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Biomedical subjects

R Carpenter

Publications and source records attributed to R Carpenter.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1995

Perioperative pain management.

The clinical anesthesia, general surgery, and gynecology literature addressing the pathophysiology and management strategies for perioperative pain were reviewed. There are few prospective, randomized studies from which to draw meaningful conclusions. Nevertheless, a theoretical construct has been developed which may help the gynecologic surgeon optimizing pain management. The era of managed care and shorter hospital stays has focused physicians and, in particular, surgeons on elements of patient care that can be addressed and improved. Reducing or eliminating postoperative pain without excessive sedation promotes rapid mobilization and return to self-care. Strategies for pain management can be adopted that reduce postoperative ileus and other adverse reactions to analgesics.

Analgesics↗
PubMed1995

Control of flower development and phyllotaxy by meristem identity genes in antirrhinum.

The flower meristem identity genes floricaula (flo) and squamosa (squa) promote a change in phyllotaxy from spiral to whorled in Antirrhinum. To determine how this might be achieved, we have performed a combination of morphological, genetic, and expression analyses. Comparison of the phenotypes and RNA expression patterns of single and double mutants with the wild type showed that flo and squa act together to promote flower development but that flo is epistatic to squa with respect to early effects on phyllotaxy. We propose that a common process underlies the phyllotaxy of wildtype, flo, and squa meristem development but that the relative timing of primordium initiation or growth is altered. This process depends on two separable events: setting aside zones for potential primordium initiation and partitioning these zones into discrete primordia. Failure of the second event can lead to the formation of continuous double spirals, which are occasionally seen in flo mutants.

Base Sequence↗
PubMed1995

Transposon induced chimeras show that floricaula, a meristem identity gene, acts non-autonomously between cell layers.

Flower meristems comprise several distinct cell layers. To understand the role of cell interactions between and within these layers, we have generated plants chimeric for a key floral homeotic gene, floricaula (flo). These chimeras arose in Antirrhinum by excision of a transposon, restoring flo gene function. Activity of flo in a subset of cell layers gives fertile flowers with an abnormal morphology. This shows that flo can act non-autonomously between layers, although some aspects of its function are impaired. In addition, we show that flo exhibits some cell-autonomy within layers.

Cell Communication↗
PubMed1995

Expression of floricaula in single cell layers of periclinal chimeras activates downstream homeotic genes in all layers of floral meristems.

We show that the flowering sectors on plants mutant for floricaula (flo), a meristem identity gene in Antirrhinum majus, are periclinal chimeras expressing flo in either the L1, L2 or L3 cell layer. Flower morphology is almost normal in L1 chimeras, but altered in L2 and L3 chimeras. Expression of flo in any one cell layer results in the expression of organ identity genes, deficiens (def) and plena (ple) in all three cell layers of the chimeras, showing that flo acts inductively to promote gene transcription. The activation of both def and ple is delayed, and the expression domain of def is reduced, accounting for some of the phenotypic properties of the chimeras. Furthermore, we show that flo exhibits some cell-autonomy with respect to autoregulation.

Amino Acid Sequence↗
PubMed1995

Clinical audit of a specialist symptomatic breast clinic.

The efficient delivery of health care requires vigilant quality assurance. We describe the audit of our symptomatic breast clinic, which includes the option of a one-stop diagnostic service. A total of 134 new and 386 follow-up patients attended over four consecutive clinics. The majority of new referrals (68%) were seen by a consultant surgeon. Urgent referrals were seen significantly sooner than routine referrals (P < 0.001, chi 2-test), and the mean wait from designated appointment to seeing the surgeon was 37.6 (range-68 to 171) min. One-stop investigations were offered to 50 patients; of these, 36 women (72%) had a total wait of less than 2 h. For those not investigated at the same clinic, the mean time until investigations was 6.1 (range 0-36) days and mean recall was 2.7 (range 1-8) weeks. Patients undergoing definitive surgery for cancer (n = 5) were operated on average 14.2 (range 7-27) days after the decision was made in outpatients, while the mean waiting time for non-cancer operations was 49.7 (range 15-98) days. Objective audit on outpatient services is possible and can lead to improvement of services.

Adult↗
PubMed1995

One-stop diagnosis for symptomatic breast disease.

A consultant-led one-stop diagnostic service has been available at a busy symptomatic breast clinic each week at St Bartholomew's Hospital for 18 months. Women can be investigated appropriately using mammography, ultrasonography and cytology with immediate reporting. The aim is to achieve a diagnosis and management plan for each patient at the initial outpatient visit. A prospective audit of four consecutive clinics was undertaken to assess the impact of this service on clinical practice. Fifty patients out of 134 new and 386 follow-up clinic attenders had one-stop investigations. As a result of immediate reporting, 48 (96%) patients had a management decision made at the first outpatient visit, 9 (18%) were offered surgery, and 18 (36%) were discharged with a benign diagnosis and no dominant mass. Four symptomatic cancers were detected and evaluated on a one-stop basis, constituting 8% of the workload of this clinic. The mean wait from designated appointment until surgical consultation was 37.7 min (range -68-171 min) and that for investigation until subsequent clinical review was 56.9 min (range -4-191 min). Thirty-six (72%) one-stop patients had a total wait of less than 2 h and 95% were seen in under 3 h. It is felt that the one-stop clinic allows optimum patient management, minimises anxiety associated with symptomatic breast disease, and maximises utilisation of hospital outpatient resources.

Adult↗
PubMed1995

Primary aortoenteric fistula.

One hundred and thirty-eight patients with abdominal aortic aneurysms were treated by aneurysmorrhaphy over an eleven-year period. Six patients, all male and aged 60-74 years, were found to have developed primary aortoenteric fistulae. Four patients presented with bleeding into the gastrointestinal tract in association with a tender abdominal swelling. In the other two cases, the aneurysm was discovered at emergency laparotomy for gastrointestinal haemorrhage. The presence of the fistula was confirmed at operation in five patients and at autopsy in one. Two patients died, one from a massive gastrointestinal haemorrhage prior to surgery, the other from sepsis complicated by Adult Respiratory Distress Syndrome and renal failure following operation.

Aged↗
PubMed1994

Fimbriata controls flower development by mediating between meristem and organ identity genes.

Two major classes of genes directing flower development have so far been described: early activated genes regulating meristem identity and later acting genes controlling organ identity. Here, we show that the fimbriata (fim) gene acts between these two classes in a sequence of gene activation. The fim gene, originally described in 1930, was cloned by transposon tagging from Antirrhinum majus and encodes a product with no detectable homology to other proteins. Mutations in fim result in partial homeotic transformations of floral organs and in reduced determinacy of the meristem. Expression and function of fim depends on the activity of meristem identity genes, and fim in turn controls the spatial and temporal expression of organ identity genes. The pattern of fim expression defines a new domain of the floral meristem that changes with time in a complementary manner to those of the meristem identity gene floricaula and the organ identity gene plena.

Amino Acid Sequence↗
PubMed1994

Interleukin-8 expression in otitis media.

Based on recent studies in the authors' laboratory on the correlation of cytokines and inflammation in otitis media (OM), the authors hypothesized that in chronic otitis media with effusion (COME) interleukin-8 (IL-8) is responsible for 1. the accumulation of leukocytes in the middle ear cleft and 2. in situ leukocyte activation with subsequent tissue damage. Additionally, the authors hypothesized that IL-8 expression is at least in part under the control of interleukin-1 (IL-1) and tumor necrosis factor (TNF). To begin to test this hypothesis, middle ear effusions (MEE) obtained from children ages 2 to 90 months (mean age, 29 months) undergoing tympanostomy tube placement for the presence of these inflammatory cytokines were analyzed. For these studies, IL-8, interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and tumor necrosis factor-beta (TNF-beta) were measured in MEE by radioimmunoassay (RIA) or enzyme-linked immunoassay (ELISA). IL-8, IL-1 beta, TNF-alpha, and TNF-beta were present in 92%, 67%, 77%, and 0% of effusions, respectively. The mean (+/- SEM) values for IL-8, IL-1 beta, and TNF-alpha were 4805 (+/- 913) pg/mg, 4076 (+/- 1510) pg/mg, and 163 (+/- 90) pg/mg. Further analysis indicated that levels of IL-8 correlated with IL-1 beta (R2 = .500, P = .000) and TNF-alpha (R2 = .387, P = .023). Thus the authors' studies clearly demonstrate that IL-8 is consistently present in the MEE of children with COME and is strongly correlated with levels of IL-1 beta and TNF-alpha, both known inducers of IL-8 production. These results support the authors' hypothesis that IL-1 beta, TNF-alpha, and IL-8 are intimately involved in the inflammatory cascade in the middle ear and suggest regulation of these cytokines as possible sites of future therapeutic intervention in otitis media with effusion (OME).

Age Factors↗
PubMed1994

Prognosis of neuroblastic tumours in children.

A retrospective analysis of 26 children with neuroblastic tumours treated at the University Hospital of the West Indies (UHWI) between 1970 and 1991 was undertaken to evaluate factors affecting prognosis. The peak incidence was between 48 months and 60 months of age, and 75% of the deaths occurred in children older than 3 years. The abdomen was the most common site of the tumours 79% of which were from the adrenal gland and carried a dismal outcome. Other sites were thoracic, pelvic and cervical. Extra-adrenal tumours have a good outcome even when the histology is unfavourable; 92% of the tumours were in Stages III or IV at the time of initial presentation. Stage IV disease accounted for all but one of the deaths. Of the 8 children with favourable histology (ganglioneuroma or well-differentiated ganglioneuroblastoma), only one (12.5%) died, wheras of the remaining 18 cases with unfavourable histology (neuroblastoma and undifferentiated ganglioneuroblastoma), eleven (61.1%) died. When managed by surgery alone or with adjuvant chemo- and/or radio-therapy, only 36.4% succumbed while all 4 children with chemotherapy only died. Ten children are alive without disease for more than three years post-therapy. A scoring system was designed which takes into account the factors influencing the outcome in neuroblastic tumours, namely, age, location, stage and histological types of the tumours and therapy. All the children with a score of 21 or less survived, whereas all those with scores of 22 or above succumbed. This underlines the multifactorial influences on the final outcome of neuroblastic tumours.

Abdominal Neoplasms↗
PubMed1994

Admissions for trauma at the University Hospital of the West Indies. A prospective study.

Trauma accounted for 20% of all admissions to the general surgery wards of this University Hospital in a developing country. It was the most common reason for admission. This condition affects the young, males more commonly than females, and results in the need for operation in almost 40% of admitted trauma patients. Trauma surgery accounts for 17% of all operations done. Hospital stay and age are significantly greater in those requiring operation. The head, chest and abdomen are, in order of frequency, the most commonly affected areas of the body, and injury is mainly the result of interpersonal violence (52%), accidental injuries including burns (20%), and road traffic accidents (20%). In-patient mortality was 4.5%, significantly higher in older patients and mainly in those with head injuries and burns. Scarce resources and resource misallocation mandate preventive measures to minimize the human and economic waste.

Adolescent↗