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Biomedical subjects

M Ferguson

Publications and source records attributed to M Ferguson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Best practice and enterprise bargaining.

The Australian Council of Trade Unions (ACTU) and its affiliated health unions have strongly supported and actively participated in the Federal Government Best Practice in Health initiative over the past two years. We believe the initiative has been an important vehicle in fostering the development of the Best Practice approach in this vital sector of the economy. Healthcare expenditure in this country runs to some $34.3 billion (1992/93 figures) annually, financed by a mix of Commonwealth, State and private sources and constituting approximately 9% of GDP. Hospital expenditure alone absorbs just over a third of the total at $11.8 billion (1990/91). At the same time, we have developed one of the most accessible and equitable healthcare systems in the world and an increasing source of valuable export dollars. The Australian trade union movement, like others in the community, recognizes that real cost constraints exist on governments in healthcare as elsewhere. Those constraints can lead to a variety of responses, such as to withdraw money from the system, combined with total reorganization of financing through the introduction of casemix and hospital reorganization, to see whether the system survives. The alternative is one epitomized by a Best Practice type approach. It is these types of approaches and their relationships with enterprise bargaining on which I intend to focus. However, I hasten to add that the issue of context is all important. Whilst it may be possible to create a microcosm of Best Practice change in a particular healthcare setting, it is unlikely to be maintained. The interface with the socio-ecomonic and political context cannot be avoided and it is this context which will determine the continuing success of Best Practice initiatives--whether in health or elsewhere.

Australia↗
PubMed1994

The construction and characterization of poliovirus antigen chimeras presenting defined regions of the human T lymphocyte marker CD4.

Defined regions of the CDR2-like region of the T cell antigen CD4 that are implicated in the binding of the surface glycoprotein (gp120) of human immunodeficiency virus type 1 (HIV-1) to CD4+ T lymphocytes have been engineered in place of antigenic site 1 of Sabin type 1 poliovirus. The antigenic properties of the recovered chimeric virus particles were investigated using monoclonal antibodies (MAbs) and polyclonal serum to CD4. None of the MAbs tested neutralized the chimeras, presumably because they are directed against conformational determinants of the V1 domain of CD4. In contrast, the three antigen chimeras were neutralized by polyclonal serum to CD4, which suggested that the CD4-derived sequences were presented in a relevant conformation. A panel of six MAbs were raised against one of the chimeras, and the epitopes were mapped by the selection of neutralization-resistant mutants and cross-neutralization studies. Five of the six MAbs reacted with soluble CD4 (sCD4) in ELISA, and one (MAb 1686) bound to CD4 expressed at the surface of HeLa cells. The high affinity interaction between gp120 and sCD4 was not blocked by MAb 1686, and the poliovirus-CD4 chimeras did not interact with gp120. These results demonstrate that poliovirus can be used as an epitope expression vector for the presentation of sequences in an immunodominant location on the virus particle which adopt a native or near-native conformation, and supports the findings of previous studies involving the presentation of epitopes derived from pathogens.

Amino Acid Sequence↗
PubMed1994

Possible role of Helicobacter pylori serology in reducing endoscopy workload.

We validated a commercial enzyme-linked immunosorbent assay (ELISA), Helico-G, in diagnosing H. pylori in 129 patients (mean age 50 years, range 15-86). We analysed the results of endoscopy against serology to see whether there was a possibility of adopting the strategy of not endoscoping dyspeptic subjects under the age of 45. H. pylori infection was considered present if either histology and/or culture were positive. The ELISA had a sensitivity of 88%, specificity of 72%, positive predictive value of 85%, negative predictive value of 77% and accuracy of 82% in detecting H. pylori. In a subgroup of 52 subjects aged 45 or less (mean age 35 years, range 15-45), 17 out of 25 patients with positive endoscopic findings were H. pylori seropositive while 16 out of 27 patients had normal endoscopic findings. Eighteen out of the 52 patients (35%) were H. pylori seronegative and normal endoscopically except for five patients (10%) who had mild to moderate oesophagitis and two who had non-erosive gastritis (4%). All patients with duodenal ulcer disease (7) were seropositive giving predictive values of positive and negative serology for a diagnosis of duodenal ulcer disease as 28% and 100%, respectively. Therefore adopting a strategy of endoscoping subjects under the age of 45 only if they were H. pylori seropositive would have saved 35% of endoscopies in this age group but missed oesophagitis in 10%. Negative serology would tend to exclude duodenal ulcer disease while positive serology discriminates poorly for it. Serology may be a useful adjunct in screening to reduce endoscopy workload provided that patients with gastro-oesophageal reflux symptoms are excluded.

Aged↗
PubMed1994

Lipoprotein lipase is produced by cardiac myocytes rather than interstitial cells in human myocardium.

Lipoprotein lipase (LPL) may play an important role in myocardial metabolism by releasing free fatty acids from triglycerides for oxidation by myocytes. However, studies in species other than humans have differed in their conclusions as to whether LPL is produced by cardiac myocytes or interstitial cells. The location and source of LPL in human myocardium were determined on formalin-fixed samples from 25 cardiomyopathy patients and seven control patients. LPL protein was detected immunohistochemically on cardiac myocytes, adipocytes, and endothelial cells, as well as on interstitial cells consisting of both vascular pericytes and smooth muscle cells. In all 32 patients, in situ hybridization localized LPL mRNA to cardiac myocytes and adipocytes, but LPL mRNA was not detected in interstitial cells. Quantitative in situ hybridization failed to reveal correlations between LPL mRNA levels and New York Heart Association functional class, left ventricular ejection fraction, or beta-adrenergic agonist therapy. Also, quantitative in situ hybridization demonstrated apparently linear loss of detectable myocardial mRNA after onset of ischemia, with a disappearance half-time of approximately 26 hours. In summary, LPL is produced primarily by cardiac myocytes rather than by interstitial cells in human myocardium. Furthermore, LPL protein is present on cells with and without detectable LPL mRNA, suggesting that LPL is translocated from sites of synthesis to sites of utilization.

Adipocytes↗
PubMed1994

Fixation and regression in the psychoanalytic theory of homosexuality--a critical evaluation.

This essay evaluates the notions of fixation and regression in the psychoanalytic theoretical conceptualization of homosexuality. Charles Socarides has had a central role in formulating the most prominent and influential psychoanalytic metapsychological understanding of homosexuality in recent years and for that reason this essay focuses principally on him. The concepts of fixation and regression are central to his understanding and I argue that the evolution of these concepts in contemporary usage renders them irrelevant to formulating the current psychoanalytic understanding of homosexuality and that their continued use by analysts reflects a negative attitude toward homosexual behavior on the part of Socarides and many other analysts that stems from an extremely narrow and idealized conception of human development.

Adult↗
PubMed1994

Apolipoprotein E localization in human coronary atherosclerotic plaques by in situ hybridization and immunohistochemistry and comparison with lipoprotein lipase.

Apolipoprotein E (apo E) mediates both lipid accumulation by and removal from cells and may be secreted by both macrophages and smooth muscle cells in vitro, but its cellular source in atherosclerotic plaques is not known. Lipoprotein lipase (LPL) also enhances cell lipid accumulation and is synthesized by macrophage foam cells in atherosclerotic plaques. To determine the cellular source of apo E in human coronary atherosclerotic lesions and its relationship to LPL synthesis, in situ hybridization and immunohistochemistry were performed on 12 atherosclerotic plaques and six nondiseased coronary artery segments from 10 cardiac transplant recipients. Apo E messenger RNA was localized to both non-foam cell and foam cell macrophages in plaques, but not to other cell types, and was not detected in nonatherosclerotic arteries. Half of the regions with non-foam cell macrophages expressed neither apo E nor LPL messenger RNA, whereas 86% of macrophage foam cell-containing regions contained both messenger RNAs. Polyclonal antisera raised against human apo E localized apo E protein to the surface of macrophages and surrounding matrix in plaques but not in control coronary segments. An LPL-specific monoclonal antibody demonstrated that, similar to apo E, LPL protein on foam cell and non-foam cell macrophages was detected in atherosclerotic lesions, but LPL was also localized to intimal muscle smooth muscle cells and was not distributed as widely in association with matrix as was apo E. The expression of both apo E and LPL in atherosclerotic lesions but not in normal intima suggest that these molecules play a role in lipid metabolism in atherosclerosis.

Apolipoproteins E↗
PubMed1994

Smooth muscle cell expression of extracellular matrix genes after arterial injury.

Accumulation of extracellular matrix (ECM) after arterial injury is an important event in the development of intimal thickening and is modulated by heparin. To investigate the regulation of matrix protein expression, we have analyzed messenger RNA levels by Northern blotting for various ECM proteins in the rat carotid artery balloon injury model. RNA was extracted from normal arteries and from intima-medial preparations at 2 days, 1 week, 2 weeks, and 4 weeks after balloon injury of arteries in animals receiving either saline or heparin infusion. Transcripts for the heparan sulfate proteoglycans perlecan, syndecan, and ryudocan; the chondroitin sulfate proteoglycan versican; the dermatan sulfate proteoglycan biglycan; type I procollagen; and tropoelastin all were increased on Northern blots beginning at 1 week after injury. By in situ hybridization, the transcripts for elastin nd biglycan were primarily localized to smooth muscle cells in the intima and were diminished by heparin in proportion to the decrease in intimal mass. Other matrix genes (perlecan, ryudocan) were expressed in the intima and media and were not affected by heparin. The results support the conclusion that ECM gene expression is a relatively late event in the response of the carotid artery, and that some of the genes are expressed only in the intima whereas others are expressed in both the intima and media.

Animals↗
PubMed1993

Antigenic sites on type 2 poliovirus.

Monoclonal escape variants isolated from the Sabin strain of type 2 poliovirus were examined. Mutations were identified in regions known to be antigenic in other serotypes, although the extent to which they were linked by common antibodies varied. One complex site involved regions of VP2 and VP3 which were not linked in early studies, but have recently been shown by others to be linked in type 1.

Antibodies, Monoclonal↗
PubMed1993

Characterization and primary structure of a human immunodeficiency virus type 1 (HIV-1) neutralization domain as presented by a poliovirus type 1/HIV-1 chimera.

The poliovirus/human immunodeficiency virus (HIV) chimera S1/env/3 presents the sequence DRPEGIEEEGGERDRDRS, a known glycoprotein gp41 neutralizing domain (residues 735 to 752) of HIV IIIB in an antigenic site of the Sabin type 1 strain of poliovirus. Of 10 monoclonal antibodies raised against the sequence as presented in S1/env/3, eight were shown to neutralize HIV IIIB in vitro whereas all 10 neutralized S1/env/3, suggesting that the presentation of the sequence is comparable between HIV and the poliovirus/HIV chimera. The monoclonal antibodies were characterized by the selection of escape mutants from S1/env/3 and by Pepscan analysis. The two methods gave similar results, identifying two epitopes involving amino acids corresponding to residues 740 to 743, and to residues 745 to 750 of gp41. Mutations selected in the chimera with S1/env/3-specific MAbs are identical or similar to changes occurring in vivo in natural isolates of HIV-1. This finding suggests that the epitope may be significant in the neutralization of HIV in vivo.

Amino Acid Sequence↗
PubMed1993

Antigenic structure of poliovirus in inactivated vaccines.

The reactivity of D antigen-specific monoclonal antibodies with infectious virus and inactivated virus in commercial poliovaccines from two manufacturers was examined in capture enzyme immunoassays. Epitopes on inactivated poliovirus types 2 and 3 in vaccines were modified by the inactivation process to such an extent that some monoclonal antibodies which bound to the homologous infectious virus strain failed to bind to the inactivated virus in the vaccine. This was especially the case for antibodies specific for site 1, which elicits the major immune response to these serotypes in mice. Other epitopes were partially destroyed resulting in a reduction in reactivity of monoclonal antibodies with inactivated virus in vaccines compared to infectious virus. These studies indicate that inactivated virus in vaccine differs antigenically from native virus so that measuring the potency of vaccine in assays in vitro may require careful selection of an appropriate antibody. In addition it is possible that some of the antibodies produced by recipients of formalin-inactivated polioviruses may not contribute to the protective immune response.

Antibodies, Monoclonal↗
PubMed1993

Working standards for hepatitis B surface antigen for use in the UK Blood Transfusion Service: results of a collaborative study.

Twenty-six laboratories including 22 Blood Transfusion Centres in England, Scotland, Wales and Northern Ireland participated in a collaborative study to assess the suitability of proposed working standards for hepatitis B surface antigens (HBsAg) for use in the UK Blood Transfusion Service. Data from 88 assays indicated that all laboratories could detect HBsAg in the proposed working standard at a concentration of 0.5 IU/ml. Samples containing HBsAg at a concentration of 0.125 IU/ml were scored positive in 80% of assays and it was concluded that this would be a suitable concentration for inclusion in a monitor sample which would indicate whether the sensitivity of an assay system in routine use is varying over a period of time. The use of a batch of 'provisional' working standard tested under field conditions over a period of 4 months has been monitored. HBsAg was not detected in only 2 out of 6,523 assays.

Blood Banks↗
PubMed1993

Cell proliferation in human arteriovenous fistulas used for hemodialysis.

The long-term patency of arteriovenous (AV) fistulas created for hemodialysis of renal-failure patients is usually measured in months, particularly when polytetrafluoroethylene (PTFE) material is interposed between the artery and vein. This is due to the rapid development of intimal hyperplastic lesions in the anastomosis region of the PTFE graft material with the vein. We studied the proliferative patterns in seven human AV fistulas removed at the time of fistula revision. Cell proliferation was determined by using an antibody to the proliferating cell nuclear antigen (PCNA), and specific cell types were identified by immunochemical reagents for smooth muscle cells, monocytes/macrophages, monocytes, lymphocytes, and endothelial cells. All venous segments exhibited a markedly hyperplastic intima. Vascularization of the intima and media by capillary-sized vessels was found. The main intimal cellular component was smooth muscle. Macrophages were usually seen around microvessels, and many also populated the perigraft region of the adventitia. In contrast to human atherosclerotic lesions, high rates of cell proliferation were observed in these fistulas. PCNA indices (percentage of cells that were PCNA positive [mean +/- SD]) were as follows: intima 17.7 +/- 11.3%, media 24 +/- 11.2%, and adventitia 20 +/- 11.6%. However, the distribution of PCNA-positive cells was not uniform. Instead, the PCNA index in microvessel-containing intimal fields was five to six times that of avascular fields (28.9 +/- 10.6% versus 4.9 +/- 4.5%, respectively, p < 0.001). Double immunolabeling revealed a large proportion of PCNA-positive microvascular endothelial cells and surrounding pericyte-like smooth muscle cells, as well as smooth muscle cells without visual connection to either microvessels or the lumen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Proliferation in primary and restenotic coronary atherectomy tissue. Implications for antiproliferative therapy.

On the basis of animal models of arterial injury, smooth muscle cell proliferation has been posited as a dominant event in restenosis. Unfortunately, little is known about this proliferation in the human restenotic lesion. The purpose of this study was to determine the extent and time course of proliferation in primary and restenotic coronary atherectomy-derived tissue. Primary (n = 118) and restenotic (n = 100) coronary atherectomy specimens were obtained from 211 nonconsecutive patients. Immunocytochemistry for the proliferating cell nuclear antigen (PCNA) was used to gauge proliferation in the atherectomy specimens. The identity of PCNA-positive cells was then determined using immunohistochemical cell-specific markers. Eighty-two percent of primary specimens and 74% of restenotic specimens had no evidence of PCNA labeling. The majority of the remaining specimens had only a modest number of PCNA-positive cells per slide (typically < 50 cells per slide). In the restenotic specimens, PCNA labeling was detected over a wide time interval after the initial procedure (eg, 1 to 390 days), with no obvious proliferative peak. Cell-specific immunohistochemical markers identified primary and restenotic PCNA-positive cells as smooth muscle cells, macrophages, and endothelial cells. In conclusion, the findings were as follows: (1) Proliferation in primary and restenotic coronary atherectomy specimens, as indicated by PCNA labeling, occurs infrequently and at low levels. (2) The response to injury in existing animal models of angioplasty may follow a very different course of events from the clinical reality in human atherosclerotic coronary arteries and may help explain why current approaches to restenosis therapy have been ineffective.

Adult↗
PubMed1993

Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques. Implications for the mode of progression of advanced coronary atherosclerosis.

Endothelial attachment is the initial step in leukocyte recruitment into developing atherosclerotic lesions. To determine whether vascular cell adhesion molecule-1 (VCAM-1) expression may play a role in inflammatory cell recruitment into human atherosclerotic lesions, immunohistochemistry was performed with a polyclonal rabbit antisera, raised against recombinant human VCAM-1, on 24 atherosclerotic coronary plaques and 11 control coronary segments with nonatherosclerotic diffuse intimal thickening from 10 patients. Immunophenotyping was performed on adjacent sections to identify smooth muscle cells, macrophages, and endothelial cells. To confirm VCAM-1-expressing cell types, double immunostaining with VCAM-1 antisera and each of the cell-specific markers and in situ hybridization were performed. All atherosclerotic plaques contained some VCAM-1, compared to 45% of control segments. VCAM-1 was found infrequently on endothelial cells at the arterial lumen din both plaques (21%) and in control segments (27%), but was prevalent in areas of neovascularization and inflammatory infiltrate in the base of plaques. Double immunostaining and in situ hybridization confirmed that most VCAM-1 was expressed by subsets of plaque smooth muscle cells and macrophages. The results document the presence of VCAM-1 in human atherosclerosis, demonstrate VCAM-1 expression by human smooth muscle cells in vivo, and suggest that intimal neovasculature may be an important site of inflammatory cell recruitment into advanced coronary lesions.

Animals↗
PubMed1993

Nerve growth factor receptor expression in fetal, mature, and diseased human kidneys.

BACKGROUND: Nerve growth factor (NGF) has been proposed to be critical to normal renal development in rodents. However, little is known about expression of NGF or its receptors in human kidneys, or their potential function in development or disease. EXPERIMENTAL DESIGN: A previously characterized monoclonal antibody (NGFR 5) was utilized for immunohistochemical localization of the p75 NGF receptor (NGFR) in alcohol-fixed tissue sections of human fetal kidney (N = 27, 54 to 105 days gestation), normal mature kidney obtained from nephrectomies for neoplasia (N = 7), and renal biopsies (N = 54) with various glomerulopathies previously characterized for degree of mesangial alpha smooth muscle actin (alpha SM) expression. A second monoclonal antibody (NGFR2) was also utilized on fetal and normal kidney. Immunohistochemical localization of alpha SM and proliferating cell nuclear antigen expression was also performed. RESULTS: Glomerular expression of NGFR in the fetus is limited to the mesangium in later stages of glomerulogenesis; at these stages this expression is similar to that which has been previously reported for platelet-derived growth factor receptor-beta and alpha SM. There is focal, weak persistence of NGFR in normal adult glomeruli, similar to alpha SM. In renal biopsies, glomerular NGFR expression was upregulated in a variety of disease states, which frequently but not invariably correlated with alpha SM expression. Fetal and adult expression of NGFR is also prominent in periarterial connective tissue cells and nerve. Apparent de novo expression by many interstitial cells in normal and diseased adult kidneys is also present. CONCLUSIONS: These studies indicate: (a) NGF or other neurotrophins that bind NGFR may be important in human kidney development and glomerular response to injury; (b) NGFR is a marker of developing mesangial cells similar to alpha SM and platelet-derived growth factor receptor-beta; (c) enhanced expression of NGFR, like alpha SM, is a marker of mesangial cell injury or activation, and that their coordinate upregulation in some glomerular disease states appears to recapitulate a normal developmental state; (d) a population of NGFR and platelet-derived growth factor-beta expressing interstitial cells can be identified in normal kidneys, which suggests potential signaling mechanisms to recruit or activate these cells at sites of tubulointerstitial injury.

Antibodies, Monoclonal↗
PubMed1993

Approaches to the construction of new candidate poliovirus type 3 vaccine strains.

The World Health Organization has called for improvements to oral polio vaccines (OPV), particularly the type 3 component. Our improved understanding of the genetic basis of attenuation and antigenicity of this strain gives rise to possibilities for constructing new derivatives via mutagenesis of infectious cDNA. This article reviews progress made with various approaches to constructing a new type 3 candidate vaccine strain. These include the construction of antigen chimaeras of poliovirus based on the Sabin type 1 strain, the introduction of new genetically stable attenuation mutations into the 5' non-coding region (NCR) of the type 3 poliovirus genome, and the introduction of mutations which may increase the thermostability of the type 3 vaccine.

Antibodies, Viral↗
PubMed1992

In situ hybridization to the Crithidia fasciculata kinetoplast reveals two antipodal sites involved in kinetoplast DNA replication.

Kinetoplast DNA is a network of interlocked minicircles and maxicircles. In situ hybridization, using probes detected by digital fluorescence microscopy, has clarified the in vivo structure and replication mechanism of the network. The probe recognizes only nicked minicircles. Hybridization reveals prereplication kinetoplasts (with closed minicircles), donut-shaped replicating kinetoplasts (with nicked minicircles on the periphery and closed minicircles in the center), and postreplication kinetoplasts (with nicked minicircles). Replicating kinetoplasts are associated with two peripheral structures containing free minicircle replication intermediates and DNA polymerase. Replication may involve release of closed minicircles from the center of the kinetoplast and their migration to the peripheral structures, replication of the free minicircles therein, and then peripheral reattachment of the progeny minicircles to the kinetoplast.

Animals↗