Photosensitization of the sunscreen octyl p-dimethylaminobenzoate by UVA in human melanocytes but not in keratinocytes

Sunscreens penetrate human epidermis and modify the biology of proliferating cells. This study addressed the question whether the UV response of cultured human cells is affected by direct treatment with nontoxic levels of sunscreens. Cell survival following exposure to UVC or unfiltered UVB was not altered by preincubation with 25 μg/mL of octyl p-dimethylaminobenzoate (o-PABA), 2-ethylhexyl p-methoxycinnamate (EHMC) or oxybenzone. However, UVA or UVB filtered to reproduce the solar UV spectrum penetrating to the basal layer of the epidermis, highly sensitized cells to killing by o-PABA but not by its hydrolysis product, 4-dimethylaminobenzoic acid. Sensitization was found in all cell types tested, except normal keratinocytes, and could be prevented by certain antioxidants particularly pyruvate and the hydroxyl radical scavenger mannitol. o-PABA and EHMC applied without UV reduced the adherence of cells. The results indicate that sunscreens may increase cell mobility and the combination of o-PABA with solar UV may selectively damage melanocytes in the skin.

Surgical outcomes of a randomized prospective trial involving patients with a proximal femoral fracture

Background: An orthopaedic management/patient-focused care unit (OMPFCU) involving a dedicated orthopaedic-geriatrics liaison team was established at the Royal Brisbane Hospital in 1994 in an effort to safely accelerate rehabilitation of patients with proximal femoral fractures. Methods: The surgical outcomes of the patients were monitored in order to determine whether accelerated rehabilitation had any significant adverse effects on the surgical outcomes, measured by mortality, readmission to hospital, deep wound infection, fracture union delay, mobility and the revision surgery rate. Results: No significant difference was recorded in mortality and morbidity, deep wound infection and revision surgery rates between patients in the Royal Brisbane Hospital OMPFCU and those in standard care in the orthopaedic surgery wards. Conclusion: Accelerated rehabilitation for patients with a proximal femoral fracture in a major teaching hospital can be accomplished safely.

Sexual recombination in Phytophthora cinnamomi in vitro and aggressiveness of single-oospore progeny to Eucalyptus

Fifty single oospore progeny were established from an in vitro mating of A1 and A2 mating type isolates of Phytophthora cinnamomi from South Africa. Forty-nine progeny were identified as F-1 hybrids using seven random amplified polymorphic DNA (RAPD) primers, and one was a selfed isolate of the A1 mating type parent. Among the hybrid progeny, 24 and 25 were A1 and A2 mating type, respectively. Aggressiveness of progeny and parental isolates was assessed on 1-year-old seedlings of Eucalyptus smithii. The mean aggressiveness of hybrid oosporic isolates, expressed as lesion length, was significantly (P = 0.0001) lower than that of the parental isolates. No significant difference in aggressiveness of A1 and A2 mating type F-1 hybrid isolates was observed. This is the first report demonstrating sexual recombination in vitro in P. cinnamomi.

The influence of posture on perineal ultrasound imaging parameters

A prospective clinical study was carried out to evaluate the influence of posture on perineal ultrasound imaging parameters. One hundred and thirty-two consecutive women presenting with symptoms of lower urinary tract dysfunction were examined by multichannel videourodynamics and perineal ultrasound, both supine and standing. Ultrasound included color Doppler imaging when available, i.e. in a subgroup of 99 patients. The position of the bladder neck at rest was higher in the supine position (P

Sox18 expression in blood vessels and feather buds during chicken embryogenesis

Sox18 encodes a transcription factor known to be important for the development of blood vessels and hair follicles in mice. In order to study the functional conservation of this gene through evolution, we have isolated and characterized Sox18 in chickens. cSox18 shows a high degree of sequence homology to both the mouse and human orthologues, particularly in the high mobility group DNA-binding domain and to a lesser extent in the transcriptional activation domain. A region of unusually high sequence conservation at the C-terminus may represent a further, previously unrecognized functional domain. Both the chicken and human proteins appear to be truncated at the N-terminus relative to mouse SOX18. In situ hybridization analyses showed expression in the developing vasculature and feather follicles, consistent with reported expression in the mouse embryo. In addition, cSox18 mRNA was observed in the retina and claw beds. (C) 2001 Elsevier Science B.V. All rights reserved.

Transcriptional modulation of mouse mu-opioid receptor distal promoter activity by Sox18

Previously, we reported the presence of dual promoters, referred to as distal (DP) and proximal, with a negative regulatory element between them in the mouse mu -opioid receptor (mor) gene. Here we have identified a positive regulatory element influencing mor DP transcription, which contains multiple consensus binding motifs for Sox factors (sex-determining Sry-like high mobility group box-containing genes). In gel supershift assays, the Sox family member Sox18 bound directly to the multiple Sox consensus binding motifs of the mor DP enhancer. Overexpression of Sox18 cDNA increased luciferase activity regulated by the mor DP, and did so in a Sox18 concentration-dependent manner. In contrast, overexpression of another Sox member, Sox5, triggered no such trans-activation of mor DP-driven luciferase activity or DNA-protein binding activity. These results suggest that Sox18 directly and specifically stimulates mor gene expression, by trans-activating the mor DP enhancer.

Sox18 is transiently expressed during angiogenesis in granulation tissue of skin wounds with an identical expression pattern to Flk-1 mRNA

Sox18 encodes a member of the Sry-related high mobility group box (SOX) family of developmental transcription factors. Examination of Sox18 expression during embryogenesis has shown that Sox18 is expressed transiently in endothelial cells of developing blood vessels, and mutations in Sox18 have been found to underlie the mouse vascular and hair follicle mutant ragged. In this study we have examined the expression of Sox18 in angiogenesis during wound healing. Full-thickness skin wounds were created in mice, and subsequent expression of vascular endothelial growth factor (VEGF), the VEGF receptor Flk-1, alpha1 (iv) collagen (Col4a1), and Sox18 were studied using in situ hybridization. As has been previously reported, VEGF was expressed predominantly in the keratinocytes at the wound margins. Sox18 expression was found Rye days after wounding during capillary sprouting in granulation tissue and persisted through the proliferative phase of healing, but was not detected in fully epithelialized wounds 21 days after wounding. Sox18 mRNA expression was detected in capillaries within the granulation tissue and showed an identical pattern of distribution to Flk-1 and Col4a1 mRNA expression in endothelial cells. Immunostaining with a polyclonal anti-Sox18 antibody showed SOX18 protein localized in capillary endothelial cells within the granulation tissue. capillaries in the subcutaneous tissue of unwounded skin showed no Sox18 expression. Sox18 may therefore represent a transcription factor involved in the induction of angiogenesis during wound healing and tissue repair, but not in the maintenance of endothelial cells in undamaged tissue.

Structural characterization of the N-terminal autoregulatory sequence of phenylalanine hydroxylase

Phenylalanine hydroxylase (PAH) is activated by its substrate phenylalanine, and through phosphorylation by cAMP-dependent protein kinase at Ser 16 in the N-terminal autoregulatory sequence of the enzyme. The crystal structures of phosphorylated and unphosphorylated forms of the enzyme showed that, in the absence of phenylalanine, in both cases the N-terminal 18 residues including the phosphorylation site contained no interpretable electron density. We used nuclear magnetic resonance (NMR) spectroscopy to characterize this N-terminal region of the molecule in different stages of the regulatory pathway. A number of sharp resonances are observed in PAH with an intact N-terminal region, but no sharp resonances are present in a truncation mutant lacking the N-terminal 29 residues. The N-terminal sequence therefore represents a mobile flexible region of the molecule. The resonances become weaker after the addition of phenylalanine, indicating a loss of mobility. The peptides corresponding to residues 2-20 of PAH have different structural characteristics in the phosphorylated and unphosphorylated forms, with the former showing increased secondary structure. Our results support the model whereby upon phenylalanine binding, the mobile N-terminal 18 residues of PAH associate with the folded core of the molecule; phosphorylation may facilitate this interaction.

Heterogeneous nuclear ribonucleoprotein A3, a novel RNA trafficking response element-binding protein

The cis-acting response element, A2RE, which is sufficient for cytoplasmic mRNA trafficking in oligodendrocytes, binds a small group of rat brain proteins. Predominant among these is heterogeneous nuclear ribonucleoprotein (hnRNP) A2, a trans-acting factor for cytoplasmic trafficking of RNAs bearing A2RE-like sequences. We have now identified the other A2RE-binding proteins as hnRNP A1/A1(B), hnRNP B1, and four isoforms of hnRNP A3. The rat and human hnRNP A3 cDNAs have been sequenced, revealing the existence of alternatively spliced mRNAs. In Western blotting, 38-, 39-, 41 -, and 41.5-kDa components were all recognized by antibodies against a peptide in the glycine-rich region of hnRNP A3, but only the 41- and 41.5-kDa bands bound antibodies to a 15-residue N-terminal peptide encoded by an alternatively spliced part of exon 1. The identities of these four proteins were verified by Edman sequencing and mass spectral analysis of tryptic fragments generated from electrophoretically separated bands. Sequence-specific binding of bacterially expressed hnRNP A3 to A2RE has been demonstrated by biosensor and UV cross-linking electrophoretic mobility shift assays. Mutational analysis and confocal microscopy data support the hypothesis that the hnRNP A3 isoforms have a role in cytoplasmic trafficking of RNA.

Standardised audit of hip fractures in Europe

The objectives of this study were to evaluate the outcomes of our patients admitted with hip fractures, and to benchmark these results with other hospitals, initially in Europe and subsequently in Australia. The Standardised Audit of Hip Fractures in Europe (SAHFE) questionnaires was used as the data gathering instrument. The participants were all patients admitted to Redcliffe Hospital with a fractured neck of femur prior to surgery. This paper reports the results of the first 70 consecutive patients admitted to Redcliffe Hospital with a fractured neck of femur from November 1st 2000. The main outcome measures were mobility, independence, residence prior to fracture; type of fracture and surgical repair; and time to surgery, survival rates and discharge destination. Results: 43 patients were admitted from home, but only 13 returned home directly from the orthopaedic ward. It is hoped that most of the 26 transferred to the rehabilitation ward will ultimately return home. 7 patients died, these were aged 82 to 102, and all had premorbid disease. Delays in surgery were apparent for 13 patients, mainly due to administrative problems. Conclusions: We support the recommendation in the Fifteenth Scottish Intercollegiate Guidelines Network Publication on the management of hip fractures, that all units treating this condition should enter an audit to evaluate their management. (author abstract)

PFG-NMR measurements of the self-diffusion coefficients of water in equilibrium poly(HEMA-co-THFMA) hydrogels

The self-diffusion coefficients for water in a series of copolymers of 2-hydroxyethyl methacrylate, HEMA, and tetrahydrofurfuryl methacrylate, THFMA, swollen with water to their equilibrium states have been studied at 310 K using PFG-NMR. The self-diffusion coefficients calculated from the Stejskal-Tanner equation, D-obs, for all of the hydrated polymers were found to be dependent on the NMR storage time, as a result of spin exchange between the proton reservoirs of the water and the polymers, reaching an equilibrium plateau value at long storage times. The true values of the diffusion coefficients were calculated from the values of D-obs, in the plateau regions by applying a correction for the fraction of water protons present, obtained from the equilibrium water contents of the gels. The true self-diffusion coefficient for water in polyHEMA obtained at 310 K by this method was 5.5 x 10(-10) m(2) s(-1). For the copolymers containing 20% HEMA or more a single value of the self-diffusion coefficient was found, which was somewhat larger than the corresponding values obtained for the macroscopic diffusion coefficient from sorption measurements. For polyTHFMA and copolymers containing less than 20% HEMA, the PFG-NMR stimulated echo attenuation decay curves and the log-attenuation plots were characteristic of the presence of two diffusing water species. The self-diffusion coefficients of water in the equilibrium-hydrated copolymers were found to be dependent on the copolymer composition, decreasing with increasing THFMA content.

Novel molecular sieve silica (MSS) membranes: characterisation and permeation of single-step and two-step sol-gel membranes

High quality MSS membranes were synthesised by a single-step and two-step catalysed hydrolyses employing tetraethylorthosilicate (TEOS), absolute ethanol (EtOH), I M nitric acid (HNO3) and distilled water (H2O). The Si-29 NMR results showed that the two-step xerogels consistently had more contribution of silanol groups (Q(3) and Q(2)) than the single-step xerogel. According to the fractal theory, high contribution of Q(2) and Q(3) species are responsible for the formation of weakly branched systems leading to low pore volume of microporous dimension. The transport of diffusing gases in these membranes is shown to be activated as the permeance increased with temperature. Albeit the permeance of He for both single-step and two-step membranes are very similar, the two-step membranes permselectivity (ideal separation factor) for He/CO2 (69-319) and He/CH4 (585-958) are one to two orders of magnitude higher than the single-step membranes results of 2-7 and 69, respectively. The two-step membranes have high activation energy for He and H-2 permeance, in excess of 16 kJ mol(-1). The mobility energy for He permeance is three to six-fold higher for the two-step than the single-step membranes. As the mobility energy is higher for small pores than large pores and coupled with the permselectivity results, the two-step catalysed hydrolysis sol-gel process resulted in the formation of pore sizes in the region of 3 Angstrom while the single-step process tended to produce slightly larger pores. (C) 2002 Elsevier Science B.V. All rights reserved.

Transport safety for older people: A study of their experiences, perceptions and management needs

With evidence of increasing accident risk due to age-related declines in health and cognition affecting driver performance, there is a need for research promoting safe mobility of older people. The present study aimed to identify transport options and licensing issues for a group of older people in an Australian community. Ninety-five participants aged 75 and over were interviewed about their driving status and accident record and tested for cognitive ability. After stratification on cognitive level and driver status (current, ex-driver or non-driver), 30 were selected for further in-depth interviews concerning demographics, licence status and impact of change, travel options available and used, and travel characteristics. Considerable reliance on the motor vehicle as the mode of transport and the decision to cease driving were major quality-of-life issues. There was little evidence of planning and support in making the decision to stop driving. Some differences in transport decisions on the basis of cognitive level were evident; however, people with severely compromised cognitive ability (and, therefore, unable to give informed consent) had been excluded. The study suggested the need for resources to assist older people/carers/health professionals to plan for the transition from driver to non-driver and to manage alternative transport options more effectively

Comparison of lumbar range of movement and lumbar lordosis in back pain patients and matched controls

Inconclusive findings have been shown in previous studies comparing lumbar range of movement (LROM) and lumbar lordosis between back pain patients and healthy subjects. In these studies, confounding variables such as age, gender, height, obesity, and pain level were usually not well controlled. The present study aimed to compare LROM and lumbar lordosis between back pain patients and matched controls. Fifteen male back pain patients and 15 age-, height-, obesity-, and physical activity-matched male controls were investigated. To minimize the effect of pain on the measurements, only patients with minimal or no pain at the time of testing were included in the study. Inclinometer technique was used for the evaluation of LROM in flexion, extension and lateral flexion as well as lumbar lordosis. A lumbar rotameter was used for measuring axial rotation. Pelvic motion was limited by a pelvic restraint device during LROM measurements. Results showed that there were no significant differences between the back pain and control groups in flexion, extension, lateral flexion and axial rotation LROM and also in lumbar lordosis. This may indicate that when a back pain patient is not in pain, LROM and lumbar lordosis may not be the measures that distinguish between back pain patients and subjects without back pain.

Bracken (Pteridium aquilinum)-induced DNA adducts in mouse tissues are different from the adduct induced by the activated form of the bracken carcinogen ptaquiloside

Following treatment with bracken fern (Pteridium aquilinum) extract and bracken spores a number of DNA adducts were detected by P-32-postlabeling. Three of these adducts have been described previously (Povey et al., Br. J. Cancer (1996) 74, 1342-1348) and in this study, using a slightly different protocol, four new adducts, with higher chromatographic mobility, were detected at levels ranging from 50 to 230% of those previously described, When DNA was treated in vitro with activated ptaquiloside (APT) and analysed by butanol extraction or nuclease P1 treatment, only one adduct was detected by P-32-postlabeling, This adduct was not present in the DNA from mice treated with bracken fern or spores, suggesting either that bracken contains genotoxins other than ptaquiloside or that the metabolism of ptaquiloside produces genotoxins not reflected by activated ptaquiloside. However, as the ATP-derived adduct has been detected previously in ileal DNA of bracken-fed calves, species-specific differences in the metabolism of bracken genotoxins may exist, thereby leading to differences in their biological outcomes. (C) 2001 Academic Press.