Biomedical subjects

G Parry

Publications and source records attributed to G Parry.

At least 73 records · Page 4Linked to original sources

PubMed1994

Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users. Primary end points analysis from the ATACS trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group.

BACKGROUND: The purpose of this study was to compare combination antithrombotic therapy with aspirin plus anticoagulation versus aspirin alone, when added to conventional antianginal therapy in patients with unstable rest angina or non-Q-wave myocardial infarction who were nonprior aspirin users. METHODS AND RESULTS: Two hundred fourteen patients were randomized; 109 were randomized to receive aspirin alone (162.5 mg daily) and 105 to receive a combination of aspirin plus anticoagulation, ie, aspirin 162.5 mg daily plus heparin (activated partial thromboplastin time, two times control) followed by aspirin 162.5 mg daily plus warfarin (international normalized ratio, 2 to 3). Trial therapy was begun by 9.5 +/- 8.8 hours of qualifying pain and was continued for 12 weeks. Primary end points were recurrent angina with ECG changes, myocardial infarction, and/or death. Analysis by intention to treat of primary events at 12 weeks was performed. At 14 days, there was a significant reduction in total ischemic events in the combination group versus aspirin alone (10.5% versus 27%, P = .004). An efficacy analysis of primary events at 12 weeks also revealed a large reduction in total ischemic events in the combination group versus aspirin alone (13% versus 25%, P = .06). Bleeding complications were slightly more common with combination therapy. CONCLUSIONS: In nonprior aspirin users, combination antithrombotic therapy with aspirin plus anticoagulation significantly reduces recurrent ischemic events in the early phase of unstable angina.

Angina, Unstable↗

PubMed1993

The CRIB score.

Explore the source record for details and available documents.

Hospital Mortality↗

PubMed1993

Prospective comparison of unstable angina versus non-Q wave myocardial infarction during antithrombotic therapy. Antithrombotic Therapy in Acute Coronary Syndromes Research Group.

OBJECTIVES: This study was designed to compare the response of unstable angina and non-Q wave myocardial infarction during treatment with antithrombotic therapy. BACKGROUND: Antithrombotic therapy is beneficial in patients with these two coronary syndromes. METHODS: In a multicenter trial of antithrombotic therapy in unstable angina or non-Q wave myocardial infarction, 358 patients admitted within 48 h of chest pain were randomized to antithrombotic therapy with either 1) aspirin alone, or 2) aspirin plus heparin followed by aspirin plus warfarin, and were prospectively followed up for 12 weeks. Admission cardiac enzyme analyses revealed unstable angina in 268 patients and non-Q wave myocardial infarction in 62. Given an event rate of about 25%, this study has a power of 80% to detect a 50% difference between the two groups. RESULTS: Patients with unstable angina and non-Q wave myocardial infarction were similar with regard to age, gender, coronary risk factors and prior antianginal medication. Primary end points at 12 weeks were recurrent ischemia, infarction and death. [table: see text] In the non-Q wave group, all infarctions and death occurred within the 1st week. CONCLUSIONS: Patients with unstable angina or non-Q wave myocardial infarction on antithrombotic therapy have a similar total number of ischemic events by 12 weeks. However, despite maximal medical therapy with antianginal and antithrombotic medication, patients with non-Q wave infarction have a significantly higher rate of reinfarction and death.

Adrenergic beta-Antagonists↗

PubMed1993

Stage-specific remodeling of the mammary gland basement membrane during lactogenic development.

Several in vitro studies have highlighted the importance of extracellular matrix proteoglycans as regulators of mammary epithelial cell differentiation. In this study monospecific antibodies to heparan (HS) and chondroitin/dermatan sulfate (CS/DS) proteoglycans were used to determine their possible significance in vivo. Immunohistochemical studies of proteoglycan distribution in virgin, pregnant, and lactating tissue demonstrated that heparan sulfate proteoglycan was found in the epithelial cell basement membrane at all stages of development. This was also true for CS/DS proteoglycans, but the relative proportions of CS and DS were strikingly modulated during lactogenesis. Notably DS glycosaminoglycans were the dominant components of the basement membrane in lactating tissue but CS glycosaminoglycans were the major proteoglycans of pregnant tissue. The possible significance of these results for gene expression in the gland is discussed.

Animals↗

PubMed1993

Hormonal regulation of the polarized function and distribution of Na/H exchange and Na/HCO3 cotransport in cultured mammary epithelial cells.

The time course for development of polarized function and morphological distribution of pH regulatory mechanisms has been examined in a mouse mammary epithelial cell line (31EG4). Monolayers grown on permeable supports had tight junctions when grown 3-4 days in the presence of the lactogenic hormones dexamethasone (D, a synthetic glucocorticoid) and insulin (I), or in D, I, and prolactin (P), but there were no tight junctions in the absence of D. Microspectrofluorimetry of the pH-sensitive dye BCECF was used to measure pH (pHi) in cells mounted in a two-sided perfusion chamber to distinguish pH regulatory activity at the apical and basolateral membranes. Na/H exchange was assayed as the Na-dependent, amiloride-sensitive component of pHi recovery from an acid load induced by a pulse of NH3/NH4-containing solution. When monolayers were grown 3-4 d in the presence of P, D, and I, Na/H exchange was restricted to the basolateral membrane. In contrast, in the absence of P, Na/H exchange was present on both the apical and basolateral membranes. After 5-6 days, in the presence or absence of P, Na/H exchange was present only on the basolateral membrane. An antibody to the NHE-1 isoform of the Na/H exchanger was used to determine its morphological distribution. In all hormone conditions the antibody recognized a protein of approximately 110 kD (Western blot), and confocal immunofluorescence microscopy of this antibody and of an anti-ZO-1 (the marker of the tight junctions) antibody showed that the morphological distribution of the Na/H exchanger was similar to the functional distribution under all hormonal treatments. In addition, a putative Na/HCO3 cotransport system was monitored as a Na-dependent, amiloride-insensitive pHi recovery mechanisms that was inhibited by 200 microM H2DIDS. After treatment with D+I (but not with I alone) cotransport appeared exclusively on the basolateral membrane, and the polarized expression of this transporter was not altered by P. We conclude that when mammary cells are grown in D+I-containing media, the Na/H exchanger is expressed initially (i.e., after 3-4 d) on both the apical and basolateral membranes and later (5-6 d) on only the basolateral membrane. P (in the presence of D+I) selectively speeds this polarization, which is determined by polarized distribution of the exchanger to the apical and/or basal membrane and not by the activation and/or inactivation of transporters.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

What is vestibular papillomatosis? A study of its prevalence, aetiology and natural history.

OBJECTIVES: To clarify the prevalence, aetiology, symptoms and natural history of vestibular papillomatosis. DESIGN: Study in two parts: 1. prevalence assessed by colposcopic examination of the vulva of unselected patients by one doctor (J.M.W.); 2. patients selected by clinical appearance as having vestibular papillomatosis (by J.M.W. and other doctors) assessed in a research clinic. SETTING: Outpatient genitourinary medicine clinic in South London. SUBJECTS: Part 1 study: 295 female clinic attenders; part 2 study: 18 women with clinical vestibular papillomatosis. MAIN OUTCOME MEASURES: Part 1 study: number of unselected patients found to have vestibular papillomatosis. Part 2 study: associated symptoms, histology, DNA hybridisation and polymerase chain reaction on vulval biopsies. Clinical regression of lesions. Cervical cytology and colposcopy. RESULTS: Part 1 study: Vestibular papillomatosis was identified by colposcopic examination of the vulva in 3/295 (1%) of women. Part 2 study: 9/18 (50%) women with vestibular papillomatosis were asymptomatic; the other nine had intermittent mild symptoms. Thirteen (72%) had a history of genital warts. Vulval biopsies had features suggestive of wart virus infection on histology in 17/18 (94%) and HPV16 was found by DNA hybridisation studies or polymerase chain reaction in 7/18 (39%). On follow up (mean duration 9 months) the vulval lesions had regressed in 9/12 patients. Ten patients had cervical wart virus infection or intraepithelial neoplasia (CIN), or both, and five needed laser treatment for this. CONCLUSIONS: In this study vestibular papillomatosis was associated with human papillomavirus (HPV) infection. This study suggests that vestibular papillomatosis need not be treated, but patients with it may be at increased risk for CIN.

Adolescent↗

PubMed1993

Delays to thrombolysis in the treatment of myocardial infarction.

In-hospital delays to thrombolysis were significantly shorter when thrombolysis was available on admission to the accident and emergency department than after transfer to the coronary care unit (median 60 min v 84 min, p < 0.0001). With direct admission by general practitioners to a coronary care unit the subsequent in-hospital delay was shorter (median 39 min p = 0.0004), but overall delay to thrombolysis longer (median 220 v 170 min, p = 0.0019) because of longer pre-hospital delays. Overall delay was shortest with emergency ambulance referral and thrombolysis being administered in the accident and emergency department.

Aged↗

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

Molecular cloning, sequence analyses, and expression of complementary DNA encoding murine progesterone receptor.

Progesterone receptors exist in two molecular forms commonly designated as "A" and "B" forms, the relative proportion of which can vary among species. In murine tissues, progesterone receptor exists predominantly as the "A" form which, in mammary glands, is also under developmental regulation [Shyamala et al. (1990) Endocrinology 126, 2882-2889]. Therefore, toward resolving the molecular mechanisms responsible for the predominance of the "A" form of progesterone receptor in murine tissues and its developmental regulation, we have isolated, sequenced, and expressed the complementary DNA corresponding to the mouse progesterone receptor. Nucleotide sequence analysis revealed two in-frame ATG codons, such that the largest open reading frame beginning with the first codon could encode a polypeptide with an estimated molecular weight of 99,089, while the shorter open reading frame beginning with the second codon could produce a polypeptide with a calculated molecular weight of 81,829. The murine progesterone receptor had complete identity for the DNA binding domain of human and rabbit progesterone receptors and 99% homology with the chicken progesterone receptor; for the steroid binding domain, it had 96% homology with human and rabbit progesterone receptors and 86% homology with chicken progesterone receptors. Expression of the complete complementary DNA in Chinese hamster ovary cells yielded a protein which bound the synthetic progestin promegestone with an equilibrium dissociation constant of approximately 1 nM, and in Western blot analyses revealed both "A" and "B" forms of immunoreactive receptor.

Amino Acid Sequence↗

PubMed1991

Metacestode-induced depression of the production of, and response to, sex pheromone in the intermediate host Tenebrio molitor.

Hymenolepis diminuta infection of Tenebrio molitor is associated with an impairment of vitellogenesis and a reduction in host fecundity. In this communication the effect of infection upon an additional aspect of host reproduction, the initiation of mating behavior, has been examined. Copulatory release pheromone, extracted from control virgin females 6-7 days old, was shown to stimulate a positive mating response in 88% of 5- to 6-day-old control males; however, only a 56% response was elicited by pheromone from infected females. In addition, parasitization adversely effected male response to pheromone from control females. A significant (P less than 0.001) depression of copulatory response occurred in infected 6- to 7-day-old males (age of peak response) although this effect was not sustained in older beetles. The possibility that an endocrine interaction between metacestodes and host may mediate these effects is discussed in the light of our knowledge of the role of host juvenile hormone in controlling both pheromone production and vitellogenesis in T. molitor.

Animals↗