bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development
Authors: Burns Jennifer M. , Summers Bretton C. , Wang Yu , Melikian Anita , Berahovich Rob , Miao Zhenhua , Penfold Mark E. T. , Sunshine Mary Jean , Littman Dan R. , Kuo Calvin J. , Wei Kevin , McMaster Brian E. , Wright Kim , Howard Maureen C. , Schall Thomas J.
Published: August 2006

The chemokine stromal cell–derived factor (SDF-1; also known as chemokine ligand 12 [CXCL12]) regulates many essential biological processes, including cardiac and neuronal development, stem cell motility, neovascularization, angiogenesis, apoptosis, and tumorigenesis. It is generally believed that SDF-1 mediates these many disparate processes via a single cell surface receptor known as chemokine receptor 4 (CXCR4). This paper characterizes an alternate receptor, CXCR7, which binds with high affinity to SDF-1 and to a second chemokine, interferon-inducible T cell α chemoattractant (I-TAC; also known as CXCL11). Membrane-associated CXCR7 is expressed on many tumor cell lines, on activated endothelial cells, and on fetal liver cells, but on few other cell types. Unlike many other chemokine receptors, ligand activation of CXCR7 does not cause Ca2+ mobilization or cell migration. However, expression of CXCR7 provides cells with a growth and survival advantage and increased adhesion properties. Consistent with a role for CXCR7 in cell survival and adhesion, a specific, high affinity small molecule antagonist to CXCR7 impedes in vivo tumor growth in animal models, validating this new receptor as a target for development of novel cancer therapeutics.
NF-κB translocation prevents host cell death after low-dose challenge byLegionella pneumophila
Authors: Losick Vicki P. , Isberg Ralph R.
Published: August 2006

Legionella pneumophila, the causative agent of Legionnaires' disease, grows within macrophages and manipulates target cell signaling. Formation of a Legionella-containing replication vacuole requires the function of the bacterial type IV secretion system (Dot/Icm), which transfers protein substrates into the host cell cytoplasm. A global microarray analysis was used to examine the response of human macrophage-like U937 cells to low-dose infections with L. pneumophila. The most striking change in expression was the Dot/Icm-dependent up-regulation of antiapoptotic genes positively controlled by the transcriptional regulator nuclear factor κB (NF-κB). Consistent with this finding, L. pneumophila triggered nuclear localization of NF-κB in human and mouse macrophages in a Dot/Icm-dependent manner. The mechanism of activation at low-dose infections involved a signaling pathway that occurred independently of the Toll-like receptor adaptor MyD88 and the cytoplasmic sensor Nod1. In contrast, high multiplicity of infection conditions caused a host cell response that masked the unique Dot/Icm-dependent activation of NF-κB. Inhibition of NF-κB translocation into the nucleus resulted in premature host cell death and termination of bacterial replication. In the absence of one antiapoptotic protein, plasminogen activator inhibitor–2, host cell death increased in response to L. pneumophila infection, indicating that induction of antiapoptotic genes is critical for host cell survival.
Laser manipulation in liquid crystals: an approach to microfluidics and micromachines
Authors: Gleeson Helen F , Wood Tiffany A , Dickinson Mark
Published: August 2006

Laser trapping of particles in three dimensions can occur as a result of the refraction of strongly focused light through micrometre-sized particles. The use of this effect to produce laser tweezers is extremely common in fields such as biology, but it is only relatively recently that the technique has been applied to liquid crystals (LCs). The possibilities are exciting: droplets of LCs can be trapped, moved and rotated in an isotropic fluid medium, or both particles and defects can be trapped and manipulated within a liquid crystalline medium. This paper considers both the possibilities. The mechanism of transfer of optical angular momentum from circularly polarized light to small droplets of nematic LCs is described. Further, it is shown that droplets of chiral LCs can be made to rotate when illuminated with linearly polarized light and possible mechanisms are discussed. The trapping and manipulation of micrometre-sized particles in an aligned LC medium is used to provide a measure of local shear viscosity coefficients and a unique test of theory at low Ericksen number in LCs.
Primary culture and histological characterization of phagocytic cells from rainbow trout Oncorhynchus mykiss
Authors: Olwell P. M. , Lyng F. M. , Ni Shuilleabhain S. , Maderna P. , Mothersill C. , Cottell D. C.
Published: August 2006

In this study the pronephros of rainbow trout Oncorhynchus mykiss was explanted and cultured. The morphology of cultured cells suggested they were leukocyte derived. To confirm this, cells were incubated with non‐opsonized fluorescent beads and human apoptotic polymorphonuclear leukocytes (PMN) to establish that they were capable of phagocytosis and that they became activated following exposure to apoptotic bodies. The cells were studied using light microscopy, transmission electron microscopy and a live cell observer system. Cells in culture were also stained with phalloidin to identify actin reorganization following activation. Cultured cells ingested the inert beads and apoptotic PMNs and c. 80% of cells became activated following exposure to the apoptotic PMN, evidenced by enhanced filopodial extensions. This methodology may play a role in future studies, in particular, the competence of macrophages following exposure to radiation can now be tested.
A molecular approach to detect hybridization between bream Abramis brama, roach Rutlius rutilus and rudd Scardinius erythrophthalmus
Authors: Wyatt P. M. W. , Pitts C. S. , Butlin R. K.
Published: August 2006

Hybridization between roach Rutilus rutilus, bream Abramis brama and rudd Scardinius erythrophthalmus was investigated using morphological and genetic analysis employing both nuclear (ITS1) and mitochondrial (cytochrome b) markers. Allele‐specific amplification (ASA) reactions for both markers were developed and ITS1 sequence data for all three species are presented. Sequencing detected two ITS1 haplotypes within both roach and bream which most likely evolved in isolation and were subsequently brought together as a result of restocking by anglers. Analysis of cloned hybrid nuclear ribosomal DNA revealed evidence of recombination between parental ITS1 sequences. ASA proved to be an effective method for identifying hybrids and detected multiple ITS1 copies in fishes identified as purebred by morphological analysis. In addition this suggests post‐F1 hybridization and introgression may be occurring between roach and bream, and rudd and bream, although some barriers appear to be suppressing backcrosses within the hybrid population. Analysis of the hybrid population demonstrated that hybridization has occurred in both directions.
Development and characterization of cell lines from heart, liver, spleen and head kidney of sea perch Lateolabrax japonicus
Authors: Ye H.‐Q. , Chen S.‐L. , Sha Z.‐X. , Xu M.‐Y.
Published: August 2006

Five cell lines (LJHK, LJS, LJL, LJH‐1 and LJH‐2) were established from the head kidney, spleen, liver and heart of sea perch Lateolabrax japonicus. The cell lines LJHK, LJS, LJL, LJH‐1 and LJH‐2 were subcultured 46, 32, 32, 36 and 34 times in minimum essential medium (MEM) supplemented with foetal bovine serum (FBS), sea perch serum and 10 ng ml−1 basic fibroblast growth factor (bFGF). Morphology of primary cultures and subcultures of the five cell lines were observed continuously by microscopy. The suitable temperature for growth was 18 to 30° C for all of these cell lines with the optimum growth at 24° C and a reduced growth rate <18° C. The optimum concentration of FBS was found to be 10% and addition of bFGF to the medium significantly increased the growth rate of the cells. The doubling time of LJS, LJH‐1, LJL, LJH‐2 and LJHK cells was determined to be 52·7, 54·9, 57, 58·7 and 66 h at a plating density of 1 × 105 cells ml−1 at 24° C, respectively. Chromosome analysis revealed that 42, 48, 38, 43 and 45% cells maintained normal diploid chromosome number (48) in the LJH‐1, LJH‐2, LJHK, LJL and LJS cell lines, respectively. The LJHK cells were successfully transfected with green fluorescent protein (GFP) reporter plasmids and the expression of GFP gene in the cells indicated the possible utility of the cells in gene expression studies. Furthermore, treatment of the LJHK cells with lipopolysaccharide led to increased expression of IL‐1β, demonstrating that LJHK cells might be a valuable tool for studying the expression and function of immunomodulatory gene in fishes.
Application of a rapid method of SNP analysis (glycosylase mediated polymorphism detection) to mtDNA and nuclear DNA of cod Gadus morhua
Authors: O’Leary D. B. , Coughlan J. , McCarthy T. V. , Cross T. F.
Published: August 2006

A novel method of single nucleotide polymorphism (SNP) analysis in fishes [glycosylase mediated polymorphism detection (GMPD)] was applied, for the first time in any fish species, to polymorphisms present in the Atlantic cod Gadus morhua mtDNA D‐loop and nuclear transferrin genes. The utility of the GMPD technique for population genetics of Atlantic cod is highlighted, since significant haplotype frequency differences were observed between Baltic and Atlantic samples of cod at a D‐loop SNP and allele frequencies differences between west and east Atlantic samples at an SNP located in the transferrin gene.
Identification of oligopeptides binding to peritoneal tumors of gastric cancer
Authors: Akita Noriyuki , Maruta Fukuto , Seymour Leonard W. , Kerr David J. , Parker Alan L. , Asai Tomohiro , Oku Naoto , Nakayama Jun , Miyagawa Shinichi
Published: August 2006

This is a report of in vivo intraperitoneal biopanning, and we successfully identified a novel peptide to target the multiple peritoneal tumors of gastric cancer. A phage display library was injected directly into the abdominal cavity of mice bearing peritoneal tumors of human gastric cancer, and phages associated with the tumors were subsequently reclaimed from isolated samples. The tumor‐associated phages were amplified and the biopanning cycle was repeated five times to enrich for high affinity tumor‐selective binding peptides. Finally, a tri‐peptide motif, KLP, which showed homology with laminin 5 (a ligand for α3β1 integrin), was identified as a binding peptide for peritoneal tumors of gastric cancer. Phage clones displaying the sequence KLP showed 64‐fold higher binding to peritoneal tumors than control phage and were preferentially distributed in tumors rather than in normal organs after intraperitoneal injection into mice. In addition, the KLP phages were more likely to bind to cancer cells in malignant ascites derived from a patient with recurrent gastric cancer. Synthesized peptide containing the motif KLP (SWKLPPS) also showed a strong binding activity to peritoneal tumors without cancer growth effect. Liposomes conjugated with SWKLPPS peptide appeared significantly more often in tumors than control liposomes after intraperitoneal injection into mice. Furthermore, modification of liposomes with SWKLPPS peptide enhanced the antitumor activity of adriamycin on gastric cancer cells. The peptide motif KLP seems a potential targeting ligand for the treatment of peritoneal metastasis of gastric cancer. (Cancer Sci 2006; 97: 1075–1081)
Heterogeneous nuclear ribonucleoprotein B1 expression in malignant mesothelioma
Authors: Hiraki Akio , Murakami Tomoyuki , Aoe Keisuke , Sueoka Eisaburo , Sueoka Naoko , Taguchi Koji , Kamei Toshiaki , Sugi Kazuro , Ueoka Hiroshi , Kishimoto Takumi
Published: August 2006

Heterogeneous nuclear ribonucleoprotein B1, an RNA‐binding protein required for mRNA maturation, reportedly is overexpressed in early lung cancer and in several other tumors, including precancerous lesions. Expression of the protein was assessed immunohistochemically in 39 specimens of malignant mesothelioma and five of non‐neoplastic pleura, and by flow cytometry in a human epithelioid mesothelioma cell line. No tumor showed overexpression, but 29 of 39 cases showed modest expression. Patients whose tumors showed expression had significantly better survival rates than others. Epithelioid tumors and reactive mesothelial cells were more likely to express the protein than sarcomatoid tumors and resting mesothelial cells. Flow cytometric analysis of an epithelioid mesothelioma cell line demonstrated stronger expression in exponentially growing than growth‐restricted cells. Heterogeneous nuclear ribonucleoprotein B1 is expressed widely in malignant mesotheliomas and in reactive mesothelial cells, but is not overexpressed. This protein may regulate proliferation linked with differentiation toward epithelioid morphology in mesothelial cells. Expression of the protein may be a prognostic indicator for patents with malignant mesothelioma. (Cancer Sci 2006; 97: 1175–1181)
The role of area enclosures and fallow age in the restoration of plant diversity in northern Ethiopia
Authors: Abebe Muluberhan Hailu , Oba Gufu , Angassa Ayana , Weladji Robert B.
Published: August 2006

This study investigated the roles played by area enclosures and fallow age in the restoration of plant species richness and soil seed bank species richness in degraded mountain rangelands in northern Ethiopia. Management types (enclosures versus grazed) influenced woody and herbaceous species richness, while fallow age showed no effect on the woody species. Management, age and the doubling of fallow age influenced the herbaceous species richness and species diversity. Management showed no effect on soil seed bank species richness. Fallow age and the doubling of fallow time also showed no influence on the soil seed bank of grass species, but they were influential on the forbs species soil seed bank. The trends for restoration of plant species richness and diversity and grass seed bank in response to fallow age were positive‐linear, but they declined when the fallow ages were doubled. The exception was the forbs seed bank showed linear trends when age of restoration was doubled. The data suggest that the restoration of degraded rangelands in the high mountain zones of northern Ethiopia was still in the weedy succession stages. Long‐term monitoring will be required to gain an informed understanding of the roles played by area enclosures and fallow age in the restoration of plant biodiversity.
Influence of soil fertility on the physiognomy of the African savanna tree Colophospermum mopane
Authors: Mlambo Donald
Published: August 2006

This study investigated the influence of soil fertility on the physiognomy of Colophospermum mopane, one of the dominant tree or shrub species in savannas of central and southern Africa. The study was conducted in Gonarezhou National Park (GNP) in the south‐east of Zimbabwe. Mopane stands at the study site were divided into three physiognomic forms or mopane ‘types’: short mopane (SM, 1–2 m in height); medium mopane (MM, 8–12 m) and tall mopane (TM, >15 m). In each mopane type, soil samples were collected up to a depth of 15 cm to investigate the level of soil nutrient concentrations. SM stands were associated with low phosphorus and high levels of calcium and sodium relative to MM and TM. The low levels of phosphorus in SM relative to other mopane types suggest that phosphorus may be an important nutrient limiting growth in dwarf mopane. Alternatively, plant nutrients may be limiting because of interaction with factors such as the high soil sodicity present in the dwarf mopane habitats that may affect nutrient uptake or plant nutrient demand.
Platelet mass has prognostic value in patients with myelodysplastic syndromes
Authors: Bowles Kristian M. , Warner Brian A. , Baglin Trevor P.
Published: August 2006

Platelet mass (mean platelet volume × platelet count) can be derived from data obtained from the routine full blood count and separates patients with myelodysplastic syndromes (MDS) at diagnosis into three distinct prognostic groups: low platelet mass group – median survival 5 months and 5‐year survival 0%; intermediate platelet mass group – median survival 30 months and 5‐year survival 34%; high platelet mass group median survival – not reached at 82 months follow‐up with a 5‐year survival of 82%. These data provide a simple rapid prognostic index at the time of diagnosis in MDS.
Downregulation of hepcidin and haemojuvelin expression in the hepatocyte cell‐line HepG2 induced by thalassaemic sera
Authors: Weizer‐Stern Orly , Adamsky Konstantin , Amariglio Ninette , Levin Carina , Koren Ariel , Breuer William , Rachmilewitz Eliezer , Breda Laura , Rivella Stefano , Ioav Cabantchik Z. , Rechavi Gideon
Published: August 2006

β‐Thalassaemia represents a group of diseases, in which ineffective erythropoiesis is accompanied by iron overload. In a mouse model of β‐thalassaemia, we observed that the liver expressed relatively low levels of hepcidin, which is a key factor in the regulation of iron absorption by the gut and of iron recycling by the reticuloendothelial system. It was hypothesised that, despite the overt iron overload, a putative plasma factor found in β‐thalassaemia might suppress liver hepcidin expression. Sera from β‐thalassaemia and haemochromatosis (C282Y mutation) patients were compared with those of healthy individuals regarding their capacity to induce changes the expression of key genes of iron metabolism in human HepG2 hepatoma cells. Sera from β‐thalassaemia major patients induced a major decrease in hepcidin (HAMP) and lipocalin2 (oncogene 24p3) (LCN2) expression, as well as a moderate decrease in haemojuvelin (HFE2) expression, compared with sera from healthy individuals. A significant correlation was found between the degree of downregulation of HAMP and HFE2 induced by β‐thalassaemia major sera (r = 0·852, P < 0·0009). Decreased HAMP expression was also found in HepG2 cells treated with sera from β‐thalassaemia intermedia patients. In contrast, the majority of sera from hereditary haemochromatosis patients induced an increase in HAMP expression, which correlated with transferrin (Tf) saturation (r = 0·765, P < 0·0099). Our results suggest that, in β‐thalassaemia, serum factors might override the potential effect of iron overload on HAMP expression, thereby providing an explanation for the failure to arrest excessive intestinal iron absorption in these patients.
Denis Burkitt and his contribution to haematology/oncology
Authors: Coakley Davis
Published: August 2006

Denis Burkitt was motivated by Christian Evangelism from his early years. It was a critical factor not only in his personal development and decision to work in Uganda, but also in his medical achievements. The events in his life which led to his description of Burkitt lymphoma in 1958 are described together with his discovery of the endemic nature of the condition and its treatment. His research on the aetiology of the condition is also described. The endemic form of the lymphoma is still a major cause of childhood mortality in Africa due to a lack of basic resources to treat the condition. Burkitt Lymphoma has been used as a model to advance research and treatment on a wide range of conditions in haematology and oncology. Burkitt's work in later life on dietary fibre and its implications are summarised.
α+‐Thalassaemia and pregnancy in a malaria endemic region of Papua New Guinea
Authors: O'Donnell A. , Raiko A. , Clegg J.B. , Weatherall D.J. , Allen S.J.
Published: August 2006

The effect of maternal α+‐thalassaemia on pregnancy was assessed in the north coastal region of Papua New Guinea (PNG), where malaria is hyperendemic and α+‐thalassaemia is extremely common. In a prospective study of 987 singleton hospital deliveries, we correlated maternal α‐globin genotype with markers of reproductive fitness (age in primigravidae, gravidity, pregnancy interval and the number of miscarriages and stillbirths), Plasmodium falciparum(P. falciparum) infection of the mother and placenta, maternal haemoglobin, preterm delivery and birthweight. The frequency of the −α genotype in mothers was 0·61. Markers of reproductive fitness were similar in women with and without α+‐thalassaemia. Median haemoglobin concentration during pregnancy and after delivery was about 1·0 g/dl lower in homozygous α+‐thalassaemia than in women with a normal α‐ globin genotype (P ≤ 0·001). The frequency of placental P. falciparum infection and systemic malaria infection after delivery showed no consistent relationship to α‐globin genotype. The frequency of preterm delivery and low birthweight did not vary significantly according to maternal α‐globin genotype. Maternal α+‐thalassaemia does not affect reproductive fitness or susceptibility to malaria during pregnancy. Although median haemoglobin concentration was significantly lower in mothers homozygous for α+‐thalassaemia than those with a normal α‐globin genotype, this did not result in an adverse outcome of pregnancy.
P‐12 A RETROSPECTIVE AUDIT OF FINE NEEDLE ASPIRATION CYTOLOGY OF PANCREAS
Authors: Lynch M. A. , Rana D. N. , Charan V. , Desai M.
Published: August 2006

Background:  Fine needle aspiration cytology (FNAC) of pancreas is a widely accepted method of diagnosis of pancreatic mass lesions. We have performed a retrospective analysis of all radiological (CT/ultrasound) and endoscopic ultrasound guided procedures at our institution.

Aim:  (1) To review the results of FNAC of pancreas from January 2000 to April 2006. (2) To calculate the inadequate rate. (3) To account for discrepancies between the cytological and histological diagnoses. (4) To identify any false positive cases if present.

Method:  The results of all pancreatic FNAC reported at our institute from January 2000 to April 2006 were identified from the laboratory system. All results were classified as follows: Inadequate, inconclusive, benign, suspicious and malignant. The results were further categorised depending on whether they were CT/ultrasound guided or EUS guided. The histological diagnosis where available was used as the gold standard and where discrepancies were present the cytological preparations were reviewed.

Results:  Seventy‐three patients underwent pancreatic FNAC during the study period. Table 1 illustrates our results.

Number
Inadequate
Inconclusive
Benign
Suspicious
Malignant

CT/US
53
8 (11%)
1(1%)
17(23%)
6(8%)
21(29%)

Endoscopic ultrasound
20
1 (1%)
2(3%)
14(19%)
1(1%)
2(3%)

Total
73
9 (12%)
3(4%)
31(42%)
7(10%)
23(32%)

Three false negative cases where a later histological diagnosis of malignancy was present contained no diagnostic cellular material. To date no false positive diagnosis has occurred and all patients with malignant diagnosis have died except those diagnosed in the last 6 months.

Conclusion:  Pancreatic FNAC is a useful procedure in the majority of cases at our institute. Our inadequate/inconclusive rate is low. In fact our analysis shows that the inadequate rate for EUS guided FNAC pancreas is only 5% despite the fact that on site assessment of adequacy is not yet carried out. This is in a small group of patients however. No false positive diagnosis was identified. Discrepancies between cytological and histological diagnosis have been due to unrepresentative samples. We intend to proceed with on site assessment of adequacy in future cases. We will continue to review all cases where pancreatic FNA is carried out at our weekly pancreatic/hepatobiliary clinicopathological multidisciplinary team meeting and within our department at peer review meetings.
P‐13 CERVICAL SMEAR REPORTING IN NORTHERN IRELAND SLE PATIENTS
Authors: McHenry M. T. , Clarke R. , Anderson N. , Bell A. L.
Published: August 2006

Introduction:  SLE is an autoimmune disease with the potential for multi‐organ involvement. It has been suggested that SLE patients may be at increased risk of cervical dysplasia. We studied a cohort of Northern Ireland Lupus patients and compared them to controls within the same geographical location assessing their cervical smear histories and performing an up‐to‐date cervical smear.

Methods:  A total of 141 SLE patients fulfilling the ACR criteria for lupus were enrolled into the study. They were compared to 138 control patients who were due to attend for a routine cervical smear within the same geographical location. Each patient gave written consent to be involved in the study including access to medical records and pathology data.

Results: 

Cervical Smear report
SLE n = 141
Controls n = 138

Unsuitable
5.7% (8/141)
9.4% (13/138)

Low grade
15.6% (22/141)
10.9% (15/138)

High grade
4.3% (6/141)
2.2% (3/138)

Life time occurrence of any abnormal cervical smear
41.8% (59/141)
29% (40/138)

Discussion:  Latest cervical smear reports between the two groups showed an increase in low‐grade and high‐grade cervical smear abnormalities in the SLE group. SLE patients appear to have an increased rate of lifetime occurrence of abnormal smear. The control group of patients were younger than SLE patients and when this was taken into consideration using logistic binary regression to correct for co‐variates the risk of lupus patients having an abnormal smear history compared to controls became highly significant RR 2.53 (1.44–4.43) P = 0.001.
P‐15 COMPARISON OF RESULTS FOR A NON‐GYNAECOLOGICAL CYTOLOGY EQA SCHEME
Authors: Da Gama‐Rose B. M. , Hodgson E. , Hales S. A. , Desai M.
Published: August 2006

The problems encountered with a glass slide circulation are legion but timely circulation is a major problem and is an inherent deficiency of our Non‐gynaecological EQA scheme. This applies not only to consultants but also to specialist registrars (SpRs) and technical staff that are not formally included in the circulation list. In 2005 only 7 technical staff and 4 out of 47 SpRs took part on a formal basis, their participation being dependant on access to slides during their cytology attachment. The results for the 2005 circulation have been analysed and despite the small numbers of participating technical staff and SpRs their answers concur with the consultant body. To address the issues of timeliness and circulation problems a pilot teaching set has been developed by SlidePath into a virtual microscope web based circulation and sent to all SpRs in our region. They have recorded their answers and been given immediate access to the consensus consultant opinion with illustrations of follow up histology. A questionnaire was completed to evaluate the scheme. The facility of immediate feedback of consultant consensus is particularly pertinent to the educational element of the scheme and use of virtual microscopy addresses the issue of timely circulation. If further funding was made available technical staff could also be given the opportunity to try this web‐based circulation.
P‐16 DEFAULT FROM CYTOLOGICAL SURVEILLANCE OF LOW‐GRADE SMEARS: LEVELS OF DEFAULT AND CHARACTERISTICS OF DEFAULTERS IN THE TRIAL OF MANAGEMENT OF BORDERLINE AND OTHER LOW‐GRADE ABNORMAL SMEARS (TOMBOLA)
Authors: Thornton A. J. , Cotton S. C. , Sharp L. , Gray N. M. , Smart L. M.
Published: August 2006

Introduction:  We report levels of default in women with low‐grade cytological abnormalities managed by cytological surveillance and identify factors associated with default.

Method:  TOMBOLA is an RCT comparing cytological surveillance (repeat smears every 6 months in primary care) with hospital‐based colposcopy in women with a low‐grade smear. TOMBOLA recruits were aged 20–59, with a recent mild or borderline smear, plus up to one previous borderline smear, detected within the NHS‐CSPs. This analysis includes 2224 women randomised to cytological surveillance. Default was defined as non‐attendance within 6 months of each surveillance smear being due.

Results:  11% (95% CI 9.3–12.0) of women defaulted from the first surveillance smear. 13% (11.0–14.1) of those having a first surveillance smear defaulted from the second. 14% (12.1–15.5) of those having a second surveillance smear defaulted from the third. The median time from the recruitment smear to the first surveillance smear was 7 months (interquartile range 6–8 months). In univariate analyses, at each surveillance smear, younger women were more likely to default (first smear: 16% aged 20–29 versus 2% aged 50–59). Default was slightly higher among women with a mild (12% for first smear) than a borderline (10%) recruitment smear. For the first surveillance smear, women with a college/university degree were less likely (7%) than those without a degree (11%) to default, but this difference was not apparent for subsequent smears. For the first and second surveillance smears, default was higher among smokers than non‐smokers. Multivariate analyses of these and other sociodemographic factors will be presented.

Conclusions:  Default was 11% from the first surveillance smear and increased slightly with subsequent smears. Some sub‐groups of women are more likely to default (eg younger women, smokers). Analyses such as these may help inform strategies to ensure maximum attendance by women for cytological follow‐up of low‐grade abnormal smears.
P‐20 DIAGNOSTIC ACCURACY OF CONVENTIONAL SMEARS AND THINPREP SAMPLES IN CERVICAL SCREENING
Authors: Shah B. , Rana D. , Marshall J. , Desai M.
Published: August 2006

Objective:  Liquid Based Cytology has been recommended in England and Wales as the primary means of processing samples in cervical screening programme. We conducted this study to compare the positive predictive value (PPV) of conventional smears (CS) and ThinPrep samples (TP) reported as high‐grade squamous dyskaryosis and glandular neoplasia from September ’01 to August ’05. The performance of both techniques was compared with histological results.

Methods:  The database of the cytology department was searched and figures were obtained from September 2001 to August 2004 for high‐grade dyskaryosis and from September 2001 to August 2005 for glandular neoplasia. Only primary care samples were taken into consideration for determining positive predictive value (PPV).

Results:  The total number of samples for CS and TP were 373 990 (86.8%) and 48 216 (11.2%) respectively. Inadequate rate for CS and TP was 10.68% and 1.64% respectively. PPV of moderate and severe dyskaryosis including invasive carcinoma in CS was 71.7% and 90.4%; while for TP, it was 65.8% and 89.4% respectively. PPV of glandular neoplasia for CGIN/Adenocarcinoma was 66.7% and 64.3% in CS and TP respectively. PPV of glandular neoplasia for CIN2 and more in CS and TP was 82.7% and 85.7% respectively. The PPV for a diagnosis of CIN2 or worse in CS and TP was 79.3% and 73.3% respectively.

Discussion:  The PPV for a diagnosis of CIN2 or worse in both systems are within acceptable range for the U.K. (65–87%). The difference in PPV for varied categories in both systems is statistically insignificant. The inadequate rate is significantly reduced with TP.
P‐21 POSITIVE PREDICTIVE VALUE OF CERVICAL SMEARS REPORTED AS MILD DYSKARYOSIS
Authors: Shah B. , Rana D. , Marshall J. , Desai M.
Published: August 2006

Objective:  Recent national guidelines (NHSCSP Document 20) recommend the referral of patients having the first occurrence of mild dyskaryosis. We evaluated the usefulness of this guideline and determined the positive predictive value (PPV) of conventional smears (CS) and ThinPrep samples (TP) reported as the first occurrence of mild dyskaryosis.

Methods:  This was a retrospective study where we looked at the cases of mild dyskaryosis from January’05 to June’05 received at our laboratory. Of these, the cases of mild dyskaryosis at the first instance were only taken into consideration. Histological diagnosis of these cases where available were retrieved from the laboratory database and were correlated with the cytological findings.

Results:  There were 1016 cases, which were reported as mild dyskaryosis. Out of them, 51.1% (519 cases) were first report of mild dyskaryosis: 61.8% (321 cases) and 38.2% (198 cases) were CS and TP respectively. Of these, 181 CS (56.4%) and 120 TP (60.6%) had a histological follow up. The results showed that 54.1% CS and 56.7% TP had a low‐grade outcome, 26.0% CS and 25.8% TP had a high‐grade outcome and 19.9% CS and 17.5% TP had a normal outcome. The PPV of mild dyskaryosis for CIN1 or worse result was 53.0% and 50.0% in CS and TP respectively. The PPV of mild dyskaryosis for CIN1 only was 27.1% and 24.2% in CS and TP respectively.

Discussion:  The difference in PPV for both systems is statistically insignificant. This result endorses usefulness of colposcopic referral after the first report of mild dyskaryosis.
P‐22 P16INK4A AS A MARKER FOR CERVICAL DYSKARYOSIS IN THINPREP® LIQUID BASED CYTOLOGY SAMPLES
Authors: Fallon A. , Oldfield N. , O'Grady T. , McBrearty P. , Grace A. , Leader M. , Kay E.
Published: August 2006

Cervical cancer is the second most common cancer amongst women worldwide. It is now accepted that almost all cervical cancers arise through the disruption of the pathways of p53 and the product of the retinoblastoma gene (pRb) by high‐risk Human Papilloma Virus (HPV) oncoproteins E6 and E7. In cervical cancer p16INK4a is strongly over expressed when pRb is inactivated by HPV E7. This over expression highlights the potential of p16INK4a as a marker for cervical intraepithelial neoplasia and cervical cancer. Immunocytochemical (ICC) analysis of P16INK4a expression was performed on 30 negative, 30 Borderline, 30 CIN1 and 30 High Grade ThinPrep® cervical samples selected from 1094 consented samples received for routine cervical screening assessment. The results were correlated with HR‐HPV status as determined by a PCR assay and the cytology findings. In addition a real time RT‐PCR technique was employed to evaluate P16INK4a gene expression in 50 of the 120 study samples. Eighty‐five of the 120 cervical samples were found positive by the ICC assay, 13/30 Negative, 23/30 Borderline, 20/30 CIN 1 and 29/30 High Grade. The ICC staining results were supported by the results of the P16INK4a real time RT‐PCR analysis and the HR‐HPV PCR assay. Interestingly not all HR‐HPV positive samples were P16INK4a ICC positive, suggesting the marker may be capable of discriminating between productive viral infections and active cell transformation. In conclusion P16INK4a is a useful marker of HR‐HPV mediated cervical dyskaryosis in ThinPrep® samples and may be utilized as an adjunct to the Pap smear to aid in the identification of patients with lesions which are more likely to progress to cervical cancer. Additional studies correlating p16INK4a ICC with viral load, viral integration and E6/E7 expression are required to establish how discriminatory a marker p16INK4a truly is.
P‐26 CONVENTIONAL V THIN LAYER TECHNIQUES: A COMPARATIVE STUDY OF BRONCHIAL SPECIMENS USING CONVENTIONAL AND TWO LBC METHODS, THINPREP AND SUREPATH
Authors: Conachan J. L.
Published: August 2006

The current, conventional method used is quick, easy and reasonably cheap but the nature of bronchial specimens themselves creates the need for a better preparation technique. Bronchial specimens often present with many obscuring features, such as blood and mucus, which can affect definitive diagnosis. In the study, the bronchial specimens underwent routine conventional preparation and that remaining was used to prepare an LBC slide. Both LBC methods were separately evaluated alongside the conventional method where, of the 44 specimens used, half were prepared using the conventional and ThinPrep and half with the conventional and SurePath. Evaluation forms were completed by pathologists who assessed all preparations. The results showed both LBC methods produced superior preparations that were better fixed, more cellular and had improved nuclear detail. They also removed a high percentage of background debris, were more diagnostically accurate and reduced the inadequate rate by a third. The conventional slides prepared from the same specimen as the SurePath had a lower average than those prepared with the ThinPrep. This indicated that the specimens used to evaluate the SurePath method were in fact inferior to those used for ThinPrep, with the SurePath slides showing only a slight improvement in overall quality. Despite LBC preparations reducing pathologist screening and reporting time, both methods are more labour intensive and less cost effective. The majority of laboratories are not in the financial situation to trial new methods that require extra training and more staff hours, and as such this study has highlighted an important question ‘Do the benefits of better quality preparation and diagnostic accuracy offset an increase in time and cost’.
P‐3 THE VALUE OF PERITONEAL WASHING CYTOLOGY IN THE STAGING OF GYNAECOLOGICAL MALIGNANCY
Authors: Joshi P , Evans A. , Rana D. N. , Hale R. , Wilson G. E. , Desai M. , Ismail S. M.
Published: August 2006

Introduction:  Current protocols for staging gynaecological cancers include cytopathological examination of peritoneal washings taken at the time of definitive surgery. We investigated the clinical usefulness of this procedure.

Methods:  During 2004 and 2005, 140 peritoneal washings were submitted for cytopathological examination in our institutions for staging of 36 ovarian, 101 endometrial and 3 synchronous ovarian/endometrial cancers.

Results:  The washings contained malignant cells in 39 cases (28%). 35 of these cases had high stage disease – not confined to the organ of origin (i.e. stage 2 or more for ovary and stage 3 or more for endometrial). The other 4 were stage 1C ovarian cancers where there was either rupture or tumour involvement of the capsule. In only 2 of the 39 positive cases the cancer was marginally upstaged by the positive washings – these were ovarian cancers upstaged from 2A /B to 2C.

Discussion:  These findings suggest that peritoneal washing cytology as a routine procedure for staging ovarian and endometrial cancer is of limited clinical value. A larger study is needed to determine whether this procedure should continue to be included in staging protocols for gynaecological cancer.
P‐4 TRANSFORMATION ZONE COMPONENT IN LIQUID BASED CERVICAL CYTOLOGY
Authors: Joseph P. , Marshall J. , Rana D. , Desai M.
Published: August 2006

Introduction:  Quality assurance guidelines for the UK cervical screening programme recommend that more than 80% of cervical samples from women aged 20–50 years should contain adequate numbers of Transformation zone (TZ) cells i.e. 10 or more endocervical or squamous metaplastic cells. This study was conducted to assess the frequency of TZ component in Liquid Based Cytology (LBC) both for ThinPrep (TP) and SurePath (SP) LBC. Also to assess the degree to which this is recorded by individual screeners and to determine the percentage of samples with evidence of TZ component for the different smear takers.

Method:  All LBC cervical specimens received at a tertiary cytology centre in the year 2004 from women aged 20–50 years were included in the study. Evidence of TZ sampling was recorded as: TP = TZ present (10 or more TZ cells)TA = TZ absentTS = TZ scanty (less than 10 TZ cells)TN = atrophic smears, TZ cells not recognisable

Results:  The total number of LBC cervical cases was 7445. TP = 4300 (mostly primary care) and SP = 3145 (mostly colposcopy). Overall TZ sampling rate in LBC was 82%. TP = 77.17%; SP = 88.24%. When scanty TZ was included, the standard was met for both systems (TP = 93.7%; SP = 88.24%). Presence/absence of TZ component was recorded in 6370 cases (85.1%); range 0%–97.79%. 56.7% of smear takers achieved the minimum standard for TZ sampling.

Discussion:  The percentage of ThinPrep samples containing adequate TZ cells was 77.17% compared to SurePath, which was 88.24%. This may be due to different patient populations i.e. primary care versus colposcopy. Screeners recorded TZ sampling in approximately 85% of samples. 56.7% of smear takers met the standard for TZ sampling.
P‐5 AN UNUSUAL FORM OF THYROID PAPILLARY CARCINOMA: COLUMNAR CELL VARIANT WITH NEUROENDOCRINE FEATURES
Authors: Sarkady E. , Rana D. , Desai M.
Published: August 2006

Case:  Our aim is to present an unusual form of poorly differentiated papillary thyroid carcinoma associated with inherited cancer syndromes, the neuroendocrine variant with columnar cell features. The patient was 42‐year‐old man with a known history of familial adenomatous polyposis (FAP) syndrome. A hard thyroid mass was identified in his right thyroid lobe. FNA showed microbiopsies of glandular structures, papillaroid groups of atypical cells with some histiocytes and colloid. The atypical cells showed columnar cell morphology with oval nuclei, fine chromatin and small nucleoli. Some crowding and pseudostratification was seen, also a few grooves were identified, but no intranuclear inclusions were present. The cells were positive for CK19, CK7, TTF‐1, beta‐catenin and chromogranin. They were negative for thyroglobulin, CEA, calcitonin, CK20 and Ki‐67. The thyroidectomy specimen showed a poorly differentiated papillary carcinoma showing neuroendocrine features and focal columnar cell change. The immunohistochemical findings were the same as for the FNA specimen and also CD56 and synaptophysin positivity was shown.

Discussion:  Inherited cancer syndromes may present with thyroid tumours in 1–2% of cases. They are usually multifocal with female predominance and an onset of less than 30 years of age in 90% of cases. They are most frequently the cribriform‐morular variant of papillary carcinoma. The columnar cell variant is an aggressive form of papillary carcinoma usually lacking the classical nuclear features and in some cases can even be thyroglobulin negative due to their less differentiated nature. Neuroendocrine differentiation is also known to worsen the prognosis. The beta‐catenin positivity is shown to be specific for FAP‐associated papillary carcinomas. Although clinically a good prognostic index was calculated for this patient (MACIS score 5.67, which has a 99% 20 year survival), cytologically both the neuroendocrine and the columnar cell features imply a bad prognosis.
P‐6 SCREENER SENSITIVITY – ALL CHANGE FOR LBC
Authors: Curran G. J.
Published: August 2006

Introduction:  This poster aims to provide a discussion point for the calculation of screener performance. LBC has brought about changes in the way slides are interpreted, single dispersed isolated dyskaryotic cells take on a new meaning and the process of quality control, rapid review has changed. These changes challenge the rationale behind screener sensitivity calculations especially as many laboratories are in an early learning phase with regard to LBC.

Method:  Screener sensitivities and the PPV of reporting consultants for a period of six months post LBC conversion are compared with those since the introduction of LBC.

Results:  Screener sensitivities have dropped below the 95% threshold for high‐grade dyskaryosis.

Discussion:  The change in rapid review or preview from a partial stepped rescreening of a conventional smear to a full rescreening of LBC slides has meant that all missed abnormalities that may not have been visualised in the conventional slide have a greater possibility of detection in the LBC slide. In analysing screener sensitivity a holistic approach that assesses the reasons for missing or misdiagnosing high‐grade abnormalities is advised. Over reporting by consultants as indicated by PPV and slide review should be taken into account when there is a suspected poor performer. The recent move to refer all mild dyskaryotic smears for colposcopic assessment and the EQA requirement for screeners to detect dyskaryosis without the necessity for grading suggests that there may be a need to reassess the basis of current screener sensitivity calculations.
P‐9 A COMPARISON OF THE REPORTING MORPHOLOGICAL FEATURES OF GLANDULAR NEOPLASIA FOR CONVENTIONAL AND LIQUID BASED CYTOLOGY FOR CERVICAL SAMPLES
Authors: Salmasi S.
Published: August 2006

Cervical cancer accounts for approximately 15% of cancer diagnosed in women worldwide with up to 190 000 deaths per annum. One of the major causes of cervical cancer is the infection of human papillomavirus (HPV), a DNA virus. This virus is epidermotropic; there are over 75 subtypes and subtypes 16, 18, 31 and 33 are associated with cervical intraepithelial neoplasia (CIN) and carcinomas. Since the start of the cervical screening in mid 1960s, the cervical cancer rate has decreased. There are two techniques used for slide preparation and staining: conventional cytology and liquid based cytology (LBC). Due to the differences in sample collection and preparation, certain aspects of cell morphology, architecture and patterns will present differently from each other on the slide. The study was conducted in a County Hospital. Twenty conventional slides and eight LBC slides already reported as ? Glandular neoplasia were reviewed and assessed with regards to their morphological features. Moreover, conventional slides were compared with LBC slides to determine the differences in their cell morphology, sensitivity and specificity. Furthermore, a semi‐quantitative method was used and also true‐positive and false‐positive rates were evaluated using positive predictive value (PPV). The findings indicated that despite the differences in cell morphology there are many similarities between the two techniques. The study also showed that it was difficult to distinguish between abnormal glandular cells and abnormal squamous cells, which may end in a false positive result and over reporting of glandular neoplasia. Finally, it showed that LBC slides were easier to screen and also had a higher positive predictive value (PPV) resulting in higher sensitivity and specificity. In conclusion, the LBC technique is more accurate and conversion to this technique is the positive step in the screening program.
CAN HPV BE THE SOLE PRIMARY CERVICAL CANCER SCREENING TEST?
Authors: Cuzick J.
Published: August 2006

Infection by certain types of human papilloma virus is now recognised as the main factor for cervical cancer. About 50% of cancers contain HPV 16 and over 95% contain one or more of the high‐risk types (16, 18, 31, 33, 35, 45, 51, 52, 56, 58). Several studies have shown that HPV testing is considerably more sensitive than conventional cytology. However it is not as specific, especially for younger women. These studies will be reviewed and overall comparisons with cytology will be made. Data from the 11 000 women HART study will be presented which suggest that for women aged 30 or over, a rational strategy would be to use HPV testing as the sole primary screening test, reserving cytology for the triage of HPV positive women. The results of this study indicate that HPV positive cytology negative women can be safely managed by repeat testing at one year. This reverses the current role of HPV testing as a triage test for women with borderline (ASCUS) cytology. Use of liquid‐based collection media will facilitate the transition to this new approach to screening. A detailed algorithm will be presented.