Search PubMed⌕ Search

Biomedical subjects

F McDonald

Publications and source records attributed to F McDonald.

At least 19 recordsLinked to original sources
PubMed2003

Clinical significance of eosinophils in suspicious or borderline renal allograft biopsies.

AIMS: Renal allograft biopsies play a critical role in renal transplantation. Acute rejection characterized by tubulitis and intimitis is of primary concern. There is an association between eosinophilic infiltrates and irreversible acute rejection; however, the significance of eosinophils in biopsies that fall short of the diagnostic threshold for acute rejection has not been well studied. This report describes clinical course, treatment and long-term outcome of 5 transplant recipients with biopsy histology that showed borderline changes associated with eosinophilic infiltrates. METHODS: Clinical records were selected for review on the basis of biopsy histology satisfying the following criteria: presence of interstitial infiltrates with eosinophils, absence of definitive criteria for acute rejection and absence of findings suggestive of infection or cyclosporine toxicity. RESULTS: All identified biopsies occurred within the first month of transplantation, and histology showed varying degrees of patchy mononuclear cell infiltrates composed of lymphocytes, with eosinophilic infiltrates, but no evidence of acute rejection based on Banff criteria. These patients were taking trimethoprim-sulfamethoxazole and ranitidine at the time of biopsy. Serum creatinine returned to baseline levels in each case after stopping both drugs, and remained stable during the duration of follow-up without any documented episode of acute rejection. No patient received specific therapy for acute rejection. CONCLUSION: This report suggests that independent of decisions on treatment with high-dose steroids or anti-lymphocyte antibody preparations, the management algorithm should include stopping drugs associated with acute interstitial nephritis when non-diagnostic biopsies show eosinophilic infiltrates.

Adult↗
PubMed2002

An evaluation of accelerated Portland cement as a restorative material.

Biocompatibility of two variants of accelerated Portland cement (APC) were investigated in vitro by observing the cytomorphology of SaOS-2 osteosarcoma cells in the presence of test materials and the effect of these materials on the expression of markers of bone remodelling. Glass ionomer cement (GIC), mineral trioxide aggregate (MTA) and unmodified Portland cement (RC) were used for comparison. A direct contact assay was undertaken in four samples of each test material, collected at 12, 24, 48 and 72 h. Cell morphology was observed using scanning electron microscopy (SEM) and scored. Culture media were collected for cytokine quantification using enzyme-linked immunosorbent assay (ELISA). On SEM evaluation, healthy SaOS-2 cells were found adhering onto the surfaces of APC variant, RC and MTA. In contrast, rounded and dying cells were observed on GIC. Using ELISA, levels of interleukin (IL)-1beta, IL-6, IL-18 and OC were significantly higher in APC variants compared with controls and GIC (p<0.01), but these levels of cytokines were not statistically significant compared with MTA. The results of this study provide evidence that both APC variants are non-toxic and may have potential to promote bone healing. Further development of APC is indicated to produce a viable dental restorative material and possibly a material for orthopaedic

Biocompatible Materials↗
PubMed2002

Analysis of facial growth in subjects with syndromic ectodermal dysplasia: a longitudinal analysis.

OBJECTIVE: To examine the craniofacial growth pattern of patients diagnosed with syndromic ectodermal dysplasia. DESIGN: Mixed longitudinal analysis of lateral cephalograms. SETTING: The data were analysed using a multilevel modelling technique with the MLwiN application software and the results presented numerically and graphically. SAMPLE POPULATION: All 61 subjects had severe hypodontia with the number of absent teeth (excluding third molars) ranging from 6 to 28 (mean = 15.4). At presentation the subjects had a mean age of 133 months and were followed longitudinally for between one and five subsequent occasions (mean 2.66 occasions; mean age at completion of observation 207 months). OUTCOME MEASURES: Lateral cephalograms taken at each visit. EXPERIMENTAL VARIABLES: Analysis of four angular measurements and four linear measurements, together with one calculated ratio. RESULTS: Growth curves are presented showing the trends of craniofacial growth. CONCLUSIONS: The most significant findings were for a universal tendency for the individuals to undergo a change in sagittal relationship of the jaws, becoming markedly more Class III with time. We have also demonstrated a significant difference in growth between the anterior and posterior face heights indicating that the subjects have a tendency to an anterior growth rotation.

Adolescent↗
PubMed2002

Analysis of the morbidity of submerged deciduous molars: the use of imaging techniques.

A case is presented of a 13-year-old patient who had a class I occlusion on a class I skeletal base but with a retained and submerged deciduous molar causing impaction of the second premolar. Diagnostic imaging illustrates the potential challenges of the removal of the retained deciduous molar. Magnetic resonance imaging used to identify the path of the inferior alveolar neurovascular bundle clearly delineates its intimate association with the impacted teeth and underscores the risk of trauma during extraction. This is discussed with regard to other cases of submerged molars, and a strategy is outlined.

Adolescent↗
PubMed2001

Nasopalatine duct cyst: a case report.

A case of a nasopalatine duct cyst is reported in an 8-year-old. The clinical presentation was of intermittent palatal swelling and the diagnosis was confirmed with radiological and histological examination. This type of cyst is rare in children and should not be excluded from a differential diagnosis in younger age groups.

Child↗
PubMed2001

A radiographic analysis of computer prediction in conjunction with orthognathic surgery.

This retrospective study analysed the accuracy and reliability of predictions generated in patients treated with orthognathic surgery by comparing Quick Ceph Image software (Quick Ceph Image Pro version 3.0) predictions with post-surgical lateral cephalographs. Pre- and post-surgical lateral cephalographs of 28 adult patients (12 males and 16 females) were scanned into the computer and 28 landmarks were identified and digitized. Digitization error was assessed from repeated digitization. Fourteen measurements of the predicted and actual postsurgical hard tissue landmarks were compared using Student's t-test. Results showed a good correlation between repeated digitization for all measurements. Student's t-test indicated that 10 of the 14 measurements showed no statistically significant differences. Only the ANB (P=0.008), FMA (P=0.001), SN-Mxl (P=0.03) and Wit's (P=0.0001) showed statistically significant differences between the predicted and actual measurements. However only the Wit's showed clinical significant differences between the two measurements. Caution still must remain as the surgeon may not achieve his planned position in an individual patient. In some cultures there may also be medico-legal implications of these predictions.

Adolescent↗
PubMed2000

Analysis of the vertical facial form in patients with severe hypodontia.

We examined the lateral cephalograms of Russian patients in the following categories: control with acceptable occlusions (group 1); severe hypodontia with absence of six or more teeth (group 2); and severe hypodontia associated with hypohidrotic ectodermal dysplasia (HED) (group 3). Analysis was in a cross-sectional manner, comparing dimensions at the start of the mixed dentition phase (age 6-10) and in the permanent dentition (age 12-18). The groups were matched for age and sex. Thirty-one hard- and soft-tissue landmarks were traced, and 35 linear, 19 angular, and 7 ratioed measurements were taken and compared, using analysis of variance to compare the means of each group. A reduced anterior face height was found in groups 2 and 3 as a consequence of a reduced anterior lower face height. In group 2 in the mixed dentition, the posterior face height was also reduced. The inclination of the mandible (<Se S Go Gn) was significantly reduced to 28.22 degrees +/- 0.71 degrees in group 2 and to 24.07 degrees +/- 0.97 degrees in group 3. The facial profile appeared flat or concave (<se pn pg was increased up to 8.42 degrees +/- 1.56 degrees in children and 16.81 degrees +/- 2.18 degrees in adolescents). The subnasion point was behind the aesthetic line (EL), and in group 2 patients the naso-labial angle was obtuse when compared to nonaffected patients. In group 3 patients, the naso-labial angle became acute and lips were protuberant and everted as a consequence of the reduced vertical height. Groups 2 and 3 have the typical facial characteristics unique to hypodontia, with reduced vertical dimensions as a consequence of limited alveolar bone growth. However, group 3 patients have a unique abnormal craniofacial development.

Adolescent↗
PubMed2000

A cross-cultural examination of weight-related teasing, body image, and eating disturbance in Swedish and Australian samples.

OBJECTIVE: To evaluate, cross-culturally, a model for the prediction of eating disturbance from factors such as body image disturbance, negative verbal feedback regarding appearance (teasing), and body mass index (BMI). METHODS: Three samples of adolescent girls from Sweden (Grade 8: n = 260; mean age = 14.3) and Australia (Grade 7: n = 159; mean age = 12.8 and Grade 8: n = 210; mean age = 13.7) completed two measures of eating restraint and one scale each reflective of bulimic symptomatology, teasing history, and body dissatisfaction. RESULTS: Path analyses revealed that BMI predicted teasing and body dissatisfaction, and body dissatisfaction predicted level of eating restraint. In all three samples, there was evidence of partial mediation by teasing of the connection between BMI and restraint. DISCUSSION: The results partially replicate previous work with U.S. samples. The findings are discussed with regard to the need for further cross-cultural work and its relevance for identifying factors for early intervention and prevention programs.

Adolescent↗
PubMed1999

G-protein signalling pathways and oestrogen: a role of balanced maintenance in osteoblasts.

Oestrogen (E2) is an important regulator of bone cell function and alterations in oestrogen levels may cause abnormal bone metabolism in vivo. In this study we examined the long term effects of 17beta-oestradiol (17beta-E2) on G-proteins and the secondary signalling pathways of phospholipase C (PLC), cyclic adenosine monophosphate (cAMP), and 1,4,5-inositol triphosphate (IP3). Cells from neonatal mouse calvariae were cultured in phenol red-free RPMI 1640 medium supplemented with charcoal stripped foetal calf serum for 192 h with either oestrogen (10(-8) M), or oestrogen withdrawal after 48 h. Cultures were stimulated for the final 48 h with IL-6 (10(-10) M), or left unstimulated. Western blot analysis was undertaken on osteoblast membrane preparations obtained by 10 mM Tris-HCl, 0.1 mM EDTA pH 7.8 and centrifugation at 40,000 x g for 2 h. For cAMP study, cells were stimulated with IL-6 for either 15 min or 30 min. Intracellular cAMP was extracted from cells and measured by ELISA methodology. For the IP3 assay, cells were stimulated with IL-6 for 20 s and IP3 levels measured using radioimmunoassay. The blots revealed increased levels of Gialpha-, and Gqalpha-proteins with oestrogen withdrawal and IL-6 stimulation. This was in comparison to cells which were unstimulated, or stimulated with IL-6 with continuous 17beta-E2, or IL-6 alone. Gsalpha expression decreased with oestrogen withdrawal compared to the control. Limited amounts of Gialpha-, Gsalpha-, and Gqalpha-proteins were identified with continuous 17beta-E2. The levels of PLC isoforms PLCbeta1-2 were not affected by the differing oestrogen conditions. The cAMP production induced by IL-6 stimulation for 30 min and withdrawal of 17beta-E2 was lower and significantly different compared to the control study (P<0.05). Also IL-6 activation with continuous oestradiol increased cAMP levels and was significantly different from the control cells (P<0.01). However, 17beta-E2 had no effect on the formation of intracellular IP3, although IL-6 significantly lowered IP3 levels in all the groups compared to the control (P<0.01). These results suggest that oestrogen modulates the signal transduction pathways of G-protein molecules, and the secondary pathways of cAMP in mouse osteoblast-like cells.

Animals↗
PubMed1999

Osteoblast biocompatibility of mineral trioxide aggregate.

This study investigated the biocompatibility of variants of mineral trioxide aggregate (MTA), by culturing human MG63 osteosarcoma cells in the presence of materials, observing cytomorphology and cell growth, and then assaying cytokine expression from the cells. Reference materials were employed. Cell growth was quantified by preparing samples (n = 6) at 2, 4 and 7 days, for viewing by scanning electron microscopy and then scoring the amount of material that was covered by healthy cells. Subsequently, samples of culture media were tested using ELISA assays for expression of Interleukin (IL)-1alpha, IL-6, IL-8, IL-11 and macrophage colony stimulating factor (M-CSF). These assays were compared with controls where no material was present, and where media and fetal calf serum had not been exposed to cells. Results showed good cell growth on MTA. Expression of IL-6 from cells was only evident in the presence of MTA and Interpore 200. Interleukin-8 was expressed in high concentrations only in the presence of MTA. There was no evidence of expression of IL-1alpha or IL-11 with any material. Production of M-CSF was high for all materials. It appears that the variants of MTA are biocompatible and suitable for use in clinical trials.

Aluminum Compounds↗
PubMed1999

Laser light transmission in teeth: a study of the patterns in different species.

AIM: The aim of this study was to investigate the pattern of light transmission through teeth of different species and to examine laser light propagation within enamel from various animal sources. METHODOLOGY: Sectioned teeth from five species--pig, horse, sheep, cat and rat--were evaluated. Samples were illuminated individually by a helium-neon laser light from the buccal surface using a probe 0.5 mm in diameter placed at varying angles between 60 and 120 degrees C. The pattern of light transmission was observed macroscopically. Further evaluation of laser light transmission in enamel was achieved using confocal microscopy. RESULTS: In each species, light was transmitted through the tooth to the pulp, but in the cat and the rat, light was also transmitted to the far side of the tooth. Despite the different patterns of enamel in the species, light was transmitted through enamel to dentine. CONCLUSION: Light from a laser Doppler probe appeared to reach the dental pulp in all the species: however, in the mammals with smaller teeth, light may also have been able to reach the periodontium and thus the reflected signal may not be entirely of pulpal origin.

Animals↗
PubMed1998

ZK200775: a phosphonate quinoxalinedione AMPA antagonist for neuroprotection in stroke and trauma.

Stroke and head trauma are worldwide public health problems and leading causes of death and disability in humans, yet, no adequate neuroprotective treatment is available for therapy. Glutamate antagonists are considered major drug candidates for neuroprotection in stroke and trauma. However, N-methyl-D-aspartate antagonists failed clinical trials because of unacceptable side effects and short therapeutic time window. alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonists derived from the quinoxalinedione scaffold cannot be used in humans because of their insolubility and resulting renal toxicity. Therefore, achieving water solubility of quinoxalinediones without loss of selectivity and potency profiles becomes a major challenge for medicinal chemistry. One of the major tenets in the chemistry of glutamate antagonists is that the incorporation of phosphonate into the glutamate framework results in preferential N-methyl-D-aspartate antagonism. Therefore, synthesis of phosphonate derivatives of quinoxalinediones was not pursued because of a predicted loss of their selectivity toward AMPA. Here, we report that introduction of a methylphosphonate group into the quinoxalinedione skeleton leaves potency as AMPA antagonists and selectivity for the AMPA receptor unchanged and dramatically improves solubility. One such novel phosphonate quinoxalinedione derivative and competitive AMPA antagonist ZK200775 exhibited a surprisingly long therapeutic time window of >4 h after permanent occlusion of the middle cerebral artery in rats and was devoid of renal toxicity. Furthermore, delayed treatment with ZK200775 commencing 2 h after onset of reperfusion in transient middle cerebral artery occlusion resulted in a dramatic reduction of the infarct size. ZK200775 alleviated also both cortical and hippocampal damage induced by head trauma in the rat. These observations suggest that phosphonate quinoxalinedione-based AMPA antagonists may offer new prospects for treatment of stroke and trauma in humans.

Animals↗
PubMed1998

Cellular response to Mineral Trioxide Aggregate.

This investigation studied the cytomorphology of osteoblasts in the presence of Mineral Trioxide Aggregate (MTA) and examined cytokine production. MTA and Intermediate Restorative Material (IRM) were prepared and placed in separate Petri dishes. Osteoblasts (cell-line MG-63), grown to confluence in Hams F12/Dulbecco's modified Eagle's medium, were seeded into the dishes, which were incubated for 1 to 7 days. The specimens were viewed by scanning electron microscopy. For cytokine evaluation, cells were grown either alone or in other dishes containing the test materials for 1 to 144 h. Media were removed for ELISA analysis of interleukin (IL)-1 alpha, IL-1 beta, IL-6, and macrophage colony-stimulating factor. Scanning electron microscopy revealed healthy cells in contact with MTA at 1 and 3 days; in contrast, cells in the presence of IRM appeared rounded. The ELISA assays revealed raised levels of all ILs at all periods when cells were grown in the presence of MTA; in contrast, cells grown alone or with IRM produced undetectable amounts. The macrophage colony-stimulating factor was produced by cells irrespective of the group. It seems that MTA offers a biologically active substrate for bone cells and stimulates IL production.

Aluminum Compounds↗
PubMed1998

An analysis of Ca2+ release by DGEA: mobilization of two functionally distinct internal stores in Saos-2 cells.

Osteoblasts can be activated by their collagen matrix and in particular the DGEA peptide motif. We have reported that DGEA is able to activate Ca2+ signaling pathways in the human osteoblast-like cell line, Saos-2, by a tyrosine kinase-dependent pathway (T. J. McCann, W. T. Mason, M. C. Meikle, and F. McDonald. Matrix Biol. 16: 271-280, 1997). In the present study, we show that this activity is due to coupling of the signal to intracellular Ca2+ stores, since the DGEA action is not blocked by La3+ but is lost when Ca2+ stores are depleted with 2 microM and blocked by 10 microM ryanodine. The activated stores also differ functionally from those activated by thrombin, as blockade with U-73122 obstructs only thrombin-activated Ca2+ release. We have shown that the DGEA activity was not due to its high-charge density, since the two acidic residues can be substituted with their uncharged homologues (asparagine and glutamine) without significant loss of activity. This was in turn measured by an adhesion assay that also demonstrated this level of specificity. Furthermore, by constructing DGEA bound to FITC, we have shown that DGEA binding was dependent on divalent cations. We have also demonstrated that an intact actin cytoskeleton is not required for Ca2+ activation by inhibiting actin polymerization with the addition of cytochalasin B. These data strengthen the argument that collagen has a significant role in regulating osteoblast function via this peptide motif.

Amino Acid Sequence↗
PubMed1997

Mineral trioxide aggregate stimulates a biological response in human osteoblasts.

We report a novel material that appears to stimulate cytokine production in human osteoblasts and allow good adherence of the cells to the material. We have examined cultured osteoblasts (MG-63) in the presence of mineral trioxide aggregate (MTA) as set in moist conditions; secondly, we examined the behavior of these MG-63 cells with respect to cytokine and osteocalcin production and alkaline phosphatase activity. Standard ELISA assays were used for assessment of interleukin (IL)-1 alpha, IL-1 beta, IL-6, macrophage colony stimulating factor (M-CSF), and osteocalcin. Furthermore the levels of alkaline phosphatase were measured to establish the level of differentiation of the cells. Cells without MTA served as controls. Cells also were grown in the presence of polymethylmethacrylate (PMA), the commonly used orthopedic cement. In all dishes cells were seen adhering to the base and MTA at 6 h and had increased to confluence at 144 h. IL-1 alpha (175.1 +/- 32.6 pg/mL), IL-1 beta (154.0 +/- 26.7 pg/mL), and IL-6 (214.7 +/- 21.8 pg/mL) were raised when the cells were grown in the presence of MTA at 144 h, with raised values at all time intervals. M-CSF appeared to be unaffected although the overall value was high (7,045.0 +/- 89.5 pg/mL). In contrast, cells grown in the absence of MTA produced negligible amounts of these cytokines (< pg/mL) as did those cells grown in the presence of PMA. Osteocalcin production increased when cells were grown on MTA from 3.8 +/- 0.87 ng/mL to 19.7 +/- 2.8 ng/mL. No osteocalcin could be detected with PMA. Cells in contact with MTA also appeared to have levels of alkaline phosphatase similar to those reported elsewhere (4.3 +/- 0.21 mumol/mg protein/min). No cells could be found attached to PMA and so no alkaline phosphatase activity could be measured.

Alkaline Phosphatase↗
PubMed1997

A collagen peptide motif activates tyrosine kinase-dependent calcium signalling pathways in human osteoblast-like cells.

A collagen peptide motif (DGEA) which is a putative alpha 2 beta 1 integrin binding site was examined for its ability to activate Ca2+ signalling pathways in the human osteoblast-like cell line SaOS-2. We show that these cells express both alpha 2 beta 1 integrin subunits (by immunocytochemistry) and that an anti-beta 1 monoclonal antibody (DF5) mobilizes Ca2+ in these cells. DGEA elevated intracellular Ca2+ in fura-2-loaded cells, in a concentration- and sequence-dependent fashion, with an EC50 of 250 microM. The tyrosine kinase inhibitor herbimycin A reduced the number of cells responding to DGEA and to transforming growth factor alpha. Thrombin also stimulated a rise in intracellular Ca2+, but the number of cells responding was not reduced by herbimycin A. The DGEA response was dependent on extracellular Ca2+, but was not due to Ca2+ influx, since it was blocked by thapsigargin and not by lanthanum. Using three different anti-alpha 2 monoclonal antibodies, we were unable to show that the DGEA-induced Ca2+ signal was mediated by the alpha 2 beta 1 integrin. In summary, the DGEA collagen motif does appear to activate receptor-mediated Ca2+ signalling events in SaOS-2 cells, in a divalent cation-dependent manner, but we were unable to demonstrate a role for alpha 2 beta 1 integrin in this response.

Benzoquinones↗
PubMed1996

Calcium waves in fluid flow stimulated osteoblasts are G protein mediated.

Calcium (Ca2+) entry upon cell perturbation has been examined in transformed human osteoblast cells (U-2/OS). The cells were deformed by fluid flow from a patch pipette held in proximity to the cell by applying a positive pressure (+50 mm Hg) for the passage of saline over the membrane. Intracellular calcium [Ca2+]i was examined following loading with 5 microM Fura-2 AM. The changes in ratio were determined at 330-ms intervals. Waves of [Ca2+]i were seen spreading along the length of the individual cell following stimulation (n = 30). The initial change in Ca2+ at the site of stimulation occurred within 660 ms after applying the stimulus. Following 1.3 (+/- 0.33) s of raised [Ca2+]i, the values returned to those of predeformation. The Ca2+ response following fluid flow stimulation was blocked by 300 microM Cd2+, a specific blocker of Ca2+ channels, demonstrating an extracellular source of Ca2+. Preincubation with cholera toxin (250 ng/ml for 6 h) prolonged the elevation of Ca2+ induced by fluid flow stimulation (n = 20). In contrast, pertussis toxin (250 ng/ml for 6 h) completely eliminated the Ca2+ response to fluid flow stimulation (n = 20). Cells maintained in solutions free of Ca2+ demonstrated no change in [Ca2+]i. Tetraethylammonium (6 mM) had no effect on the response (n = 10). In addition pretreatment with ryanodine (2 and 10 microM; each group n = 10) in media showed a reduced wave of Ca2+ in response to mechanical deformation. The response to a phospholipase C inhibitor also eliminated the response to the mechanical deformation (n = 10). In addition cells that demonstrated changes in Ca(2+)-containing media lost the ability to respond when EGTA was added to the media. Following this, 2 microM ryanodine was added to the cells, demonstrating a response too small to replicate the fluid flow stimulated wave, but supporting the view that the cells were vital following preincubation.

Biological Transport↗