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N Coleman

Publications and source records attributed to N Coleman.

At least 37 records · Page 2Linked to original sources
PubMed2002

Early recurrence of benign meningioma correlates with expression of mini-chromosome maintenance-2 protein.

We have investigated the potential utility of monoclonal antibodies against mini-chromosome maintenance-2 protein (Mcm2) in predicting meningioma recurrence. MCM proteins are members of the DNA-binding prereplicative complex and are essential for eukaryotic DNA replication. They are present throughout the cell cycle, but are down-regulated in quiescence and cell differentiation, making them specific markers of proliferating cells. We analysed 10 benign meningiomas that subsequently recurred within a 5-year period, together with 20 matched non-recurrent benign meningiomas. There was no significant correlation between histological subtype, mitotic count or Ki-67 labelling index and tumour recurrence. We observed that whilst the average Mcm2 labelling index (LI) of the tumour section as a whole (LI(Ave)) is not significantly different between recurrent and nonrecurrent meningiomas, the Mcm2 labelling index in the area of highest proliferative activity within the tumour section (LI(Max)) is significantly higher in recurrent meningiomas (p < 0.0001). Seven out of the 10 recurrent meningiomas displayed a Mcm2 LI((Max) greater than 30%, compared to 0 out of 20 for non-recurrent tumours. In conclusion, these results suggest that analysis of Mcm2 expression may facilitate identification of patients with a high risk of meningioma recurrence, for whom adjuvant radiotherapy may be of benefit.

Adult↗
PubMed2002

Ewing's tumour: novel recurrent chromosomal abnormalities demonstrated by molecular cytogenetic analysis of seven cell lines and one primary culture.

Conventional cytogenetics has led to the identification of the primary t(11;22)(q24;q12) translocation in the Ewing's family of tumours, and to the demonstration of certain recurring secondary aberrations that may contribute to neoplastic progression. Other important cytogenetic abnormalities may previously have been overlooked due to the limited resolution of chromosome banding. Here, we have applied the molecular cytogenetic techniques of spectral karyotyping, multiplex-fluorescence in situ hybridisation and comparative genomic hybridisation to the characterisation of seven Ewing's tumour cell lines and one primary culture. These complementary techniques have enabled us to produce a detailed description of the karyotypes of the cell lines and to demonstrate recurring numerical and structural abnormalities. In particular, we have identified a novel, unbalanced translocation involving chromosomes 16 and 17 in three of eight samples, including the primary culture. The unbalanced translocation was associated with comparative genomic hybridisation evidence of loss of 16q and 17p, copy number imbalances that were seen in five and four of the eight samples respectively. Recurrent breakpoints at 16p11.2, 16q11.1, 17p11.2 and 17q11.2 were identified. Our findings indicate that chromosomes 16 and 17 should be investigated further in the search for genes involved in the development of Ewing's family tumours.

Chromosome Aberrations↗
PubMed2001

DC-SIGNR, a DC-SIGN homologue expressed in endothelial cells, binds to human and simian immunodeficiency viruses and activates infection in trans.

DC-SIGN, a C-type lectin expressed on the surface of dendritic cells (DCs), efficiently binds and transmits HIVs and simian immunodeficiency viruses to susceptible cells in trans. A DC-SIGN homologue, termed DC-SIGNR, has recently been described. Herein we show that DC-SIGNR, like DC-SIGN, can bind to multiple strains of HIV-1, HIV-2, and simian immunodeficiency virus and transmit these viruses to both T cell lines and human peripheral blood mononuclear cells. Binding of virus to DC-SIGNR was dependent on carbohydrate recognition. Immunostaining with a DC-SIGNR-specific antiserum showed that DC-SIGNR was expressed on sinusoidal endothelial cells in the liver and on endothelial cells in lymph node sinuses and placental villi. The presence of this efficient virus attachment factor on multiple endothelial cell types indicates that DC-SIGNR could play a role in the vertical transmission of primate lentiviruses, in the enabling of HIV to traverse the capillary endothelium in some organs, and in the presentation of virus to CD4-positive cells in multiple locations including lymph nodes.

Amino Acid Sequence↗
PubMed2001

Early genetic events in HPV immortalised keratinocytes.

Cancer of the uterine cervix (CaCx) is the second most common cancer in women worldwide. More than 99% of all cervical cancers contain high-risk human papillomaviruses (HPVs), with type 16 predominating. HPV infection alone is not sufficient for neoplastic progression; the HPV-infected cell must undergo additional genetic changes. Cytogenetic analysis of CaCx has been limited due to difficulties in obtaining good-quality banded chromosome preparations. Oncogenic HPVs immortalise primary genital keratinocytes in vitro, and evidence suggests that the molecular genetic and cytogenetic abnormalities observed in HPV immortalised cells reflect the in vivo changes. Therefore, these lines represent suitable models for HPV-induced carcinogenesis. We have used both spectral karyotyping (SKY) and multiplex-FISH (M-FISH) analysis to identify karyotypic changes in HPV-16 immortalised keratinocyte cell lines and established CaCx lines. SKY and M-FISH identified chromosomal abnormalities in all cell lines examined, with a translocation of chromosome 10 or i(10q) occurring in 9 of the 12 cell lines investigated. Further studies with chromosome 10 band-specific probes identified the translocation event as involving 10q with the breakpoint at 10p11.2 in some cell lines or 10q11.2 in others. The pericentric region of chromosome 10 is known to contain duplicated sequences flanking the centromeric satellites. The duplicated sequences contain many zinc finger transcription factor encoding genes and disruption of these in HPV immortalised cell lines may alter the transcription with consequences for both cellular and viral gene expression.

Aneuploidy↗
PubMed2001

Placental expression of DC-SIGN may mediate intrauterine vertical transmission of HIV.

Mechanisms of transplacental transmission of human immunodeficiency virus (HIV) are poorly understood. DC-SIGN is a C-type lectin able to bind HIV gp120 with high affinity, mediating HIV adsorption to the surface of dendritic cells for up to several days. Via this mechanism, DC-SIGN significantly enhances the infection of CD4(+) co-receptor (CCR5 or CXCR4)(+) T lymphocytes in trans. In this study, DC-SIGN-specific serum was developed to investigate the cell type responsible for the high level of DC-SIGN RNA expression previously observed in the placenta. DC-SIGN expression was shown on CD68(+) HLA-II(+) CD14(low) S100(+/-) CD83(-) CD86(-) cmrf-44(-) villous cells consistent with Hofbauer cells and also on CD68(+) HLA-II(+) CD14(high) S100(-) CD83(-) CD86(-) cmrf-44(-) decidual macrophages. The DC-SIGN(+) Hofbauer cells co-express CD4 and the chemokine receptors, CCR5 and CXCR4, observations which may account for the ability of these cells to become infected with HIV. These fetal DC-SIGN(+) cells are separated by only a layer of trophoblast from both DC-SIGN(+) maternal cells and maternal blood, potential sources of HIV in infected mothers. Previous studies have suggested that this trophoblast layer is frequently breached during pregnancy. It is therefore proposed that DC-SIGN may facilitate the transplacental transmission of HIV.

Antibody Specificity↗
PubMed2001

Tie2 ligands angiopoietin-1 and angiopoietin-2 are coexpressed with vascular endothelial cell growth factor in growing human bone.

Angiogenesis is essential for bone growth and repair. Recent studies have shown that the endothelial-specific mitogen vascular endothelial growth factor (VEGF) is a key regulator of vascular invasion into the growth plate in infant and adolescent animals. In order to identify mechanisms regulating VEGF-induced angiogenesis in growing bone, we have investigated the expression of the angiopoietins (Ang-1 and Ang-2) in human neonatal ribs. Ang-1 and Ang-2 exhibited similar patterns of staining in the growing rib. In the cartilage, expression of Ang-1 and Ang-2 increased with chondrocyte maturation. Ang-1, Ang-2, and VEGF were not detected in the resting zone except adjacent to vascular canals, and maximum expression was detected at the cartilage bone interface. In the cartilage, Ang-2 was more highly expressed than Ang-1 or VEGF, with staining observed in the proliferating, hypertrophic, and mineralized zones. In the bone, Ang-1, Ang-2, and VEGF were detected in modeling and remodeling sites. Ang-1 was detected in the majority of osteoblasts, osteoclasts, and in some marrow space cells. Ang-2 was expressed at variable levels by osteoblasts and osteoclasts in modeling and remodeling bone. VEGF was detected in cells at bone surfaces and in the marrow spaces. Strong staining for VEGF was observed in osteoblasts and osteoclasts in modeling and remodeling bone. In the perichondrium, Ang-1, Ang-2, and VEGF were most highly expressed adjacent to the hypertrophic zone and at sites of bone collar formation. In the periosteum, Ang-1, Ang-2, and VEGF expression colocalized with alkaline phosphatase expression. These observations provide the first evidence for the expression of the angiopoietins in growing human bone in vivo. The distribution of Ang-1, Ang-2, and VEGF indicate these factors may play key roles in the regulation of angiogenesis at sites of endochondral ossification, intramembranous ossification, and bone turnover in the growing human skeleton.

Angiopoietin-1↗
PubMed2001

The accuracy of antenatal ultrasound in the detection of facial clefts in a low-risk screening population.

OBJECTIVES: To evaluate the accuracy of prenatal ultrasound in the detection of facial clefts in a low-risk screening population and to report on the outcome of these pregnancies. DESIGN: We retrospectively reviewed antenatal ultrasound records from the obstetric ultrasound department, postnatal records from the regional craniofacial unit and autopsy reports of fetuses over 16 weeks' gestational age from the regional pathology department over a 5-year period (1993-97). Cross-referencing between the three data sets identified all cases of facial clefts. RESULTS: Out of 23 577 live and still births, 30 had facial clefts; four were excluded from the study. Of the remaining 26 cases, 10 had associated major anomalies. There were 19 live births and seven terminations. Six of the seven terminations had other major abnormalities. Our detection rate for cleft lip and palate was 93% and the detection rate for isolated cleft palate was 22%. Isolated cleft lip was detected in 67% of cases. The overall detection rate for facial clefts was 65%. CONCLUSION: From our results and a review of the literature it is clear that before standards can be set we need to define which facial clefts are sonographically demonstrable. Our data provide information for effective counseling and setting of standards for clinical practice.

Abnormalities, Multiple↗
PubMed2001

Cellular characteristics of nipple aspiration fluid during the menstrual cycle in healthy premenopausal women.

Cellular characteristics of nipple aspiration fluid during the menstrual cycle in healthy premenopausal women Fifteen healthy premenopausal female volunteers underwent weekly nipple aspiration of ductal fluid from both breasts during two menstrual cycles to investigate the variability of the cellular profile of the ductal fluid. Ductal fluid was successfully obtained using breast massage and nipple-areolar suction from 247/280 (89%) breasts. 83% of samples available for cytological analysis were cellular and 30% of cellular aspirates contained ductal epithelial cells identified using standard morphological criteria. No significant variation in cell number or cell type was identified during the menstrual cycle. All samples tested had an 'H' score of zero for oestrogen receptor. Seven out of 14 women expressed the proliferation marker Mcm-2 in the cells of at least one of the specimens, with no evidence of a menstrual cycle influence on expression. In conclusion, the cellular profile of breast ductal fluid did not vary consistently during the menstrual cycle, permitting future breast cancer screening studies incorporating serial nipple aspirations to be performed independent of the phase of the cycle.

Adult↗
PubMed2001

Antral motility measurements by magnetic resonance imaging.

Magnetic resonance imaging has been recently proposed as a promising, noninvasive technique to assess the motility of the gastric antrum. However, so far the reproducibility and dependence on test meal composition has not been evaluated. In this study, snapshot echo-planar magnetic resonance imaging was used to measure the frequency, propagation speed and percentage occlusion of antral contractions in 28 healthy volunteers. They were fed either liquid (n=12), mixed liquid/solid (n=8) or mixed viscous/solid (n=8) nutrient (1350 kJ) test meals, and a total of 208 motility measurements were performed. No effect of meal type on antral motility parameters was observed. Antral contraction frequency was 3.0 +/- 0.2 min(-1) (mean +/- SD, n=164), propagation speed was 1.6 +/- 0.2 mm s(-1) (n=164) and the percentage occlusion was 58 +/- 14% (n=76). Overall, 21% of measurements did not provide useful antral motility data, because, in the supine position, the antrum was not filled by the test meal. Simple methods to overcome this and reduce scanning time to a minimum are proposed. The results show that the noninvasive magnetic resonance imaging evaluation of antral motility is accurate and reproducible and has potential to become a standard tool for such investigations.

Adolescent↗
PubMed2001

cis Expression of DC-SIGN allows for more efficient entry of human and simian immunodeficiency viruses via CD4 and a coreceptor.

DC-SIGN is a C-type lectin expressed on dendritic cells and restricted macrophage populations in vivo that binds gp120 and acts in trans to enable efficient infection of T cells by human immunodeficiency virus type 1 (HIV-1). We report here that DC-SIGN, when expressed in cis with CD4 and coreceptors, allowed more efficient infection by both HIV and simian immunodeficiency virus (SIV) strains, although the extent varied from 2- to 40-fold, depending on the virus strain. Expression of DC-SIGN on target cells did not alleviate the requirement for CD4 or coreceptor for viral entry. Stable expression of DC-SIGN on multiple lymphoid lines enabled more efficient entry and replication of R5X4 and X4 viruses. Thus, 10- and 100-fold less 89.6 (R5/X4) and NL4-3 (X4), respectively, were required to achieve productive replication in DC-SIGN-transduced Jurkat cells when compared to the parental cell line. In addition, DC-SIGN expression on T-cell lines that express very low levels of CCR5 enabled entry and replication of R5 viruses in a CCR5-dependent manner, a property not exhibited by the parental cell lines. Therefore, DC-SIGN expression can boost virus infection in cis and can expand viral tropism without affecting coreceptor preference. In addition, coexpression of DC-SIGN enabled some viruses to use alternate coreceptors like STRL33 to infect cells, whereas in its absence, infection was not observed. Immunohistochemical and confocal microscopy data indicated that DC-SIGN was coexpressed and colocalized with CD4 and CCR5 on alveolar macrophages, underscoring the physiological significance of these cis enhancement effects.

CD4 Antigens↗
PubMed2001

Molecular cytogenetic analysis consistently identifies translocations involving chromosomes 1, 2 and 15 in five embryonal rhabdomyosarcoma cell lines and a PAX-FOXO1A fusion gene negative alveolar rhabdomyosarcoma cell line.

Rhabdomyosarcoma in children is a "small round blue cell tumour" that displays skeletal muscle differentiation. Two main histological variants are recognised, alveolar (ARMS) and embryonal (ERMS) rhabdomyosarcoma. Whereas consistent chromosome translocations characteristic of ARMS have been reported, no such cytogenetic abnormality has yet been described in ERMS. We have used multiple colour chromosome painting to obtain composite karyotypes for five ERMS cell lines and one PAX-FOXO1A fusion gene negative ARMS. The cell lines were assessed by spectral karyotyping (SKY), tailored multi-fluorophore fluorescence in situ hybridisation (M-FISH) using series of seven colour paint sets generated to examine specific abnormalities, and comparative genomic hybridisation (CGH). This approach enabled us to obtain karyotypes of the cell lines in greater detail than previously possible. Several recurring cytogenetic abnormalities were demonstrated, including translocations involving chromosomes 1 and 15 and chromosomes 2 and 15, in 4/6 and 2/6 cell lines respectively. All six cell lines demonstrated abnormalities of chromosome 15. Translocations between chromosomes 1 and 15 have previously been recorded in two primary cases of ERMS by conventional cytogenetics. Analysis of the translocation breakpoints may suggest mechanisms of ERMS tumourigenesis and may enable the development of novel approaches to the clinical management of this tumour.

Child↗
PubMed2000

Development of T-leukaemias in CD45 tyrosine phosphatase-deficient mutant lck mice.

The CD45 tyrosine phosphatase lowers T-cell antigen receptor signalling thresholds by its positive actions on p56(lck) tyrosine kinase function. We now show that mice expressing active lck(F505) at non-oncogenic levels develop aggressive thymic lymphomas on a CD45(-/-) background. CD45 suppresses the tumorigenic potential of the kinase by dephosphorylation of the Tyr394 autophosphorylation site. In CD45(-/-) thymocytes the kinase is switched to a hyperactive oncogenic state, resulting in increased resistance to apoptosis. Transformation occurs in early CD4(-)CD8(-) thymocytes during the process of TCR-beta chain rearrangement by a recombinase-independent mechanism. Our findings represent the first example in which a tyrosine phosphatase in situ prevents the oncogenic actions of a SRC: family tyrosine kinase.

Animals↗
PubMed2000

Assessment, re-design and evaluation of changes to the driver's cab in a suburban electric train.

A new type of electric train, called the Tangara, began replacing older trains on the Sydney city and suburban network in 1990. Shortly afterwards, some of the train drivers began reporting pain in the arms while driving the new train. The Ergonomics Unit of Worksafe Australia was then engaged to identify and assess ergonomic problems in the driver's cab. This process included direct observation of drivers at work, distribution of a self-administered questionnaire to all drivers, and analysis of anthropometric problems using a computer-aided design package. The analysis of 193 completed questionnaires and the problems shown by the design study were used in developing an improved design. A mock-up of the modified cab was made and tried out by 134 drivers whose comments led to further changes. The modified design was applied to new production, and existing cabs were modified during major maintenance. By 1996, 96% of the driver's cabs were to the new design. An evaluation of the new design was undertaken using written questionnaires, which were completed by 227 drivers. The results were strongly in favour of the new design, showing the effectiveness of the ergonomic modifications.

Computer-Aided Design↗
PubMed2000

Analysis of pilocytic astrocytoma by comparative genomic hybridization.

Very little is known about genetic abnormalities involved in the development of pilocytic astrocytoma, the most frequently occurring brain tumour of childhood. We have analysed 48 pilocytic astrocytoma specimens using comparative genomic hybridization. Only five of 41 tumours from children showed abnormalities detectable by comparative genomic hybridization, and in each case this represented gain of a single chromosome. Interestingly, two of seven tumours from adults showed abnormalities, which were multiple and relatively complex. Six of the seven tumours showing abnormalities were from female patients (two adults and four children). The most frequently detectable abnormality was gain of 9q34.1-qter, which was present in three cases (two adult and one paediatric).

Adolescent↗
PubMed2000

The E1E4 protein of human papillomavirus type 16 associates with a putative RNA helicase through sequences in its C terminus.

Human papillomavirus type 16 (HPV16) infects cervical epithelium and is associated with the majority of cervical cancers. The E1E4 protein of HPV16 but not those of HPV1 or HPV6 was found to associate with a novel member of the DEAD box protein family of RNA helicases through sequences in its C terminus. This protein, termed E4-DBP (E4-DEAD box protein), has a molecular weight of 66,000 (66K) and can shuttle between the nucleus and the cytoplasm. It binds to RNA in vitro, including the major HPV16 late transcript (E1E4. L1), and has an RNA-independent ATPase activity which can be partially inhibited by E1E4. E4-DBP was detectable in the cytoplasm of cells expressing HPV16 E1E4 (in vivo and in vitro) and could be immunoprecipitated as an E1E4 complex from cervical epithelial cell lines. In cell lines lacking cytoplasmic intermediate filaments, loss of the leucine cluster-cytoplasmic anchor region of HPV16 E1wedgeE4 resulted in both proteins colocalizing exclusively to the nucleoli. Two additional HPV16 E1E4-binding proteins, of 80K and 50K, were identified in pull-down experiments but were not recognized by antibodies to E4-DBP or the conserved DEAD box motif. Sequence analysis of E4-DBP revealed homology in its E4-binding region with three Escherichia coli DEAD box proteins involved in the regulation of mRNA stability and degradation (RhlB, SrmB, and DeaD) and with the Rrp3 protein of Saccharomyces cerevisiae, which is involved in ribosome biogenesis. The synthesis of HPV16 coat proteins occurs after E1E4 expression and genome amplification and is regulated at the level of mRNA stability and translation. Identification of E4-DBP as an HPV16 E1E4-associated protein indicates a possible role for E1E4 in virus synthesis.

Cell Nucleus↗
PubMed2000

A novel and consistent amplicon at 13q31 associated with alveolar rhabdomyosarcoma.

Rhabdomyosarcomas are the most common soft-tissue sarcoma found in children. The alveolar subtype is clinically more aggressive than the embryonal subtype. In addition to the presence of specific chromosome translocations and associated fusion gene products in a high proportion of the alveolar subtype, we previously showed that tumors with this histology frequently show evidence of genomic amplification. Here, we substantially extended the number of alveolar rhabdomyosarcoma samples examined by comparative genomic hybridization analysis. Regions of loss were noted, including the smallest overlapping regions corresponding to 16q, 17/17p, and 9q32-34, in 16%, 10%, and 10% of cases, respectively (44 primary samples/6 cell lines). Amplification or gain at 12q13-15 in the region of the MDM2/GLI1/SAS/CDK4 loci and 2p24 at the MYCN locus was found in 28% and 32% of cases, respectively. Single amplicons were found at locations that in other samples showed consistent gain, including the regions 5q15-23, 7q21-31, 11p11-14, 17q23-24, and 20q13, and amplification was found in two cases at 15q24-26. However, most striking was a novel region of amplification or gain at 13q31 in 19% of cases (51 primary samples/6 cell lines). This indicates that a gene or genes at 13q31 are significant in the development or progression of alveolar rhabdomyosarcoma.

Adolescent↗