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Biomedical subjects

G Parry

Publications and source records attributed to G Parry.

At least 91 records · Page 5Linked to original sources

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↗

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↗

Coxsackie B4 viral myocarditis causing ventricular aneurysm.

This report describes a patient with viral myocarditis who developed acute dilated cardiomyopathy. The patient recovered well but a left ventricular aneurysm was detected angiographically. There was no history of myocardial infarction and the coronary arteries were normal. This is the first reported case of left ventricular aneurysm due to viral myocarditis.

Adult↗

cDNA cloning of a mouse mammary epithelial cell surface protein reveals the existence of epidermal growth factor-like domains linked to factor VIII-like sequences.

A 2.1-kilobase cDNA coding for a surface protein of mammary epithelial cells has been isolated from a mouse mammary gland lambda gt11 cDNA library. Sequence analysis of this cDNA reveals an open reading frame of 1389 base pairs that defines a protein with a molecular mass of 51.5 kDa. Structural analysis of the predicted sequence identifies two putative functional domains of the protein: (i) an N-terminal cysteine-rich region that is similar to epidermal growth factor-like domains of Drosophila Notch-1 protein and (ii) a large segment of the sequence that exhibited 54.5% identity with C-terminal domains of human coagulation factors VIII and V. These similarities in structure are used to predict the possible functions of the protein and its means of interaction with the cell surface. mRNA expression was detectable in mammary tissue from nonpregnant animals but was maximal in the lactating gland. In cultured cells, mRNA levels also correlated with the degree of cellular differentiation.

Amino Acid Sequence↗

Antibodies to GM1 and GD1b in patients with motor neuron disease without plasma cell dyscrasia.

Fifty-nine percent of 49 patients with motor neuron disease and 25% of 91 control subjects had IgM antibodies to ganglioside GM1 but usually not to GD1b at titers less than 1:80. This suggests that antibodies to GM1 may be part of the normal human antibody repertoire. However, given the higher incidence of antibodies to GM1 in patients with motor neuron disease, there may be specific epitopes important in antiganglioside antibodies associated with motor neuron disease.

Autoantibodies↗

Subacute rupture of a pseudoaneurysm formed by late rupture of a true left ventricular aneurysm.

A man aged 34 in whom rupture of a true aneurysm at least four weeks after acute myocardial infarction led to the development of a pseudoaneurysm is described. Because the pseudoaneurysm ruptured subacutely and the haemodynamic, clinical, and echocardiographic signs were not consistent, diagnosis of the cardiac rupture was delayed. Operative repair was successful, but the patient died.

Adult↗

Antibody-mediated peripheral neuropathies associated with ARC and AIDS: successful treatment with plasmapheresis.

Peripheral neuropathy is increasingly recognized in patients with AIDS as well as AIDS-related complex (ARC). Thirty homosexual men with polyneuropathy were evaluated in this study. Twenty-one had ARC and nine had AIDS. We observed three distinct clinical syndromes: distal sensorimotor polyneuropathy, chronic inflammatory demyelinating polyrediculoneuropathy (CIDP), and mononeuropathy multiplex. Circulating antibodies to peripheral nerve tissues were found in all patients. In six patients, treatment with plasma exchange was undertaken because of severe, progressive weakness. Four patients with clinical, electrophysiologic, and histologic evidence of CIDP improved with plasma exchange, three regaining normal function. These results suggest that the peripheral neuropathy associated with ARC and AIDS is immunologically mediated and that plasma exchange is an effective treatment in a subgroup of patients with this disorder.

AIDS-Related Complex↗

Cell-to-cell heterogeneity in the expression of carbohydrate-based epitopes of a mucin-type glycoprotein on the surface of human mammary carcinoma cells.

A large, O-linked glycoprotein, termed PAS-O, is a major differentiation antigen on the surface of normal lactating breast epithelia and is also found on the surface of many mammary tumors and mammary carcinoma cell lines. A characteristic feature of populations of tumor cells that express PAS-O is the cell-to-cell heterogeneity with respect to the presence or absence of the molecule. In this study, we used the human mammary carcinoma line 734B and a set of six monoclonal antibodies reactive with PAS-O to study the basis of this heterogeneity. Extensive Western blot analysis of antibody binding to PAS-O in milk fat globule membranes and in skim milk revealed that the antibodies all recognized different epitopes of PAS-O. Moreover, the epitopes were destroyed by periodic acid oxidation, demonstrating their oligosaccharide basis. All six monoclonal antibodies stained the 734B cells heterogeneously. In addition, five clones derived from the parent 734B population also exhibited heterogeneity in the expression of each of the epitopes. An analysis of staining of the 734B clones revealed that, in some cases, certain cells within the cloned population stained with one monoclonal antibody but not with another antibody. Significantly, though, when the 734B cells were treated with neuraminidase prior to antibody staining, most of the heterogeneity was eliminated, and all but one of the monoclonal antibodies stained 90-100% of the cells. This increase in cell staining was matched by an increase in PAS-O staining on Western blots. We conclude that heterogeneity in PAS-O expression on 734B cells is due partly to masking of epitopes by sialic acid and a variation (on a cell-to-cell basis) in the extent of PAS-O sialylation.

Antibodies, Monoclonal↗

p-nitrophenyl-beta-D-xyloside modulates proteoglycan synthesis and secretory differentiation in mouse mammary epithelial cell cultures.

Primary cultures of mouse mammary epithelial cells synthesize significant quantities of chondroitin and heparan sulfate proteoglycans (16). Long term treatment of such cultures with p-nitrophenyl-beta-D-xylopyranoside leads to a 10-20 fold increase in the synthesis and secretion of free chondroitin sulfate glycosaminoglycan (GAG) chains and assembly of a cell-associated matrix that is relatively enriched in heparan sulfate proteoglycan. This modulation of cell-synthesized proteoglycans leads to significant changes in cell morphology and cellular differentiation. Notably cells cultured on plastic culture dishes change from being flattened to cuboidal. The synthesis of the milk proteins alpha 1, and beta-casein is also increased as is the formation of fat droplets and fat droplet membrane components. Promotion of differentiation increases with increasing xyloside concentration in the range 0-1.5 mM, but there may be a block in secretion at higher xyloside concentrations. While the detailed mechanisms remain to be elucidated, we conclude that the composition of proteoglycans incorporated into the matrix (and possibly the glycosaminoglycans secreted into the medium), may play a significant role in maintaining the phenotypic characteristics of terminally differentiated mammary epithelial cells.

Animals↗

Fine adjustment of thyroxine replacement dosage: comparison of the thyrotrophin releasing hormone test using a sensitive thyrotrophin assay with measurement of free thyroid hormones and clinical assessment.

Thyroxine replacement therapy for 21 adult patients with primary hypothyroidism was adjusted to the dosage at which each patient had a normal thyrotrophin (TSH) response to thyrotrophin releasing hormone (TRH). Clinical assessment and measurement of TSH (by sensitive immunoradiometric assay), free thyroxine (FT4) and free tri-iodothyronine (FT3) were made at this dosage and at higher and lower doses of thyroxine. Clinical observations, FT3 and FT4 assays were relatively insensitive to small alterations of thyroxine dosage, in contrast to which basal TSH measurements correlated well with TRH responsiveness and were sensitive to fine adjustments of thyroxine dosage.

Adult↗

Cognitive style and depression: symptom-related, event-related or independent provoking factor?

Three models of the relation of negative cognitive style to depression are outlined: (1) a symptom model, where negative cognitions are a symptom of depression, (2) a vulnerability model, where a negative life-event in combination with cognitive vulnerability leads to depression and (3) an alternative aetiologies model, where depression can be precipitated either by stressful life-events or by a negative cognitive style. Differential predictions from the three models were examined in data from a general population survey of 193 mothers where a reliable case identification procedure and life-events interview were used together with measures of attributional style and self-esteem. Results were mostly consistent with the alternative aetiologies model, but also gave some support for the symptom model. In some cases, negative cognitive style may act to increase the risk of depression onset in the absence of life-event stress.

Adjustment Disorders↗

Transferrin is a major mouse milk protein and is synthesized by mammary epithelial cells.

We have identified a major mouse milk protein as transferrin (Tf) using immunoprecipitation, 2-dimensional electrophoresis, Ouchterlony diffusion and V-8 protease digests. We show that Tf is synthesized by mammary epithelial cells themselves and that its synthesis and secretion is regulated distinctly from that of other milk proteins. In culture, the kinetics of Tf synthesis and secretion are distinct from that of beta-casein; furthermore, Tf is relatively insensitive to lactogenic hormones whereas beta-casein is hormone-dependent. In vivo, however, Tf is regulated by pregnancy. While the virgin gland produces small amounts of Tf, its production is greatly increased during pregnancy and lactation. Thus, Tf synthesis in the mammary gland is modulated by as yet unknown factors in vivo. These observations are discussed in terms of Tf's possible role in mammary gland growth, differentiation and function.

Animals↗

Collagen-fibronectin interactions in normal and Rous sarcoma virus-transformed avian tendon cells: possible mechanisms for increased extracellular matrix turnover after transformation.

Using gelatin, casein, and fibronectin as substrates and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), we have identified protein-degrading enzymes in both normal and Rous sarcoma virus-transformed primary avian tendon cells. Although there are some consistent differences in the profile of the gelatinolytic activities (mainly metalloproteinases) between normal and transformed cells, the amounts of fibronectin-degrading activities seem to be comparable. In vitro studies reported here demonstrate that the degradation of fibronectin is partially and specifically inhibited by gelatin and collagen. We therefore propose that the abundant collagen present in normal tendon cells protects fibronectin against degradation. Conversely, in transformed cells, where collagen levels are drastically reduced, fibronectin may be more accessible to degradation. Thus differences in the steady-state levels of fibronectin on normal and transformed cells may be, at least in part, a consequence of changes in collagen levels.

Animals↗

Regulation of differentiation and polarized secretion in mammary epithelial cells maintained in culture: extracellular matrix and membrane polarity influences.

Several previous studies have demonstrated that mammary epithelial cells from pregnant mice retain their differentiated characteristics and their secretory potential in culture only when maintained on stromal collagen gels floated in the culture medium. The cellular basis for these culture requirements was investigated by the monitoring of milk protein synthesis and polarized secretion from the mouse mammary epithelial cell line, COMMA-1-D. Experiments were directed towards gaining an understanding of the possible roles of cell-extracellular matrix interactions and the requirements for meeting polarity needs of the epithelium. When cells are cultured on floating collagen gels they assemble a basal lamina-like structure composed of laminin, collagen (IV), and heparan sulfate proteoglycan at the interface of the cells with the stromal collagen. To assess the role of these components, an exogenous basement membrane containing these molecules was generated using the mouse endodermal cell line, PFHR-9. This matrix was isolated as a thin sheet attached to the culture dish, and mammary cells were then plated onto it. It was found that cultures on attached PFHR-9 matrices expressed slightly higher levels of beta-casein than did cells on plastic tissue culture dishes, and also accumulated a large number of fat droplets. However, the level of beta-casein was approximately fourfold lower than that in cultures on floating collagen gels. Moreover, the beta-casein made in cells on attached matrices was not secreted but was instead rapidly degraded intracellularly. If, however, the PFHR-9 matrices with attached cells were floated in the culture medium, beta-casein expression became equivalent to that in cells cultured on floating stromal collagen gels, and the casein was also secreted into the medium. The possibility that floatation of the cultures was necessary to allow access to the basolateral surface of cells was tested by culturing cells on nitrocellulose filters in Millicell (Millipore Corp., Bedford, MA) chambers. These chambers permit the monolayers to interact with the medium and its complement of hormones and growth factors through the basal cell surface. Significantly, under these conditions alpha 1-, alpha 2-, and beta-casein synthesis was equivalent to that in cells on floating gels and matrices, and, additionally, the caseins were actively secreted. Similar results were obtained independently of whether or not the filters were coated with matrices.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Sex-role beliefs, work attitudes and mental health in employed and non-employed mothers.

The attitudes of mothers to their home and child-care role, to their employment role and to sex roles are potentially important correlates of mental health but have been little researched. Results from a general population survey of 160 working-class mothers of young children suggest that dissatisfaction with the home-maker role is associated with higher levels of psychiatric symptoms, psychological distress and self-depreciation. These relationships are strongest for full-time home-makers. For employed mothers, dual-role conflict was more strongly associated with psychological distress than was job satisfaction. Liberal sex-role attitudes were associated with lower psychiatric symptom levels in employed mothers and with higher self-esteem in non-employed mothers. There was a significant interaction between employment status and sex-role beliefs in relation to anxiety. Employed mothers with traditional attitudes and non-employed mothers with liberal attitudes were more anxious. This result was replicated in an independent sample of 200 working-class and middle-class mothers.

Affective Symptoms↗