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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 163 records · Page 9Linked to original sources
PubMed2001

A candidate prostate cancer susceptibility gene at chromosome 17p.

It is difficult to identify genes that predispose to prostate cancer due to late age at diagnosis, presence of phenocopies within high-risk pedigrees and genetic complexity. A genome-wide scan of large, high-risk pedigrees from Utah has provided evidence for linkage to a locus on chromosome 17p. We carried out positional cloning and mutation screening within the refined interval, identifying a gene, ELAC2, harboring mutations (including a frameshift and a nonconservative missense change) that segregate with prostate cancer in two pedigrees. In addition, two common missense variants in the gene are associated with the occurrence of prostate cancer. ELAC2 is a member of an uncharacterized gene family predicted to encode a metal-dependent hydrolase domain that is conserved among eukaryotes, archaebacteria and eubacteria. The gene product bears amino acid sequence similarity to two better understood protein families, namely the PSO2 (SNM1) DNA interstrand crosslink repair proteins and the 73-kD subunit of mRNA 3' end cleavage and polyadenylation specificity factor (CPSF73).

Amino Acid Sequence↗
PubMed2001

Geographical patterns of genetic variation in two species of Stylosanthes Sw. using amplified fragment length polymorphism.

Understanding the extent and distribution of genetic diversity within a species is essential for the development of effective conservation strategies. The objective of this study was to assess genetic variation using amplified fragment length polymorphisms (AFLP) in two species of the tropical legume genus Stylosanthes Sw. Annual, S. humilis (2n = 20) and perennial, S. viscosa (2n = 20) are found throughout tropical America, and are sympatric for much of their range of distribution. One hundred and eleven accessions, covering a wide geographical range, were selected for AFLP analysis. Binary data matrices derived from DNA banding patterns were analysed using the software programs NTSYS-PC and ARLEQUIN. Several accessions were found to be misidentified. Of the S. humilis accessions, the overall average similarity value was (0.72) slightly higher than the value obtained for S. viscosa (0.67). Cluster analysis and principal coordinate analysis grouped accessions from both species by geographical origin, with a few exceptions. Analysis of molecular variance (AMOVA) in S. humilis revealed 59.4% of the variation among groups formed from the cluster analysis. This was highly significant (P < 0.001). For S. viscosa AMOVA also revealed more variation among than within groups (66.5%). This was also highly significant (P < 0.001). The majority of accessions of both species conserved ex situ are of Brazilian and Venezuelan origin. This study has identified areas in Central America and Mexico for which novel genetic variation may be found and where conservation activities should be focused.

Evolution, Molecular↗
PubMed2001

Synovial fluid studies in navicular disease.

The purpose of this study was to investigate biochemical changes in synovial fluid in navicular disease, and to establish if synovial fluid from the distal interphalangeal joint (DIP) could be used diagnostically to assess alterations in the synovial fluid of the navicular bursa. Cartilage oligomeric matrix protein (COMP), total glycosaminoglycans (GAG), hyaluronan (HA), metalloproteinases 2 and -9 (MMP-2 and MMP-9) and total protein (TP) levels were determined in synovial fluids obtained from 18 navicular bursae and 35 DIP -joints from animals suffering from navicular disease, and the same synovial structures in 16 joints of horses with no evidence of abnormalities involving the foot. To avoid dilution effects, GAG/COMP, HA/COMP, MMP-2/ COMP and MMP-9/COMP ratios were also calculated for different synovial cavities. There was a good correlation, for COMP, GAG, HA, MMP-2 and TP levels, between synovial fluid from the navicular bursa and fluid from the DIP -joint in healthy animals. However, in animals with navicular disease, only COMP levels showed no difference between the navicular bursal fluid and the DIP-joint fluid concentration. Thus, enabling the use of COMP to standardise other biochemical concentration measurements from the synovial joint fluids. In horses with navicular disease, there was a significantly lower absolute concentration of GAG, and a significantly lower GAG/COMP ratio, in the synovial fluid of the navicular bursa and the DIP-joint compared to synovial fluid from the same joints from healthy horses. In contrast, the absolute HA concentration and HA/ COMP, MMP-2/COMP and MMP-9/COMP ratios were higher in synovial fluid from the DIP-joint of horses with navicular disease, and MMP-2 and MMP-9 relative activity levels and MMP-2/COMP and MMP-9/ COMP ratios were increased in fluid from navicular bursae in horses with navicular disease when compared to a control group.

Animals↗
PubMed2001

Improving clinical management for consumers with co-existing mental health and substance use disorders: an integrated approach.

Using Quality Improvement project methodology, complex organisational and clinical practice change was brought about to improve services for people with co-existing mental health and alcohol and drug misuse. The project describes local uptake and adaptation of national and state policy to achieve change that is sustainable within existing resources. Emphasis on engagement of staff and consumers and carers throughout the change was an essential component. The project has implications for the introduction of changes in response to other national policy directives.

Diagnosis, Dual (Psychiatry)↗
PubMed2001

Falls Clinics in Australia: a survey of current practice, and recommendations for future development.

The aim of this study was to identify common themes and differences in structure and function of Falls Clinics in Australia, to provide a framework for planning future activity. A paper-based survey was circulated to 20 identified Falls Clinic services throughout Australia in late 2000. Fifteen responses (75%) were received, although two of the 15 Clinics were not operating at the time of the survey, and so their responses were not included. Nine of the Clinics had commenced operation since 1998. Staffing commonly included a physiotherapist, geriatrician, and an occupational therapist, with the comprehensive multidisciplinary assessment process taking an average of 130 minutes. Although standard assessment tools were used by more than half of the Clinics, there were no universally applied assessment tools. Waiting lists for initial assessments ranged up to 16 weeks (average 6 weeks). Most Clinics instituted a number of management options themselves, but also used a range of existing community services to provide some of the planned interventions. Limited formal evaluation of the effectiveness of Clinics was reported. Recommended future activity included increasing staff levels and operating times for Clinics to more adequately meet identified need, increased networking and data sharing between Clinics, and a greater emphasis on research and staff training. We conclude that the recent increase in the number of Falls Clinics around Australia has occurred in a relatively unstructured manner, with many differences in staffing, operation and evaluation. There is a need for improved communication and standardisation of core procedures and assessment tools to facilitate best practice in all Clinics, and to provide a framework for a systematic evaluation of the effectiveness of Falls Clinics in Australia.

Accidental Falls↗
PubMed2001

Distribution and localization of CMP-N-acetylneuraminic acid hydroxylase and N-glycolylneuraminic acid-containing glycoconjugates in porcine lymph node and peripheral blood lymphocytes.

An immunohistochemical analysis was performed on paraplast-embedded sections of porcine lymph node with antibodies specific for CMP-N-acetylneuraminic acid hydroxylase (h-3 antibody) and glycoconjugate-bound N-glycolylneuraminic acid (Neu5Gc), which appears as a result of the hydroxylase reaction (a-Gc antibody). The observed localization of the enzyme in cells of the perifollicular zone, including lymphocytes, was reflected in a similar distribution of glycoconjugate-bound Neu5Gc. This result confirms previous biochemical investigations on the role of the hydroxylase in regulating Neu5Gc biosynthesis in vitro on a histological level. An analysis of lymphocytes isolated from porcine thymus, spleen, lymph node and peripheral blood revealed differences in the amount of Neu5Gc in the various lymphocytes that correlated well with the activity of the hydroxylase determined in these cells. The largest amount of Neu5Gc and highest activity of the enzyme were detected in the peripheral blood lymphocytes (PBL). Immunohistochemical studies with a-Gc and h-3 antibodies on sections of paraplast-embedded PBL showed that these antigens were located at the cell surface and in the cytosol, respectively. Ultrastructural immunocytochemistry with the h-3 antibody and immunogold labelling was used to investigate the subcellular localization of the hydroxylase. The enzyme was detected in the cytosol in the vicinity of the nuclear membrane and the outer membrane of mitochondria, in particular those close to the nucleus. The antigen was also detected on cytoplasmic tubular structures. In addition, a weak labelling of the Golgi apparatus was also observed occasionally. The possibility that this localization may be related to the availability of the substrate CMP-Neu5Ac and the redox partner cytochrome b5 is discussed.

Animals↗
PubMed2001

The Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI).

The development and testing of an observational gait assessment instrument, the Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI) is described. To assess validity and reliability, 22 subjects with incomplete spinal cord injury were scored by four raters. Raters scored each subject three times, once live (LS) and twice from videotaped records (VS1, VS2). A moderate-good negative correlation (r = -0.742 and -0.700, for VS1 and VS2, respectively) was found between the gait score and time required to walk a demarcated path. Inter-rater reliability was moderate-good for the live score and the videotaped records (ICC = 0.703, 0.800, and 0.840, respectively). Intra-rater reliability was good (ICC = 0.903, 0.960, 0.942, and 0.850 for Raters 1-4, respectively). To assess sensitivity, another group of 19 subjects with SCI were assessed prior to and following participation in an intensive walking program. A moderate correlation was found between change in gait score and change in lower extremity strength (Pearson r = 0.58). These results indicate that the SCI-FAI is a reliable, valid and sensitive measure of walking ability in individuals with spinal cord injury. In addition, the results suggest that gait analysis using this instrument is equally reliable whether the observation is performed live or from videotaped records.

Adult↗
PubMed2001

Long-term follow-up on an intensified treatment regimen for advanced resectable head and neck squamous cell carcinomas.

From February 1993 through July 1994, 37 patients with stage III-IV squamous cell carcinomas of the oral cavity, oropharynx, or hypopharynx (stage II-IV) were registered to a treatment regimen consisting of preoperative continuous infusion cisplatin (80 mg/m2/80 hours) with hyperfractionated external beam radiotherapy (9.1 Gy/7 fractions of 1.3 Gy BID), surgical resection, intraoperative radiotherapy (7.5 Gy), and postoperative radiotherapy (40 Gy) with concurrent cisplatin (100 mg/m2 x 2 courses). The objectives of the regimen were to improve patient compliance while also increasing treatment intensity. The purpose of this article is to report the local, regional (nodal), and distant disease control of these patients after an extended time at risk (median 40 months). Overall compliance (73%), local control at primary site (97%), and regional nodal control (95%) were excellent. The rate of distant metastasis was 19%. Absolute survival at 48 months was 45.9%.

Carcinoma, Squamous Cell↗
PubMed2001

Ovine IFN-tau modulates the expression of MHC antigens on murine cerebrovascular endothelial cells and inhibits replication of Theiler's virus.

Interferon-beta (IFN-beta) has been used successfully to treat patients with relapsing-remitting multiple sclerosis (MS). IFN-tau is a new class of type I IFN that is secreted by the trophoblast and is the signal for maternal recognition of pregnancy in sheep. IFN-tau has potent immunosuppressive and antiviral activities similar to other type I IFN but is less cytotoxic than IFN-alpha/beta. The current investigation concerns the effect of recombinant ovine IFN-tau (rOvIFN-tau) on the modulation of MHC class I and II expression on cloned mouse cerebrovascular endothelial (CVE) cells. IFN-tau induced tyrosine phosphorylation of Stat1 and upregulated the expression of MHC class I on CVE. One proposed action by which type I IFN reduce the relapse rate in MS is via interference with IFN-gamma-induced MHC class II expression. IFN-tau was shown to downregulate IFN-gamma-induced MHC class II expression on CVE and, hence, may be of potential therapeutic value in downregulating inflammation in the central nervous system (CNS). IFN-tau did not upregulate the expression of MHC class II on CVE. IFN-tau also inhibited the replication of Theiler's virus in CVE. These in vitro results suggest that IFN-tau may be of therapeutic value in the treatment of virus-induced demyelinating disease.

Animals↗
PubMed2001

Müllerian inhibitory substance induces growth of rat preantral ovarian follicles.

Müllerian inhibitory substance (MIS), also known as anti-Müllerian hormone, is best known as the hormone that regulates the regression of the Müllerian duct in males. In females, MIS is expressed in granulosa cells of preantral and early antral follicles. The specific MIS type II receptor is present in granulosa and theca cells of these small, growing follicles. Because the role of MIS in preantral follicle development is unknown, we have evaluated the effect of MIS on the growth, differentiation, and apoptosis of intact preantral follicles in a serum-free culture system. In this system, treatment with FSH induces an increase in both follicle diameter, cell number, and follicle cell differentiation based on increased inhibin-alpha synthesis. Of interest, treatment with MIS enhances the effect of FSH both on follicle diameter and cell number. Although treatment with activin A also enhances FSH effects on follicle growth, treatment with transforming growth factor (TGF)-ss inhibits the FSH effects on follicle growth. Based on in situ staining of fragmented DNA, MIS was found to have no effect on follicle cell apoptosis, unlike its proapoptotic action on Müllerian ducts. In contrast to MIS and activin, TGF-ss was a potent proapoptotic factor for preantral follicles in culture. Analysis of inhibin-alpha expression of cultured preantral follicles further indicated that in contrast to activin, treatment with MIS did not enhance FSH-stimulated follicle differentiation. Thus, MIS is a unique factor that promotes preantral follicle growth but not preantral follicle cell differentiation and apoptosis.

Animals↗
PubMed2001

Enhancing staff development with a structured preceptor program.

The unexpected expansion of a 14-bed medical intensive care unit exposed the need for a structured preceptor/orientation program. Staff feedback and a review of quality indicators further substantiated this finding and revealed a decrease in standards of practice and problems in staff development. A restructured preceptor/orientation program yielded improvements in communication and staff satisfaction. Preceptors and orientees now have a better understanding of their roles and expectations, and quality of care is improving in an environment that promotes personal and professional growth.

Humans↗
PubMed2001

Evaluation of recurrent squamous cell carcinoma of the head and neck with FDG positron emission tomography.

PURPOSE: This study compared the effectiveness of fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT), magnetic resonance imaging (MRI), or both for the assessment of recurrent squamous cell carcinoma of the head and neck. The value of quantifying the standardized uptake values (SUV) to distinguish recurrent neoplasm from inflammatory lesions and normal structures was also evaluated. METHODS: Forty-three patients with head and neck cancer were examined with F-18 FDG PET at least 4 months after their last course of radiation therapy (mean, 11 months). The SUVs were measured in visually identified regions of abnormally increased activity and were compared with the values in normal mucosa, the base of the tongue, and the hard palate to determine if an optimal cutoff value exists for diagnosing recurrence of malignant lesions. The final diagnosis of recurrence was made based on biopsy or at least 6 months' clinical follow-up. RESULTS: FDG PET correctly detected recurrence in 20 of 22 patients who had 45 discrete lesions located in the field of the upper aerodigestive tract. Two false-negative and three false-positive results were identified. The accuracy of FDG PET was 88% (38 of 43 patients), compared with 66% (25 of 38 patients) for CT, MRI, or both. Although there was a significant difference of SUVs (P = 0.0036) between the recurrent lesions and normal structures, the optimal cutoff values were difficult to define. CONCLUSIONS: Visual analysis of FDG PET is significantly more accurate in the diagnosis of recurrent squamous cell cancer of the head and neck than are CT or MRI. However, single SUV quantification does not significantly enhance efficacy.

Algorithms↗
PubMed2001

Role of IFN-gamma in bacterial containment in a model of intra-abdominal sepsis.

Interferon-gamma (IFN-gamma) is a specific activator of macrophage function and plays a critical role in the host immune defense to bacterial infection. In this study we examined the role of IFN-gamma in the regulation of bacterial load in the cecal ligation and puncture (CLP) model of intra-abdominal sepsis in the rat. In initial studies, levels of IL-12, MCP-1, and IFN-gamma were measured in the peritoneal lavage fluid 24 and 48 h after CLP. IL-12 and MCP-1 levels were both significantly increased at 24 h after CLP compared to sham controls and this difference was maintained at 48 h after CLP. Interestingly, IFN-gamma levels were not significantly increased 24 h after CLP, but were increased at 48 h after CLP. These results clearly suggest that although an inflammatory response had occurred 24 h post-surgery, with increases in the proinflammatory cytokine IL-12 and the potent chemotactic agent MCP-1, levels of IFN-gamma in CLP rats were similar to sham controls. To further investigate the role of IFN-gamma on the development of sepsis we examined the effect(s) of administering anti-IFN-gamma antibody on bacterial load after CLP. We show that use of anti-IFN-gamma antibody can significantly decrease bacterial load in the peritoneum. The mechanism of the effect(s) of anti-IFN-gamma is probably by increasing intestinal adhesions to seal the cecum and reduce bacterial movement into the peritoneum.

Animals↗
PubMed2001

Nocardia veterana sp. nov., isolated from human bronchial lavage.

A nocardioform bacterium was isolated from the bronchoscopic lavage of a 78-year-old man with a past history of tuberculous pleurisy, who presented with bilateral upper lobe lesions at Austin and Repatriation Medical Centre, Heidelberg, Australia. The strain was aerobic, Gram-positive, produced beige substrate mycelium and scant white aerial mycelium. It showed chemotaxonomic markers which were consistent with the classification of Nocardia: i.e. meso-diaminopimelic acid, N-glycolylmuramic acid, arabinose and galactose as diagnostic sugars; phospholipids phosphatidylinositol mannosides, phosphatidylinositol, phosphatidylethanolamine and diphosphatidylglycerol; a menaquinone with a cyclic isoprene side chain, MK-8(H4cycl.); a fatty acid pattern composed of unbranched saturated and monounsaturated fatty acids with a considerable amount of tuberculostearic acid; and mycolic acids composed of 54-62 carbon atoms with three principal mycolic acids which were mono- and polyunsaturated, showing a chain length C56, C58 and C60 and accounting for over 70% of the entire pattern. The 16S rDNA sequence showed the highest similarity to the type strain of Nocardia vaccinii; the DNA-DNA similarity of the two strains was 31%. These data, together with distinct physiological traits and molecular biological analyses, as well as chemotaxonomic results, led to the conclusion that the novel isolate represents a new species within the genus Nocardia for which the name Nocardia veterana sp. nov. is proposed. The type strain is M157222T (DSM 44445T = NRRL B-24136T).

Aged↗