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Biomedical subjects

R Carpenter

Publications and source records attributed to R Carpenter.

At least 73 records · Page 4Linked to original sources
PubMed1997

Dual role for fimbriata in regulating floral homeotic genes and cell division in Antirrhinum.

The fimbriata (fim) gene of Antirrhinum affects both the identity and arrangement of organs within the flower, and encodes a protein with an F-box motif. We show that FIM associates with a family of proteins, termed FAPs (FIM-associated proteins), that are closely related to human and yeast Skp1 proteins. These proteins form complexes with F-box-containing partners to promote protein degradation and cell cycle progression. The fap genes are expressed in inflorescence and floral meristems in a pattern that incorporates the domain of fim expression, supporting an in vivo role for a FIM-FAP complex. Analysis of a series of novel fim alleles shows that fim plays a key role in the activation of organ identity genes. In addition, fim acts in the regions between floral organs to specify the correct positioning and maintenance of morphological boundaries. Taking these results together, we propose that FIM-FAP complexes affect both gene expression and cell division, perhaps by promoting selective degradation of regulatory proteins. This may provide a mechanism by which morphological boundaries can be aligned with domains of gene expression during floral development.

Amino Acid Sequence↗
PubMed1997

Inflorescence commitment and architecture in Arabidopsis.

Flowering plants exhibit one of two types of inflorescence architecture: indeterminate, in which the inflorescence grows indefinitely, or determinate, in which a terminal flower is produced. The indeterminate condition is thought to have evolved from the determinate many times, independently. In two mutants in distantly related species, terminal flower 1 in Arabidopsis and centroradialis in Antirrhinum, inflorescences that are normally indeterminate are converted to a determinate architecture. The Antirrhinum gene CENTRORADIALIS (CEN) and the Arabidopsis gene TERMINAL FLOWER 1 (TFL1) were shown to be homologous, which suggests that a common mechanism underlies indeterminacy in these plants. However, unlike CEN, TFL1 is also expressed during the vegetative phase, where it delays the commitment to inflorescence development and thus affects the timing of the formation of the inflorescence meristem as well as its identity.

Amino Acid Sequence↗
PubMed1997

Altered cell-matrix contact: a prerequisite for breast cancer metastasis?

The integrins are receptors that regulate interaction between epithelial cells and the extracellular matrix. Previous studies have shown that a reduction in the expression of the alpha2beta1, alpha3beta1, alpha6beta1, alpha(v)beta1 and alpha(v)beta5 integrins in primary breast cancer is associated with positive nodal status. In order to assess the functional significance of altered integrin expression, primary breast cancer cells were derived from individual patients with known tumour characteristics using immunomagnetic separation. Purified human fibronectin, vitronectin, laminin and type IV collagen were used to represent the principal extracellular matrix proteins in an in vitro adhesion assay. Primary breast cancer cells from lymph node-positive patients were significantly less adhesive to each of the matrix proteins studied (P<0.001, Mann-Whitney U-test). Matrix adhesion of primary breast cancer cells from node-negative patients was inhibited by appropriate integrin monoclonal antibodies (P<0.001, paired Wilcoxon test). Adhesion to fibronectin, vitronectin and laminin, but not type IV collagen, was influenced by the inhibitor arginine-glycine-aspartate, suggesting that breast cancer cell recognition of collagen IV is mediated through alternative epitopes. Weak matrix adhesion correlated with loss of integrin expression in tissue sections from corresponding patients assessed using immunohistochemistry. This study demonstrates a link between altered integrin expression and function in primary breast cancers predisposed to metastasize.

Adult↗
PubMed1996

Origin of floral asymmetry in Antirrhinum.

Dorsoventral asymmetry in flowers is thought to have evolved many times from a radially symmetrical ancestral condition. The first gene controlling floral asymmetry, cycloidea in Antirrhinum, has been isolated. The cycloidea gene is expressed at a very early stage in dorsal regions of floral meristems, where it affects growth rate and primordium initiation. Expression continues through to later stages in dorsal primordia to affect the asymmetry, size and cell types of petals and stamens.

Alleles↗
PubMed1996

Control of inflorescence architecture in Antirrhinum.

Flowering plants exhibit two types of inflorescence architecture: determinate and indeterminate. The centroradialis mutation causes the normally indeterminate inflorescence of Antirrhinum to terminate in a flower. We show that centroradialis is expressed in the inflorescence apex a few days after floral induction, and interacts with the floral-meristem-identity gene floricaula to regulate flower position and morphology. The protein CEN is similar to animal proteins that associate with lipids and GTP-binding proteins. We propose a model for how different inflorescence structures may arise through the action and evolution of centroradialis.

Amino Acid Sequence↗
PubMed1996

Growth enhancement of implanted human colorectal cancer cells by the addition of fibroblasts in vivo.

The effect of fibroblasts on the growth of HT29 human colorectal cancer cells was used to study stromal modulation of tumour growth dynamics. Fibroblasts were isolated from rat livers, 1, 2.5 and 4 days after two-thirds partial hepatectomy and from normal livers. Cells harvested 2.5 and 4 days after hepatectomy ('fast' fibroblasts) had a significantly faster growth rate in vitro than those harvested on day 1 or those from normal livers (P < 0.02). The fibroblasts were inoculated with HT29 colorectal cancer cells into nude mice. Controls received cancer cells with or without a fibroblast cell line (C3H10T 1/2). At 3 weeks both tumour take and growth (size) were significantly greater in the group inoculated with cancer cells and 'fast' fibroblasts than in the other groups (tumour take 100 versus 42-75 per cent, P < 0.03; median tumour size 3.5 versus 0.3-0.4 g, P < 0.02). In conclusion, tumour growth is enhanced by fibroblasts, especially by those derived from actively regenerating liver. It is suggested that the stimulation is not only mechanical but may also involve a humoral mechanism.

Animals↗
PubMed1996

Integrin expression in breast cancer cytology: a novel predictor of axillary metastasis.

The integrins are heterodimeric transmembrane receptors of varying alpha and beta subunits that modulate cell adhesion to each other and to the extracellular matrix. Loss of integrin expression on primary breast cancer frozen sections measured by immunohistochemistry may be related to the presence of axillary metastasis. The clinical application of this finding would be increased if integrin expression could also be shown to be reliably measured on breast cancer cells obtained by fine needle aspiration cytology. Axillary operations may be planned as a single stage procedure from outpatients, and neoadjuvant therapy protocols may be developed without surgery to the axilla. Expression of the alpha 1, alpha 2, alpha 3, alpha 6, alpha v, beta 1, beta 3 and beta 5 integrin subunits were measured by immunohistochemistry and immunocytochemistry in 58 patients. Integrin measurement by both these methods were found to be closely associated using the kappa-test. Loss of expression of the alpha 1, alpha 2, alpha 3, alpha 6, alpha v, beta 1 and beta 5 integrin subunits measured by cytology and histology were each related to positive nodal status (chi(2) test). Measuring integrin expression on cytology is of clinical value and may prove to have prognostic significance.

Adult↗
PubMed1996

Molecular probes for sweeteners: immunorecognition of superpotent guanidinium compounds.

Monoclonal antibodies (MAb) were made to two different superpotent guanidino sweet tasting ligands, N-(p-cyanophenyl)-N'-(diphenylmethyl)-guanidineacetic acid and N-(p-cyanophenyl)-N'-(cyclooctyl)-guanidineacetic acid. In the present study we examined the binding specificity of three MAb clones (denoted as NC10.7, NC10.13, and NC37.3). The isotypes of these MAb were determined to be IgG1 kappa for NC10.7 and NC37.3, while NC10.13 was IgG2b, kappa. The dissociation constants for the MAb were 19 nM (NC10.7), 28 nM (NC10.13), and 16 nM (NC37.3). The binding specificity of each MAb was characterized by a competitive inhibition radioimmunoassay using related sweetener analogues. Antibodies to this family of sweet tasting compounds may be useful probes for the study of sweet taste chemistry and identification of novel sweet taste ligands.

Acetates↗
PubMed1996

Induction, recovery, and safety characteristics of sevoflurane in children undergoing ambulatory surgery. A comparison with halothane.

BACKGROUND: Sevoflurane is an inhalational anesthetic with characteristics suited for use in children. To determine whether the induction, recovery, and safety characteristics of sevoflurane differ from those of halothane, the following open-labeled, multicenter, randomized, controlled, phase III study in children undergoing ambulatory surgery was designed. METHODS: Three hundred seventy-five children, ASA physical status 1 or 2, were randomly assigned in a 2:1 ratio to receive either sevoflurance or halothane, both in 60% N2O and 40% O2. Anesthesia was induced using a mask with an Ayre's t piece or Bain circuit in four of the centers and a mask with a circle circuit in the fifth center. Maximum inspired concentrations during induction of anesthesia were 7% sevoflurane and 4.3% halothane. Anesthesia was maintained by spontaneous ventilation, without tracheal intubation. End-tidal concentrations of both inhalational anesthetics were adjusted to 1.0 MAC for at least 10 min before the end of surgery. Induction and recovery characteristics and all side effects were recorded. The plasma concentration of inorganic fluoride was measured at induction of and 1 h after anesthesia. RESULTS: During induction of anesthesia, the time to loss of the eyelash reflex with sevoflurane was 0.3 min faster than with halothane (P < 0.001). The incidence of airway reflex responses was similar, albeit infrequent with both anesthetics. The total MAC.h exposure to sevoflurane was 11% less than the exposure to halothane (P < 0.013), although the end-tidal MAC multiple during the final 10 min of anesthesia was similar for both groups. Early recovery as evidenced by the time to response to commands after sevoflurane was 33% more rapid than it was after halothane (P < 0.001), although the time to discharge from hospital was similar for both anesthetics. The mean ( +/- SD) plasma concentration of inorganic fluoride 1 h after discontinuation of sevoflurane was 10.3 +/- 3.5 microM. The overall incidence of adverse events attributable to sevoflurane was similar to that of halothane, although the incidence of agitation attributable to sevoflurane was almost threefold greater than that attributable to halothane (P < 0.004). CONCLUSIONS: Sevoflurane compared favorably with halothane. Early recovery after sevoflurane was predictably more rapid than after halothane, although this was not reflected in a more rapid discharge from the hospital. The incidence of adverse events was similar for both anesthetics. Clinically, the induction, recovery, and safety characteristics of sevoflurane and halothane are similar. Sevoflurane is a suitable alternative to halothane for use in children undergoing minor ambulatory surgery.

Ambulatory Surgical Procedures↗
PubMed1996

Origin of allelic diversity in antirrhinum S locus RNases.

In many plant species, self-incompatibility (SI) is genetically controlled by a single multiallelic S locus. Previous analysis of S alleles in the Solanaceae, in which S locus ribonucleases (S RNases) are responsible for stylar expression of SI, has demonstrated that allelic diversity predated speciation within this family. To understand how allelic diversity has evolved, we investigated the molecular basis of gametophytic SI in Antirrhinum, a member of the Scrophulariaceae, which is closely related to the Solanaceae. We have characterized three Antirrhinum cDNAs encoding polypeptides homologous to S RNases and shown that they are encoded by genes at the S locus. RNA in situ hybridization revealed that the Antirrhinum S RNase are primarily expressed in the stylar transmitting tissue. This expression is consistent with their proposed role in arresting the growth of self-pollen tubes. S alleles from the Scrophulariaceae form a separate group from those of the Solanaceae, indicating that new S alleles have been generated since these families separated (approximately 40 million years). We propose that the recruitment of an ancestral RNase gene into SI occurred during an early stage of angiosperm evolution and that, since that time, new alleles subsequently have arisen at a low rate.

Amino Acid Sequence↗
PubMed1996

Pathways for inflorescence and floral induction in Antirrhinum.

The presentation of flowers on a modified stem, the inflorescence, requires the integration of several aspects of meristem behaviour. In Antirrhinum, the inflorescence can be distinguished by its flowers, hairy stem, modified leaves, short internodes and spiral phyllotaxy. We show, by a combination of physiological, genetical and morphological analysis, that the various aspects of the inflorescence are controlled by three pathways. The first pathway, depends on expression of the floricaula gene, and is rapidly and discretely induced by exposure to long daylength. Activation of this pathway occurs in very young axillary meristems, resulting in a floral identity. In addition, the length of subtending leaves and hairiness of the stem are partially modified. The second pathway affects leaf size, internode length, and stem hairiness, but does not confer floral meristem identity. This pathway is induced by long daylength, but not as rapidly or discretely as the floricaula-dependent pathway. The third pathway controls the switch in phyllotaxy from decussate to spiral and is activated independently of daylength. The coordination of these three programmes ensures that apical and axillary meristem behaviour is integrated.

Base Sequence↗
PubMed1996

The prevalence of seat belt use in Jamaica. An observational study.

An observational cross-sectional survey showed that 21.1% of private motor vehicle drivers and 13.5% of front seat passengers voluntarily wore seat belts in Kingston, Jamaica, where there is no law requiring this. Rear passenger utilisation was not examined. Compared to males, females were significantly more likely to wear seat belts when driving but not as front seat passengers. Of all motor vehicles examined, 10.1% were not equipped with seat belts. The oldest group of vehicles were mostly not fitted with seat belts. Drivers of older vehicles were significantly less likely to use seat belts even when the vehicles were equipped with belts. Implementation of legislation can reduce mortality, morbidity and costs from road traffic accidents which are relatively frequent in Jamaica. Male drivers, drivers of older vehicles and all passengers may require specific targeting in an educational and enforcement campaign should legislation, which is highly desirable, be implemented.

Adult↗
PubMed1995

Cell lineage patterns and homeotic gene activity during Antirrhinum flower development.

BACKGROUND: Homeotic genes controlling the identity of flower organs have been characterized in several plant species. To determine whether cells expressing these genes are specified to follow particular developmental fates, we have studied the pattern of cell lineages in developing flowers of Antirrhinum. Each flower has four whorls of organs, and progenitor cells of these can be marked at particular stages of development using a temperature-sensitive transposon. This allows the cell lineages in the flower to be followed, as well as giving information about rates of cell division. RESULTS: We show here that, prior to the emergence of organ primordia, cells in the floral meristem have not been allocated organ identities. After this time, lineage restrictions arise between whorls, correlating with the onset of expression of genes that control organ identity. A further lineage restriction appears slightly later on, between the dorsal and ventral surfaces of the petal. Our results further suggest that the rates of cell division fluctuate during key stages of meristern development, perhaps as a consequence of meristem-identity gene expression. CONCLUSIONS: The patterns of lineage restriction and organ-identity gene expression in early floral meristems are consistent with some cells being allocated specific identities at about this stage of development. Plant cells cannot move relative to each other, so lineage restrictions in plants may reflect particular orientations and/or rates of growth at boundary regions.

Genes, Homeobox↗
PubMed1995

In vitro regulation of human breast cancer cell adhesion and invasion via integrin receptors to the extracellular matrix.

The extracellular matrix consists of the interstitium and the basement membrane. Cellular interaction with fibronectin, laminin and collagen provides a possible mechanism by which cancer cells adhere, invade and metastasize. The integrins are a major family of adhesion molecules that recognize epitopes on the extracellular matrix as ligands. These include the alpha 2 beta 1, alpha 3 beta 1, alpha v beta 1 and alpha v beta 5 integrins, most of which were found to be expressed on MCF-7, T47D, MDA-MB-231, ZR75-1 and Hs578T breast cancer cell lines. Each cell line adhered to the matrix proteins in a dose-dependent manner and was inhibited by monoclonal antibodies against relevant integrins. Only Hs578T was significantly invasive through fibronectin but both Hs578T and MDA-MB-231 invaded through laminin and type IV collagen in an in vitro assay. The invasive potential of these cell lines could be inhibited by integrin antibodies added to cells before incubation, but the addition of antibodies after cells were allowed to adhere to the matrix failed to inhibit invasion. Inhibition of cellular adhesion to the matrix reduced the invasive potential of breast cancer cell lines. As integrin antibodies inhibit cell invasion in vitro, the integrins may be of potential value as antitumour therapeutic agents.

Antibodies, Monoclonal↗
PubMed1995

Benign biopsies in the prevalent round of breast screening: a review of 137 cases.

In the first round of the National Health Service Breast Screening Programme, 35,533 women attended for screening at the two breast screening units served by St Bartholomew's Hospital. Further assessment was necessary in 2212 women (6.2%), of whom 412 (1%) subsequently underwent surgical biopsy. Of these 137 had benign lesions. The predominant mammographic abnormality leading to biopsy was microcalcification in 55, a mass in 48, parenchymal asymmetry in 18 and architectural distortion in 16. Histology revealed fibrocystic change in 66, fibroadenoma in 27, radial scar/complex sclerosing lesion in 23, atypical ductal hyperplasia only in eight, and a variety of unusual benign lesions in 13. In an attempt to determine criteria which would minimize unnecessary biopsy of benign lesions in future, the mammographic and cytological features of these benign lesions were reviewed and compared with the final histology. The most common diagnostic problems were clustered and variable microcalcification, the radial scar/complex sclerosing lesion, and mammographic features shown to be atypical hyperplasia on histology.

Biopsy↗
PubMed1995

Integrin expression in primary breast cancer and its relation to axillary nodal status.

BACKGROUND: Integrins are transmembrane receptors that modulate cell adhesion. Each is a heterodimer of varying alpha and beta subunits. In malignancy, loss of integrin expression may result in less adhesive cells more likely to metastasize. Our aim was to characterize the integrins in human breast tissue and to examine the relationship between integrin expression and nodal metastasis in breast cancer. METHODS: Cryostat sections from 12 benign and 61 malignant (50 ductal and 11 lobular) samples were stained by the avidin-biotin complex method with monoclonal antibodies to the beta 1, beta 3, beta 4, and beta 5 subfamilies. All slides were read by two independent assessors with consensus agreement. Integrin expression was compared to variables by using the chi-squared test with Yates' correction and multivariate analysis based on logistic regression. RESULTS: All integrin subunits studied were significantly reduced on breast cancer compared with benign cells (chi-squared test) but were not related to tumor differentiation. Loss of alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, alpha 6 beta 1, alpha v beta 1, and alpha v beta 5 were related to the presence of axillary metastasis. Independently the integrins were of limited clinical value as predictors of axillary spread. However, on multivariate analysis the combination of beta 1, alpha v, alpha 1, tumor size, and vascular invasion gave a cumulative overall accuracy in predicting nodal disease of 97%. CONCLUSIONS: Integrin expression is reduced in breast cancer and may explain tumor progression. Measuring the integrins might thus provide a means of selection for aggressive axillary treatment.

Adult↗
PubMed1995

Modulation of very late activation-2 laminin receptor function in breast cancer metastasis.

BACKGROUND: Very late activation-2 (VLA-2) is an integrin receptor for laminin that consists of an alpha 2- and a beta 1-subunit. In human breast cancer, down-regulation of VLA-2 expression is related to positive nodal status. The functional significance of altered integrin expression in individual patients has never been investigated. To test the hypothesis that less adhesive primary breast cancer cells were predisposed to metastasize, variation in VLA-2 modulation of cell attachment to laminin with nodal status was studied. METHODS: Integrin expression was measured by means of immunohistochemistry on cryostat sections. Primary breast cancer cells were isolated by enzymatic disaggregation and immunomagnetic separation. Cell adhesion to laminin was evaluated in an in vitro assay, and the effect of monoclonal antibodies against the component subunits of VLA-2 was assessed. RESULTS: Adhesion of primary breast cancer cells from women with positive nodes to laminin was significantly reduced compared with women with negative nodes (p < 0.001, Wilcoxon signed rank test). VLA-2 antibodies inhibited primary breast cancer cell attachment of women with negative nodes but not women with positive nodes. Strong adhesion to laminin was related to node-negative status (chi-squared, 16.33; p < 0.001) and to positive integrin expression (chi-squared, 31.54; p < 0.001). CONCLUSIONS: VLA-2-mediated adhesion of primary breast cancer cells to laminin differs with nodal status. Measurement of VLA-2 expression may thus be of clinical value as a prognostic indicator in the assessment of breast cancer.

Adult↗