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Biomedical subjects

C Murdoch

Publications and source records attributed to C Murdoch.

16 recordsLinked to original sources
PubMed2003

Pneumococcal nasopharyngeal carriage in children following heptavalent pneumococcal conjugate vaccination in infancy.

AIMS: To ascertain whether the reduction in nasopharyngeal carriage of vaccine serotypes induced by pneumococcal conjugate vaccine (PnCV) administered to infants persists beyond the age of 2 years. METHODS: Non-randomised, unblinded controlled study of 2-5 year old children who had received three doses of heptavalent PnCV (7VPnCV) in infancy and 23-valent pneumococcal polysaccharide vaccine at 13 months, and unimmunised controls. Nasopharyngeal swabs were taken in summer (150 vaccinated subjects, 126 controls) and winter (143 vaccinated subjects, 188 controls). The swabs were cultured and serotyped for Streptococcus pneumoniae. RESULTS: Carriage rates (vaccinated subjects: 24.7% and 43.4%; controls: 27.0% and 41.0%, in summer and winter respectively) and carriage of vaccine serotypes (subjects: 10.0% and 30.0%; controls: 13.5% and 31.5%, in summer and winter respectively) were similar in the two groups. CONCLUSIONS: Effects of vaccination in infancy on rates of nasal carriage of pneumococcus and serotype replacement in children living in a largely unvaccinated population are no longer evident by 2-5 years of age.

Anti-Bacterial Agents↗
PubMed2003

Parents and carers' choice of drinks for infants and toddlers, in areas of social and economic disadvantage.

BACKGROUND: Sugar rich drinks are a recognised risk factor in early childhood caries. Currently, in depth knowledge of factors influencing parents' choice of infant drinks is incomplete. OBJECTIVES: This study investigated parents and carers understanding of feeding practices potentially detrimental to oral health; barriers to adopting safe feeding practices and commercial factors influencing feeding bottle and cup contents. METHODOLOGY: A qualitative approach using semi-structured interviews was employed. Interviews were conducted by an experienced researcher and tape recorded. Following full transcription, emerging themes were identified, systematically explored and validated within the verbatim accounts. Thirty-three parents/carers of children aged three years and under, resident in areas of high caries prevalence in Cardiff, Wales, were interviewed. RESULTS: Overall understanding of the prolonged effect of exposure to sugared drinks in feeding bottles and cups was poor. Greater concern was expressed over the use of bottles on the development of the occlusion. Milk was viewed as a food rather than as a drink. Many barriers to giving water were described: children reject it; mothers don't like it; it was 'cruel' to offer water instead of sweet drinks; water in feeding bottles or cups was seen as a sign of poverty. Commercial influences on choices were strong. Products offered by baby food manufacturers were viewed as safe, but a recently marketed "Toothsafe" drink was viewed with suspicion. CONCLUSIONS: There are significant barriers to adopting the traditional oral health education message, that only milk and water are truly safe for teeth. Future oral health education and promotion programmes must recognise and account for these factors.

Adolescent↗
PubMed2001

Uropathogenic Escherichia coli-induced neutrophil adhesion to urinary epithelium is strain-specific and mediated by CD11b/CD18.

Adherence of Escherichia coli to urinary tract epithelium induces neutrophil migration across the uroepithelium to combat bacterial infection. Neutrophil adherence to the apical membrane of uroepithelial cells may be an important factor for bacterial clearance. We used an in vitro model of urinary tract infection to examine the effects of uropathogenic E. coli on neutrophil adhesion to the uroepithelial cell line RT4. We found that distinct clinical isolates caused different levels of neutrophil adherence. One particular isolate caused significant neutrophil adhesion in a dose- and time-dependent manner. The neutrophil adhesion-promoting effect induced by this isolate was not caused by bacterial secreted products, suggesting that contact between intact E. coli and uroepithelial cells is required for promoting neutrophil adhesion. This adhesion was almost exclusively mediated by CD11b/CD18, suggesting that E. coli upregulates CD11b/CD18 counterligands on the uroepithelial surface. These data suggest that certain uropathogenic E. coli selectively promote adhesion of neutrophils to ligands on uroepithelial cells by a CD11b/CD18-dependent mechanism.

CD18 Antigens↗
PubMed2000

Chemokine receptors and their role in inflammation and infectious diseases.

Chemokines are small peptides that are potent activators and chemoattractants for leukocyte subpopulations and some nonhemopoietic cells. Their actions are mediated by a family of 7-transmembrane G-protein-coupled receptors, the size of which has grown considerably in recent years and now includes 18 members. Chemokine receptor expression on different cell types and their binding and response to specific chemokines are highly variable. Significant advances have been made in understanding the regulation of chemokine receptor expression and the intracellular signaling mechanisms used in bringing about cell activation. Chemokine receptors have also recently been implicated in several disease states including allergy, psoriasis, atherosclerosis, and malaria. However, most fascinating has been the observation that some of these receptors are used by human immunodeficiency virus type 1 in gaining entry into permissive cells. This review will discuss structural and functional aspects of chemokine receptor biology and will consider the roles these receptors play in inflammation and in infectious diseases.

Amino Acid Sequence↗
PubMed2000

CXCR4: chemokine receptor extraordinaire.

Current investigations show that chemokine receptor CXCR4 is functionally expressed on a multitude of tissues and cell types, including different leukocyte subsets, hematopoietic progenitor cells and non-hematopoietic cells such as endothelial and epithelial cells. In 1996 CXCR4 was discovered as one of the co-factors required for supporting T-lymphocyte tropic HIV infection into permissive cells and, as a consequence, much attention has been paid to this receptor in terms of HIV pathophysiology. The sudden surge of interest and subsequent growth in CXCR4 research following this discovery has led to a number of surprising findings. As well as being important for lymphocyte trafficking and recruitment at sites of inflammation, it appears that CXCR4 and its ligand stromal cell-derived factor-1 play an important role in hematopoiesis and developmental processes such as organogenesis, vascularization and embryogenesis. These findings provide new insight into the activities of chemokine receptors on both hematopoietic and non-hematopoietic cells and indicate that these molecules have both a more widespread cellular expression pattern and a wider biological role than first envisaged.

Animals↗
PubMed1999

Cxc chemokine receptor expression on human endothelial cells.

CXC chemokines play a important role in the process of leukocyte recruitment and activation at sites of inflammation. However, recent evidence suggests that these molecules can also regulate endothelial cell functions such as migration, angiogenesis and proliferation. In this study we have investigated CXC chemokine receptor expression in both primary cultures of human umbilical vein endothelial cells (HUVEC) and the spontaneously transformed HUVEC cell line, ECV304. We found that both cell types express mRNA for chemokine receptors CXCR1, CXCR2 and CXCR4, but not CXCR3. Flow cytometric analysis revealed low levels of CXCR1 but higher levels of CXCR4 cell surface expression. HUVECs responded to SDF-1alpha with a rapid and robust calcium flux, however no calcium flux was seen with either IL-8 or Gro-alpha. HUVECs and ECV304 cells did not proliferate in response to CXC chemokines, although ECV304 cells did migrate towards SDF-1alpha and IL-8. These data demonstrate that HUVECs and the endothelial cell line, ECV304 express functional CXC chemokine receptors.

Calcium Signaling↗
PubMed1999

Chemokines induce the cellular migration of MCF-7 human breast carcinoma cells: subpopulations of tumour cells display positive and negative chemotaxis and differential in vivo growth potentials.

We previously reported that chemotactic cytokines (chemokines) induce the directional migration of cells derived from the breast carcinoma cell line MCF-7 in vitro, however it was apparent that only a small percentage of cells displayed the ability to migrate upon stimulation. In the present study three sub-lines derived from the parental MCF-7 cell line were selected for their ability to migrate in response to MIP-1alpha, MIP-1beta or RANTES across Transwell filters of 8 microm pore size. The first round selection of migratory cells resulted in sub-populations which demonstrated an increased chemotactic response compared with parental cells. Cells migrating to MIP-1beta were subjected to four further rounds of positive or negative selection, resulting in two sub-lines, MCF-7L4 and MCF-7U4 which displayed an increased and decreased chemotactic response respectively to MIP-1alpha MIP-1beta and RANTES. No difference in chemokine receptor RNA message expression between these sub-lines and the parental MCF-7 line were detected, although increased levels of alpha3, alpha6 and alphav integrin sub-units were shown for MCF-7L4 (positively selected sub-line) compared with MCF-7U4 cells. Moreover, the in vivo growth of cells derived from the two MCF-7 sub-lines was inversely correlated with their chemotactic response. The results of this study depict further the inherent heterogeneity in cancer, suggesting that the chemotactic response may influence the migratory traits of sub-populations within the tumour and potentially contribute to their in vivo behavior, growth and survival.

Breast Neoplasms↗
PubMed1999

Functional expression of chemokine receptor CXCR4 on human epithelial cells.

Chemokines and their receptors play an important role in the process of leucocyte recruitment at sites of inflammation. However, recent evidence suggests that these proteins can also regulate non-leucocyte cell functions such as angiogenesis, migration and proliferation. We have investigated the expression of the CXC chemokine receptor 4 (CXCR4) on primary cultures of type II alveolar epithelial cells, their transformed counterpart, the A549 cell line and also on other epithelial cell lines from various tissues. We found that all epithelial cell types tested express mRNA for CXCR4. Flow cytometric analysis and immunocytochemical staining shows that CXCR4 chemokine receptor is abundantly expressed on the surface of A549 epithelial cells. Furthermore, A549 cells responded to the CXCR4 ligand, stromal-derived factor-1alpha (SDF-1alpha) with a rapid and robust calcium mobilization and not to other CXC chemokines, suggesting that CXCR4 is functionally active and is able to couple to G-protein signalling mechanisms. A549 cells did not proliferate in response to either SDF-1alpha or interleukin-8 (IL-8) CXC chemokines. These findings may have important implications for epithelial physiology and pathology.

Animals↗
PubMed1997

Frequent loss of chromosome 14 in atypical and malignant meningioma: identification of a putative 'tumor progression' locus.

Formation of meningiomas has been associated with the loss of genetic material on chromosome 22. To approach the additional chromosomal events that underlie progression of these tumors to malignancy, we have examined several other chromosomal regions for loss of heterozygosity (LOH) in these tumors. Fifty-eight tumors, comprising 43 benign meningiomas, 11 atypical meningiomas and four malignant meningiomas, were examined. While the loss of chromosome 22 was seen in approximately half of all these tumors, regardless of their malignancy, the most frequent chromosomal losses observed in the malignant and atypical tumors were on the long arm of chromosome 14. Thirty-nine tumors were informative for at least one of the three markers on chromosome 14 that we tested. Of these, 7/14 malignant and atypical tumors showed LOH in contrast to only 1/25 benign tumors. Other loci that showed LOH in malignant tumors, although at a much lower frequency, were on chromosomes 17p and 1p. The high frequency of LOH for loci on chromosome 14q in atypical and malignant tumors suggests the presence of a tumor progression gene at this locus. In one of the malignant meningiomas heterozygosity was lost at D14S13 and D14S16 but retained at the proximal marker D14S43 as well as the more distal marker D14S23. This suggests that an interstitial deletion occurred in this tumor which should be useful for further refining the position of the putative tumor progression locus.

Chromosome Deletion↗
PubMed1996

Computer graphic three-dimensional reconstruction of normal human embryo morphogenesis.

Three-dimensional computer graphic reconstructions of four human embryos at Carnegie stages 11 to 23 portray the relationships and dimensions of individual organ systems. This paper illustrates the cranial, neural, pharyngeal, gut, vascular and nephric architecture in these developing embryos. This technology can be applied to in situ hybridization and immunohistochemistry to map zones and times of developmental gene activity.

Embryo, Mammalian↗
PubMed1994

The inefficacy of intravenous propafenone for rate control in atrial fibrillation.

The antiarrhythmic agent propafenone has been reported to prolong atrioventricular node conduction and may be suitable for rate control in atrial fibrillation (AF). To evaluate this, 10 patients (seven men and three women aged 29 to 67 years, mean +/- SD 48 +/- 14) were given intravenous propafenone during AF in both the supine and upright positions. Intracardiac catheters measured local electrograms from the high right atrium and right ventricular apex during AF. Atrial rate, ventricular rate and blood pressure were recorded in the control state and after head-up tilt with these measurements repeated after propafenone 1.5 mg/kg was infused over 5 mins. Four of 10 patients reverted to sinus rhythm. Propafenone increased the mean ventricular cycle length (496 +/- 147 versus 556 +/- 152 ms, P = 0.1), although this did not reach significance. In contrast, propafenone markedly increased the mean atrial cycle length (136 +/- 35 versus 226 +/- 39, P < 0.001). The mean ventricular cycle length reverted to baseline after tilt (447 +/- 103 ms) while the mean atrial cycle length decreased but not to baseline levels (170 +/- 21 ms). The authors conclude that intravenous propafenone is generally inadequate for rate control in AF, especially in the upright position.

Adult↗
PubMed1989

Are postmortem studies of glossal candidal infection useful? An experimental study.

Autopsy studies have suggested that candidal pseudohyphae may be found in dorsal glossal epithelium in 38% to 42% of cases. Candidal yeast forms, and occasionally free pseudohyphae, are found as oral commensals in about 44% of the population. This study examined the possible distorting influence in autopsy studies that could be caused by postmortem hyphal transformation of candidal yeast forms followed by saprophytic infestation. Candida albicans yeast forms were topically applied to the middorsal glossal mucosa of five healthy pigs, immediately after killing. Biopsy specimens from this mucosa were subsequently maintained, in vitro, for periods of 12 and 24 hours in humid conditions at different temperature regression rates chosen to approximate those of the oral cavity after death. Biopsy specimens subjected to a temperature regression of 35 degrees C (oral temperature) to 23 degrees C (room temperature) over 11 hours showed infestation of epithelium by pseudohyphae in all cases. Biopsy specimens subjected to a similar temperature regression over 5 hours showed infestation in two of five cases. Control biopsy specimens showed that there was no candidal infection at the time of killing. The results indicate that in vitro saprophytic candidal infestation is possible in the time intervals and the declining oral temperatures preceding autopsy. It suggests that postmortem saprophytic candidal infestation may distort results from autopsy studies that do not anticipate this problem.

Animals↗
PubMed1986

Early dentinogenesis in mice: von Korff fibres and their possible significance. A preliminary study by light and electron microscopy.

By light and electron microscopy we have confirmed the collagenous nature of von Korff fibres in early dentinogenesis in mice. Each fibre array begins as an argyrophil 'stem' lying between the outermost cells of the dental papilla, with finer divisions passing into the papilla. With the appearance of odontoblasts, a cone-like 'spray' of nonargyrophil fibres in continuity with the stem spreads peripherally between these cells to the dental epithelial basement membrane. After the sprays become immured in dentine matrix, the stems are removed. Later, new stems appear. Sprays are restricted to enamel-bearing parts of teeth. The possible nature and functions of von Korff fibres are discussed.

Animals↗
PubMedDate not supplied

Chemokine receptors and their role in vascular biology.

Chemokines play an important role in the process of leukocyte recruitment and activation at sites of inflammation. Until recently, the actions of chemokines and the expression of their receptors have only been described on different leukocyte populations. However, increasing evidence has suggested that non-haematopoietic cell types are capable of binding and responding to a number of chemokines. The functional expression of certain chemokine receptors has recently been described on vascular endothelial and smooth muscle cells. These findings provide new insight into the activities of chemokines and indicate that these molecules have a more widespread cellular target than first envisaged. Studies carried out to date indicate that chemokines and their respective receptors play an important role in the regulation of angiogenesis and angiostasis. They may also be involved in developmental and pathological processes such as organ vascularization, embryogenesis and arteriosclerosis.

Blood Vessels↗