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Biomedical subjects

D Higgins

Publications and source records attributed to D Higgins.

At least 19 recordsLinked to original sources
PubMed2006

Classifications used by Australian forensic odontologists in identification reports.

Forensic odontologists are repeatedly called upon to assist in the identification of deceased persons. A great deal of information is available in the literature as to how and why comparative dental investigation of identification is performed but there is little information on the descriptive terms used in reporting these identifications. A forensic odontology report sets out the findings of a comparison between antemortem and postmortem evidence and indicates the odontologist's opinion on the identification. This opinion needs to be defendable in a court of law. This paper investigates the classifications utilised in the six states and two territories of Australia and reflects on the differences. Three states of Australia use American Board of Forensic Odontology classifications, whilst the remaining regions use a modified format. Since there are no significant legal, cultural or religious differences, and similar practitioners and clients, variation between regions within Australia would seem hard to justify. National standard terminology should be encouraged.

Australia↗
PubMed2005

Prophage-like elements in bifidobacteria: insights from genomics, transcription, integration, distribution, and phylogenetic analysis.

So far, there is only fragmentary and unconfirmed information on bacteriophages infecting the genus Bifidobacterium. In this report we analyzed three prophage-like elements that are present in the genomes of Bifidobacterium breve UCC 2003, Bifidobacterium longum NCC 2705, and Bifidobacterium longum DJO10A, designated Bbr-1, Bl-1, and Blj-1, respectively. These prophagelike elements exhibit homology with genes of double-stranded DNA bacteriophages spanning a broad phylogenetic range of host bacteria and are surprisingly closely related to bacteriophages infecting low-G+C bacteria. All three prophage-like elements are integrated in a tRNA(Met) gene, which appears to be reconstructed following phage integration. Analysis of the distribution of this integration site in many bifidobacterial species revealed that the attB sites are well conserved. The Blj-1 prophage is 36.9 kb long and was induced when a B. longum DJO10A culture was exposed to mitomycin C or hydrogen peroxide. The Bbr-1 prophage-like element appears to consist of a noninducible 28.5-kb chimeric DNA fragment composed of a composite mobile element inserted into prophage-like sequences, which do not appear to be widely distributed among B. breve strains. Northern blot analysis of the Bbr-1 prophage-like element showed that large parts of its genome are transcriptionally silent. Interestingly, a gene predicted to encode an extracellular beta-glucosidase carried within the Bbr-1 prophage-like element was shown to be transcribed.

Base Sequence↗
PubMed2004

Outcome analysis and patient satisfaction following octant transrectal ultrasound-guided prostate biopsy: a prospective study comparing consultant urologist, specialist registrar and nurse practitioner in urology.

PURPOSE: To determine whether transrectal ultrasound-guided biopsy of the prostate is equally reliable and acceptable if performed by urology nurse practitioner or urologist. SCOPE: Octant biopsies were taken by each operator (consultant urologist n=2, urology specialist registrar n=1 and urology nurse practitioner n=2) from 50 consecutive unselected patients and demographics and cancer detection rate were compared between the groups. A postal survey was performed following nurse practitioner biopsy to assess patient satisfaction and acceptance of nurse practitioner biopsy. CONCLUSION: Transrectal ultrasound-biopsy of prostate whether performed by nurse practitioner or urologist is equally reliable if adequate training is provided. Patients are happy to undergo prostate biopsy and receive information about the diagnosis from an appropriately trained prostate cancer nurse specialist.

Aged↗
PubMed2002

Bone morphogenetic protein-7 stimulates initial dendritic growth in sympathetic neurons through an intracellular fibroblast growth factor signaling pathway.

Bone morphogenetic protein-7 (BMP-7), a member of the transforming growth factor (TGF)-beta superfamily of signaling cytokines, induces dendritic growth in rat sympathetic neurons. In this study, we present evidence that the recently discovered integrative nuclear FGFR1 signaling (INFS) pathway is involved in dendrite outgrowth mediated by BMP-7. Immunocytochemical analysis of expressed fibroblast growth factors (FGFs) showed that little FGF-2 was detected in control neurons, but the expression of this molecule in the cytoplasm and nucleus increased within 6 h after BMP-7 treatment. In contrast, FGF-1 was constitutively present in the peripheral cytoplasm and in neurites under control conditions, and its distribution did not change with BMP-7 exposure. The high-affinity receptor FGFR1 was present in low amounts in control neurons and was associated with the cytoplasm, the plasma membrane, and the nucleus. Twenty-four hours of BMP-7 treatment elicited an increase in FGFR1 nuclear localization. Overexpressed constructs of FGFR1 that lack the tyrosine kinase domain, and have been shown to act in a dominant-negative manner on FGFR1 signaling, inhibited BMP-7 mediated initial dendrite outgrowth in transfected neurons by approximately 50%. However, targeted inhibition of extracellular FGF-2 by overexpression of a secreted receptor mutant FGFR1(TM-) lacking the transmembrane domain failed to affect BMP-7 induced dendritic growth, as did treatment with the extracellular FGFR antagonist inositol hexakisphosphate. These results suggest that the INFS, which has already been implicated in a broad range of activities in other cell types, may also be required for BMP-7 to stimulate dendritic development.

Animals↗
PubMed2001

Bone morphogenetic protein-5 (BMP-5) promotes dendritic growth in cultured sympathetic neurons.

BACKGROUND: BMP-5 is expressed in the nervous system throughout development and into adulthood. However its effects on neural tissues are not well defined. BMP-5 is a member of the 60A subgroup of BMPs, other members of which have been shown to stimulate dendritic growth in central and peripheral neurons. We therefore examined the possibility that BMP-5 similarly enhances dendritic growth in cultured sympathetic neurons. RESULTS: Sympathetic neurons cultured in the absence of serum or glial cells do not form dendrites; however, addition of BMP-5 causes these neurons to extend multiple dendritic processes, which is preceded by an increase in phosphorylation of the Smad-1 transcription factor. The dendrite-promoting activity of BMP-5 is significantly inhibited by the BMP antagonists noggin and follistatin and by a BMPR-IA-Fc chimeric protein. RT-PCR and immunocytochemical analyses indicate that BMP-5 mRNA and protein are expressed in the superior cervical ganglia (SCG) during times of initial growth and rapid expansion of the dendritic arbor. CONCLUSIONS: These data suggest a role for BMP-5 in regulating dendritic growth in sympathetic neurons. The signaling pathway that mediates the dendrite-promoting activity of BMP-5 may involve binding to BMPR-IA and activation of Smad-1, and relative levels of BMP antagonists such as noggin and follistatin may modulate BMP-5 signaling. Since BMP-5 is expressed at relatively high levels not only in the developing but also the adult nervous system, these findings suggest the possibility that BMP-5 regulates dendritic morphology not only in the developing, but also the adult nervous system.

Animals↗
PubMed2001

Polyethyleneimine-mediated transfection of cultured postmitotic neurons from rat sympathetic ganglia and adult human retina.

BACKGROUND: Chemical methods of transfection that have proven successful with cell lines often do not work with primary cultures of neurons. Recent data, however, suggest that linear polymers of the cation polyethyleneimine (PEI) can facilitate the uptake of nucleic acids by neurons. Consequently, we examined the ability of a commercial PEI preparation to allow the introduction of foreign genes into postmitotic mammalian neurons. Sympathetic neurons were obtained from perinatal rat pups and maintained for 5 days in vitro in the absence of nonneuronal cells. Cultures were then transfected with varying amounts of a plasmid encoding either E. coli beta-galactosidase or enhanced green fluorescence protein (EGFP) using PEI. RESULTS: Optimal transfection efficiency was observed with 1 microg/ml of plasmid DNA and 5 microg/ml PEI. Expression of beta-galactosidase was both rapid and stable, beginning within 6 hours and lasting for at least 21 days. A maximum yield was obtained within 72 hours with approximately 9% of the neurons expressing beta-galactosidase, as assessed by both histochemistry and antibody staining. Cotransfection of two plasmids encoding reporter genes was achieved. Postmitotic neurons from adult human retinal cultures also demonstrated an ability to take up and express foreign DNA using PEI as a vector. CONCLUSIONS: These data suggest that PEI is a useful agent for the stable expression of plasmid-encoded genes in neuronal cultures.

Animals↗
PubMed2001

Cerebrospinal fluid contains biologically active bone morphogenetic protein-7.

Bone morphogenetic proteins (BMPs) regulate the development and function of many types of neurons. However, little is known of the actual concentrations of BMPs in the various parts of the brain. In this study, we considered the possibility that BMPs might be present in cerebrospinal fluid (CSF). Western blot analysis of normal adult bovine CSF revealed the presence of dimeric and monomeric forms of BMP-7, and the concentration of this molecule was found to be approximately 12 ng/ml in a radioimmunoassay. Since BMP-7 is known to induce dendritic growth in rat sympathetic neurons, this was used as a bioassay to examine the biological activity of the BMP-7 present in CSF. Addition of normal bovine CSF to cultures of sympathetic neurons produced a dose-dependent increase in dendritic growth and the magnitude of this response approximated that obtained with maximally effective concentrations of exogenous BMP-7. Moreover, CSF-induced dendritic growth was inhibited by follistatin, a protein that can sequester BMPs, and by either of two monoclonal antibodies that react with BMP-7. These results show that, unlike most other neurotrophic factors, BMP-7 is a constituent of normal CSF and is present at concentrations sufficient to elicit a near maximal biological response.

Activins↗
PubMed2001

Dendritic growth induced by BMP-7 requires Smad1 and proteasome activity.

Bone morphogenetic proteins (BMPs) induce dendritic growth in cultured sympathetic neurons; however, the signaling pathways that mediate this dendrite-promoting activity have not been previously characterized. Here we report studies of the signaling events that regulate the growth of these afferent processes. We find that Smad1 is expressed in sympathetic neurons and that BMPs rapidly induce its phosphorylation and translocation from the cytoplasm to the nucleus. Furthermore, a dominant negative form of Smad1 inhibits BMP-7-induced dendritic growth, suggesting a requirement for Smad1 activation in this biological activity of BMP-7. A physical interaction between Smad1 and components involved in the proteasome-mediated degradation system was detected with a yeast two-hybrid screen, thereby prompting an examination of the effects of proteasome inhibitors on dendritic growth. Lactacystin and ALLN (N-acetyl-Leu-Leu-norleucinal) selectively blocked BMP-7-induced dendritic growth without adversely affecting either cell viability or axonal growth. Moreover, studies of transfected P19 cells suggest that the proteasome inhibitors directly block the effects of Smad1 on the transcriptional activity of the Tlx-2 promoter. These data indicate that BMP-induced dendritic growth requires Smad1 activation and involves proteasome-mediated degradation events.

Acetylcysteine↗
PubMed2000

Differential localization of divalent metal transporter 1 with and without iron response element in rat PC12 and sympathetic neuronal cells.

Two isoforms of divalent metal transporter 1 (DMT1) (Nramp2 and DCT1) are encoded by two mRNA species, one of which contains an iron response element (IRE) motif in the 3'-noncoding region. The subcellular distribution of the two isoforms of DMT1 is distinct, and the -IRE species accumulates in the nucleus of neuronal or neuronal-like cells. Reverse transcription-PCR and Western blot analysis of PC12 cells reveals that these cells express both forms of DMT1. Immunofluorescence and immunoblotting studies, using immunospecific antibodies to the -IRE form of DMT1, demonstrate that this form of the transporter, in PC12 cells, is predominantly localized in the nucleus, cell membrane, and neurites with only weak staining of the cell body. Studies using antibodies to the +IRE form indicate that this species of DMT1 is distributed within vesicles in the cell body and neurite projections, with minimal nuclear staining. Similar staining patterns are observed for the two forms of DMT1 in cultures of sympathetic ganglion neurons isolated from perinatal rat pups. To determine whether nuclear localization of the -IRE form of DMT1 is constrained to neuronal or neuronal-like cells, immunocytochemical studies were performed with human embryonic kidney 293T (HEK293T), HEP2G hepatoma and medulloblastoma, and rat Schwann cells. The -IRE-specific antibodies stained nuclei from medulloblastoma, whereas little nuclear staining was observed with HEK293T, hepatoma, or Schwann cells. The unexpected finding that the -IRE species of DMT1 selectively accumulates in the nucleus of neuronal and neuronal-like cells leads us to postulate that the two proteins may have different functions in vivo.

Animals↗
PubMed2000

Development of T-leukaemias in CD45 tyrosine phosphatase-deficient mutant lck mice.

The CD45 tyrosine phosphatase lowers T-cell antigen receptor signalling thresholds by its positive actions on p56(lck) tyrosine kinase function. We now show that mice expressing active lck(F505) at non-oncogenic levels develop aggressive thymic lymphomas on a CD45(-/-) background. CD45 suppresses the tumorigenic potential of the kinase by dephosphorylation of the Tyr394 autophosphorylation site. In CD45(-/-) thymocytes the kinase is switched to a hyperactive oncogenic state, resulting in increased resistance to apoptosis. Transformation occurs in early CD4(-)CD8(-) thymocytes during the process of TCR-beta chain rearrangement by a recombinase-independent mechanism. Our findings represent the first example in which a tyrosine phosphatase in situ prevents the oncogenic actions of a SRC: family tyrosine kinase.

Animals↗
PubMed2000

Development, dissemination, implementation and evaluation of a clinical pathway for oxygen therapy.

BACKGROUND: Oxygen is commonly administered to patients in hospital, but prescribing and monitoring of such therapy may be suboptimal. The objective of this study was to develop, disseminate, implement and evaluate a multidisciplinary clinical pathway for the administration of oxygen. METHODS: The authors developed a clinical pathway for the ordering, titration and discontinuation of oxygen, which was disseminated through teaching sessions, in-service training sessions and information posters in a medical clinical teaching unit (CTU). Implementation of the pathway was ensured by means of reminders and patient-centred audit and feedback to CTU nurses and house staff. During a 3-month intervention phase, consecutive patients requiring supplemental oxygen were treated according to the pathway. During a 1-month "wash-out" phase followed by a 3-month non-intervention phase, patients were treated at the discretion of the CTU team. Clinical and economic data were collected in both phases. RESULTS: In the 2 phases, patient characteristics, the concentration and duration of oxygen prescribed, the frequency of oxygen saturation monitoring, the frequency of arterial blood gas testing and the clinical outcomes were similar. However, there were more discontinuation orders in the intervention phase (p < 0.001). In the intervention phase, costs were higher for monitoring of oxygen saturation ($44.95/patient v. $36.17/patient, p = 0.048) and for order transcription ($2.71/patient v. $1.28/patient, p < 0.001); total costs, including those for personnel, were also higher in the intervention phase ($76.93/patient v. $56.67/patient, p = 0.02). The cost of education about the oxygen pathway was $45.71/patient. When the education cost was included, the total cost of oxygen therapy during the intervention phase was $122.64/patient; this was significantly higher than the total cost of oxygen therapy during the non-intervention phase ($56.67/patient) (p < 0.001). INTERPRETATION: This multidisciplinary, multimethod oxygen pathway led to changes in oxygen-prescribing behaviour, consumed more resources than standard management and was not associated with changes in patient outcome. Appropriate management of oxygen prescribing and monitoring by physicians and nurses take time and costs money.

Aged↗
PubMed2000

Bone morphogenetic protein-7 enhances dendritic growth and receptivity to innervation in cultured hippocampal neurons.

Members of the bone morphogenetic protein (BMP) family of growth factors are present in the central nervous system during development and throughout life. They are known to play an important regulatory role in cell differentiation, but their function in postmitotic telencephalic neurons has not been investigated. To address this question, we examined cultured hippocampal neurons following treatment with bone morphogenetic protein-7 (BMP-7, also referred to as osteogenic protein-1). When added at the time of plating, BMP-7 markedly stimulated the rate of dendritic development. Within 1 day, the dendritic length of BMP-7-treated neurons was more than twice that of controls. By three days the dendritic arbors of BMP-7-treated neurons had attained a level of branching similar to that of 2-week-old neurons cultured under standard conditions. Several findings indicate that BMP-7 selectively enhances dendritic development. While dendritic length was significantly increased in BMP-7-treated neurons, the length of the axon was not. In addition, the mRNA encoding the dendritic protein MAP2 was significantly increased by BMP-7 treatment, but the mRNA for tubulin was not. Finally, BMP-7 did not enhance cell survival. Because dendritic maturation is a rate-limiting step in synapse formation in hippocampal cultures, we examined whether BMP-7 accelerated the rate at which neurons became receptive to innervation. Using two separate experimental paradigms, we found that the rate of synapse formation (assessed by counting synapsin I-positive presynaptic vesicle clusters) was increased significantly in neurons that had been exposed previously to BMP-7. Because BMP-7 and related BMPs are expressed in the hippocampus in situ, these factors may play a role in regulating dendritic branching and synapse formation in both development and plasticity.

Animals↗
PubMed2000

Retinoic acid regulates the morphological development of sympathetic neurons.

Interactions between all-trans-retinoic acid (RA) and bone morphogenetic proteins (BMPs) affect the expression of neurotrophin receptors in sympathetic neurons (Kobayashi et al., 1998). In this study, we examined the possibility that similar interactions might regulate the morphological development of these neurons. Under control conditions, embryonic rat sympathetic neurons formed axons but not dendrites; cells exposed to RA had a similar appearance. Profuse dendritic growth was observed upon exposure to BMP-7, and this was reduced by approximately 70% by RA. This inhibitory effect of RA was mediated primarily by retinoic acid receptors (RARs) and it exhibited substantial specificity because it was not associated with changes in either axonal elongation or cell survival. Moreover, mRNAs for enzymes required for synthesis of RA were expressed in the sympathetic neurons and retinoid activity was released from superior cervical ganglia. These observations suggest that retinoids may function as endogenous morphogens and regulate neural cell shape and polarity in developing sympathetic ganglia.

Alcohol Oxidoreductases↗
PubMed2000

The role of the prostate cancer nurse specialist.

Prostate cancer is becoming an increasing burden on health services. It is essential that any man undergoing investigations for prostate cancer should be counselled by a specialist nurse utilising research-based information. Ideally, a prostate cancer nurse specialist should be able to carry out all diagnostic tests. This would enable the provision of a rapid access prostate cancer diagnosis service.

Humans↗
PubMed1999

Leukemia inhibitory factor and ciliary neurotrophic factor cause dendritic retraction in cultured rat sympathetic neurons.

Dendritic retraction occurs in many regions of the developing brain and also after neural injury. However, the molecules that regulate this important regressive process remain largely unknown. Our data indicate that leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) cause sympathetic neurons to retract their dendrites in vitro, ultimately leading to an approximately 80% reduction in the size of the arbor. The dendritic retraction induced by LIF exhibited substantial specificity because it was not accompanied by changes in cell number, in the rate of axonal growth, or in the expression of axonal cytoskeletal elements. An antibody to gp130 blocked the effects of LIF and CNTF, and both cytokines induced phosphorylation and nuclear translocation of stat3. Moreover, addition of soluble interleukin-6 (IL-6) receptor to the medium endowed IL-6 with the ability to cause dendritic regression. These data indicate that ligands activating the gp130 pathway have the ability to profoundly alter neuronal cell shape and polarity by selectively causing the retraction of dendrites.

Animals↗
PubMed1999

OP-1 enhances dendritic growth from cerebral cortical neurons in vitro.

Osteogenic protein-1 (OP-1), a member of the transforming growth factor-beta (TGF-beta) superfamily, has been demonstrated to stimulate dendrite growth from sympathetic neurons in culture. However, it is not known whether OP-1 affects dendrite growth from central nervous system neurons. Therefore we quantified axon and primary, secondary, and total dendritic growth from embryonic mouse cortical neurons (E 18) grown in vitro in a chemically defined medium. Morphology and double immunolabeling (MAP2, NF-H) were used to identify cortical dendrites and axons after 3 days in vitro. Cell morphology, neuron survival, and axon length were similar under all experimental conditions. The number of primary dendrites also was similar; however, the length of primary dendrites and the length and number of secondary dendrites were significantly increased by the addition of OP-1 to the culture medium. This increase in dendrite growth was dose-dependent; maximal dendritic growth was observed after the addition of 30-100 ng/ml of OP-1 to the culture medium. Specific support of dendrite growth was not observed when neurons were exposed to other members of the TGF-beta superfamily. These findings demonstrate that OP-1 selectively increases dendrite growth from cerebral cortical neurons in vitro.

Animals↗