiding interpreting information for laymen are ways of minimizing liability. If court proceedings do take place, professional indemnity insurance can reduce financial loss.
E‐cadherin and calretinin: a useful combination of immunochemical markers for differentiation between mesothelioma and metastatic adenocarcinoma
Authors: Leers  , Aarts  , Theunissen
Published: March 2003

Aims:

To assess the diagnostic accuracy of combinations of antibodies in the differential diagnosis of metastatic carcinomas and mesotheliomas in pleural lesions.

Methods and results:

The specificity and sensitivity of the commercially available antibodies Ber‐EP4, MOC‐31, CEA, B72.3, CD15, E‐cadherin and calretinin were evaluated using an indirect immunoperoxidase staining technique. This technique was applied to formalin‐fixed, paraffin‐embedded tissue blocks of pleural lesions. Twenty‐one patients with metastatic carcinoma (MC) and 20 patients with malignant mesothelioma (MM) were included. The combination E‐cadherin/calretinin had the highest specificity (MC 100% and MM 91%) and sensitivity (MM 100% and MC 91%) considering both categories of tumours.

Conclusions:

The combination of E‐cadherin/calretinin appears to be a suitable panel for distinguishing metastatic carcinomas and mesotheliomas in pleural lesions. The additional value of other markers is limited.
Epithelioid haemangioendothelioma of the thyroid gland: a case report and review of literature
Authors: Siddiqui  , Evans  , Ro  , Ayala
Published: March 2003

Aims

This is a hitherto unreported case of an epithelioid haemangioendothelioma of the thyroid gland.

Methods and results

The patient was a 44‐year‐old woman who presented with a right thyroid mass. A right subtotal thyroidectomy was performed. Histologically the lesion had characteristic epithelioid and spindle cell proliferation in a background of chondromyxoid stroma. Cytoplasmic vacuolization in the epithelioid and spindle cells was present. No atypical mitotic activity or necrosis was noted. The tumour cells were positive for factor VIII‐related antigen, Ulex europeus and CD 31 and were negative for cytokeratin.

Conclusion

The patient has been followed for 24 months and is free of recurrent and metastatic disease, which is supportive of a benign course in the thyroid gland.
Altered contractile proteins and neural innervation in idiopathic megarectum and megacolon
Authors: Gattuso J M , Smith V V , Kamm M A
Published: March 2003

Aim: The aetiology of idiopathic megarectum and idiopathic megacolon is unknown. We postulated that biochemical or ultrastructural abnormalities may be pathophysiologically important, as has been observed in patients with chronic idiopathic intestinal pseudo‐obstruction.

Methods and results

Resection specimens from five patients with idiopathic megarectum or megacolon were processed for paraffin wax‐embedded tissue histology (haematoxylin and eosin, Gomori trichrome and picrosirius stains, acid phosphatase activity and periodic acid–Schiff staining), and frozen tissue for histochemistry and electron microscopy. The antibodies used in the immunohistochemistry were to myosin light chain kinase, smooth muscle myosin, alpha and beta actins, filamin, tropomyosin, phosphorylated and de‐phosphorylated neurofilaments and N‐CAM. Variable hypertrophy of the muscularis mucosae and externa, no atrophy, and a variable nerve density decrease in longitudinal muscle and increase in the lamina propria was seen. In one patient beta actin and myosin light chain kinase immunoreactivity was reduced.

Conclusion

Variable changes in innervation, and an abnormal contractile protein immunoreactivity pattern in one patient, may be of pathogenic importance. These clinically homogeneous conditions are likely to be due to a range of underlying pathogenic abnormalities. A search for further specific biochemical abnormalities is justified.
Focal endometrial stromal hyperplasia
Authors: Stewart C J R , Michie B A , Kennedy J H
Published: March 2003

Aims

To describe a patient in whom multiple endometrial biopsies revealed stromal proliferative lesions causing diagnostic difficulty.

Methods and results

A 39‐year‐old woman with a history of menorrhagia and dysmenorrhoea underwent two endometrial biopsies and hysterectomy. In each case histopathology revealed apparently multifocal benign stromal proliferative lesions with no evidence of invasive growth pattern. The lesions were characterized by increased cellularity, nuclear enlargement and spindle cell morphology but no mitotic activity or nuclear pleomorphism were seen. The possibility of low grade stromal neoplasm was considered in the biopsy specimens. The hysterectomy revealed no evidence of malignancy but foci of ovarian endometriosis and cervical stromal endometriosis were present.

Conclusion

We suggest that the lesions represent focal endometrial stromal hyperplasia, a potential mimic of stromal nodule or stromal sarcoma in biopsy samples.
Reduced expression of retinoic acid receptor beta protein (RARβ) in human papillary thyroid carcinoma: immunohistochemical and Western blot study
Authors: Rochaix Ph , Monteil‐Onteniente S , Rochette‐Egly C , Caratero C , Voigt J J , Jozan S
Published: March 2003

Aims

To investigate the role of retinoic acid receptor beta (RARβ) in thyroid carcinogenesis, we have investigated its expression in human thyroid samples by combined immunohistochemistry and Western blotting.

Methods and results

Fifty‐eight paraffin‐embedded thyroid samples (40 normal or benign tissues, 16 papillary and two follicular carcinomas) were analysed by immunohistochemistry using a specific monoclonal antibody. Western blotting was also carried out on 11 selected samples (seven normal or benign tissues, three papillary carcinomas and one follicular carcinoma) and two human ovarian carcinomas as controls. RARβ immunostaining was nuclear and limited to the normal epithelial thyroid tissue. A dramatic decrease in RARβ immunostaining was observed in all the papillary carcinomas and in one follicular carcinoma. The other follicular carcinoma exhibited strong RARβ immunostaining. By immunoblotting, a 51 kDa signal corresponding to the RARβ was observed in nuclear extracts from normal thyroids and for one follicular carcinoma. However, this signal was lacking in the papillary carcinomas. These results were in complete agreement with the observations obtained by immunohistochemistry on the same samples.

Conclusion

We present here the first demonstration of RARβ protein in normal human thyroid follicular cells. In addition, we found that its expression is decreased in papillary thyroid carcinoma.
Synovial sarcoma of the pleura and its differentiation from other primary pleural tumours: a clinicopathological and immunohistochemical review of three cases
Authors: Nicholson  , Goldstraw  , Fisher
Published: March 2003

Aims: Synovial sarcomas are rare tumours occasionally arising in the pleural cavity, a site where their histological characteristics may be mistaken for those of malignant mesothelioma. We examined three cases of primary pleural synovial sarcoma in order to look for clinicopathological features that may help in distinguishing them from both mesotheliomas and other sarcomas that may arise in the pleura.

Methods and results

All three patients were male, aged 42, 28 and 42, respectively, and had no known exposure to asbestos. One biphasic tumour contained neutral mucin in focal epithelial elements that also stained positively for BerEP4 and AUA1. All three tumours showed focal positivity for either keratin or EMA in the sarcomatous elements, and they also stained positively for bcl‐2 protein and MIC2 gene product (CD99).

Conclusions

Our results emphasize the importance of being aware of synovial sarcoma as a possible primary pleural malignancy, especially in a young patient with a localized mass. In addition, the presence of bcl‐2 protein perhaps represents a useful marker in distinguishing synovial sarcoma, especially monophasic variants, from mesothelioma within a panel of antibodies.
Primary juxtaarticular soft tissue lymphoma arising in the vicinity of inflamed joints in patients with rheumatoid arthritis
Authors: Goodlad  , Hollowood  , Smith  , Chan  , Fletcher
Published: March 2003

Aims

Primary soft tissue lymphoma is uncommon and little is known regarding its aetiology and pathogenesis. In a review of 37 soft tissue lymphomas we uncovered three cases associated with rheumatoid arthritis which we report herein.

Methods and results

The clinical records and pathology of the cases are described together with the results of in situ hybridization studies with oligonucleotide probes to Epstein–Barr virus (EBV) encoded RNA (EBER). All three patients were females with a long‐standing history of rheumatoid arthritis ranging from 9 to 17 years. Each presented with a soft tissue mass in the vicinity of a joint affected by rheumatoid disease. All had received prior treatment with nonsteroidal anti‐inflammatory drugs and one also received gold, penicillamine and intra‐articular steroids to affected joints. None had received methotrexate. Histologically, the juxtaarticular soft tissue masses were all B‐cell lymphomas. None were associated with EBV as determined by in situ hybridization.

Conclusions

These cases document an association between rheumatoid arthritis and soft tissue lymphoma of B‐cell type, arising in the vicinity of an affected joint. Chronic local immune stimulation may have played a significant role in the genesis of these lymphomas, unlike the frequently reversible and EBV‐positive lymphomas that occur in rheumatoid patients on immunosuppressive therapy.
p53 expression in phyllodes tumours is associated with histological features of malignancy but does not predict outcome
Authors: Feakins R M , Mulcahy H E , Nickols C D , Wells C A
Published: March 2003

Aims

To study p53 protein expression in phyllodes tumours of the breast, with particular attention to its prevalence and to its relationship with histological features and clinical outcome.

Methods and results

Stromal and epithelial p53 immunohistochemical expression was studied in 57 phyllodes tumours (27 benign, 17 borderline, 13 malignant) using an avidin–biotin peroxidase method. High levels of expression (> 30% of stromal nuclei) were found in eight phyllodes tumours (14%). p53 expression was associated with tumour grade (P = 0.001), prominent stromal overgrowth (P = 0.0003), prominent stromal nuclear pleomorphism (P = 0.006), high stromal mitotic count (P = 0.05), and an infiltrative tumour margin (P = 0.05). Six patients were lost to follow‐up after surgery. Mean follow‐up time of the remaining 51 patients was 7.3 years (median 4.3, range 0.5–25) or until death. Sixteen patients (31%) experienced tumour recurrence. Recurrence was more likely if there was an infiltrative tumour margin (P = 0.006) or prominent stromal overgrowth (P = 0.04) but not p53 expression (P = 0.55). A minority of recurrences expressed p53 more extensively than their primary counterparts. There were five tumour‐related deaths (10% of patients). Death was associated with high grade (P = 0.0002), prominent stromal overgrowth (P = 0.0001), an infiltrative margin (P = 0.0002), prominent nuclear pleomorphism (P = 0.005), a high mitotic count (P = 0.01) and tumour size (P = 0.03). Again, p53 expression was not associated with tumour‐related survival (P = 0.13).

Conclusions

p53 abnormalities occur in a minority of borderline and malignant phyllodes tumours. p53 expression is associated with known negative prognostic factors, but does not appear to be a useful determinant of tumour recurrence or long‐term survival.
Adenoid cystic carcinoma of the breast: a tumour commonly devoid of oestrogen receptors and related proteins
Authors: Trendell‐Smith  , Peston  , Shousha
Published: March 2003

Aim

Adenoid cystic carcinoma (ACC) of the breast is an uncommon well‐differentiated tumour with good prognosis, and sometimes difficult to distinguish from in‐situ and invasive cribriform carcinoma (ICC) which are relatively more common. Recently, we encountered a case of ACC that proved to be totally oestrogen receptor (ER) negative by immunohistochemistry. We investigated the possibility that this may be a consistent feature that can help in differentiating ACC from ICC which are usually ER positive.

Methods and results

The immunoperoxidase technique was used to study the expression of ER and other related proteins in six cases of ACC and two cases of ICC. All ACC cases were negative for oestrogen (ER) and progesterone (PgR) receptors whereas the two ICC were strongly positive for ER and showed a variable degree of PgR positivity. In addition, ACC cases were pS2 negative and showed minimal expression of prolactin receptors (PrlR), while the two ICC showed widespread and strong staining for pS2 and PrlR. The percentages of cells staining positively for Ki67 and p27 were generally lower in ACC than in ICC. Both tumour types were c‐erbB‐2 negative, but p53 was weakly to moderately positive.

Conclusions

The findings suggest that a negative immunoperoxidase staining for ER would confirm the diagnosis of ACC in contrast to the positive staining which is always seen in ICC. The findings also raise the issue of the presence of a specific class of ER negative breast carcinomas which are negative not because of poor differentiation, but because of their derivation from, or differentiation along, an ER negative cell lineage.
Intravascular tumour in intra‐oral pleomorphic adenomas: a diagnostic and therapeutic dilemma
Authors: Coleman  , Altini
Published: March 2003

Aims

Intravascular tumour has been described very rarely in pleomorphic adenomas. The aim of this study was to establish the frequency of intravascular tumour in pleomorphic adenomas arising in minor salivary glands and to determine the biological significance of this phenomenon.

Methods and results

Representative sections of 67 widely excised pleomorphic adenomas were examined for the presence of intravascular tumour. Sixty‐two cases were derived from the palate while the remaining five were from the cheeks and lips. In instances where intravascular tumour was identified, multiple serial sections were assessed and immunohistochemical stains were performed. None of these cases showed cytological evidence of malignancy. Solid cords of intravascular tumour were present in six palatal tumours (8.9%) and consisted of plasmacytoid myoepithelial cells permeating muscular walled blood vessels and capillaries both within the tumour and capsule. Immunoperoxidase staining confirmed that the intravascular cells were phenotypically identical to those of the tumour being S100‐ and smooth muscle actin (SMA) positive. There is some evidence that this phenomenon represents true vascular invasion although artefactual spillage cannot be excluded.

Conclusions

Although the biological significance of intravascular tumour in pleomorphic adenomas of minor salivary glands remains unknown, the occurrence of metastatic disease has not been demonstrated nor have aggressive behaviour or recurrences.
Augmented expression of endothelin‐1, endothelin‐3 and the endothelin‐B receptor in breast carcinoma
Authors: Alanen  , Deng  , Chakrabarti
Published: March 2003

Aims

Endothelins (ETs) are peptides expressed in many tumours which may stimulate angiogenesis and desmoplasia. Because ETs have not been extensively studied mammary neoplasia, we assessed ET protein and mRNA expression and receptor mRNA expression in normal and neoplastic breast tissues.

Methods and results

Tissues from five normal breasts, six fibroadenomas, seven ductal carcinomas in situ (DCIS) and 25 invasive carcinomas were stained with anti‐ET‐1 and anti‐ET‐3 antibodies and analysed using a grading system. ET‐1, ET‐3, ETA and ETB mRNA expression was assessed by quantitative RT‐PCR from eight carcinomas and five normals. Weak staining for ET‐1 and ET‐3 was detected in all normals. Moderate to strong staining was seen in 72% and 64% of carcinomas for ET‐1 and ET‐3, respectively. Most fibroadenomas showed weak positivity for ET‐1 (83%) and ET‐3 (67%). ET‐1 and ET‐3 mRNA levels were upregulated in carcinomas compared with normal breast. No ETA mRNA was not detected in any tissue. ETB mRNA was detected in normal breast and was increased in carcinomas.

Conclusion

These results suggest that the ET system is altered in breast carcinomas and this may be of importance in the progression from in‐situ to invasive carcinoma.
The impact of information technology on histopathology
Authors: Rashbass
Published: March 2003

Pathology is one of the most computer intensive areas of medicine and as a result diagnostic pathologists in histopathology have often been at the cutting edge of computer literacy. The majority of laboratories use laboratory information systems to issue and store pathology reports. Many of these systems provide the diagnostician with the ability to retrieve reports and cases using coding systems such as SNOMED, but more advanced computer facilities that might assist the pathologist in the diagnosis or interpretation of a case are often lacking. In recent years advances in computer technology have begun to have a much wider impact on the practice of medicine and newer technologies are beginning to find their way into the reporting room. In this review, I cover some of the recent and emerging advances in IT that have the potential to revolutionize the practice of diagnostic histopathology in the next 5 years. The major area of telepathology has been a subject of several recent reviews and will not be covered here.
Neutrophil and endothelial cell activation in the vasa vasorum in vasculo‐Behçet disease
Authors: Kobayashi  , Ito  , Nakagawa  , Matsushita  , Nishikimi  , Sakurai  , Nimura
Published: March 2003

Aim

The aim of this study was to analyse the immunopathological mechanisms of vasculo‐Behçet disease, which were also compared to cases of Takayasu's arteritis and inflammatory aneurysm to evaluate differences in inflammatory mechanisms.

Method and results

We reviewed six cases of vasculo‐Behçet disease, four of Takayasu's arteritis and seven inflammatory aneurysms which underwent surgical repair. Immunohistochemical studies were performed on paraffin‐embedded tissue using a labelled streptavidin–biotin method, as was in‐situ hybridization for Epstein–Barr virus. Microscopically, neutrophils and lymphocytes accumulated around the vasa vasorum. Neutrophils were prominent as compared to Takayasu's arteritis and inflammatory aneurysm. Elastic fibres were not severely destroyed. Endothelial cells (ECs) of most vasa vasorum expressed HLA‐DR. The number of vasa vasorum around which inflammatory infiltrating cells were observed in vasculo‐Behçet disease was significantly greater than in inflammatory aneurysms and Takayasu's arteritis (P < 0.001). The cytokines IL‐1α, TNF‐β and IFN‐γ were expressed in neutrophils and lymphocytes which were distributed around vasa vasorum, as well as neutrophils adherent to HLA‐DR positive ECs.

Conclusion

Our results suggest that vasculo‐Behçet disease should be classified as a neutrophilic vasculitis targeting the vasa vasorum. Aneurysm formation may be related to degeneration of arterial wall caused by inflammation of the vasa vasorum.
Structural and cell surface antigen expression in the rete ovarii and epoophoron differs from that in the Fallopian tube and in endometriosis
Authors: Russo L , Woolmough E , Heatley M K
Published: March 2003

Aims

We compared the immunohistochemical profiles of the rete ovarii and endometriosis in order to identify a panel which distinguishes between these structures. The immune profiles of the epoophoron, Fallopian tube and ovarian surface epithelium were also studied.

Materials and methods

Twenty‐four women with no evidence of endometriosis and seven who had endometriosis in the uterine adnexae were studied using nine antibodies to intermediate filament proteins and cell surface markers. None of the structures studied shared an identical profile of immunohistochemical reaction. The immunoprofile of endometriosis showed some similarities to that of the Fallopian tube, but differed from that of the rete ovarii, epoophoron and ovarian surface epithelium

Conclusions

A panel including Ca‐125, epithelial membrane antigen and the epithelial glycoprotein BerEp4 would permit the distinction between endometriosis and the rete ovarii in problematic cases. The study showed some commonality in reaction between endometriosis and the Fallopian tube which indicates that they may share a common (paramesonephric) origin. There was little commonality in the immunoprofile of endometriosis and the ovarian surface epithelium implying that endometriosis is unlikely to develop as a result of serosal metaplasia.