bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationships between molecular structure and physical properties in bent-core mesogens
Authors: Weissflog Wolfgang , Shreenivasa Murthy H.N , Diele Siegmar , Pelzl Gerhard
Published: August 2006

New five-ring bent-core mesogens that possess only ester connecting groups between the aromatic rings and different lateral substituents at the central phenyl ring are presented. The mesophases have been assigned by polarizing microscopy, differential scanning calorimetry, X-ray diffraction and electro-optical measurements. It is shown that the mesophase behaviour depends strongly on the position of the lateral substituents. Compounds, which are derived from 4-cyano-, 4-chloro- and 4,6-dichloro-resorcinol, show polymorphism variants where polar phases (SmAP, SmCP) occur together with nematic and conventional smectic phases, e.g. SmA–SmAP, SmA–SmC
S
P
A
–Col
ob
–SmC
S
P
A
, N–SmA–SmCP
A
, SmA–SmC–SmCP
A
and SmC–SmCP
A
. On the basis of the behaviour of two series of materials, the occurrence of different polar-switching mechanisms could be demonstrated. Apart from the usual mechanism by director rotation around the tilt cone, the polar switching can also take place through collective rotation of the molecules around their long axes, which corresponds to a field-induced switching of the layer chirality. A remarkable finding is the polar switching in the crystalline modification of long-chain, bent-core compounds with a methyl group in 2-position, which is accompanied by a clear change of the optical texture and by a relatively high switching polarization (approx. 600 nC cm
−2
). It was found for selected bent-core compounds that, above the transition temperature of a polar to a non-polar phase, the non-polar phase can be transformed to the polar phase by application of an electric field, which was proved for the transitions isotropic–SmCP
F
, SmA–SmCP
F
and isotropic–CrII polar.
Ontogeny of American paddlefish lymphoid tissues
Authors: Peterman A. E. , Petrie‐Hanson L.
Published: August 2006

The temporal and spatial distribution of American paddlefish Polyodon spathula immune cell populations was determined using enzyme cytochemistry and immunohistochemistry. Monocytes and macrophages were present in the renal haematopoietic tissue, spleen, meningeal myeloid tissue, cardiac myeloid tissue and lamina propria of the spiral valve at 7 days post‐hatch (dph). Immature lymphocytes were present in the renal haematopoietic tissue, spleen, meningeal myeloid tissue, cardiac myeloid tissue, thymus and lamina propria of the spiral valve at 7 dph. Type A lymphocytes (T‐cell like) were demonstrated in the thymus by 21 dph. Type B immunoglobulin positive lymphocytes (B‐cell like) were present in the renal haematopoietic tissue, cardiac myeloid tissue and lamina propria of the spiral valve by 7 dph, the thymus at 21 dph, the spleen by 56 dph, and were not observed in the meningeal myeloid tissue of paddlefish aged 7–28 dph. Granulocytes were present in the renal haematopoietic tissue, thymus, spleen, meningeal myeloid tissue, cardiac myeloid tissue and lamina propria of the spiral valve by 7 dph. The spleens in 7–28 dph fish were predominately red pulp. Differentiation of leukocytic and erythrocytic compartments (white and red pulp, respectively) was not apparent in the spleen until 56 dph. Remarkable thymic cortical and medullary differentiation was not yet present at 28 dph, and the thymus was not sampled at 56, 84 or 112 dph. The cardiac myeloid tissue was not developed until 56 dph. Peyer’s patches were present in the lamina propria by 56 dph. Paddlefish lympho‐myeloid structures are therefore slow to develop, and vaccination procedures should be performed at 2–4 months post‐hatch.
Reproductive isolation and genetic differentiation of ferox trout from sympatric brown trout in Loch Awe and Loch Laggan, Scotland
Authors: Duguid R. A. , Ferguson A. , Prodöhl P.
Published: August 2006

Molecular marker studies reported here, involving allozymes, mitochondrial DNA and microsatellites, demonstrate that ferox brown troutSalmo truttain Lochs Awe and Laggan, Scotland, are reproductively isolated and genetically distinct from co‐occurring brown trout. Ferox were shown to spawn primarily, and possibly solely, in a single large river in each lake system making them particularly vulnerable to environmental changes. Although a low level of introgression seems to have occurred with sympatric brown trout, possibly as a result of human‐induced habitat alterations and stocking, ferox trout in these two lakes meet the requirements for classification as a distinct biological, phylogenetic and morphological species. It is proposed that the scientific nameSalmo feroxJardine, 1835, as already applied to Lough Melvin (Ireland) ferox, should be extended to Awe and Laggan ferox.
Contrasting sex ratios in juvenile and adult chinook salmon Oncorhynchus tshawytscha (Walbaum) from south‐west Alaska: sex reversal or differential survival?
Authors: Olsen J. B. , Miller S. J. , Harper K. , Nagler J. J. , Wenburg J. K.
Published: August 2006

A sex‐specific genetic marker (growth hormone pseudogene) and age‐at‐maturation data were used to infer the cause of male‐biased phenotypic sex ratios in adult chinook salmon Oncorhynchus tshawytscha from the Kwethluk and Tuluksak Rivers, south‐west Alaska. The results showed that: (1) adult genetic and phenotypic sex ratios were similar and were male biased, (2) genetic sex ratios of pre‐smolts were not male biased and (3) the average age‐at‐maturation for males was significantly less than for females. These results suggest that the sex ratio distortion is due to gender bias in marine survival probably related to gender differences in marine life‐history strategies.
Assessment of restocking as a strategy for rehabilitating a native population of brown trout Salmo trutta L. in a fast‐flowing mountain stream in the northern French Alps
Authors: Caudron A. , Champigneulle A. , Guyomard R.
Published: August 2006

An attempt was made to extend the area of distribution of a native population of brown trout Salmo trutta belonging to a Mediterranean lineage (ML), which has maintained itself in the Dranse d’Abondance, a fast‐flowing alpine stream (Haute‐Savoie, France), despite several decades of intensive restocking with brown trout derived from the Atlantic lineage (AL). This was done by releasing an ML component into the predominantly AL population still present on the Ugine, the main tributary of the Dranse d’Abondance. This strategy of rehabilitation restocking was tested using fluoro‐marked juveniles produced from a captive breeding stock derived from the wild Dranse d’Abondance ML stock. Samples of 0+ year fish were collected over the period 1995–2003 in order to assess the impact of the restocking. Percentages of fluoro‐marked otoliths revealed significant contributions of ML restocking in the 0+ year autumnal standing population, with levels ranging from 34·3 to 61·4%. The change in the genetic characteristics of the 0+ year population produced by natural recruitment was monitored by analysing the unmarked subjects. Frequencies observed at two microsatellite loci revealed a considerable rise (from 0 to 60%) in the level of Mediterranean alleles in the natural 0+ year population since the introduction of restocking using ML individuals.
Induction of cell apoptosis in non‐small cell lung cancer cells by cyclin A1 small interfering RNA
Authors: Cho Nam Hoon , Choi Yoon Pyo , Moon Dong Suk , Kim Haeryoung , Kang Suki , Ding Owen , Rha Sun Young , Yang Yeon Ju , Cho Sang Ho
Published: August 2006

Cyclin A1 and cyclin B1 are overexpressed in various tumors but are present at low levels in normal tissues. Cyclin A1 is restricted to germ cells undergoing meiosis. In order to explore the possibility of using cyclin A1 and cyclin B1 as anticancer targets, we knocked them down in two lung cancer cell lines, H157 and H596, using siRNA. As with cyclin A1 siRNA in lung cancer cell lines, cyclin B1, Cdc2 and CDK2 were all significantly downregulated. The S phase fraction increased significantly, and they eventually underwent apoptosis by way of downregulated intrinsic apoptotic pathways and modulators with upregulated extrinsic apoptotic pathways. Our study suggests that cyclin A1 might be a promising anticancer target specific to lung cancer. (Cancer Sci 2006; 97: 1082–1092)
Nuclear expression of S100A4 is associated with aggressive behavior of epithelial ovarian carcinoma: An important autocrine/paracrine factor in tumor progression
Authors: Kikuchi Norihiko , Horiuchi Akiko , Osada Ryosuke , Imai Tsutomu , Wang Cuiju , Chen Xiaojun , Konishi Ikuo
Published: August 2006

Although S100A4 expression has reportedly been associated with metastasis of various malignancies, little is known about its biological significance in ovarian carcinomas. In this study, we investigated expression and secretion of S100A4 and its extracellular function in ovarian carcinoma cells. We first used immunohistochemistry to examine the expression and localization of S100A4 in 113 epithelial ovarian neoplasms (24 benign, 20 borderline, and 69 malignant tumors) and analyzed its prognostic significance in patients with ovarian carcinoma. Then we investigated the expression, subcellular localization, and secretion of S100A4 in four ovarian carcinoma cell lines. Finally, we examined the effect of S100A4 treatment on the cell proliferation and invasiveness of ovarian carcinoma cells, along with activation of small GTPase, RhoA. Both cytoplasmic and nuclear expressions of S100A4 were significantly stronger in carcinomas than those in benign and borderline tumors. Ovarian carcinoma patients with strong nuclear S100A4 expression showed a significantly shorter survival than those without (P = 0.0045). This was not the case for cytoplasmic S100A4 expression. Ovarian carcinoma cell lines were shown to express S100A4, and secrete S100A4 into the culture media. Treatment with recombinant S100A4 resulted in the upregulation of S100A4 expression, translocation of S100A4 into the nucleus, and enhancement of invasiveness, which was associated with the upregulation of small GTPase, RhoA. These findings suggest that the nuclear expression of S100A4 is involved in the aggressive behavior of ovarian carcinoma and S100A4 is an autocrine/paracrine factor that plays an important role in the aggressiveness of ovarian carcinoma cells. (Cancer Sci 2006; 97: 1061–1069)
Do browsing elephants damage female trees more?
Authors: Hemborg Åsa M. , Bond William J.
Published: August 2006

Herbivory in unisexual plants has mainly been assessed in studies of invertebrates, mostly insects. At a different scale of disturbance, browsing by large animals has rarely been studied. Elephants can seriously damage or kill trees by removing parts of the canopy, debark, or break the stem. We compared browsing by African elephants (Loxodonta africana) in male and female Marula trees (Sclerocarya birrea ssp. caffra). We expected females to incur more damage because of their sweet and fleshy fruits, known to attract elephants from far. Following this, we expected females to give more resistance through a denser branch wood that would break off at a larger diameter than in males. We tested this by pulling branches down to simulate elephant browsing as to compare branch resistance and design. All trees showed signs of browsing and females were generally more injured. However, there was no sexual difference in wood density and diameter at breaking point. Female branches were shorter, less ramified and carried fewer reproductive shoots than male branches. This sexual dimorphism could result from costly reproductive allocation in females and sexual selection, promoting intensive male flowering. Indirectly, elephants could reinforce this difference by engaging females more in tissue repair after browsing.
Analysis of human leukaemias and lymphomas using extensive immunophenotypes from an antibody microarray
Authors: Belov Larissa , Mulligan Stephen P. , Barber Nicole , Woolfson Adrian , Scott Mike , Stoner Kerryn , Chrisp Jeremy S. , Sewell William A. , Bradstock Kenneth F. , Bendall Linda , Pascovici Dana S. , Thomas Mervyn , Erber Wendy , Huang Pauline , Sartor Mary , Young Graham A.R. , Wiley James S. , Juneja Surender , Wierda William G. , Green Anthony R. , Keating Michael J. , Christopherson Richard I.
Published: August 2006

A novel antibody microarray has been developed that provides an extensive immunophenotype of leukaemia cells. The assay is a solid phase cell‐capture technique in which 82 antigens are studied simultaneously. This paper presents the analysis of 733 patients with a variety of leukaemias and lymphomas from peripheral blood and bone marrow. Discriminant Function Analysis of the expression profiles from these 733 patients and 63 normal subjects were clustered and showed high levels of consistency with diagnoses obtained using conventional clinical and laboratory criteria. The overall levels of consensus for classification using the microarray compared with established criteria were 93·9% (495/527 patients) for peripheral blood and 97·6% (201/206 patients) for bone marrow aspirates, showing that the extensive phenotype alone was frequently able to classify the disease when the leukaemic clone was the dominant cell population present. Immunophenotypes for neoplastic cells were distinguishable from normal cells when the leukaemic cell count was at least 5 × 109 cells/l in peripheral blood, or 20% of cells obtained from bone marrow aspirates. This technique may be a useful adjunct to flow cytometry and other methods when an extensive phenotype of the leukaemia cell is desired for clinical trials, research and prognostic factor analysis.
Long‐term outcome results of the first tandem autotransplant trial for multiple myeloma
Authors: Barlogie Bart , Tricot Guido J. , Van Rhee Frits , Angtuaco Edguardo , Walker Ron , Epstein Joshua , Shaughnessy John D. , Jagannath Sundar , Bolejack Vanessa , Gurley Jennifer , Hoering Antje , Vesole David , Desikan Raman , Siegel David , Mehta Jayesh , Singhal Seema , Munshi Nikhil C. , Dhodapkar Madhav , Jenkins Bonnie , Attal Michel , Harousseau Jean‐Luc , Crowley John
Published: August 2006

Total Therapy 1, the first tandem autotransplant trial for newly diagnosed patients with multiple myeloma, was designed to increase the frequency of complete response (CR) and thereby extend survival. With a median follow‐up of 12 years, 62 of 231 initially enrolled patients are alive (17% at 15 years); 31 remain event free (7% at 15 years) including 16 of 94 (41%) that initially achieved CR. Currently alive patients less frequently had cytogenetic abnormalities (CAs) at baseline (P = 0·002), postenrolment (P < 0·001) and at relapse (P = 0·004); elevations of serum C‐reactive protein (CRP) (P = 0·003) and lactate dehydrogenase (P = 0·029), anaemia (P = 0·029) and they more often completed two transplants within 12 months (P = 0·019). Postenrolment overall survival (OS) and event‐free survival (EFS) were superior in the absence of CA of the hypodiploidy or deletion 13 variety (P < 0·001 and 0·037 respectively) and in the presence of low CRP at baseline (P = 0·001 and 0·017 respectively). Postrelapse survival was longer in the absence of CA at relapse (P < 0·001), IgA isotype (P = 0·002), International Staging System stage 3 (P = 0·014), and when patients had two protocol transplants prior to relapse (P = 0·038). Ten‐year EFS and OS could be accomplished in 15% and 33% of patients, respectively, when all agents available in 1989, especially high‐dose melphalan, were applied together upfront for the management of myeloma.
Outcomes of alemtuzumab‐based reduced intensity conditioning stem cell transplantation using unrelated donors for myelodysplastic syndromes
Authors: Lim Zi Yi , Ho Aloysius Y. L. , Ingram Wendy , Kenyon Michelle , Pearce Laurence , Czepulkowski Barbara , Devereux Stephen , Duarte Rafael F. , Pagliuca Antonio , Mufti Ghulam J.
Published: August 2006

This prospective study evaluated the outcomes of 75 successive patients receiving a FBC (fludarabine, busulphan, alemtuzumab) reduced‐intensity conditioning (RIC) regimen for myelodysplastic syndromes (MDS) using volunteer unrelated donors(VUD). The prognostic significance of a variety of clinical variables including the recently described haematopoietic cell transplantation co‐morbidity index (HCT‐CI) was assessed. The median age of the cohort was 52·0 years (range: 19–68 years) with a median follow‐up of 1038·5 d. Forty‐nine patients (65%) had an International Prognostic Scoring System stage of ≥Intermediate‐2, 35 (46%) had intermediate or poor risk cytogenetics, and 23 patients(31%) were human leucocyte antigen‐mismatched. The actuarial 3‐year overall survival (OS) and disease‐free survival (DFS) was 43% [95% confidence interval (CI): 37–49] and 41% (95%CI: 35–47) respectively, and the cumulative incidence of extensive chronic graft‐versus‐host disease was 22%. On multivariate analysis, presence of either one class II mismatch or a two‐antigen mismatch adversely influenced transplant‐related mortality, DFS and OS. In addition, disease status at transplantation and the haematopoietic cell transplantation‐specific comorbidity index were independent variables for overall survival. In contrast, both advanced age and pre‐transplant cytogenetic status did not significantly affect overall outcomes. RIC regimens using VUD was associated with durable long‐term survival even in older patients with MDS, and the use of a pre‐transplant comorbidity index may help to improve patient selection for transplantation.
O‐1 10 YEAR AUDIT OF GLANDULAR CYTOLOGY REPORTS WITH SPECIAL REGARD TO THE EFFECT OF CONVERSION TO LBC
Authors: Shore E. , Ash A. , Smith J. H. F.
Published: August 2006

Recent reviews of glandular reports have confirmed a wide variation in specificity.1–3 We have reviewed our performance over the last 10 years and evaluated the effect of conversion to Liquid Based Cytology (LBC) on our reporting rates and accuracy. Audit revealed an upward trend in ability to accurately detect glandular lesions, with particular improvement in identification of Cervical Glandular Intraepithelial Neoplasia (CGIN).

Year
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005

Cases reported As? glandular neoplasia
39
26
18
27
28
16
22
12
23
29

PPV for any % significant pathology
51
58
83
78
50
63
59
92
78
93

PPV for correctly identified lesion %
21
42
67
56
36
50
41
83
78
83

Reasons for this general increase will be discussed, including changes to the laboratory staffing structure and better recognition of such lesions through improved training. In addition, the recent introduction of LBC technology may have resulted in improved sampling of the endocervical component through use of the Cervex Broom and smear taker training. In addition SurePath™ cell collection techniques with enhanced preservation of morphology may have lead to better recognition.

References:  1. Mathers et alCytopathology 2002, 13, 83–91

2. Pisal et al Eur J Obstet Gynaecol Reprod Biol 2003, 108, 209–212

3. Kirwan et alCytopathology 2004, 15, 188–194
O‐7 AUDIT OF THYROID FINE NEEDLE ASPIRATION CYTOLOGY: A PROBABILISTIC APPROACH
Authors: Venkatraman L. , Dillon K. , Anderson N. H.
Published: August 2006

Introduction:  Recent proposals from the Papanicolaou Society of Cytopathology for reporting fine needle aspiration (FNA) specimens from thyroid nodules suggest using 6 cytodiagnostic categories. This probabilistic approach to detection of malignancy seeks to clarify clinical implications for individual categories. Our audit aims to determine the rates for neoplasia and malignancy in the five diagnostic categories currently used in our department. We have evaluated the effect of refining cytodiagnosis in the aspirates reported as equivocal.

Methods:  A total of 392 thyroid FNA specimens reported between Jan 2003 and Dec 2005 were classed as inadequate, benign, equivocal, suspicious and malignant. 85 follow‐up thyroidectomies were received during this period; the histological diagnoses were correlated with the initial FNA diagnosis.

Results:  The FNA diagnoses for the 85 thyroidectomies were: 7 inadequate, 37 benign, 31 equivocal, 5 suspicious for malignancy and 5 malignant. The rates for neoplasia and cancer were respectively:

Inadequate: 2/7 (28.5%) & 0/7(0%)

Benign: 4/37(10.8%) & 2/37(5.4%)

Equivocal: 18/31(58.1%) & 11/31(35.4%)

Suspicious: 4/5(80%) & 4/5(80%)

Malignant: 5/5(100%) & 5/5(100%)

On subdividing the category equivocal into:

(1) Cellular lesion cannot exclude follicular neoplasm: the neoplasia rate was 4/12(33.3%) and the cancer rate 3/12(25%)

(2) Follicular neoplasm/lesion with nuclear atypia: the neoplasia rate was 14/19 (73.7%) and the cancer rate 8/19 (42.2%)

Excluding microcarcinomas, the false negative rate was 2.7%; there were no false positives.

Conclusion:  The diagnostic certainty of cancer for FNA thyroid reported suspicious or malignant is high. If cytology is equivocal, thyroidectomy is appropriate for those reported follicular neoplasm ± nuclear atypia while repeat FNA is more suitable for cellular lesions where a follicular neoplasm is not the primary cytodiagnosis. neoplasm is not the primary cytodiagnosis.
O‐11 EXTERNAL QUALITY ASSESSMENT IN CERVICAL CYTOLOGY – AN ALTERNATIVE APPROACH
Authors: Smart L. M. , Rogers C. , Wilson A. J. , Anderson J. , Scullion H. C.
Published: August 2006

Participation in External Quality Assessment (EQA) is a requirement of NHS CSP laboratories. As highlighted by the 1998 NHS executive letter, its principal function is educational with identification of poor performance likely to be exceptional. In 2003, NHS CSP published a protocol for laboratories in England for the EQA Scheme in Gynaecological Cytology, piloted in Trent and developed in line with RCPath recommendations. In Scotland and Northern Ireland, however, a different EQA system has evolved. Building on existing independent schemes, we have developed an integrated, comprehensive national programme of EQA, with three components designed to address three fundamental aspects: external assessment of smear reporting, continuing education in cervical cytology and evaluation of laboratory technical quality. The Interpretive Assessment component measures reporting performance by regularly testing individuals. Although recognised as one method of demonstrating competence, testing, scoring and assessment methods require sensitive interpretation. The Slide Circulation component is educational, providing regular exposure to, and discussion of, slides that are interesting or challenging. Technical QA provides impartial and confidential assessment of the quality of routine Papanicolaou staining, providing data to assist laboratories in auditing technical performance and in facilitating technical improvements. Through these components, the Scheme aims to contribute to upholding minimum national standards, promote consistency and confidence in cytology reporting, facilitate professional development, contribute to improving the quality of technical procedures, and assist laboratories in meeting accreditation standards relating to EQA. Participation is mandatory for all Scottish cervical cytology laboratories, and cervical cytology laboratories in Northern Ireland also participate. A Steering Committee oversees the scheme. Integral to the scheme is the initiation of confidential, supportive and constructive remedial action following individual or laboratory poor performance. This presentation describes the Scheme's components, its organisation and quality management, trends in laboratory and individual performance and experience with transition to LBC technology.
P‐1 DIRECT‐TO‐VIAL USE OF THE LIQUI‐PREP™ CYTOLOGY SYSTEM
Authors: Park J. , Jung E.‐H. , Kim C. , Choi Y. H.
Published: August 2006

Introduction:  The authors initiated the use of Liqui‐PREP™ (LGM International Inc., Fort Lauderdale, FL, USA) in August, 2005. Cytotechnologists received extensive (one month) training by cytopathologists experienced in Liquid‐based cytology. The Liqui‐PREP™ direct‐to‐vial procedure (LP) was compared to the conventional Pap smears in a routine screening population.

Methods:  Data derived from 26 178 LP cervical‐vaginal (CV) specimens were compared to data derived from 218 548 conventional Pap smears (CS). Both data sets reflect patient samples collected concurrently (August–December, 2005) by 117 participating outpatient medical practices from a well‐defined geographic area. There were no significant personnel changes during the study period. The diagnostic results, classified according to Bethesda criteria were calculated.

Results: 

% ASC‐US
% ASC‐H
% LSIL
% HSIL+
ASCUS/ LSIL+
% Unsat.

Liqui‐PREP™
6.5
0.24
1.55
0.39
3.8
0.02

Conv. Smear
2.8
0.09
0.50
0.25
4.0
0.05

Discussion:  Liqui‐PREP™ direct‐to‐vial method for CV specimens identified 210% more LSIL and 56% more HSIL+ lesions compared to the conventional smears. The ASCUS rate was increased (perhaps due to the conservative nature of our staff and their cautious interpretation of a new preparation). The ratio of ASCUS to LSIL+ was reduced by 5% for Liqui‐Prep™. Available biopsy data showed high correlation between both LP and CS abnormal cytology diagnoses (94.1% and 89.9% respectively). These findings suggest that the Liqui‐PREP™ cytology preparation procedure identifies more pre‐malignant lesions than the conventional smear.
P‐7 P16 ANTIBODY AS AN ADJUNCT TO ROUTINE CERVICAL SCREENING IN PROBLEMATIC CASES: A COMPARISON OF TWO COMMERCIALLY AVAILABLE ANTIBODIES
Authors: Govan L.
Published: August 2006

Objective:  The introduction of Liquid Based Technology (LBC) offers numerous advantages for cervical screening including the facility to make additional preparations after the sample has been reported. Could this additional preparation be used effectively for immunocytochemical (ICC) staining for p16? The aim of this study was to establish working techniques, a scoring system and assess the suitability of p16 for use in diagnostically difficult cases.

Study design:  A working technique for two commercially available antibodies, DakoCytomation Cintec p16INK4a and Vision Biosystems Novocastra p16 was established and applied to three groups of control samples, consisting of negative, borderline and dyskaryotic cases. All dyskaryotic cases were biopsy confirmed. The results obtained were used to formulate a scoring system (0–9), based on the percentage of positive cells and intensity of stain, which could then be applied to test cases. This group of test cases consisted of diagnostically difficult samples, which had been discussed or reviewed in the laboratory.

Results:  The results showed that p16 could aid in the diagnosis of difficult cases and should be assessed together with the original Papanicalaou stained slide to identify the cells in question. The scoring system with a cut off score of 4 for a positive result proved significant.

Conclusion:  Use of p16 in a routine laboratory could help further reduce false positive or negative results thus improving the service offered.
CYTOLOGY IN BREAST DISEASE: THE SURGEON'S PERSPECTIVE
Authors: Dixon M.
Published: August 2006

The management of breast disease has changed significantly over the last decade. Whereas 10 years ago cytology was commonly used to diagnose breast masses, this has now been almost completely replaced by core biopsy. The major reasons are that first core biopsy can differentiate between invasive and in situ cancer, second core has a much higher specificity than fine needle aspiration (FNA) cytology and third core biopsy can be carried out painlessly whereas FNA cytology is uncomfortable. Fourth on core biopsy it is possible not only to establish a histological diagnosis but also get hormone receptors and HER2 status and fifth the accuracy of core biopsies has increased dramatically with the use of image guidance. What is currently the role of cytology in the clinical management of patients with breast cancer? A major advantage of cytology is that it can be reported immediately. Cytology can also be used in situations where core biopsy is sometimes difficult e.g. high in the axilla and in the supraclavicular fossa. Cytology does not have to be FNA cytology, increasingly it is cytology of rolled core biopsies. Studies which have looked at one‐stop clinics have shown they are only effective if there is a large volume of patients in each clinic. Our own studies in Edinburgh have shown that patients like to have all the investigations performed and reported in one day and they do not like having to wait for results. Cytology still has a role but it is a changing role. The role of FNA cytology is reducing but core biopsy with rolled cytology is becoming more common. The big advantage of rolled core cytologies is that you can select what cores you roll for cytology. You also know if you get a C3 or C4 call on cytology the histology which follows is from exactly the same area. You can also guarantee to deliver to the pathologist a high quality specimen which is not overrun with blood cells. One problem is benign lesions. Cytologists looking at the roll cytology are initially overwhelmed by the numbers of cells that are presented to them from benign lesions but once they get used to this, the sensitivity and specificity of rolled core cytology is exceedingly high. One area that is rapidly expanding is preoperative diagnosis of lymph nodes in patients with breast cancer. All patients with breast cancer should now have their axilla scanned by ultrasound and any abnormal nodes core biopsied or aspirated. Fine needle cytology has a particular role where the nodes are in difficult positions against the chest wall or high in the axilla. In these situations core biopsy is not straight forward. Approximately 40% of patients with involved nodes can be identified preoperatively with image guided FNA or core. This knowledge of the node status allows better preoperative planning and selection of patients for axillary section or sentinel node biopsy.
Multivariate calibration of hyperspectral γ‐ray energy spectra for proximal soil sensing
Authors: Viscarra Rossel R. A. , Taylor H. J. , McBratney A. B.
Published: August 2006

The development of proximal soil sensors to collect fine‐scale soil information for environmental monitoring, modelling and precision agriculture is vital. Conventional soil sampling and laboratory analyses are time‐consuming and expensive. In this paper we look at the possibility of calibrating hyperspectral γ‐ray energy spectra to predict various surface and subsurface soil properties. The spectra were collected with a proximal, on‐the‐go γ‐ray spectrometer. We surveyed two geographically and physiographically different fields in New South Wales, Australia, and collected hyperspectral γ‐ray data consisting of 256 energy bands at more than 20 000 sites in each field. Bootstrap aggregation with partial least squares regression (or bagging‐PLSR) was used to calibrate the γ‐ray spectra of each field for predictions of selected soil properties. However, significant amounts of pre‐processing were necessary to expose the correlations between the γ‐ray spectra and the soil data. We first filtered the spectra spatially using local kriging, then further de‐noised, normalized and detrended them. The resulting bagging‐PLSR models of each field were tested using leave‐one‐out cross‐validation. Bagging‐PLSR provided robust predictions of clay, coarse sand and Fe contents in the 0–15 cm soil layer and pH and coarse sand contents in the 15–50 cm soil layer. Furthermore, bagging‐PLSR provided us with a measure of the uncertainty of predictions. This study is apparently the first to use a multivariate calibration technique with on‐the‐go proximal γ‐ray spectrometry. Proximally sensed γ‐ray spectrometry proved to be a useful tool for predicting soil properties in different soil landscapes.
Effects of a fishing gear on an artisanal multispecific penaeid fishery in a coastal lagoon of Mexico: mesh size, selectivity and management implications
Authors: ARELLANO‐TORRES A. , PÉREZ‐CASTAÑEDA R. , DEFEO O.
Published: August 2006

Abstract  The spatiotemporal effects of a bottom net used in an artisanal multispecific penaeid fishery at Celestun Lagoon, Mexico, were evaluated. Selectivity experiments, based on the covered codend method, were carried out with two bottom nets operating simultaneously but using different mesh size codends: 13 mm (MS13: currently used in the fishery) and 25 mm (MS25). Length at 50% retention, L50, was twice as high with MS25 (15.34 mm carapace length, CL) than with MS13 (6.95 mm CL); this global pattern was recurrent for all species, seasons and hydrological zones. These differences in selectivity determined that MS13 mainly retained recruits and juveniles, whereas MS25 mainly retained sub‐adults. However, smaller shrimps were caught by both mesh sizes during the ‘nortes’ season (November to February) and at the outer zones of the lagoon. Thus, an increase in mesh size from 13 to 25 mm, together with fishery closures within specific area–season windows, is suggested to reduce risks of overfishing of these shrimp populations.
Hydroacoustic assessment of young‐of‐year perch, Perca fluviatilis, population dynamics in an oligotrophic lake (Lake Annecy, France)
Authors: GUILLARD J. , PERGA M. E. , COLON M. , ANGELI N.
Published: August 2006

Abstract  A cohort of perch, Perca fluviatilis (L.) was monitored from hatching to first winter in the oligotrophic Lake Annecy, France, by combining hydroacoustic and direct capture methods (fish plankton net and pelagic trawl). The total stock of pelagic fish increased by a factor of 10 during the season, reaching a maximum in August and decreasing in autumn. Juvenile perch were mainly pelagic, being aggregated into schools in the daytime and dispersed at night. Migration of young‐of‐year (Y‐O‐Y) perch to the pelagic zone of Lake Annecy in late spring did not significantly affect zooplankton population abundance. It did, however, result in changes in zooplankton vertical distribution, with Daphnia remaining deeper in the water column. The increase in Y‐O‐Y biomass during summer was possibly associated with collapse of the Daphnia population by late July, and copepods one month later.
Transforming growth factor‐beta pathway disruption and infiltration of colorectal cancers by intraepithelial lymphocytes
Authors: Baker K , Chong G , Foulkes W D , Jass J R
Published: August 2006

Aims Colorectal cancers deficient in DNA mismatch repair (MMR) are often characterized by the presence of numerous intraepithelial lymphocytes (IELs). These CD8+ T cells selectively express CD103, which is upregulated locally by transforming growth factor (TGF)‐β, and adhere to E‐cadherin expressed by mucosal epithelia. Many of these cancers also possess inactivating mutations in the type II TGF‐β receptor and are believed to be insensitive to TGF‐β. The present study aimed to explore whether such refractoriness to TGF‐β is an independently contributing factor to IEL retention.

Methods and results A panel of colorectal cancers enriched for DNA MMR deficiency was examined by immunohistochemistry to explore the expression levels and localization of various components in the TGF‐β signalling pathway. Logistic regression was then carried out in order to identify predictors of elevated lymphocytic infiltration independent of DNA MMR status. Increases in Smad4 expression, tumour cell proliferation and TGF‐β secretion each emerged as independent predictors of marked lymphocyte infiltration.

Conclusions These results strongly support the hypothesis that refractoriness to normal TGF‐β signalling in colorectal cancers plays a role in the retention of lymphocytes within tumour epithelium. Since IEL infiltration is an independent predictor of favourable prognosis, the TGF‐β pathway may represent an important therapeutic target.
Hepatic progenitor cells, stem cells, and AFP expression in models of liver injury
Authors: Kuhlmann Wolf D. , Peschke Peter
Published: August 2006

Adult hepatocytes and liver‐cell progenitors play a role in restoring liver tissue after injury. For the study of progenitor cells in liver repair, experimental models included (a) surgical removal of liver tissue by partial hepatectomy; (b) acute injury by carbontetrachloride; (c) acute injury by d‐galactosamine (GalN) and N‐nitrosomorpholine (NNM); and (d) chemical hepatocarcinogenesis by feeding NNM in low and high doses. Serological and immunohistological detection of alpha‐fetoprotein gene expression served to follow pathways of cellular differentiation. Stem cells were not required in models of surgical removal of parenchyma and in carbon tetrachloride intoxication of adult hepatocytes. In contrast, regeneration of liver occurred through biliary epithelial cells in injuries induced by GalN and NNM. These biliary epithelial cells, collectively called oval cells, are most probably derived from the canals of Hering. Proliferating bile duct cells reached a level of differentiation with reactivation of foetal genes and significant alpha‐1‐fetoprotein (AFP) synthesis signalling a certain degree of retrodifferentiation with potential stemness. Due to the same embryonic origin of bile ducts and hepatocytes, biliary epithelium and its proliferating progeny (oval cells) have a defined role in liver regeneration as a transit and amplification compartment. In their early proliferation stage, oval cells were heavily engaged in DNA synthesis ([3H]thymidine labelling). Pulse‐chase experiments during experimental hepatocarcinogenesis exhibited their development into hepatocytes with high risk for transformation and leading to foci of altered hepatocytes. Hepatocellular carcinomas may arise either from proliferating/differentiating oval cells or from adult hepatocytes; both cell types have stem‐like properties. AFP‐positive and AFP‐negative carcinomas occurred in the same liver. They may represent random clonal origin. The heterogeneity of phenotypic marker (AFP) correlated with a process of retrodifferentiation.
Light cigarette smoke‐induced emphysema and NFκB activation in mouse lung
Authors: Santos Valenca Samuel , Castro Paulo , Alves Pimenta Wagner , Lanzetti Manuella , Vargas Silva Simone , Barja‐Fidalgo Cristina , Gonçalves Koatz Vera Lúcia , Porto Luís Cristóvão
Published: August 2006

Light cigarette (LC) exposure is supposed to be less hazardous with a decreased incidence of cancer and tobacco‐associated diseases. C57BL/6 mouse groups were subjected to smoke from 3, 6 or 12 LC for 60 days and compared with mice exposed to ambient air (EAA) in order to study lung injury by morphometrical and biochemical methods. Bronchoalveolar lavage (BAL) analysis and histology and stereology were performed. Tissue from the right lung was used for measuring thiobarbituric acid reactive substances (TBARS) and Western blot analysis. One way anova was performed followed by the Student–Newman Keuls post‐test (P < 0.05). The cellular content of BAL was 95% alveolar macrophages in all groups except in mice exposed to 3 LC, where 23% neutrophils were observed. Emphysema was not observed in three and 6 LC, but it was found in 12 LC parallel to increased volume density (Vv) of airspaces from 61.0 ± 0.6 (EAA) to 80.9 ± 1.0 (12 LC) and decreased Vv of elastic fibres from 17.8 ± 0.9 (EAA) to 11.8 ± 0.6 (12 LC). All exposed groups to LC showed low TBARS levels compared with mice EAA. Lung tissue from animals exposed to 12 LC showed decreased tissue inhibitor of metalloprotease‐2 and increased matrix metalloprotease‐12 detection, which suggests an imbalance in extracellular matrix (ECM). Increased tumour necrosis factor‐α and nuclear factor‐κB detection were observed in exposed groups to LC when compared with mice EAA. The data suggest that LC is so dangerous to lungs as full‐flavour cigarettes inducing ECM imbalance and emphysema.
Effect of Matrigel on adenoid cystic carcinoma cell line differentiation
Authors: Marques Márcia M. , Martins Manoela D. , França Cristiane M.
Published: August 2006

Adenoid cystic carcinoma (ACC) is a frequent malignant salivary gland neoplasm presenting different growth patterns described as tubular, cribriform and solid, which represent distinct differentiation stages. Cell lines originated from ACCs grown inside three‐dimensional environments have not been capable to reproduce all in vivo ACC growth patterns. As ACC cells in vivo present replicated basement membrane, to mimic this situation in vitro ACC cells (CAC2 cells) were grown on the top of a reconstituted basement membrane (Matrigel). Phenotype differences were assessed by light, fluorescence and transmission electron microscopy. The cultures grown on the top of Matrigel presented three‐dimensional arrangement of cells intercepted by cellular cords. At these, cell nests pseudocyst formations were observed. This morphological structure entirely reproduced the cribriform growth pattern of ACC. We suggest that the cribriform differentiation of ACC in culture is dependent of proteins and growth factors associated in a bi‐dimensional structure.
Cognitive‐behavioural stress management does not improve biological cardiovascular risk indicators in women with ischaemic heart disease: a randomized‐controlled trial
Authors: CLAESSON M. , BIRGANDER L. S. , JANSSON J.‐H. , LINDAHL B. , BURELL G. , ASPLUND K. , MATTSSON C.
Published: August 2006

Objectives.  Psychosocial factors, such as stress and vital exhaustion, are associated with an increased risk of cardiovascular events, and women report more psychosocial ill‐being after an acute myocardial infarction than men. We have earlier shown that a cognitive‐behavioural intervention in women with ischaemic heart disease (IHD) improved psychosocial well‐being. In the present study, we tested the hypothesis that the improvement in psychosocial well‐being is associated with an improvement in biochemical indicators of cardiovascular risk.

Design.  Randomized‐controlled trial in northern Sweden.

Setting.  Outpatient care.

Subjects.  Women with IHD were randomized to either a 1‐year cognitive‐behavioural stress management programme or usual care. Of the 159 women who completed the study, 77 were in the intervention group, and 82 in the control group.

Interventions.  A 1‐year cognitive‐behavioural stress management programme versus conventional care.

Results.  Group assignment was not found to be a determinant of waist circumference, high sensitive C‐reactive protein (hs‐CRP), fibrinogen, von Willebrand factor (vWF), plasminogen activator inhibitor type 1 (PAI‐1) activity, tissue plasminogen activator (tPA) activity, tPA antigen, tPA–PAI‐1 complex, leptin, or HOMA2 insulin resistance index (HOMA2‐IR) at follow up. Changes in psychosocial variables were not associated with changes in any of the biological risk indicators.

Conclusions.  Even if our cognitive‐behavioural stress management programme had effects on proximal targets, such as stress behaviour and vital exhaustion, we found no improvement in intermediate biochemical targets related to the metabolic syndrome and IHD. Our results challenge the proposition that the relationship between psychological well‐being and biological cardiovascular risk indicators is a direct cause–effect phenomenon.
Phylogeography and Pleistocene refugia of the adder (Vipera berus) as inferred from mitochondrial DNA sequence data
Authors: URSENBACHER S. , CARLSSON M. , HELFER V. , TEGELSTRÖM H. , FUMAGALLI L.
Published: August 2006

In order to contribute to the debate about southern glacial refugia used by temperate species and more northern refugia used by boreal or cold‐temperate species, we examined the phylogeography of a widespread snake species (Vipera berus) inhabiting Europe up to the Arctic Circle. The analysis of the mitochondrial DNA (mtDNA) sequence variation in 1043 bp of the cytochrome b gene and in 918 bp of the noncoding control region was performed with phylogenetic approaches. Our results suggest that both the duplicated control region and cytochrome b evolve at a similar rate in this species. Phylogenetic analysis showed that V. berus is divided into three major mitochondrial lineages, probably resulting from an Italian, a Balkan and a Northern (from France to Russia) refugial area in Eastern Europe, near the Carpathian Mountains. In addition, the Northern clade presents an important substructure, suggesting two sequential colonization events in Europe. First, the continent was colonized from the three main refugial areas mentioned above during the Lower‐Mid Pleistocene. Second, recolonization of most of Europe most likely originated from several refugia located outside of the Mediterranean peninsulas (Carpathian region, east of the Carpathians, France and possibly Hungary) during the Mid‐Late Pleistocene, while populations within the Italian and Balkan Peninsulas fluctuated only slightly in distribution range, with larger lowland populations during glacial times and with refugial mountain populations during interglacials, as in the present time. The phylogeographical structure revealed in our study suggests complex recolonization dynamics of the European continent by V. berus, characterized by latitudinal as well as altitudinal range shifts, driven by both climatic changes and competition with related species.
Phytochrome‐mediated development in land plants: red light sensing evolves to meet the challenges of changing light environments
Authors: MATHEWS SARAH
Published: August 2006

Phytochromes are photoreceptors that provide plants with circadian, seasonal, and positional information critical for the control of germination, seedling development, shade avoidance, reproduction, dormancy, and sleep movements. Phytochromes are unique among photoreceptors in their capacity to interconvert between a red‐absorbing form (absorption maximum of ∼660 nm) and a far‐red absorbing form (absorption maximum of ∼730 nm), which occur in a dynamic equilibrium within plant cells, corresponding to the proportions of red and far‐red energy in ambient light. Because pigments in stems and leaves absorb wavelengths below about 700 nm, this provides plants with an elegant system for detecting their position relative to other plants, with which the plants compete for light. Certain aspects of phytochrome‐mediated development outside of flowering plants are strikingly similar to those that have been characterized inArabidopsis thalianaand other angiosperms. However, early diverging land plants have fewer distinct phytochrome gene lineages, suggesting that both diversification and subfunctionalization have been important in the evolution of the phytochrome gene family. There is evidence that subfunctionalization proceeded by the partitioning among paralogues of photosensory specificity, physiological response modes, and light‐regulated gene expression and protein stability. Parallel events of duplication and functional divergence may have coincided with the evolution of canopy shade and the increasing complexity of the light environment. Within angiosperms, patterns of functional divergence are clade‐specific and the roles of phytochromes inA. thalianachange across environments, attesting to the evolutionary flexibility and contemporaneous plasticity of phytochrome signalling in the control of development.