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S Rice

Publications and source records attributed to S Rice.

At least 19 recordsLinked to original sources
PubMed2006

Ensembl 2007.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of chordate genome sequences. Over the past year the number of genomes available from Ensembl has increased from 15 to 33, with the addition of sites for the mammalian genomes of elephant, rabbit, armadillo, tenrec, platypus, pig, cat, bush baby, common shrew, microbat and european hedgehog; the fish genomes of stickleback and medaka and the second example of the genomes of the sea squirt (Ciona savignyi) and the mosquito (Aedes aegypti). Some of the major features added during the year include the first complete gene sets for genomes with low-sequence coverage, the introduction of new strain variation data and the introduction of new orthology/paralog annotations based on gene trees.

Animals↗
PubMed2005

Proposed Sheffield quantitative criteria in cervical cytology to assist the diagnosis and grading of squamous intra-epithelial lesions, as some Bethesda system definitions require amendment.

OBJECTIVE: This study assesses the accuracy of published quantitative and qualitative criteria in the Bethesda System (TBS) for squamous intra-epithelial lesions. METHODS: Quantitative image analysis was undertaken on illustrations from TBS publications and also from slides in Cytology Training Centre teaching sets. Comparisons were also made with the British Society for Clinical Cytology (BSCC) terminology in cervical cytology, using the illustrations in their terminology publication and amalgamating the results into their proposed new two-tier model. RESULTS: TBS quantitatively defines low-grade squamous intra-epithelial lesions (LSIL) in both conventional and liquid-based cytology (LBC) preparations as showing nuclear enlargement more than x3 the area of a normal intermediate squamous cell nucleus. This study found that the increase in mean nuclear area was limited to only x2 in conventional preparations. In LBC (SurePath preparations, there was only a statistically non-significant x1.2 increase. This study identified a progressive and statistically significant reduction in mean cytoplasmic area from normal intermediate cells to LSIL and then to high-grade squamous intra-epithelial lesions (HSIL) in both conventional and LBC preparations. Furthermore, the most consistent quantitative finding in both conventional and LBC preparations was a statistically significant increase in the mean area and diameter ratios from normal intermediate cells to LSIL and then to HSIL. In all instances this varied from x2 to just below x3. This is in agreement with TBS, which states that the cytoplasmic area in HSIL is decreased leading to a marked increase in nuclear to cytoplasmic (NC) ratio. With the exception of an increase in mean nuclear area in conventional preparations from normal intermediate cells to LSIL, the predominant cause for this increase in NC ratios was a reduction in mean cytoplasmic area. The numerical increase in NC ratio for LSIL identified in this study was greater than implied by the 'slightly increased' statement in TBS. TBS comments that some HSIL cells can have the same degree of nuclear enlargement as in LSIL and that other HSIL cells may have much smaller nuclei than in LSIL. Both of these qualitative comments were supported in this study. The mean diameter NC ratios of 33% and 50% could provide useful diagnostic assistance in the distinction of normal intermediate cells and LSIL and between LSIL and HSIL, respectively. Because of overlapping individual ranges, however, additional diagnostic features such as nuclear morphology must be used in the distinction of normal intermediate cells, LSIL and HSIL. No statistical difference was identified in the mean diameter NC ratios between ASC-US and LSIL in TBS publications. In addition, the proposed new BSCC low and high grades of squamous abnormality were not statistically different from ASC-US/LSIL and HSIL, respectively. This provides support that the proposed BSCC two-tier system of squamous abnormalities is comparable to TBS. This study shows that LBC has variable but major and significant effects on nuclear and cytoplasmic morphology and that quantitative definitions in conventional preparations cannot be automatically extrapolated to LBC methodology. CONCLUSIONS: The study shows that some TBS quantitative and qualitative criteria require amendment and that an alternative quantitative approach, such as diameter NC ratio has a more valid scientific evidence base. Furthermore, use of NC ratios avoids the problems associated with the variable changes in nuclear and cytoplasmic areas, occurring between conventional and different commercial LBC preparations. By contrast, classifications based on area comparisons must be tailored to the specific conventional or commercial LBC preparation.

Carcinoma, Squamous Cell↗
PubMed2005

Proposed Sheffield quantitative criteria in cervical cytology to assist the grading of squamous cell dyskaryosis, as the British Society for Clinical Cytology definitions require amendment.

OBJECTIVE: In 1986, the British Society for Clinical Cytology (BSCC) published quantitative criteria to assist diagnosis in a three-tier grading system of squamous cell dyskaryosis. In dyskaryotic cells, area nuclear to cytoplasmic (NC) ratios below 50%, between 50% and 66% and over 66% were defined as equating with mild, moderate and severe grades respectively. Following the Terminology Conference in 2002, however, the BSCC recommended on their website that the three-tier model should be replaced by a new two-tier system of low- and high-grade squamous abnormalities. The latter broadly equate with the two-grade Bethesda System (TBS) for reporting squamous intraepithelial lesions. The purpose of this study was to assess the accuracy and reproducibility of the BSCC three-tier quantitative definitions, to investigate if they were applicable to liquid-based cytology (LBC) and to see how they related to the proposed new two-tier BSCC system. METHODS: Quantitative image analysis was undertaken on illustrations from the 1986 BSCC terminology publication and on microscope slides from external quality assessment and Cytology Training Centre teaching sets. RESULTS: Analysis of mean NC ratios showed that mild, moderate and severe dyskaryosis exist as statistically different populations. Overlap of NC ratio ranges, however, limits their practical application in the three-tier model, although interestingly no overlap was noted between mild and severe dyskaryosis. No grade of dyskaryosis had a mean area NC ratio over 50%, indicating that the BSCC quantitative definitions are incorrect. The mean diameter NC ratios for mild, moderate and severe dyskaryosis were found to be 40%, 49% and 66% respectively. Accordingly it is possible that those reporting cervical cytology could be interpreting the BSCC NC ratios as meaning diameter rather than area. Amalgamation of the three-tier results into the proposed two-tier model shows that the resulting mean NC area and diameter ratios identify statistically different low- and high-grade populations. The reduced degree of overlap, however, of NC ratio ranges in the two-tier model implies that NC ratios could have a useful practical role in the separation of the low- and high-grade categories. The two categories were reasonably well separated by mean area and diameter NC ratios of 25% and 50% respectively. A two-tier model combining mild with moderate rather than severe dyskaryosis was found to be a statistically valid alternative but gave rise to NC ratios that would be difficult to use in practice. Except for moderate dyskaryosis, no significant differences were identified between the mean NC ratios of either conventional and LBC preparations or LBC preparations using two different commercial methodologies (SurePath and ThinPrep). Differences, however, were noted in area measurements between SurePath and ThinPrep and this has potential implications for classifications (such as TBS) using area comparisons as their basis. In addition, it was found that the increased NC ratio, associated with higher grades of dyskaryosis is more a consequence of progressive cytoplasmic area reduction rather than nuclear area increase. The similar NC ratios of borderline nuclear changes associated with human papilloma virus and mild dyskaryosis support the BSCC proposal that these can be combined to constitute a low-grade category. This study shows that the BSCC area NC ratio criteria of grading squamous cell dyskaryosis require amendment. In addition, this study supports the new BSCC recommendation of low- and high-grade squamous cell categories. CONCLUSIONS: The study proposes Sheffield quantitative criteria to assist the grading of squamous cell abnormalities. Quantitative diameter NC ratio measurements, however, must always be accompanied by detailed assessment of qualitative morphological features and in particular those relating to nuclear chromatin. This is equally relevant to both two- and three-tier models.

Carcinoma, Squamous Cell↗
PubMed2004

Impaired insulin-dependent glucose metabolism in granulosa-lutein cells from anovulatory women with polycystic ovaries.

BACKGROUND: Insulin resistance and hyperinsulinaemia are well-recognized characteristics of anovulatory women with polycystic ovary syndrome (PCOS) but, paradoxically, steroidogenesis by PCOS granulosa cells remains responsive to insulin. The hypothesis to be tested in this study is that insulin resistance in the ovary is confined to the metabolic effects of insulin (i.e. glucose uptake and metabolism), whereas the steroidogenic action of insulin remains intact. METHODS: Granulosa-lutein cells were obtained during IVF cycles from seven women with normal ovaries, six ovulatory women with PCO (ovPCO) and seven anovulatory women with PCO (anovPCO). Mean body mass index was in the normal range in all three groups. Granulosa-lutein cells were cultured with insulin (1, 10, 100 and 1000 ng/ml) and LH (1, 2.5 and 5 ng/ml). Media were sampled at 24 and 48 h and analysed for glucose uptake, lactate production and (48 h only) progesterone production. RESULTS: Insulin-stimulated glucose uptake by cells from anovPCO was attenuated at higher doses of insulin (100 and 1000 ng/ml) compared with that by cells from either ovPCO (P=0.02) or controls (P=0.02). Insulin and LH stimulated lactate production in a dose-dependent manner, but insulin-dependent lactate production was markedly impaired in granulosa-lutein cells from anovPCO compared with either normal (P=0.002) or ovPCO (P<0.0001). By contrast, there was no difference in insulin-stimulated progesterone production between granulosa-lutein cells from the three ovarian types. CONCLUSIONS: Granulosa-lutein cells from women with anovPCOS are relatively resistant to the effects of insulin-stimulated glucose uptake and utilization compared with those from normal and ovPCO, whilst maintaining normal steroidogenic output in response to physiological doses of insulin. These studies support the probability of a post-receptor, signalling pathway-specific impairment of insulin action in PCOS.

Adult↗
PubMed2003

Thermodynamic properties of the kinesin neck-region docking to the catalytic core.

Kinesin motors move on microtubules by a mechanism that involves a large, ATP-triggered conformational change in which a mechanical element called the neck linker docks onto the catalytic core, making contacts with the core throughout its length. Here, we investigate the thermodynamic properties of this conformational change using electron paramagnetic resonance (EPR) spectroscopy. We placed spin probes at several locations on the human kinesin neck linker and recorded EPR spectra in the presence of microtubules and either 5'-adenylylimidodiphosphate (AMPPNP) or ADP at temperatures of 4-30 degrees C. The free-energy change (DeltaG) associated with AMPPNP-induced docking of the neck linker onto the catalytic core is favorable but small, about 3 kJ/mol. In contrast, the favorable enthalpy change (DeltaH) and unfavorable entropy change (TDeltaS) are quite large, about 50 kJ/mol. A mutation in the neck linker, V331A/N332A, results in an unfavorable DeltaG for AMPPNP-induced zipping of the neck linker onto the core and causes motility defects. These results suggest that the kinesin neck linker folds onto the core from a more unstructured state, thereby paying a large entropic cost and gaining a large amount of enthalpy.

Binding Sites↗
PubMed2002

External quality assessment in gynaecological cytology: The Trent Region experience. The Trent Regional Gynaecological Pathology Quality Assurance Group for the National Health Service Cervical Screening Programme.

A Department of Health Executive Letter stated in 1998 that the principal function of external quality assessment (EQA) is educational. Subsequently, in England, it has no longer been acceptable to assess performance in gynaecological cytology by proficiency testing. This paper describes the EQA scheme in gynaecological cytology that has been run by the Trent Regional Gynaecological Pathology Quality Assurance Group for the NHS Cervical Screening Programme (NHSCSP) since 1998. It conforms as closely as possible to the recommendations published by the Department of Health Working Group on Histopathology EQA Accreditation, and replaced the national proficiency testing protocol. The educational value of the scheme is derived predominantly from a numerical score which provides confidential and quantitative feedback to all participants. Personal performance monitoring occurs as a secondary function. For primary screeners and checkers, this is based purely on the distinction between negative, inadequate and abnormal smears. For pathologists, personal performance monitoring also includes grading of abnormalities. The EQA has been designed so that all professional groups participate in a manner that closely mimics normal practice. Only slides that have achieved an 80% consensus amongst participants are used in the EQA. Substandard performance has been defined as those participants with scores falling below the 2.5%ile. The paper describes the EQA in detail and illustrates its use by means of the second round results. The EQA protocol developed within Trent and described in this paper has contributed to proposals contained in the current national EQA in gynaecological cytology for the NHSCSP. In particular this paper highlights the effectiveness of the scoring system contained within the Trent and National EQA protocols.

Education↗
PubMed2002

Caspase activity and expression of cell death genes during development of human preimplantation embryos.

It has been observed that apoptosis occurs in human blastocysts. In other types of cell, the characteristic morphological changes seen in apoptotic cells are executed by caspases, which are regulated by the BCL-2 family of proteins. This study investigated whether these components of the apoptotic cascade are present throughout human preimplantation development. Developing and arrested two pronucleate embryos at all stages were incubated with a fluorescently tagged caspase inhibitor that binds only to active caspases, fixed, counterstained with 4,6-diamidino-2-phenylindole (DAPI) to assess nuclear morphology and examined using confocal microscopy. Active caspases were detected only after compaction, at the morula and blastocyst stages, and were frequently associated with apoptotic nuclei. Occasional labelling was seen in arrested embryos. Expression of proapoptotic BAX and BAD and anti-apoptotic BCL-2 was examined in single embryos using RT-PCR and immunohistochemistry. BAX and BCL-2 mRNAs were expressed throughout development, whereas BAD mRNA was expressed mainly after compaction. Simultaneous expression of BAX and BCL-2 proteins within individual embryos was confirmed using immunohistochemistry. The onset of caspase activity and BAD expression after compaction correlates with the previously reported appearance of apoptotic nuclei. As in other types of cell, human embryos express common molecular components of the apoptotic cascade, although apoptosis appears to be suppressed before compaction and differentiation.

Apoptosis↗
PubMed2002

DSM-IV: Diagnosis of children with traumatic brain injury.

This paper reviews the strengths and limitations of the DSM-IV in the diagnosis of children with Traumatic Brain Injury. The authors compare the DSM-IV diagnostic characteristics for effective classification and decision making in children with TBI. The DSM IV multiaxial approach can be useful in patients with brain injury because medical considerations can be incorporated with the diagnosis, along with standard mental health factors.

Brain Injuries↗
PubMed2001

Kinetics of the AHL regulatory system in a model biofilm system: how many bacteria constitute a "quorum"?

Acylated homoserine lactones (AHLs) regulate a wide variety of phenotypes in Gram-negative bacteria. Most research suggests that AHL-mediated phenotypes are not expressed in populations until late logarithmic phase or stationary phase. Here, we model how the concentration of AHLs inside bacterial cells and in a biofilm changes over time as a function of population growth rate, diffusion of AHLs and the rate of autoinduction. Our theoretical results show that the concentration of AHLs inside a single bacterium (and by implication induction of a phenotype) has a non-trivial behaviour over time, and often exhibits a rapid increase early in population growth. This rapid increase is followed by a plateau, followed by another rise in the concentration of AHLs, to a second plateau. High concentrations of AHLs inside the bacterial cell early in population growth are positively affected by slow diffusion rates out of the cell and the biofilm, slow bacterial growth rates and fast autoinduction. In contrast, fast growth rates, slow autoinduction rates and high diffusion rates result in a high concentration plateau in stationary phase. More generally, the density-dependent nature of AHL regulation can be viewed as a trade-off between factors that dilute intracellular concentrations of AHLs (diffusion out of the cell, cell division), and those that increase concentrations (a slowing or restriction of diffusion or growth, or autoinduction). These results suggest that expression of AHL-mediated phenotypes can occur at relatively low cell densities and low external/environmental AHL concentrations.

4-Butyrolactone↗
PubMed2001

Treatment demands and differential treatment of patients with cystic fibrosis and their siblings: patient, parent and sibling accounts.

Cystic fibrosis (CF) is a progressive disease with no known cure. Advances in diagnosis and treatment have resulted in patients living longer and thus families live with the illness for longer. Treatments are becoming increasingly demanding and are largely performed in the family home. Mothers are often reported to experience greater stress and poorer adjustment than mothers of well children or population norms. Patients and siblings are also reported to display adjustment difficulties. Siblings have rarely been included in research designs. This qualitative study investigates the impact of CF and treatment on eight patients, eight mothers, one father and eight siblings. A family systems perspective was adopted. Each individual was interviewed independently using semistructured interviews. Patients and siblings were aged between 9 and 21 years. Qualitative analyses revealed high levels of non-adherence (intentional and unintentional) and parental involvement in treatment, minimal involvement of siblings, and preferential treatment towards patients. Demanding treatment, coupled with the progressive nature of CF, promote high levels of parental involvement for younger children as well as older teenagers, often due to attempted or actual non-adherence. Siblings may receive less attention while patients' needs take priority. Future development of a measure of adherence suitable for children and adolescents should take into account different motivations for non-adherence, particularly regarding the level of personal control over adherence to treatment. In addition, the potential impact of having a brother or sister with CF should not be underestimated and the needs of siblings should not go unnoticed.

Adaptation, Psychological↗
PubMed2001

Rapid screening: a comparative study.

Although rapid screening of negative and inadequate cervical smears is a quality assurance requirement for all UK laboratories, there has been little attempt to standardize the method and laboratories make use of a number of different techniques and times. The aim of this study was to assess the sensitivity of these various techniques by measuring their ability to pick out known false-negative smears. Completed questionnaires from 123 laboratories across England revealed that 52% of laboratories use a "step" technique, 19% use "turret", 15% use random paths and 34% attempt to rescreen the whole slide quickly. Twenty-two percent of laboratories use a mixture of techniques. Timings are also variable, with the majority of laboratories allowing screeners to review slides at a pace decided by themselves but usually between 1 and 2 min. The study involved 120 participants who performed a total of 24 000 rapid screens. The results showed that, of the 90 abnormal slides used in the study, 62 cases (69%) were identified as abnormal or needing review by more than 50% of participants. Overall rapid screening picked out 58% of high-grade squamous abnormalities, 59% of low-grade abnormalities and 72% of glandular lesions. Step screening performed best, followed by whole slide/random and then turret. One minute was the optimum time and there was a significant fall in performance once individuals attempted to rescreen large numbers (>50). The most significant finding was the marked variation in the performance of individuals using the same slide sets.

Diagnostic Errors↗
PubMed2000

Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor and parthenolide.

The transcription factor nuclear factor-kappaB (NF-kappaB) regulates genes important for tumor invasion, metastasis and chemoresistance. Normally, NF-kappaB remains sequestered in an inactive state by cytoplasmic inhibitor-of-kappaB (IkappaB) proteins. NF-kappaB translocates to nucleus and activates gene expression upon exposure of cells to growth factors and cytokines. We and others have shown previously that NF-kappaB is constitutively active in a subset of breast cancers. In this study, we show that constitutive activation of NF-kappaB leads to overexpression of the anti-apoptotic genes c-inhibitor of apoptosis 2 (c-IAP2) and manganese superoxide dismutase (Mn-SOD) in breast cancer cells. Furthermore, expression of the anti-apoptotic tumor necrosis factor receptor associated factor 1 (TRAF1) and defender-against cell death (DAD-1) is regulated by NF-kappaB in certain breast cancer cells. We also demonstrate that NF-kappaB-inducible genes protect cancer cells against paclitaxel as MDA-MB-231 breast cancer cells modified to overexpress IkappaBalpha required lower concentrations of paclitaxel to arrest at the G2/M phase of the cell cycle and undergo apoptosis when compared to parental cells. The effect of NF-kappaB on paclitaxel-sensitivity appears to be specific to cancer cells because normal fibroblasts derived from embryos lacking p65 subunit of NF-kappaB and wild type littermate embryos were insensitive to paclitaxel-induced G2/M cell cycle arrest. Parthenolide, an active ingredient of herbal remedies such as feverfew (tanacetum parthenium), mimicked the effects of IkappaBalpha by inhibiting NF-kappaB DNA binding activity and Mn-SOD expression, and increasing paclitaxel-induced apoptosis of breast cancer cells. These results suggest that active ingredients of herbs with anti-inflammatory properties may be useful in increasing the sensitivity of cancers with constitutively active NF-kappaB to chemotherapeutic drugs. Oncogene (2000) 19, 4159 - 4169

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Homing and engraftment potential of Sca-1(+)lin(-) cells fractionated on the basis of adhesion molecule expression and position in cell cycle.

Engraftment potential of hematopoietic stem cells (HSCs) is likely to be dependent on several factors including expression of certain adhesion molecules (AMs) and degree of mitotic quiescence. The authors investigated the functional properties and engraftment potential of Sca-1(+)lin(-) cells subfractionated on the basis of expression, or lack thereof, of CD11a, CD43, CD49d, CD49e, or CD62L and correlated that expression with cell cycle status and proliferative potential of engrafting fractions. Donor-derived chimerism in mice receiving CD49e(+) or CD43(+) Sca-1(+)lin(-) cells was greater than that in mice receiving cells lacking these 2 markers, while Sca-1(+)lin(-) cells positive for CD11a and CD62L and bright for CD49d expression mediated minimal engraftment. AM phenotypes enriched for engraftment potential contained the majority of high proliferative potential-colony forming cells, low proliferative potential-colony forming cells, and cells providing rapid in vitro expansion. Cell cycle analysis of AM subpopulations revealed that, regardless of their bone marrow repopulating potential, Sca-1(+)lin(-) AM(-) cells contained a higher percentage of cells in G(0)/G(1) than their AM(+) counterparts. Interestingly, engrafting phenotypes, regardless of the status of their AM expression, were quicker to exit G(0)/G(1) following in vitro cytokine stimulation than their opposing phenotypes. When engrafting phenotypes of Sca-1(+)lin(-) AM(+) or AM(-) cells were further fractionated by Hoechst 33342 into G(0)/G(1) or S/G(2)+M, cells providing long-term engraftment were predominantly contained within the quiescent fraction. These results define a theoretical phenotype of a Sca-1(+)lin(-) engrafting cell as one that is mitotically quiescent, CD43(+), CD49e(+), CD11a(-), CD49d(dim), and CD62L(-). Furthermore, these data suggest that kinetics of in vitro proliferation may be a good predictor of engraftment potential of candidate populations of HSCs. (Blood. 2000;96:1380-1387)

Animals↗
PubMed2000

Role of the kinesin neck linker and catalytic core in microtubule-based motility.

Kinesin motor proteins execute a variety of intracellular microtubule-based transport functions [1]. Kinesin motor domains contain a catalytic core, which is conserved throughout the kinesin superfamily, followed by a neck region, which is conserved within subfamilies and has been implicated in controlling the direction of motion along a microtubule [2] [3]. Here, we have used mutational analysis to determine the functions of the catalytic core and the approximately 15 amino acid 'neck linker' (a sequence contained within the neck region) of human conventional kinesin. Replacement of the neck linker with a designed random coil resulted in a 200-500-fold decrease in microtubule velocity, although basal and microtubule-stimulated ATPase rates were within threefold of wild-type levels. The catalytic core of kinesin, without any additional kinesin sequence, displayed microtubule-stimulated ATPase activity, nucleotide-dependent microtubule binding, and very slow plus-end-directed motor activity. On the basis of these results, we propose that the catalytic core is sufficient for allosteric regulation of microtubule binding and ATPase activity and that the kinesin neck linker functions as a mechanical amplifier for motion. Given that the neck linker undergoes a nucleotide-dependent conformational change [4], this region might act in an analogous fashion to the myosin converter, which amplifies small conformational changes in the myosin catalytic core [5,6].

Adenosine Triphosphatases↗