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Biomedical subjects

R Nairn

Publications and source records attributed to R Nairn.

At least 19 recordsLinked to original sources

From source material to news story in New Zealand print media: a prospective study of the stigmatizing processes in depicting mental illness.

OBJECTIVE: The aim of this study was to analyse how newspaper articles that depict mental illnesses are generated from source materials. METHOD: From a prospectively collected national sample of print materials involving mental illness, 50 published items that related to the Privacy Commissioner's opinion about disclosure of a psychiatric patient's health information were identified. A copy of the Privacy Commissioner's original Case Note and three news stories about the Case Note distributed by the New Zealand Press Association constituted the database. These materials were subjected to discourse analysis. We identified themes and their transformation from the Case Note through the news stories and examined the impact of these transformations on the stigmatization of mental illness. RESULTS: Four themes were identified: human rights, vulnerability, risk of dangerousness and threat, and mental illness/psychiatric patient. The only potentially positive theme, human rights, was limited both by being fragmented in the source material, and by being utilized, in the published news stories to undermine the legitimacy of the patient's right to privacy. Use of the other themes was consistent with stereotypes about mental illness. CONCLUSIONS: Although there were no inaccuracies in the content of the news stories they were substantially more negative than the source material in their depiction of the identified patient. A potentially positive discourse (human rights) was not by itself sufficient to ensure a positive portrayal of mental illness. An understanding of the transformations is important for efforts to effectively combat the stigmatization of those with mental illness.

Bibliometrics↗

How mental illness is portrayed in children's television. A prospective study.

BACKGROUND: There are no published studies concerning the depiction of mental illness in children's television programmes. AIMS: To determine whether mental illness was depicted in children's television. METHOD: Sample of one complete week of children's television (57 hours, 50 minutes; 128 series episodes: 69 cartoon animations, 12 non-cartoon animations, 47 real life) provided for children under the age of 10 years. Disclosure analysis of portrayals of mental illness through repeated viewings identified patterns in the use of linguistic, semiotic and rhetorical resources. RESULTS: Of the 128 episodes, 59 (46%) contained one or more references to mental illness, predominantly in cartoons (n = 47, 80%) compared with other episode types (chi 2 = 17.1, d.f. = 2, P < 0.05). Commonly occurring terms such as 'crazy' (n = 28), 'mad' (n = 19) and 'losing your mind' (n = 13) were employed to denote loss of control. The six consistently mentally ill characters were almost entirely devoid of admirable attributes. CONCLUSION: Young viewers are being socialized into stigmatizing conceptions of mental illness.

Attitude to Health↗

Constructing mental illness as dangerous: a pilot study.

OBJECTIVE: There is a dearth of studies examining how dangerousness is constructed in media depictions of mentally ill individuals who are frequently portrayed as acting violently. The aim of the present study was to identify the contribution of diverse technical, semiotic and discursive resources utilised in portraying a character with a mental illness in a prime-time drama as dangerous. METHOD: Discourse analytic techniques, involving systematic, repeated, critical viewings, were applied to a single program drawn from a sample of prime-time television drama episodes touching on mental illness. RESULTS: Nine devices (appearance, music and sound effects, lighting, language, intercutting, jump-cutting, point of view shots, horror conventions and intertextuality) were identified as contributing to the signified dangerousness of person receiving care in the community for a mental illness. CONCLUSIONS: These techniques combine in signifying mental illness and a person suffering from it as dangerous. The findings suggest that mental health professionals working to reduce the stigma of mental illness need to have a reasonably sophisticated understanding of the practices and priorities of television production if they are to collaborate effectively with producers to create dramas that convey more human and sympathetic understandings of mental illness or to combat the negative effects of such portrayals.

Dangerous Behavior↗

Mental illness depictions in prime-time drama: identifying the discursive resources.

OBJECTIVE: The aim of this study was to determine how the mentally ill are depicted in prime-time television dramas. METHOD: Fourteen television dramas that included at least one character with a mental illness, shown in prime-time during a 1-year period, were systematically viewed and analysed. RESULTS: Fifteen of the 20 mentally ill characters were depicted as physically violent toward self or others. Characters were also depicted negatively as simple or lacking in comprehension and appearing lost, unpredictable, unproductive, asocial, vulnerable, dangerous to self or others because of incompetent behaviours, untrustworthy, and social outcasts, and positively as caring or empathic. CONCLUSIONS: These data are consistent with an overwhelming negativity of depictions of the mentally ill found in other forms of media and settings, and contribute to the stigmatisation of this population.

Humans↗

Does the use of psychiatrists as sources of information improve media depictions of mental illness? A pilot study.

OBJECTIVE: The aim of this study is to determine whether mental illnesses are depicted in less negative ways in print media when psychiatrists rather than lay persons are the source of information. METHOD: Seven items from a special report on mental health, four derived from lay sources and three from psychiatrists, were subjected to a discourse analysis informed by knowledge of media practices. RESULTS: The psychiatrists were clearly distinguished and deployed as experts in contrast to lay sources. Two of the psychiatrists presented mental illnesses in less negative ways than in the other items. These more positive depictions were undermined by the devices that the journalists used to give authority to the portrayals of mental illness and by the need to create 'newsworthy' items. CONCLUSION: If psychiatrists and other mental health professionals are to have a positive effect on how media depict mental illness, they will have to develop closer relationships with journalists and a better appreciation of media priorities and practices.

Adult↗

Suicidality among HIV-positive psychiatric in-patients.

Rates of suicidality with HIV-infected, seriously mentally ill individuals were investigated. Fifty asymptomatic HIV-positive psychiatric in-patients were compared to a demographically-matched HIV-negative cohort. The groups were similar, except that seropositive subjects were less likely to be diagnosed with schizophrenia. Both groups had high rates of suicidality, with higher rates associated with non-schizophrenic diagnoses. HIV-positive subjects had higher rates of suicidality, with those diagnosed with schizophrenia showing the greatest difference from their HIV-negative counterparts. HIV-positive patients required less in-patient treatment. These data expand previous reports showing an association between HIV and increased suicidality, even among individuals with already elevated suicidal rates.

Adult↗

The influence of a (GT)29 microsatellite sequence on homologous recombination in the hamster adenine phosphoribosyltransferase gene.

Several DNA sequence elements are thought to stimulate homologous recombination, illegitimate recombination, or both in mammalian cells. Some are implicated by their recurrence around rearrangement breakpoints, others by their effects on recombination of extrachromosomal plasmids. None of these sequences, however, has been tested on the chromosome in a defined context. In this paper we show how the adenine phosphoribosyltransferase locus in CHO cells can be used to study the recombinogenic potential of defined DNA sequences. As an example we have measured the effect on homologous recombination of a dinucleotide repeat, (GT)29, which has been shown to stimulate homologous recombination in extrachromosomal vectors 3-20 fold. On the chromosome at the adenine phosphoribosyltransferase locus, however, this sequence shows no capacity to stimulate recombination or to influence the distribution of recombination events.

Adenine Phosphoribosyltransferase↗

Dissociation of mitogen-activated protein kinase activation from the oxidative burst in differentiated HL-60 cells and human neutrophils.

In human polymorphonuclear leukocytes (PMNs), mitogen-activated protein kinases (MAPKs), also known as extracellular signal-regulated kinases (Erks), are activated within minutes upon stimulation with either chemoattractant formyl-Met-Leu-Phe (fMLP) or phorbol 12-myristate 13-acetate (PMA). This activation of MAPKs coincides with the formation of superoxide anion, which occurs through the activation of a multiple-component NADPH oxidase pathway. MAPKs have thus been suggested to be involved in signal transduction leading to the oxidative burst. To investigate whether MAPK activation plays a central role in the oxidative burst, we evaluated the effect of cAMP on MAPK activation induced by fMLP and PMA. cAMP inhibits many PMN functional responses, including the oxidative burst, and has recently been shown to reduce growth factor- and PMA-induced MAPK activities in a variety of cells. We found that in differentiated, neutrophil-like HL-60 cells, while cAMP reduced PMA-induced MAPK activation, it had no effect on fMLP-induced MAPK activation. Despite the presence of unchanged levels of activated MAPKs, the fMLP-induced oxidative burst was substantially diminished by cAMP. By contrast, O2-production induced by PMA remained the same even though MAPK activation was inhibited. In PMNs, although the levels of O2-induced by either 10 ng/ml or 100 ng/ml PMA were similar, only 100 ng/ml could stimulate MAPK activation, suggesting that the oxidative burst could occur in the absence of detectable activation of MAPKs. As in HL-60 cells, cAMP inhibited the O2-production in fMLP-stimulated PMNs but had no effect on MAPK activity. These results demonstrate that, while MAPK activation coincides with PMN activation, it can be dissociated from the oxidative burst.

Calcium-Calmodulin-Dependent Protein Kinases↗

Antigen-presenting cell lines internalize peptide antigens via fluid-phase endocytosis.

In this report, we present experimental evidence that antigen-presenting cell lines take up peptide antigens in a manner consistent with fluid-phase endocytosis. Using the fluid phase endocytic marker inulin and a mathematical model for fluid phase uptake, we have found a basal uptake rate constant of approximately 0.9-2 microns 3/cell minutes in A20, TA3, and J774 cells. An influenza virus peptide, PB2(303-313), the octapeptide, angiotensin II, an ovalbumin peptide, OVA(323-339), and a guinea pig myelin basic protein peptide, MBP(72-86), have uptake rate constants comparable to inulin, i.e., between 1 and 4 microns3/cell minutes in A20 cells. However, another influenza virus peptide, PB2(146-159), has an uptake rate constant approximately sixfold higher than that found for inulin in A20 cells. We have also determined that the peptide antigens we tested are retained in A20 cells similarly to inulin, with half-times calculated to be from 2 to 13 min as compared to 2 min for inulin. Notably, these results were obtained over short incubation times (up to 20 min) and under conditions that restrict peptide proteolysis and also protein synthesis. We conclude from these studies that peptide antigens enter antigen-presenting cells via fluid-phase endocytosis.

Animals↗

Influence of a highly focused case on the effect of small-group facilitators' content expertise on students' learning and satisfaction.

BACKGROUND: There has been considerable debate over the need for content expertise to lead a successful small-group discussion for medical students. Some authors feel process expertise related to the conduct of a small group is of more value than content expertise related to the case. At least one study has presented data that suggest content expertise can lead to teacher domination of the learning environment. In an earlier study, the present authors found that students learned more and were more satisfied with small-group instruction when the instruction was facilitated by a faculty member who was an expert in the content of the case. That study also identified no tendency for content experts to dominate the sessions (e.g., through lecturing or otherwise controlling the learning environment). The purpose of the present study was to explore the efficacy of a carefully designed and highly focused case problem to remove the influence of group facilitators' content expertise on students' learning outcomes. METHOD: The 211 students in the University of Michigan Medical School class of 1994 were randomly assigned to 28 groups in a microbiology and immunology course in the fall of 1991; each small group was led by a faculty facilitator. Complete data were available from 27 groups: 13 groups led by experts and 14 groups led by non-experts. Data collection included observers' codings of interactions between the students and the facilitators (interactional analysis), test scores, and students' ratings of the experience. RESULTS: Unlike in the previous study, group leaders who were content experts devoted significantly more time to teacher-directed activities than did non-content-expert leaders. However, overall, 62% of the time was devoted to student-initiated activity. The results of the multiple-choice tests that were related specifically to the goals of the case indicated there was no significant difference between the students' performances in the groups led by experts and those led by non-experts. With respect to students' satisfaction, all students gave consistently high ratings to the experience and there was no difference between groups led by expert and non-expert facilitators. CONCLUSION: The data from this study suggest that a facilitator's content expertise alone does not determine the amount of teacher-directed behavior in a group, the amount of students' learning, or students' satisfaction. The focus built into the case and the amount of facilitator's training directly related to the content of the case are also significant variables related to students' learning, teacher's behavior, and students' satisfaction.

Curriculum↗

Subset-specific co-stimulatory signals are required for IL-2 production but not growth inhibition responses by T cell hybrids specific for myelin basic protein.

Two distinct types of T cell hybridomas (designated THYB-1 and T-HYB-2) were derived by fusing BW5147 thymoma cells with encephalitogenic T helper cells from Lewis rats. Both subsets required MHC-restricted presentation of determinants within the 72-86 peptide sequence of myelin basic protein (MBP) as a requisite signal for IL-2 production. Unlike THYB-1 hybrids, however, THYB-2 hybrids required additional accessory cell activities that were mediated by radiosensitive nonadherent (RS-NAdh) splenocytes (SPL). In this study, we describe two observations indicating that RS-NAdh SPL enable MBP-specific responses of THYB-2 hybrids by providing subset-specific co-stimulatory signals that act independently of antigen recognition pathways. First, RS-NAdh SPL were required by THYB-2 hybrids for MBP-stimulated IL-2 production but were not needed when MBP-specific inhibition of hybrid growth was used as an alternative measure of cellular activation. Second, PMA and ionomycin induced optimal IL-2 production by both THYB-1 hybrids and BW5147 thymoma cells but only stimulated low or marginal levels of IL-2 production by THYB-2 hybrids. Together, these observations indicate that RS-NAdh SPL were required for the specific response of IL-2 production regardless of whether the response was stimulated by antigen or by mitogens that bypass initial antigen recognition events. This study thereby provides additional evidence that distinct stimulus-response relationships define two T-helper cell lineages in experimental autoimmune encephalomyelitis.

Animals↗

Effects of expert and non-expert facilitators on the small-group process and on student performance.

At the University of Michigan Medical School in 1990, the authors investigated the effects of faculty facilitators' levels of content expertise on the educational process and learning outcomes of small-group teaching sessions. The study was conducted in a microbiology course for second-year students in which four small-group sessions were used to replace 38 hours of lecture and laboratory time. The interactions between 11 expert and ten non-expert faculty facilitators and 156 students were observed and coded. The students' levels of knowledge and satisfaction were measured. The results indicate that, although significant differences in faculty-student interactions were not observed, the students in the 11 groups led by the content experts had higher levels of satisfaction and higher examination scores.

Attitude↗

Distinct accessory cell requirements define two types of rat T cell hybridomas specific for unique determinants in the encephalitogenic 68-86 region of myelin basic protein.

Six clonotypically unique T cell hybridomas from Lewis rats were used to study accessory cell activities required for class II MHC restricted T cell responses to the 68-86 encephalitogenic sequence of myelin basic protein (MBP). T cell hybrids which were cultured with GP68-86 68-86 sequence of guinea pig MBP (GPMBP) and naive splenocytes (SPL) were induced to produce IL-2 as measured by the CTLL indicator cell line. The hybrids were categorized into two subsets (designated THYB-1 and THYB-2), because two distinct subset-specific pathways of communication between accessory cells and T cells were involved in GPMBP-induced IL-2 production. These pathways were distinguished by the following six observations. First, when the duration of a pulse of SPL with GPMBP was lengthened from 1 to 4 h, these SPL lost their ability to induce IL-2 production by THYB-2 hybrids yet nevertheless retained full stimulatory activity for THYB-1 hybrids. Second, paraformaldehyde fixation of GPMBP-pulsed SPL abrogated an activity necessary for Ag-induced IL-2 production by THYB-2 hybrids. These fixed SPL were nevertheless able to stimulate THYB-1 hybrids, albeit to a lesser extent than viable unfixed SPL. Third, the addition of either cycloheximide, cytochalasin B, or 2-deoxyglucose to an Ag pulse of SPL with GPMBP dramatically inhibited the subsequent responses of THYB-2 hybrids yet had little or no effect upon the reactivity of THYB-1 hybrids. Fourth, thymocytes lacked necessary activities for GPMBP evoked IL-2 production by THYB-2 hybrids yet strongly promoted THYB-1 hybrid responses. Fifth, exposure of SPL to as little as 500 rad of gamma-irradiation markedly attenuated THYB-2 hybrid response to GPMBP but did not affect THYB-1 responses. Sixth, anti-GPMBP responses by THYB-2 hybrids were observed only in the presence of both radioresistant adherent SPL and a distinct population of radiosensitive nonadherent SPL. Conversely, THYB-1 hybrids exhibited full reactivity to GPMBP in the presence of adherent radioresistant SPL. Together, these observations reveal that two distinct accessory cell-T cell pathways mediate immune recognition of the 68-86 encephalitogenic region of MBP. Furthermore, these results indicate that subsets of Th cells can be defined by the accessory cell type-specific interactions that are necessary for Ag-mediated responses.

Animals↗

Relationship between pyrimidine dimers, 6-4 photoproducts, repair synthesis and cell survival: studies using cells from patients with trichothiodystrophy.

Trichothiodystrophy is a genetic disease which in the majority of cases studied is associated with a deficiency in the ability to repair UV damage in cellular DNA. Three categories of UV response have been identified. In type 1 the response is completely normal, whereas type 2 cells are deficient in excision-repair, with properties indistinguishable from those of XP complementation group D. Type 3 cells have normal survival following UV-irradiation and normal rates of removal of cyclobutane pyrimidine dimer sites. Nevertheless repair synthesis is reduced by 50% in these cell strains and this is associated with a marked reduction in the repair of 6-4 photoproducts from cellular DNA. The present results show that 50% or more of repair synthesis at early times after irradiation of normal primary human fibroblasts is attributable to repair of 6-4 products. They also suggest that repair of cyclobutane dimers is crucial for cell survival.

Cell Survival↗

Cross-linking studies show that herpes simplex virus type 1 glycoprotein C molecules are clustered in the membrane of infected cells.

Chemical cross-linking using ethylene glycol succinimidyl succinate (EGS) and dithiobispropionimidate (DTBP) was performed to determine the association of herpes simplex virus type 1 glycoprotein C (HSV-1 gC) with its nearest neighbours. Human embryonic lung (HEL) cells were infected with HSV-1 strain KOS, treated with EGS, lysed with Nonidet P40, immunoprecipitated with monoclonal antibodies specific for gC, and analysed by SDS-PAGE. These analyses demonstrated the presence of cross-linked complexes that migrated with an apparent Mr in the range 150,000 to 260,000. Two-dimensional SDS-PAGE (non-reduced and then reduced) analyses of HSV-1-infected HEL cells treated with the cleavable cross-linker DTBP demonstrated that molecules that comigrated with gC were the only components of these high Mr complexes. Immunoelectroblot (Western blot) analyses using polyclonal rabbit antiserum specific for gC verified that the high Mr complexes contained gC. These results indicated that gC molecules may be localized in the infected cell membrane as dimers.

Blotting, Western↗

Functional and biochemical parameters of peptide antigen presentation.

To understand the mechanism by which peptide antigens are processed and presented to T cells, we examined the T-cell response to the 13-amino-acid peptide alpha-melanocyte-stimulating hormone (alpha-MSH). To determine the fine specificity of T-cell recognition, T cells specific for alpha-MSH, and genetically restricted by I-Ab/d, were challenged with different alpha-MSH analogs and homologs. It was found that intact alpha-MSH, including the blocked amino and carboxy termini of the native molecule, was required for T-cell responsiveness. Antigen-presenting cells (APC) could be briefly pulsed with alpha-MSH and then present the alpha-MSH antigenic determinant to T cells, indicating that the relevant antigen was retained by the APC. APC stimulatory capacity was dramatically reduced by aldehyde treatment of the APC, or by pulsing the APC with alpha-MSH at low temperature. Efficient alpha-MSH pulsing was also impaired by treatment of the APC with the carboxylic ionophore, monensin, but not by the lysosomotropic agents chloroquine and methylamine. In addition, isolated APC plasma membranes added to the T cells in the presence of soluble alpha-MSH were not stimulatory. However, plasma membranes isolated from APC that had been previously pulsed with alpha-MSH retained stimulatory activity for T-cell responses. The only detectable alpha-MSH contained in these pulsed APC membranes was in an acid-stable complex of higher molecular weight than native peptide. The amount of alpha-MSH detected in the cellular membrane fraction isolated by density gradient sedimentation was also reduced by treatments that reduced the APC stimulatory capacity, such as pulsing at low temperature or in the presence of monensin. Taken together, these results suggest that processing of alpha-MSH is unlike that heretofore described for other peptide antigens and seems to involve APC handling to form the stimulatory moiety presented on the APC surface.

Animals↗

Heterogeneity in cellular antigen retention structures.

The mechanism of presentation of foreign antigens to helper T lymphocytes and the nature of the structures involved in this process are not totally understood. It is well documented that this event is carried out by antigen-presenting cells (APC) (e.g., macrophages, dendritic cells, and B lymphocytes) that internalize the antigen, process it, reexpress it on their membrane surface, and present it to the T cell in the context of major histocompatibility complex class II (Ia) molecules. Recent evidence supports the hypothesis that peptide antigens associate directly with Ia molecules on the APC surface membrane. However, the characteristics of other APC membrane structures potentially involved in antigen presentation are not entirely clear. Previous studies in our laboratories identified a guinea pig macrophage membrane-bound, non-Ia-containing antigenic complex (peak A) formed upon incubation of APC with the octapeptide antigen angiotensin (AII). This complex was capable of stimulating AII-immune guinea pig T cells and thus appeared to contain the immunologically relevant form of the antigen. For this reason it was important to establish whether such complex formation with peptides occurs with other cell types and with other peptide antigens. In the present study we found that other types of cells are also capable of forming such a membrane complex with antigen (peak A) and that this event is not unique to AII. Two other peptides, alpha-melanocyte-stimulating hormone and human fibrinopeptide B, both of which are antigenic in mice, were found to form peak A with a number of murine cell lines. As in our earlier studies with guinea pig macrophages, there was no evidence from these experiments for a role for major histocompatibility complex Ia antigens in the peptide binding observed. Differences in both the amount of peak A formation and the pattern of peptide antigen degradation were found from cell line to cell line for a given peptide, and from peptide to peptide for a given cell line, suggesting cellular heterogeneity in peptide processing and retention. In addition, cross-inhibition studies indicated that there was peptide specificity in the formation of peak A perhaps suggestive of molecular heterogeneity in the structure of peak A. These results indicate that there may be several types of cell surface molecules that specifically bind and retain peptide antigens.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Purification and structural characterization of herpes simplex virus glycoprotein C.

Purification of herpes simplex virus glycoprotein C (gC) in microgram amounts yielded sufficient material for an analysis of its secondary structure. Purification was facilitated by using the mutant virus gC-3, which bears a point mutation that interrupts the putative hydrophobic membrane anchor sequence, causing the secretion of gC-3 protein into the cell culture medium. gC-3 protein was purified by size fractionation of concentrated culture medium from infected cells on a gel filtration column of Sephacryl S-200, followed by immunoaffinity chromatography on a column constructed of gC-specific monoclonal antibodies cross-linked to a protein A-Sepharose CL-4B matrix. Purified gC-3 had a molecular weight of 130,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the size expected for gC, was reactive with gC-specific monoclonal antibodies in protein immunoblots, and contained amino acid sequences characteristic of gC as determined by radiochemical amino acid microsequence analyses. Polyclonal antisera obtained from a rabbit immunized with gC-3 reacted with wild-type gC in immunoprecipitation, enzyme immunoassay, and immunoelectroblot (western blot) assays. Deglycosylation by treatment with trifluoromethanesulfonic acid reduced the molecular weight of gC-3 by approximately 35%. Analyses of both native and deglycosylated gC-3 by Raman spectroscopy showed that the native molecule consists of about 17% alpha-helix, 24% beta-sheet, and 60% disordered secondary structures, whereas deglycosylated gC-3 consists of about 8% alpha-helix, 10% beta-sheet, and 81% disordered structures. These data were in good agreement with the 11% alpha-helix, 18% beta-sheet, 61% beta-turn, and 9% disordered structures calculated from Chou-Fasman analysis of the primary sequence of gC-3.

Amino Acid Sequence↗