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Biomedical subjects

G Parry

Publications and source records attributed to G Parry.

At least 19 recordsLinked to original sources
PubMed1992

Thrombin-induced proliferation and expression of platelet-derived growth factor-A chain gene in human vascular smooth muscle cells.

Treatment of human vascular smooth muscle cells (SMC) with human alpha-thrombin greatly increased DNA synthesis and cell proliferation. Both the integrity of the catalytic site and that of the anion binding exosite were required for expression of this activity. Experiments employing Northerns indicated induction of c-fos expression as well as a time-dependent induction of platelet-derived growth factor-A (PDGF-A) gene by thrombin. The thrombin mitogenic activity was potentiated by PDGF-BB, insulin and the vasoconstrictor peptide endothelin-1 suggesting synergism by convergence of intracellular growth-promoting signals. SMC treatment with pertussis toxin and forskolin indicated that the mitogenic activity of thrombin may be induced via signal transduction mechanism(s) involving changes in cAMP levels and activation of a Gi-like protein. These results suggest that thrombin may play a functional role in the regulation of human vascular SMC proliferation.

Aorta↗
PubMed1992

Glucocorticoid-induced formation of tight junctions in mouse mammary epithelial cells in vitro.

Phenotypically stable cultures of untransformed mouse mammary epithelial cells (denoted 31EG4) were established and utilized to investigate the lactogenic hormone (glucocorticoids, insulin, and prolactin) regulation of tight junction formation. When 31EG4 cells were grown on permeable supports for 4 days in medium containing the synthetic glucocorticoid dexamethasone and insulin, confluent cell monolayers obtained a transepithelial electrical resistance (TER) of 1000-3000 omega.cm2. In contrast, over the same time period, confluent monolayers treated with insulin or insulin and prolactin maintained a low TER (35-150 omega.cm2). Consistent with the formation of tight junctions, apical to basolateral paracellular permeability was decreased from 12% to 1% for [14C]mannitol and 3.3% to 0.3% for [3H]inulin when cells were cultured in dexamethasone. This effect of dexamethasone on TER required extracellular calcium, de novo protein synthesis, dose-dependently correlated with glucocorticoid receptor occupancy, and was not due to an increase in cell density. As shown by direct and indirect immunofluorescence microscopy, dexamethasone treatment did not modulate the production or location of filamentous actin, the tight junction protein ZO-1, or the cell adhesion protein E-cadherin. Our results suggest that glucocorticoids play a fundamental role in the function and maintenance of cell-cell contact in the mammary epithelia by inducing the formation of tight junctions.

Animals↗
PubMed1992

Coronary thrombosis postpartum in a young woman with Still's disease.

A young woman with Still's disease sustained a small myocardial infarction 12 weeks after the delivery of a healthy male infant. This pregnancy was complicated by late onset proteinuric hypertension. Coronary angiography nine days after infarction revealed intracoronary thrombus which had resolved by 3 months with antithrombotic therapy. The angiographic appearances at 3 months suggested that a local vasculitis may have been the precipitating cause.

Adult↗
PubMed1992

Septal rupture after myocardial infarction: is very early surgery really worthwhile?

Despite numerous publications, mostly with small patient populations, the management of post-infarct septal rupture is still not well defined. Although urgent surgery appears to be the therapy of choice it is still unclear whether surgery very early after septal rupture in patients with severe haemodynamic compromise salvages a significant number of patients. In this paper we present the data from a large population of consecutive patients with post-infarct septal rupture from one cardiac centre. From 1980 through 1989, 108 patients with post-infarct septal rupture were seen at this Regional centre of whom 81 had operative repair; 43 (53%) of these survived the early postoperative period. Of 32 patients with cardiogenic shock who had surgery, early operative mortality in those operated on within 48 h of rupture was 90% (18/20) compared with 33% (4/12) in those operated on later (P less than 0.001). All survivors with pre-operative shock had intra-aortic balloon counter-pulsation before operation. Concomitant coronary artery bypass grafting was not associated with improved survival in our patients. Three patients survived long-term without operation. Analysis of population statistics suggest that approximately 270 patients with post-infarction septal rupture were not transferred from peripheral hospitals to the Regional Cardiothoracic Centre for assessment during this decade.

Aged↗
PubMed1992

Improving psychotherapy services: applications of research, audit and evaluation.

Psychotherapy services face increasing demand but are vulnerable to critical scrutiny by service purchasers seeking evidence of cost-effectiveness. Psychotherapy research, although it can benefit practitioners, cannot adequately address these concerns because of poor external validity and it is argued that complementary strategies are needed. A number of service-based evaluative methods are reviewed and the distinctions clarified between service evaluation, operational research, professional audit, service audit, quality assurance and total quality management. Maxwell's (1984) six category framework is used to examine a number of issues in psychotherapy services including the assessment process, treatment-of-choice decisions, predicting negative effects of treatment, dose-response in psychotherapy, brief interventions, therapist competence, clinical significance, cost effectiveness and measures of psychotherapy service inputs, process and outcomes. This review advocates reflective practice within a self-evaluating psychotherapy service and a systemic approach which can take account of the perspectives of patients, purchasers, service managers, referrers and practitioners.

Follow-Up Studies↗
PubMed1992

Optimal pacing modes after cardiac transplantation: is synchronisation of recipient and donor atria beneficial?

OBJECTIVE: To investigate the response of the transplanted heart to different pacing modes and to synchronisation of the recipient and donor atria in terms of cardiac output at rest. DESIGN: Doppler derived cardiac output measurements at three pacing rates (90/min, 110/min and 130/min) in five pacing modes: right ventricular pacing, donor atrial pacing, recipient-donor synchronous pacing, donor atrial-ventricular sequential pacing, and synchronous recipient-donor atrial-ventricular sequential pacing. PATIENTS: 11 healthy cardiac transplant recipients with three pairs of epicardial leads inserted at transplantation. RESULTS: Donor atrial pacing (+11% overall) and donor atrial-ventricular sequential pacing (+8% overall) were significantly better than right ventricular pacing (p < 0.001) at all pacing rates. Synchronised pacing of recipient and donor atrial segments did not confer additional benefit in either atrial or atrial-ventricular sequential modes of pacing in terms of cardiac output at rest at these fixed rates. CONCLUSIONS: Atrial pacing or atrial-ventricular sequential pacing appear to be appropriate modes in cardiac transplant recipients. Synchronisation of recipient and donor atrial segments in this study produced no additional benefit. Chronotropic competence in these patients may, however, result in improved exercise capacity and deserves further investigation.

Adolescent↗
PubMed1992

Studies of Muc-1 mucin expression and polarity in the mouse mammary gland demonstrate developmental regulation of Muc-1 glycosylation and establish the hormonal basis for mRNA expression.

Muc-1 is a major mucin glycoprotein expressed on the surface of mammary epithelial cells. It has attracted considerable attention as it is expressed in an aberrant form on many breast tumor cells. Here we describe studies using a recently obtained cDNA probe of Muc-1 expression during lactogenic development in the mouse. Northern blot analysis demonstrated that Muc-1 is expressed at all stages of lactogenic development but its levels are increased very significantly during mid-pregnancy and into lactation. The basis of this was examined using CID-9 mammary epithelial cell cultures. It was found that in the presence of insulin Muc-1 mRNA levels were increased by both hydrocortisone and prolactin, with the combination of the three hormones supporting maximum expression. Muc-1 mRNA levels were also modulated by culturing cells on a basement-membrane-like extracellular matrix that promoted mRNA levels 5- to 10-fold above levels in cells cultured on plastic tissue culture dishes. Immunocytochemical studies using monoclonal antibodies to carbohydrate epitopes on Muc-1 demonstrated that while Muc-1 was found at all developmental stages, it became increasingly sialylated during the course of pregnancy and into lactation. Additionally, we found that while Muc-1 is tightly polarized to the apical surface of the epithelium of lactating and pregnant mice it exhibited a less-polarized distribution on a small proportion of ductal cells in virgin mice. We conclude that the expression of Muc-1 is regulated at several different levels and by a number of different factors. We speculate that this may reflect different functional roles for Muc-1 at different stages of mammary development.

Animals↗
PubMed1992

Protein product of a human intronless calmodulin-like gene shows tissue-specific expression and reduced abundance in transformed cells.

The recently identified NB-1 mRNA is transcribed from a single intronless gene, previously thought to be an unexpressed calmodulin pseudogene. Although expression levels of the three known human calmodulin genes fluctuate only slightly in all cell types and tissues examined, NB-1 expression is limited to certain cells of pseudostratified and stratified epithelial tissues. Like calmodulin, the protein encoded by NB-1 is heat stable and binds to phenyl-Sepharose in a calcium-dependent manner. Despite the shared identity of 85% of their 148 amino acids, however, calmodulin and NB-1 protein are easily distinguished electrophoretically and immunologically. Polyclonal antibodies prepared against recombinant NB-1 protein recognize a protein with an apparent molecular weight of 16,000 which is abundant in cultured normal human mammary epithelial cells, but which is absent or barely detectable in fibroblasts or tumor cell lines. The immunohistochemical distribution of NB-1 protein in histologically normal tissues suggests that expression of the gene is regulated during epithelial differentiation. The majority of a small number of malignant tissues examined had lowered or undetectable NB-1 protein expression relative to normal tissues. Given its restricted distribution, the NB-1 protein may be involved in the initiation or maintenance of certain differentiated functions. Its absence may be due to or necessary for the manifestation of the transformed phenotype in certain cell types.

Antibodies↗
PubMed1991

Molecular cloning and analysis of the mouse homologue of the tumor-associated mucin, MUC1, reveals conservation of potential O-glycosylation sites, transmembrane, and cytoplasmic domains and a loss of minisatellite-like polymorphism.

We present here the full-length cDNA sequence and genomic structure of the mouse homologue of the tumor-associated mucin, MUC1. This mucin (previously called polymorphic epithelial mucin) is present at the apical surface of most glandular epithelial cells. The mouse gene, Muc-1, encodes an integral membrane protein with 40% of its coding capacity made up of serine, threonine, and proline, a composition typical of a highly O-glycosylated protein. The mucin core protein consists of an amino-terminal signal sequence, a tandem repeat domain encoding 16 repeats of 20-21 amino acids, and unique sequence containing transmembrane and cytoplasmic domains. Homology with the human protein is only 34% in the tandem repeat domain, mainly showing conservation of serines and threonines, presumed sites of O-linked carbohydrate attachment. Homology rises to 87% in the transmembrane and cytoplasmic domains, suggesting that these regions may be functionally important. The pattern of expression of the mouse mucin is very similar to that of its human counterpart and accordingly the two promoter regions share high homology, 74%, although previously identified potential hormone-responsive elements are not conserved. Interestingly, the mouse homologue, unlike its human counterpart does not exhibit a variable number tandem repeat polymorphism. We present evidence that suggests that the mouse gene was at one time polymorphic but has mutated away from this state.

Amino Acid Sequence↗
PubMed1991

Complications associated with retained pacemaker leads.

Retention of functionless pacemaker leads may occur following mechanical or infective problems (potentially or definitely infected) or after electrical failure of the lead. One hundred nineteen patients with a pacemaker lead (or leads) retained between 1970 and 1990 were reviewed retrospectively. Lead retention after an intervention dictated by potential or definite infection of the pacing system resulted in complications in 27 of 53 patients (51%), which in 22 patients (42%) were major (septicemia, superior vena cava syndrome, and further surgery under general anesthesia for recurrent "infective" problems) including three deaths. Complications were less likely if lead retention occurred after electrical failure with three minor and two major (surgery under general anesthesia, superior vena cava syndrome) complications in 66 patients (P less than 0.001). Bacteriology of swabs taken at the time of retention in the patients with potential or definite infection was unhelpful in predicting future complications: 8/18 patients (44%) whose swabs were negative had complications of which 5/18 (28%) were major. In our experience retention of functionless pacemaker leads after an intervention dictated by potential or definite infection of the pacing system, is associated with significant morbidity and mortality and should be avoided.

Adolescent↗
PubMed1990

Determination of apical membrane polarity in mammary epithelial cell cultures: the role of cell-cell, cell-substratum, and membrane-cytoskeleton interactions.

The membrane glycoprotein, PAS-O, is a major differentiation antigen on mammary epithelial cells and is located exclusively in the apical domain of the plasma membrane. We have used 734B cultured human mammary carcinoma cells as a model system to study the role of tight junctions, cell-substratum contacts, and submembraneous cytoskeletal elements in restricting PAS-O to the apical membrane. Immunofluorescence and immunoelectronmicroscopy experiments demonstrated that while tight junctions demarcate PAS-O distribution in confluent cultures, apical polarity could be established at low culture densities when cells could not form tight junctions with neighboring cells. In such cultures the boundary between apical and basal domains was observed at the point of cell contact with the substratum. Immunocytochemical analysis of these cell-substratum contacts revealed the absence of a characteristic basement membrane containing laminin, collagen (IV), and heparan sulfate proteoglycan. However, serum-derived vitronectin was associated with the basal cell surface and the cells were shown to express the vitronectin receptor on their basolateral membranes. Additionally, treatment of cultures with antibodies against the vitronectin receptor caused cell detachment. We suggest, then, that interactions between vitronectin and its receptor, are responsible for establishment of membrane domains in the absence of tight junctions. The role of cytoskeletal elements in restricting PAS-O distribution was examined by treating cultures with cytochalasin D, colchicine, or acrylamide. Cytochalasin D led to a redistribution of PAS-O while colchicine and acrylamide did not. We hypothesize that PAS-O is restricted to the apical membrane by interactions with a microfilament network and that the cytoskeletal organization is dependent upon cell-cell and cell-substratum interactions.

Actin Cytoskeleton↗
PubMed1979

The uncoupled regulation of fibronectin and collagen synthesis in Rous sarcoma virus transformed avian tendon cells.

We have investigated the regulation of fibronectin and procollagen synthesis in normal and Rous sarcoma virus transformed primary avian tendon cells. These two proteins interact at the cell periphery and both are reportedly lost upon transformation. We thus examined whether their synthesis was coordinately regulated in Rous sarcoma virus-infected cells. It was found that while the synthesis of both pro alpha 1 and pro alpha 2 peptides was reduced upon transformation, the synthesis of fibronectin was not altered. Nevertheless, long term radiolabeling demonstrated that fibronectin levels were reduced in transformed cells. It is concluded that the reduction in levels of these components at the surface is brought about by different mechanisms; collagen levels being regulated by procollagen synthesis and fibronectin levels by degradation and/or release into the culture medium. The possibility is discussed that fibronectin is lost from the cell periphery of primary avian tendon cells as a consequence of decreased levels of anchoring collagen molecules.

Animals↗
PubMed1979

Cryptococcal granuloma presenting as an intracranial mass.

A case of cryptococcosis of the central nervous system presenting as an intracranial space occupying lesion is described. The world literature and epidemiology of this unusual disease are surveyed. Problems in the diagnosis and the use of modern diagnostic techniques are discussed. The authors suggest that cryptococcosis should be included in the differential diagnosis of an intracranial space occupying lesion.

Adult↗
PubMed1978

Detection of an early surface change during oncogenic transformation.

Fluorescamine, which can label surface components of cells grown as monolayers in culture, has been used to probe alterations in chicken embryo fibroblasts infected with a temperature-sensitive mutant of Rous sarcoma virus, Prague A, LA24. The fluorescence of bound fluorescamine on cells at the permissive temperature (35 degrees) was found to be about 1/3 that of cells cultured at the nonpermissive temperature (41 degrees). During development of the transformed phenotype, i.e., after transfer of the cells from 41 degrees to 35 degrees, the decrease in surface fluorescence was observed to be an early event occurring within the first 4-8 hr after temperature shift. This alteration took place on a time scale similar to that of changes in 2-deoxyglucose transport and an increased rate of DNA synthesis, but before any major morphological changes. The change was related to cell transformation rather than to growth differences of the cells at the two temperatures. Further, it was found that fluorescamine was not monitoring the loss of LETS glycoprotein from the surface or the loss of any other surface components that could be detected by lactoperoxidase-catalyzed iodination of surface proteins. When fluorescamine-labeled components were resolved by polyacrylamide gel electrophoresis, significant differences were seen between components from cells cultured at 35 degrees compared with those from cells cultured at 41 degrees. Based on these results, possible mechanisms accounting for the fluorescence differences are suggested.

Avian Sarcoma Viruses↗