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Biomedical subjects

M Freeman

Publications and source records attributed to M Freeman.

At least 91 records · Page 5Linked to original sources
PubMed1994

The reflective dialogue and repertory grid: a research approach to identify the unique contribution of nursing, midwifery or health visiting to the therapeutic milieu.

This paper seeks to demonstrate the use of two research methods within the interpretive paradigm: the reflective dialogue and the repertory grid. At first sight, the use of these two methods might appear contradictory; however this paper seeks to demonstrate the complementary fashion in which both techniques elicit rich and contextualized data. Both methods use extended interviews to illuminate practitioners' perceptions about their unique contribution to the therapeutic milieu. The approach primarily seeks to identify how practitioners' perceptions alter in the light of contextual change and seeks to enable practitioners to identify their developmental needs to meet future challenges. Fundamental assumptions underpin the approach: reciprocity, the equality of researcher and participant, and that research can be an act of empowerment and education. These issues are explored throughout the paper which closes with an invitation to add to the debate about the evolution of such an approach.

Community Health Nursing↗
PubMed1994

Misexpression of the Drosophila argos gene, a secreted regulator of cell determination.

I have examined the effects on cells in the developing eye of over-expressing the argos gene. Transgenic flies carrying argos expressed under hsp70 and sevenless control sequences were analysed. All cell types in the developing eye (except bristles) are sensitive to argos concentration: over-expression leads to too few cells forming, the opposite phenotype to that seen in argos loss-of-function mutants. This effect was only seen with HS-argos flies: sev-argos flies, which over-express the protein at a lower level are not affected, suggesting that a considerable over-expression is required to disrupt cell fate. However, sev-argos is able to rescue argos eye mutations completely, indicating that the normal expression pattern is not critical for wild-type eye development. By transfecting argos into tissue culture cells, I show that the protein is secreted in a soluble form.

Animals↗
PubMed1994

A conversation with Michael Freeman, MD.

The Institute for Behavioral Healthcare, a nonprofit organization that serves as an informational resource on issues surrounding the delivery of Behavioral Health Care Services, has been directed by Dr. Michael Freeman since its inception in 1988. In this crucial, unstable period in health care, membership in the Institute and attendance at its sponsored meetings has increased dramatically. Recently, Medical Interface talked with Dr. Freeman about topics of interest to the behavioral health care industry, ranging from any willing provider laws to the benefit itself.

Health Benefit Plans, Employee↗
PubMed1993

The collagenous domains of macrophage scavenger receptors and complement component C1q mediate their similar, but not identical, binding specificities for polyanionic ligands.

Macrophage scavenger receptors have been implicated in the development of atherosclerosis and other macrophage-associated functions, including host defense. The mechanism by which these receptors bind a wide array of polyanions, such as acetylated low density lipoprotein (Ac-LDL), with high affinity has not yet been elucidated; however, it has been proposed that the positively charged extracellular collagenous domain of scavenger receptors plays a key role in ligand binding. To test this proposal, we generated truncation mutants of the bovine and murine scavenger receptors and studied their expression in transiently transfected COS cells. These mutants contain only 8 (bovine) or 5 (murine) of the 24 Gly-X-Y tripeptide repeats found in the collagenous domains of the full-length receptors. Immunochemical analyses established that the truncation of the bovine scavenger receptor did not interfere significantly with its synthesis, trimerization, post-translational processing, intracellular transport, surface expression, or stability. However, unlike their full-length counterparts, the truncated bovine and murine receptors were unable to bind Ac-LDL. Thus, the collagenous domain was necessary for normal ligand binding. In addition, cotransfection of the expression vector for the truncated bovine scavenger receptor with that for the full-length receptor resulted in dramatically reduced activity of the full-length construct (dominant negative effect). A ligand bead-binding assay was used to show that the isolated collagenous domain from a different protein, complement component C1q, could bind a wide variety of polyanions with a specificity which was similar, but not identical, to that of scavenger receptors. These results suggest that the collagenous domain of the scavenger receptor is both necessary and sufficient to determine the broad binding specificity that characterizes this unusual receptor. Scavenger receptors and C1q, along with the mannose-binding protein, conglutinin, and lung surfactant apoprotein A, help define a set of proteins which all contain short collagenous domains and which all appear to participate in host defense. Their short collagenous domains may contribute significantly to their host-defense functions.

Animals↗
PubMed1993

Structures and high and low affinity ligand binding properties of murine type I and type II macrophage scavenger receptors.

Macrophage scavenger receptors have been implicated in various macrophage-associated processes, including atherosclerosis and clearance of bacterial endotoxin. They bind to a wide variety of polyanionic ligands and display complex binding characteristics. cDNAs from the murine macrophage-like cell line P388D1 encoding the full-length type I and type II murine scavenger receptors were cloned, sequenced, and expressed in Chinese hamster ovary cells. A fragment of the corresponding murine genomic DNA was also cloned, partially sequenced, and the positions of the cloned intron/exon boundaries were determined. Comparisons of the murine scavenger receptors' sequences with the bovine, rabbit, and human sequences were used to refine a multidomain model of these trimeric, fibrous, membrane receptors. Metabolic labeling/immunoprecipitation experiments showed that most of the macrophage scavenger receptor protein expressed by P388D1 cells was the N-glycosylated type II receptor; only small amounts of type I receptor were detected. Analysis of the binding properties of the receptors provided evidence that such differential expression of the type I and type II forms may have functional significance. There were substantial receptor-type (I vs. II), as well as receptor-species (bovine vs. murine), differences in the inhibition of 125I-labeled AcLDL (acetylated low density lipoprotein) binding by ReLPS, a form of bacterial endotoxin. These differences arose, in part, because these receptors exhibited both high (Kd1(4 degrees C) = 0.05-0.2 micrograms protein/ml) and low (Kd2(4 degrees C) = 2.5-12.8 micrograms protein/ml) affinity binding of 125I-labeled AcLDL. The ability of ReLPS (1 mg/ml) to inhibit either or both of these two classes of binding interactions varied depending on the species and type of receptor.

Amino Acid Sequence↗
PubMed1992

The argos gene encodes a diffusible factor that regulates cell fate decisions in the Drosophila eye.

The argos gene encodes a protein that is required for viability and that regulates the determination of cells in the Drosophila eye. A developmental analysis of argos mutant eyes indicates that the mystery cells, which are usually nonneuronal, are transformed into extra photoreceptors, and that supernumerary cone cells and pigment cells are also recruited. Clonal analysis indicates that argos acts nonautonomously and can diffuse over the range of several cell diameters. Conceptual translation of the argos gene suggests that it encodes a secreted protein.

Amino Acid Sequence↗
PubMed1992

Experimental studies of the biological response to a new bone cement: II Soft tissue reactions in the rat.

The biological response to a new bone cement (London Hospital cement), which contains polyethylmethacrylate/n-butylmethacrylate, has been examined experimentally and compared with polymethylmethacrylate. The cellular reaction was identical when the polymer powders of the cements were inserted subcutaneously in rats, there being a macrophage response to the polymer beads of both materials. Experimental implantation of the two cements into the paraspinal musculature of rats showed that there was less tissue damage adjacent to the new material than to polyethylmethacrylate. There was a significantly smaller macrophage and giant cell reaction in relation to the polyethylmethacrylate/n-butylmethacrylate cement. These differences may be related to the lower heat of polymerisation of the new cement and to its smoother surface contour, as demonstrated by scanning electron microscopy.

Animals↗
PubMed1992

Planning health care in South Africa--is there a role for traditional healers?

Developing health policies for the 'post-apartheid' era has become an urgent task of the early 1990s in South Africa. A neglected policy issue thus far has been the question of whether traditional healers have a role to play in future health care, and if so what this should be. Rather than developing positions on these questions, this paper sets out the main debates which need the consideration of health care planners. Arguments for and against traditional healers in health care are presented, and alternatives which could be chosen are outlined. Options adopted by countries on South Africa's borders, Zimbabwe, Mozambique and Swaziland are briefly considered.

Health Planning↗
PubMed1992

T and B cell reactivity to adrenal antigens in autoimmune Addison's disease.

Autoimmune Addison's disease is a rare condition of uncertain pathogenesis. To delineate potential autoantigens, an adrenal homogenate was fractioned by SDS-gel electrophoresis and used in immunoblotting and T cell proliferation assays. Antibodies specific for adrenal proteins with approximate molecular weights of 70, 55 and 45 were found in five out of 20 consecutive Addison's disease patients at routine follow-up. Five sera also reacted with a 52-kD protein shared with liver. T cells from six out of 10 Addison's disease patients proliferated in response to a range of adrenal-specific antigens including one, in particular, with a molecular weight of 18-24 kD. T and B cell reactivity to adrenal antigens did not appear to correlate and there was no relationship with time since diagnosis, associated autoimmunity or HLA-DR type. These results show that the autoimmune response to adrenal antigens in Addison's disease is heterogeneous and that such autoreactivity can only be inconsistently documented using these techniques and circulating antibodies or T cells.

Addison Disease↗
PubMed1992

Identifying targets of the rough homeobox gene of Drosophila: evidence that rhomboid functions in eye development.

In order to identify potential target genes of the rough homeodomain protein, which is known to specify some aspects of the R2/R5 photoreceptor subtype in the Drosophila eye, we have carried out a search for enhancer trap lines whose expression is rough-dependent. We crossed 101 enhancer traps that are expressed in the developing eye into a rough mutant background, and have identified seven lines that have altered expression patterns. One of these putative rough target genes is rhomboid, a gene known to be required for dorsoventral patterning and development of some of the nervous system in the embryo. We have examined the role of rhomboid in eye development and find that, while mutant clones have only a subtle phenotype, ectopic expression of the gene causes the non-neuronal mystery cells to be transformed into photoreceptors. We propose that rhomboid is a part of a partially redundant network of genes that specify photoreceptor cell fate.

Animals↗
PubMed1992

Viewing primary mental health care at a time of social transition in South Africa.

As South Africa shifts from a social structure based on the principles of apartheid to a democratic society, social policies must be developed that are consonant with the ideals of the "new" society. These must, however, take into account the current realities of the South African context. This article suggests that the application of the principles of primary mental health care is the approach most likely to meet mental health needs in the future South Africa, but that difficulties are likely to arise in the transition to this approach. These difficulties must be identified and dealt with. The authors discuss the problems in providing competent curative care to all and in shifting emphasis to prevention and promotion in mental health care. The discussion covers both practical and political complications. The authors conclude that though the process to primary mental health care will be a long one, the problems are unlikely to be insurmountable.

Health Planning↗
PubMed1991

A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide.

The complementary DNA encoding a 585-amino acid parathyroid hormone-parathyroid hormone-related peptide (PTH-PTHrP) receptor with seven potential membrane-spanning domains was cloned by COS-7 expression using an opossum kidney cell complementary DNA (cDNA) library. The expressed receptor binds PTH and PTHrP with equal affinity, and both ligands equivalently stimulate adenylate cyclase. Striking homology with the calcitonin receptor and lack of homology with other G protein-linked receptors indicate that receptors for these calcium-regulating hormones are related and represent a new family.

Amino Acid Sequence↗
PubMed1991

Expression of type I and type II bovine scavenger receptors in Chinese hamster ovary cells: lipid droplet accumulation and nonreciprocal cross competition by acetylated and oxidized low density lipoprotein.

Type I and type II scavenger receptors, which have been implicated in the development of atherosclerosis and other macrophage-associated functions, differ only by the presence in the type I receptor of an extracellular cysteine-rich C-terminal domain. Stable Chinese hamster ovary (CHO) cell transfectants expressing high levels of either the type I or type II bovine scavenger receptors have been generated. Type I and type II receptors in these cells mediated high-affinity saturable endocytosis of both 125I-labeled acetylated low density lipoprotein (LDL) and 125I-labeled oxidized LDL with the distinctive broad ligand specificity characteristic of scavenger receptors. After incubation for 2 days with acetylated LDL, the transfected cells accumulated oil red O-staining lipid droplets reminiscent of those in macrophage foam cells, whereas untransfected CHO cells did not. Thus, macrophage-specific gene products other than the scavenger receptor are not required for modified-LDL-induced intracellular lipid accumulation. In transfected cells, acetylated LDL efficiently competed for both its own endocytosis and that of oxidized LDL. In contrast, oxidized LDL competed effectively for its own endocytosis but only poorly for that of acetylated LDL. This nonreciprocal cross competition suggests that these ligands may bind to nonidentical but interacting sites on a single receptor. Results were similar for transfectants expressing either type I or type II scavenger receptors. Therefore, the nonreciprocal cross competition previously reported for cultured peritoneal macrophages may not be the result of differences between the type I and type II receptors. The nonreciprocal cross competition seen in the transfected CHO cells differs from that previously observed with cultured macrophages.

Acetylation↗
PubMed1991

Isolation and characterization of the disconnected gene of Drosophila melanogaster.

Mutations in the disco (disconnected) gene prevent the establishment of stable connections between the larval optic nerves, the Bolwig's nerves, and their target cells in the brain during embryonic development. The failure of this initial connection is associated with aberrant development of the optic lobes which are largely degenerate in the mutant adult fly. In order to understand the role of disco in establishing this connection, we isolated and characterized the disco gene. A 22 kb DNA fragment can completely rescue the mutant phenotype. A single transcript, 2.9 kb in length, is found in this region and is expressed throughout development of the fly. We determined the nucleotide sequence of the disco gene to be unique when compared with sequences in a number of databases. The predicted amino acid sequence contains a region with similarity to the consensus established for the zinc finger motif. Mobilization of a P-element inserted near the gene resulted in the deletion of the 5' end of the gene and produced flies indistinguishable from those carrying the disco allele.

Amino Acid Sequence↗
PubMed1991

Expression of the disconnected gene during development of Drosophila melanogaster.

Proper development of the larval visual nerve, Bolwig's nerve, of Drosophila melanogaster requires the wild type function of the disconnected (disco) gene. In disco mutants, the nerve does not make stable connections with its targets in the larval brain. We have begun to explore the role of disco in the formation of the nervous system by examining the distribution of disco mRNA and protein in embryos and third instar larvae using in situ hybridization and antibody staining respectively. No differences between the distribution patterns of the two products are detected; disco is expressed in many tissues including both neural and non-neural cells. Many of the cells which express disco undergo extensive movement during development as they participate in major morphogenetic movements. Antibody staining shows that the protein is found in the cell nucleus. Products of the disco gene are detected in cells near the terminus of the growing Bolwig's nerve. In embryos homozygous for either of two mutant alleles of disco, the disco protein is absent near the nerve terminus, although protein distribution elsewhere is indistinguishable from wild type.

Animals↗