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Biomedical subjects

L Chapman

Publications and source records attributed to L Chapman.

At least 19 recordsLinked to original sources
PubMed1999

Effects of psycho-educational interventions on sexual health risks and psycho-social adaptation in young adults with genital herpes.

The purpose of this study was to test the outcomes of group psycho-educational intervention (PEI) led by nurses on sexual health risks (knowledge, behaviour, disease burden) and psycho-social adaptation (depression, mood states, self-efficacy) in young adults with the chronic disease, genital herpes. Two hundred and fifty-two young adults with symptomatic genital herpes participated in a randomized controlled trial (RCT). The intervention was participation in a three-session group PEI facilitated by a nurse in the community. Participants completed questionnaires measuring sexual health risks (herpes knowledge, sexual risk behaviour, disease burden of patterns of recurrences of outbreaks of the disease), and psycho-social adaptation (depression using the Beck Depression Inventory [BDI], mood states using the Profile of Mood States [POMS], and feelings of self-efficacy for protection from sexually transmitted diseases [PSTD]) at induction into the study, and at 3 and 6 months. Participants were mainly employed, Caucasian, single women in their twenties (X = 27.1 years, SD = 4.3), with some college education; 23% of the sample were men. After controlling for baseline knowledge about genital herpes, the experimental group had significantly more knowledge than the control group at 3 and 6 months' post-intervention. They also reported using condoms and spermicides to prevent the spread of genital herpes more often than did the control group. The implications for nurses in the community include the following: (a) PEI is an intervention that can be used by nurses in the community with a high-risk population; (b) group intervention is a viable treatment for people with a highly stigmatized, chronic sexually transmitted disease (STD); and (c) further testing of the use of PEI by nurses in the community with other high-risk populations is needed.

Adaptation, Psychological↗
PubMed1998

Body image and HIV: implications for support and care.

Very little formal research has looked at body image change over the course of HIV illness or assessed the implications of changes for support interactions. There are three main spheres of influence on body image: the physical, psychological and the social. HIV shares some of these aspects with other chronic or fatal illnesses, but has specific elements which are distinctive, such as particular physical manifestations and the negative impact of media, social representations and stigma resulting in a radically altered experience for an HIV-positive body. This paper outlines preliminary findings using a body image measure designed specifically for use in HIV. The results suggest that people with HIV may experience significant feelings of contamination, brought about through internalization of stigma and representations, in addition to physical decline as illness progresses.

Adolescent↗
PubMed1997

Antigenic phenotypes common to rat oval cells, primary hepatocellular carcinomas and developing bile ducts.

The shared expression of monoclonal antibody-defined antigens by oval cells and by bile ducts, neoplastic nodules and primary hepatocellular carcinomas (PHC) has provided support for the ability of oval cells to undergo differentiation along ductular or hepatocyte lineages and/or to progress to hepatocellular carcinoma. With the aim of obtaining additional insight into this process, we have combined serial section and double labeling immunofluorescence analysis to determine if phenotypes expressed in vitro by four rat oval cell lines and the H5D.61 hepatocellular carcinoma cell line and in situ by ethionine-induced primary hepatocellular carcinomas reproduce antigenic patterns occurring during normal liver development. Analysis using monoclonal antibodies specific for the oval cell antigens OV6 and OC.2 and hepatocyte markers HBD.1 and H.4 defined subpopulations in four oval cell lines and neoplastic hepatocytes in PHC and H5D.61 with OC.2-/OV6+ and OC.2+/OV6+ phenotypes. Cells with an OC2+/OV6- phenotype were rarely observed in cell lines or primary tumors. In contrast, areas composed of OV6+/H.4+ cells were frequently found in PHC. Examination of fetal and neonatal rat livers demonstrated the stage-specific appearance of three of these phenotypes during liver development. The OC.2+/OV6- phenotype appeared transiently prior to embryonic day (ED) 18 in a subpopulation of HBD.1+ hepatoblasts. OV6 expression was first detected at ED18 on developing bile ducts that were negative for OC.2. These newly formed ducts rapidly acquired OC.2, starting with ducts in the hilar region and spreading outward towards the periphery. This OC.2 expression gradient persisted in the newborn rat liver but became more skewed towards doubly positive cells, with OC.2-/OV6+ cells being found primarily in the periphery. Hepatocytes expressing both OV6 and H.4 were not observed in fetal liver but appeared in neonatal liver in close proximity to OV6+ interlobular ducts. From these findings, it was concluded that oval cells and PHC display phenotypes representing normal stages in liver development, suggesting that oval cells and cells within ethionine-induced PHC are capable of initiating but are unable to complete pathways of hepatocytic or biliary differentiation.

Animals↗
PubMed1997

Effects of norepinephrine infusion and exercise on blood pressure in rats.

Two experiments were conducted to test the hypotheses that norepinephrine (NE) infusion would increase blood pressure and wheel running activity level, and, secondly, that voluntary exercise would lower NE-induced increases in blood pressure. NE-bitartrate was infused into male Sprague-Dawley rats using an implanted osmotic pump (3.75 micrograms/kg/min in 0.9% saline). Control rats received the vehicle solution. Systolic blood pressure was measured by the tail-cuff method. Voluntary wheel running activity expressed as wheel revolutions per 24 hr was measured on the 5th, 9th, and 13th day. Blood pressure on the 13th day and wheel running activity on the 9th day were significantly higher in NE-infused rats. The NE content of heart tissue was not altered, but urinary excretion of NE and epinephrine was increased in the NE-infused animals. Food intake, body weight gain, and kidney weight per 100 g body wt were not changed but heart weight per 100 g body wt was increased by NE infusion. Urinary total calcium excretion was higher in the NE-infused rats. Spontaneous voluntary exercise in running wheels attenuated increases of blood pressure in NE-infused rats. The results of the present study suggest that rats receiving exogenous NE exhibit increased blood pressure and voluntary wheel running activity. Voluntary wheel running exercise also reduces blood pressure in NE-infused rats.

Animals↗
PubMed1996

Towards an understanding of protein-DNA recognition.

Understanding how proteins recognize DNA in a sequence-specific manner is central to our understanding of the regulation of transcription and other cellular processes. In this article we review the principles of DNA recognition that have emerged from the large number of high-resolution crystal structures determined over the last 10 years. The DNA-binding domains of transcription factors exhibit surprisingly diverse protein architectures, yet all achieve a precise complementarity of shape facilitating specific chemical recognition of their particular DNA targets. Although general rules for recognition can be derived, the complex nature of the recognition mechanism precludes a simple recognition code. In particular, it has become evident that the structure and flexibility of DNA and contacts mediated by water molecules contribute to the recognition process. Nevertheless, based on known structures it has proven possible to design proteins with novel recognition specificities. Despite this considerable practical success, the thermodynamic and kinetic properties of protein/DNA recognition remain poorly understood.

Amino Acid Sequence↗
PubMed1996

The crystal structure of the DNA-binding domain of yeast RAP1 in complex with telomeric DNA.

Telomeres, the nucleoprotein complexes at the ends of eukaryotic chromosomes, are essential for chromosome stability. In the yeast S. cerevisiae, telomeric DNA is bound in a sequence-specific manner by RAP1, a multifunctional protein also involved in transcriptional regulation. Here we report the crystal structure of the DNA-binding domain of RAP1 in complex with telomeric DNA site at 2.25 A resolution. The protein contains two similar domains that bind DNA in a tandem orientation, recognizing a tandemly repeated DNA sequence. The domains are structurally related to the homeodomain and the proto-oncogene Myb, but show novel features in their DNA-binding mode. A structured linker between the domains and a long C-terminal tail contribute to the binding specificity. This structure provides insight into the recognition of the conserved telomeric DNA sequences by a protein.

Amino Acid Sequence↗
PubMed1996

Hantavirus infections in the United States: diagnosis and treatment.

Definitive diagnosis of acute hantavirus infection requires demonstration of specific IgG and IgM antibodies and a compatible clinical course; most persons with acute illness will also have viral RNA in PBMC which can be detected after RT-PCR amplification. Characteristic hematologic and hemodynamic findings are helpful in establishing a presumptive diagnosis of HPS in persons with cardiopulmonary symptoms and signs while awaiting the results of serologic testing and PCR. Diagnosis during the prodromal phase is difficult although very limited data suggest that most these patients also have hantavirus IgG and IgM antibodies. Patients with suspected hantavirus infection should be treated in a critical care unit, as sudden hemodynamic deterioration can occur at any time. Hemodynamic monitoring is encouraged in patients with cardiopulmonary symptoms and signs, and inotropic support and vasopressors should be used rather than fluids. An uncontrolled study of ribavirin therapy was inconclusive and a placebo-controlled trial is therefore planned. The latter study aims to enroll persons with prodromal findings and early cardiopulmonary disease.

Animals↗
PubMed1996

Cloning of cDNAs from a mammalian expression library by a direct selection-amplification method.

A sensitive method was devised for cloning cDNAs from a mammalian expression library based on single-cell detection and selection of transfected cells. The method is applicable for cloning cell-surface or cytoplasmic proteins for which a detection assay, such as immunofluorescence or immunohistochemical reactivity, exists. The widely used eukaryotic expression vector cdm8 is utilized, and the method is demonstrated using the gene for C-CAM, a liver glycoprotein adhesion molecule. After transfection, cells are plated out on a collagen gel substrate to allow retrieval of selected cells. Simultaneous fixation and permeabilization with acetone permits immunological and histochemical detection of cell-surface and cytoplasmic proteins without loss of plasmid vector. Inserts of interest are recovered by PCR with vector primers.

Adenosine Triphosphatases↗
PubMed1995

The oestrogen receptor recognizes an imperfectly palindromic response element through an alternative side-chain conformation.

BACKGROUND: Structural studies of protein-DNA complexes have tended to give the impression that DNA recognition requires a unique molecular interface. However, many proteins recognize DNA targets that differ from what is thought to be their ideal target sequence. The steroid hormone receptors illustrate this problem in recognition rather well, since consensus DNA targets are rare. RESULTS: Here we describe the structure, at 2.6 A resolution, of a complex between a dimer of the DNA-binding domain from the human oestrogen receptor (ERDBD) and a non-consensus DNA target site in which there is a single base substitution in one half of the palindromic binding site. This substitution results in a 10-fold increase in the dissociation constant of the ERDBD-DNA complex. Comparison of this structure with a structure containing a consensus DNA-binding site determined previously, shows that recognition of the non-consensus sequence is achieved by the rearrangement of a lysine side chain so as to make an alternative base contact. CONCLUSIONS: This study suggests that proteins adapt to recognize different DNA sequences by rearranging side chains at the protein-DNA interface so as to form alternative patterns of intermolecular contacts.

Amino Acid Sequence↗
PubMed1995

Clinical features that differentiate hantavirus pulmonary syndrome from three other acute respiratory illnesses.

To elucidate the early clinical characteristics of hantavirus pulmonary syndrome (HPS), we compared the clinical features of 24 cases of HPS with those of cases of bacteremic pneumococcal pneumonia (n = 30), influenza (n = 33), or unexplained adult respiratory distress syndrome (ARDS, n = 21). On admission, patients with HPS were less likely than outpatients with influenza to have reported sore throat (OR = 0.02, P < .01) and cough (OR = 0.1, P = .01) and were less likely than patients with pneumococcal pneumonia to have lobar infiltrates detected by chest roentgenography (OR = 0, P < .01). Multivariate discriminant analysis revealed that three clinical characteristics at admission (dizziness, nausea or vomiting, and absence of cough) and three initial laboratory abnormalities (low platelet count, low serum bicarbonate level, and elevated hematocrit level) served to identify all patients with HPS and to exclude HPS in at least 80% of patients with unexplained ARDS. These findings warrant further study and should facilitate the early recognition of patients with HPS, who may benefit from early critical-care intervention.

Acute Disease↗
PubMed1994

Promotion of parallel DNA quadruplexes by a yeast telomere binding protein: a circular dichroism study.

Repressor-activator protein 1 (RAP1) has an essential role in the maintenance of yeast telomeres. Yeast telomeric DNA consists of simple repeated G-rich sequences that are bound by RAP1. We have found that RAP1, in addition to its known binding activity for double-stranded DNA, interacts with the G-rich strand containing guanine base (G)-tetrads. We show here using circular dichroism spectroscopy that RAP1 promotes the formation of one particular type of DNA quadruplex, parallel G4-DNA. Furthermore, RAP1 is able to bind to both preformed parallel and antiparallel DNA quadruplexes. These results have implications for the possible use of DNA quadruplexes in telomere-telomere association in vivo.

Animals↗
PubMed1994

Postthaw viability of frozen human ovarian cancer tumor specimens.

Thirty-five human ovarian cancer tumor specimens were frozen by both rapid freeze and slow freeze with dimethyl sulfoxide (DMSO) to determine which method results in optimal postthaw viability. Median viability following a rapid freeze was 8% as compared to 90% with slow freeze with DMSO (P = .0001). Eighty-seven percent of tumors had a viability of > 80% following slow freeze with DMSO. When experimentation on human ovarian cancer tumor cells requires postthaw viability, we recommend slow freeze with DMSO.

Carcinoma↗
PubMed1994

Community-based parentcraft.

Some parents feel unable to ask advice from professionals, or that the advice offered is not appropriate to their own priorities. Lilian Chapman and Peter Jones describe a multi-agency, community-based approach to parentcraft teaching.

Community Health Services↗
PubMed1994

Particle concentration fluorescence immunoassay chemosensitivity assay for human epithelial ovarian cancer.

We adapted particle concentration fluorescence immunoassay technology to develop a new chemosensitivity assay. Six human epithelial ovarian cancer cell lines were incubated with cisplatin for 24 hours. Cells were then labeled with a fluorophore for 30 minutes. Removal of supernatant, washing of tumor cells, and reading of epifluorescence was performed automatically. Percent cell lysis was calculated simultaneously by chromium release assay. The particle concentration fluorescence chemosensitivity assay detected cell lysis in all six cell lines. The chemosensitivity assay detected a larger percent lysis than the chromium release assay in each of the cell lines. The advantages of our chemosensitivity assay are plating efficacy, speed, efficiency, safety, and accuracy.

Cell Death↗
PubMed1993

The crystal structure of a two zinc-finger peptide reveals an extension to the rules for zinc-finger/DNA recognition.

The Cys2-His2 zinc-finger is the most widely occurring DNA-binding motif. The first structure of a zinc-finger/DNA complex revealed a fairly simple mechanism for DNA recognition suggesting that the zinc-finger might represent a candidate template for designing proteins to recognize DNA. Residues at three key positions in an alpha-helical 'reading head' play a dominant role in base-recognition and have been targets for mutagenesis experiments aimed at deriving a recognition code. Here we report the structure of a two zinc-finger DNA-binding domain from the protein Tramtrack complexed with DNA. The amino-terminal zinc-finger and its interaction with DNA illustrate several novel features. These include the use of a serine residue, which is semi-conserved and located outside the three key positions, to make a base contact. Its role in base-recognition correlates with a large, local, protein-induced deformation of the DNA helix at a flexible A-T-A sequence and may give insight into previous mutagenesis experiments. It is apparent from this structure that zinc-finger/DNA recognition is more complex than was originally perceived.

Amino Acid Sequence↗
PubMed1993

The crystal structure of the estrogen receptor DNA-binding domain bound to DNA: how receptors discriminate between their response elements.

The nuclear hormone receptors are a superfamily of ligand-activated DNA-binding transcription factors. We have determined the crystal structure (at 2.4 A) of the fully specific complex between the DNA-binding domain from the estrogen receptor and DNA. The protein binds as a symmetrical dimer to its palindromic binding site consisting of two 6 bp consensus half sites with three intervening base pairs. This structure reveals how the protein recognizes its own half site sequence rather than that of the related glucocorticoid receptor, which differs by only two base pairs. Since all nuclear hormone receptors recognize one or the other of these two consensus half site sequences, this recognition mechanism applies generally to the whole receptor family.

Amino Acid Sequence↗