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Biomedical subjects

E Harris

Publications and source records attributed to E Harris.

At least 73 records · Page 4Linked to original sources
PubMed1997

Developing healthy local communities at local government level: lessons from the past decade.

There have been many approaches by the health sector to developing healthy communities based on local government areas in Australia in the past decade. Each has struggled with the need to establish realistic goals and to find ways of working more effectively with local government. This paper outlines four of these approaches--Healthy Cities, the Healthy Localities project, municipal health plans, and programs to address specific health problems or issues. Although the picture is one of huge diversity in the ways in which the issue is defined and action taken, a number of dimensions to a healthy community are emerging. However, if we are to be able to monitor change within and between the health of communities over time, indicators need to be developed and goals set. This will require a shift away from defining goals and targets in terms of populations (people), towards goals based on changes in organisations and systems. Engaging local government in this process will be vital and will require the health sector to develop a better understanding of the ways in which local government defines its role in creating healthy communities. It will also involve learning from local government the strategies that they have found most effective in dealing with complex problems that require action at many levels.

Australia↗
PubMed1997

Modular organization of Pax/homeodomain proteins in transcriptional regulation.

Specificity in transcriptional regulation lies in a large part in the specificity of DNA binding by transcription factors. One group of transcription factors which are of great interest for studying transcriptional specificity is the Pax/Homeodomain (Pax/HD) proteins which contain two conserved DNA binding domains, a paired domain (PD) and a Paired-class homeodomain (HD). The Pax/HD proteins can bind to at least three types of specific DNA sequences: the PD binding sites, the dimeric HD binding sites and a composite HD and PD binding site. We propose that Pax/HD proteins regulate different subsets of their target genes through modular binding to one of these three specific sequences. We show that, in a tissue culture system, a member of the Pax/HD family, Paired, is able to activate transcription after binding through either its PD or its HD. The transactivation mediated by one domain does not require DNA binding of the other domain. Furthermore, binding sites specific for the PD of Paired are sufficient to mediate embryonic expression of a reporter gene in a paired-like pattern. The expression of the reporter gene is dependent on wild type paired function and, in a prd mutant background, it can be rescued by an exogenous paired gene encoding a protein whose HD is not able to bind to DNA. Finally, we show that the Paired protein uses differently its C-terminal activation domain when transactivation is mediated through its PD or its HD. These results and recent evidence from other Pax/HD proteins strongly suggest that this class of proteins is able to achieve specific and modular transcriptional regulation through its multiple DNA binding domains.

Animals↗
PubMed1996

The mouse Engrailed-1 gene and ventral limb patterning.

During vertebrate limb development, positional information must be specified along three distinct axes. Although much progress has been made in our understanding of the molecular interactions involved in anterior-posterior and proximal-distal limb patterning, less is known about dorsal-ventral patterning. The genes Wnt-7a and Lmx-1, which are expressed in dorsal limb ectoderm and mesoderm, respectively, are thought to be important regulators of dorsal limb differentiation. Whether a complementary set of molecules controls ventral limb development has not been clear. Here we report that Engrailed-1, a homeodomain-containing transcription factor expressed in embryonic ventral limb ectoderm, is essential for ventral limb patterning. Loss of Engrailed-1 function in mice results in dorsal transformations of ventral paw structures, and in subtle alterations along the proximal-distal limb axis. Engrailed-1 seems to act in part by repressing dorsal differentiation induced by Wnt-7a, and is essential for proper formation of the apical ectodermal ridge.

Animals↗
PubMed1996

Concentration and storage of biotin in the amphibian brain.

Prominent displays of endogenous biotin reactivity can be observed at specific locations in histochemical preparations of the forebrain and midbrain in the northern leopard frog (Rana pipiens) and common American toad (Bufo americanus). At the light microscopic level, the biotin reactivity appears in clusters of darkly stained puncta of either spherical or rodlike shape in the olfactory cortex, nucleus isthmi, and hypothalamus. With the electron microscope, the biotin reactive spheres are identified as neuronal varicosities and synaptic boutons and the rods as short segments of axons. Appropriate controls demonstrate that the punctate biotin-reactive structures are sites of concentration of biotin or a biotin analog in the processes of certain neurons. These data represent the first observation on the selective concentration of a vitamin in vertebrate neurons and suggest that biotin may have specialized functions in anatomically delimited areas of the central nervous system. Localization of the densest concentration of the biotin-reactive puncta in the dorsolateral prominence of the olfactory cortex may have relevance to the functional organization of the olfactory system. The distributions of biotin-reactive puncta were observed in laboratory-housed frogs and in wild toads captured in the summer months but were sparse or absent in batches of commercially obtained frogs examined immediately upon arrival in the laboratory. Systemic administration of biotin or biocytin hydrochloride did not alter the appearance or numbers of the biotin-reactive structures either in newly received or laboratory-housed frogs. These findings suggest that the capacity of the biotin-storage mechanism in the amphibian brain may be set by environmental factors and may be readily saturable from natural dietary or enteric sources.

Animals↗
PubMed1996

The capacity of children's services in New South Wales to meet their responsibilities under the Public Health (Amendment) Act 1992.

From 1 January 1994 the New South Wales government has required directors of licensed children's services to ask parents for proof of their children's immunisation status, to record and update this information and notify public health units of outbreaks of vaccine-preventable disease. Before introduction of the legislation, we studied the health and safety policies and practices of a random sample of 77 long-day-care centres caring for children under two years of age. All but one recorded immunisation in some way; however, of the 73 centres for which adequate information was available, only 22 per cent (95 per cent confidence interval (CI) 14 to 33) recorded immunisation according to the National Health and Medical Research Council schedule. A review of the records of one in four children enrolled in the centres showed that triple antigen (TA) was recorded in some way on 94 per cent (CI 92 to 95) of records, and measles-mumps-rubella (MMR) on 80 per cent (CI 78 to 83) of records. These entries were independently verified for only 31 per cent of TA and 26 per cent of MMR records, and 38 per cent of TA and 41 per cent of MMR records had not been updated when necessary. Only 53 per cent of directors thought that the school-entry legislation would affect children's services. Directors were generally unaware of the role of the public health units and would have had difficulty in managing an outbreak of a vaccine-preventable disease. Without technical and administrative support, the directors will not be able to meet their responsibilities under the legislation.

Child Day Care Centers↗
PubMed1996

Detection of Trypanosoma brucei spp. in human blood by a nonradioactive branched DNA-based technique.

We have developed a nonradioactive branched DNA (bDNA)-based assay for the diagnosis of the African trypanosomiases in simple buffy coat preparations of human blood. Two repetitive DNA sequences specific to the Trypanosoma brucei complex were chosen as targets of the bDNA assay, a technique which amplifies the signal from a target molecule rather than the target itself. Comparable sensitivities were observed with cloned target sequences, purified T. brucei DNA, procyclic trypanosomes, and bloodstream trypomastigotes. The results of bDNA analysis of human blood samples from Côte d'Ivoire (n = 50) showed excellent agreement with those of buffy coat microscopy. The bDNA technology offers certain advantages over alternative molecular biological techniques, including the simplicity of sample preparation and of the procedure itself, the stability of the reagents, the ability to process large numbers of samples simultaneously, and freedom from crosscontamination artifacts. We have successfully applied the bDNA technique to the detection of T. brucei in clinical samples from regions where T. brucei infection is endemic; to our knowledge, this is the first report of the molecular detection of T. brucei in human blood.

Animals↗
PubMed1996

Paracetamol use, availability, and knowledge of toxicity among British and American adolescents.

Paracetamol is the commonest agent employed in self poisoning, however it is not clear whether adolescents possess insight into the serious complications associated with its misuse. Using a one page questionnaire, the availability, usage, and knowledge of toxicity of paracetamol among 1147 American and British adolescents was assessed. Although 90% of all students recognised that paracetamol could kill, the great majority of students overestimated the lethal dose. In addition, while knowledge regarding side effects of paracetamol was poor the drug was widely available to, and used by, the study population. It is proposed that gross overestimation of the number of tablets required to kill, poor understanding of paracetamol side effects, and wide availability of the drug contribute to its frequent use in adolescent suicidal behaviour. The inclusion of some over-the-counter medications in school drug education programs in addition to tighter control of the availability of paracetamol may help reduce the problem of adolescent self poisoning.

Acetaminophen↗
PubMed1996

Tandem high-dose chemotherapy supported by hematopoietic progenitor cells yields prolonged survival in stage IV breast cancer.

The aim of this phase II study was to determine the feasibility of using two (tandem) courses of high-dose alkylating agents with bone marrow or peripheral blood progenitor cell support in women with stage IV breast cancer. Women with stage IV breast cancer who had achieved a CR or PR during conventional chemotherapy were enrolled in a phase II trial of high-dose cyclophosphamide 7500 mg/m2 and thiotepa 675 mg/m2 (C+T) followed within 180 days by high-dose melphalan (M) 140 mg/m2. Bone marrow and/or GM-CSF mobilized peripheral blood hematopoietic progenitor cells were used to support high-dose C+T and high-dose M. Twenty-seven women were enrolled in this trial. The median age was 45 years (range 32-56). The median PS was 0 and all patients had achieved either a CR (4/27, 15%) or PR (23/27, 85%) to conventional chemotherapy. All 27 women underwent high dose C+T. The predominant toxicities were mucositis (81%), and diarrhea (81%); two patients (7%) died from infectious complications. Following C+T, the median time to hematologic recovery for neutrophils (ANC > 500 cells/mu 1) was 12 days and for platelets (>20 000 cell/mu 1), 23 days. Following C+T, 18 of 22 patients received high dose M; the predominant toxicities were nausea, vomiting (70%), and mucositis (91%). The median time to hematologic recovery for the ANC was 13 days and for platelets, 18 days. The overall response after high dose C+T and high dose M was 67% (CR, 15/27 patients (56%) and PR* (complete resolution of all measurable disease but persistent lytic disease or positive bone scan) 3/27 patients (11%). With median follow-up of 24 months, the actuarial freedom from relapse or treatment failure is 56% at 24 months. At 30 months 56% of patients are alive. For patients who achieve a CR or PR* the actuarial freedom from relapse or treatment failure at 24 months is 88%. In women with stage IV breast cancer who attain a CR or PR to conventional chemotherapy, tandem high-dose chemotherapy with ABMT can lead to prolonged relapse-free survival.

Adult↗
PubMed1995

Gain-of-function mutations in a human calmodulin-like protein identify residues critical for calmodulin action in yeast.

A human epithelial cell-specific transcript (NB-1) encodes a calmodulin-like protein (hCLP), which is identical in length and 85% identical in amino acid sequence to authentic human calmodulin (hCaM). Although hCaM shares only 60% amino acid sequence identity with yeast calmodulin (CMD1 gene product), hCaM was able to substitute functionally for Cmd1 in yeast cells. In contrast, hCLP was unable to support either spore germination or vegetative growth in Cmd1-deficient yeast cells, even when stably expressed at a level at least an order of magnitude above that of hCaM. Thus, hCLP provides an indicator protein for discerning those residues that are critical for calmodulin function in vivo. In addition to 20 conservative amino acid replacements, hCLP differs from hCaM (and other vertebrate calmodulins that are able to complement a cmd1 null mutation) by only three nonconservative substitutions. Site-directed mutagenesis was used to convert these three positions back to residues more typical of those found in authentic calmodulins and to prepare all possible combinations of these three mutations, specifically: three single mutants (R58V, R112N, and A128E), three double mutants (R58V A128E, R112N A128E, and R58V R112N), and the triple mutant (R58V R112N A128E). The triple mutant and one of the double mutants (R58V A128E) were able to restore an apparently normal growth rate to a cmd1 delta strain, indicating that the altered hCLPs have acquired the ability to behave as functional calmodulins in yeast. The other two double mutants were able to support growth of Cmd1-deficient cells only weakly, but cells expressing the R112N A128E mutant grew noticeably better than those expressing the R58V R112N mutant. Remarkably, one single mutant (A128E), but not the other two single mutants, was also reproducibly able to support weak growth of a cmd1 delta strain. The properties of these gain-of-function, or neomorphic, mutations implicate E128, and to a lesser extent V58, as residues critical for calmodulin action in vivo. Molecular modeling of these positions within the structure of a Ca(2+)-calmodulin.peptide complex indicates that E128 projects directly into the central cavity occupied by the bound peptide. Thus, E128 may contribute a contact that is vital for the interaction of Cmd1 with one or more of the targets that are essential for yeast cell growth.

Amino Acid Sequence↗
PubMed1994

Copper deficiency secondary to a copper transport defect: a new copper metabolic disturbance.

We describe a 21-year-old man who developed copper deficiency manifested as a demyelinating neuropathy, chronic intestinal pseudo-obstruction, osteoporosis, testicular failure, retinal degeneration, and cardiomyopathy with a tortuous aorta. His serum copper was low and did not increase despite administration of large doses of intravenous copper sulfate. The ceruloplasmin level as measured by an antibody technique was normal, yet ceruloplasmin (Cp) oxidase activity was very low. The Cp amino acid sequence was normal. This suggests that the copper deficiency was caused by a defect in hepatic processing of copper for incorporation into Cp.

Adult↗
PubMed1994

Functional consequences in yeast of single-residue alterations in a consensus calmodulin.

A synthetic gene encoding a 'consensus' calmodulin (synCaM) was able to substitute for the Saccharomyces cerevisiae calmodulin gene (CMDI), even though synCaM is only 60% identical in primary amino acid sequence to yeast Cmd1. Twelve different synCaM mutants were also expressed in yeast. Seven of the 12 mutant synCaMs supported germination and growth of Cmd1-deficient spores. Five of the 12 mutant synCaMs were incapable of supporting germination of Cmd1-deficient spores and, of these, four were also incapable of supporting vegetative growth of Cmd1-deficient haploid cells. The five nonfunctional synCaM mutants were expressed at levels equivalent to, or higher than, the seven synCaM mutants that were able to substitute for Cmd1; thus, the inability to function was not simply due to inadequate expression or rapid degradation. All nonfunctional synCaM mutants shared a single charge reversal mutation in the central helix (E84K), which was found to be sufficient to confer the lethal phenotype. The ability of another mutant synCaM (S101F) to support growth of Cmd1-deficient cells was dependent on cell ploidy. Another mutant (K115Y) supported spore germination and vegetative growth, but not meiosis and sporulation. The terminal phenotype of cells lacking a functional calmodulin included a dramatic accumulation of polymerized microtubules.

Calmodulin↗
PubMed1994

How to produce moisture chamber eyeglasses for the dry eye patient.

BACKGROUND: Moisture chambers are prosthetic devices coupled to eyeglasses that slow the evaporation of the tears from the ocular surface. The need for moisture chamber glasses is most evident when a patient suffers from Sjögren's syndrome. This disease creates a pathologically dry eye from tear anomalies. Other ocular and systemic conditions can also cause a painfully dry eye. METHODS: The concept behind a moisture chamber is to significantly minimize the air flow over the ocular surface. The chamber provides a vapor barrier that functions passively to prevent tear evaporation. This is achieved by using a polyurethane plastic to produce a chamber contiguous with spectacles. RESULTS: The chamber provides a humid environment behind the eyeglass lens and in front of the eye surface. Before deciding to produce a moisture chamber, one should consider the extensive time consumption involved in the production of these facially contoured customized devices. CONCLUSIONS: It may take 3-6 hours for a technician who has not previously made a moisture chamber to construct the first one. As the proficiency increases, one may be able to streamline the process to approximately 3 hours. This approach was investigated because of the paucity of available information about the production of moisture chamber glasses and the acute need and benefit by pathological dry eye patients for these special glasses.

Dry Eye Syndromes↗