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Biomedical subjects

G Bryson

Publications and source records attributed to G Bryson.

At least 19 recordsLinked to original sources

Carcinogenic potential of commonly used hernia repair prostheses in an experimental model.

BACKGROUND: The purpose of this study was to assess the carcinogenic potential of commonly used hernia repair prostheses in an animal model. METHODS: Three types of prosthetic material (monofilament polypropylene, multifilament polypropylene and expanded polytetrafluoroethylene) were implanted in CBA/H mice. Flat (1 cm(2)) and rolled pieces of the same material were placed subcutaneously in either flank, and a further flat piece was placed in the preperitoneal space. Owing to a high incidence of mesh extrusion in the polypropylene groups, the study protocol was modified to allow only preperitoneal placement of the material. A fourth, control, group had the pockets for the prostheses created but no material implanted. After modification of the protocol there were approximately 60 mice in each group. The mice were followed for 2 years, then killed and assessed histologically for tumour development. RESULTS: No sarcoma developed at the site of mesh implantation in any of the groups. CONCLUSION: This study indicates that the risk of sarcoma formation at the site of hernia repair prostheses is very low.

Animals↗

Epstein-Barr virus-mediated protection against etoposide-induced apoptosis in BJA-B B cell lymphoma cells: role of Bcl-2 and caspase proteins.

Epstein-Barr virus (EBV)-infected B cell lymphomas are resistant to apoptosis during cancer development and treatment with therapies. The molecular controls that determine why EBV infection causes apoptosis resistance need further definition. EBV-positive and EBV-negative BJA-B B cell lymphoma cell lines were used to compare the expression of selected apoptosis-regulating Bcl-2 and caspase proteins in EBV-related apoptosis resistance, after 8 hr or 18-24 hr etoposide treatment (80 microM). Apoptosis was quantified using morphology and verified with Hoechst 33258 nuclear stain and electron microscopy. Fluorescence activated cell sorting (FACS) was used to analyse effects on cell cycle of the EBV infection as well as etoposide treatment. Anti-apoptotic Bcl-2 and Bcl-XL, pro-apoptotic Bax, caspase-3 and caspase-9 expression and activation were analysed using Western immunoblots and densitometry. EBV-positive cultures had significantly lower levels of apoptosis in untreated and etoposide-treated cultures in comparison with EBV-negative cultures (p < 0.05). FACS analysis indicated a strong G2/M block in both cell sublines after etoposide treatment. Endogenous Bcl-2 was minimal in the EBV-negative cells in comparison with strong expression in EBV-positive cells. These levels did not alter with etoposide treatment. Bcl-XL was expressed endogenously in both cell lines and had reduced expression in EBV-negative cells after etoposide treatment. Bax showed no etoposide-induced alterations in expression. Pro-caspase-9 and -3 were seen in both EBV-positive and -negative cells. Etoposide induced cleavage of caspase-9 in both cell lines, with the EBV-positive cells having proportionally less cleavage product, in agreement with their lower levels of apoptosis. Caspase-3 cleavage occurred in the EBV-negative etoposide-treated cells but not in the EBV-positive cells. The results indicate that apoptosis resistance in EBV-infected B cell lymphomas is promoted by an inactive caspase-3 pathway and elevated expression of Bcl-2 that is not altered by etoposide drug treatment.

Antineoplastic Agents, Phytogenic↗

Cognitive remediation of working memory deficits: durability of training effects in severely impaired and less severely impaired schizophrenia.

OBJECTIVE: To determine whether augmenting work therapy (WT) with neurocognitive enhancement therapy (NET) yields greater improvement in working memory performance than WT alone and whether there is an interaction with severity of impairment. METHOD: A total of 102 participants with schizophrenia or schizoaffective disorder were categorized as severely or less severely cognitively impaired and randomly assigned to receive NET + WT or WT alone. NET consisted of cognitive training exercises in attention, memory, executive function, and social information processing, and WT was a 6-month work program. RESULTS: Comparison on Digits Backwards from intake to follow-up revealed significantly greater improvement for participants receiving NET + WT, but there was no interaction with severity group. Follow-up 6 months after training showed that training effects endured. CONCLUSION: NET + WT improved working memory for most participants regardless of impairment severity. Intensity and duration of training may have contributed to duration of effects. Findings support continued exploration of cognitive remediation.

Adult↗

Quantification of feto-maternal haemorrhage (FMH) by flow cytometry: anti-fetal haemoglobin labelling potentially underestimates massive FMH in comparison to labelling with anti-D.

Many centres now routinely use flow cytometry to quantify feto-maternal haemorrhage (FMH). However, which flow cytometric method is the most accurate in quantifying FMH is currently unknown. An audit of clinical results in which FMH had been estimated by both directly conjugated monoclonal anti-D and anti-fetal haemoglobin (HbF) labelling suggested that the anti-HbF labelling method may underestimate massive FMH in comparison to labelling with anti-D. Subsequent to this audit, 46 samples of adult D-negative blood were spiked with varying amounts of D-positive cord blood (0.05-10% fetal cells per sample), and the number of fetal cells present was quantified by both labelling methods. The percentage of fetal cells detected by anti-D was not significantly different to the estimated percentage of fetal cells added to each sample (P = 0.636). However, anti-HbF labelling significantly underestimated the percentage of fetal cells present (P = 0.0001). In comparison to anti-D, the percentage of fetal cells detected by anti-HbF was also significantly lower (P < 0.0001). The difference in fetal cell detection between anti-D and anti-HbF labelling was only apparent in the spiked samples containing > or =1% fetal cells per sample. In samples containing < or =0.6% fetal cells, no significant difference in the detection of fetal cells between anti-D and anti-HbF labelling was observed (P = 0.11). To allow adequate immunoprophylaxis in D-negative mothers with massive FMH, we recommend that anti-D labelling should be used in the routine flow cytometric estimation of FMH.

Adult↗

Memory and executive function impairments in deficit syndrome schizophrenia.

The relationship between deficit syndrome schizophrenia, as determined by the Schedule for the Deficit Syndrome, and impairments in memory and executive function was investigated by administering the Wisconsin Card Sorting Test, the Wechsler Adult Intelligence Test, and the Wechsler Memory Scales to outpatients with deficit (n=33) and non-deficit (n=57) syndrome. A factor analysis of test variables revealed three factors: executive functioning; simple verbal memory; and semantic verbal memory. Results indicated that the deficit group performed significantly worse on the executive functioning factor, but not on either of the verbal memory factors. These findings support the hypothesis that deficit syndrome schizophrenia represents a specific cognitive impairment in executive processing and not necessarily graver global cognitive impairment.

Adult↗

Neurocognitive enhancement therapy with work therapy: effects on neuropsychological test performance.

BACKGROUND: Cognitive deficits are a major determinant of social and occupational dysfunction in schizophrenia. In this study, we determined whether neurocognitive enhancement therapy (NET) in combination with work therapy (WT) would improve performance on neuropsychological tests related to but different from the training tasks. METHODS: Sixty-five patients with schizophrenia or schizoaffective disorder were randomly assigned to NET plus WT or WT alone. Neurocognitive enhancement therapy included computer-based training on attention, memory, and executive function tasks; an information processing group; and feedback on cognitive performance in the workplace. Work therapy included paid work activity in job placements at the medical center (eg, mail room, grounds, library) with accompanying supports. Neuropsychological testing was performed at intake and 5 months later. RESULTS: Prior to enrollment, both groups did poorly on neuropsychological testing. Patients receiving NET + WT showed greater improvements on pretest-posttest variables of executive function, working memory, and affect recognition. As many as 60% in the NET + WT group improved on some measures and were 4 to 5 times more likely to show large effect-size improvements. The number of patients with normal working memory performance increased significantly with NET + WT, from 45% to 77%, compared with a decrease from 56% to 45% for those receiving WT. CONCLUSIONS: Computer training for cognitive dysfunction in patients with schizophrenia can have benefits that generalize to independent outcome measures. Efficacy may result from a synergy between NET, which encourages mental activity, and WT, which allows a natural context for mental activity to be exercised, generalized, and reinforced.

Adult↗

Patterns of object relations and reality testing deficits in schizophrenia: clusters and their symptom and personality correlates.

Bell Object Relations Reality Testing Inventory (BORRTI) profile scores were used to cluster 222 outpatients with schizophrenia or schizoaffective disorder. An eight-cluster solution was subjected to replication analysis, and six clusters were found valid and replicable. These clusters were sorted into three pairs that were interpreted as follows: Residually Impaired consisted of Sealed-Over Recovery and Integrated Recovery; Socially Withdrawn consisted of Socially Withdrawn and Socially Withdrawn-Autistic; and Psychotically Egocentric consisted of Psychotically Egocentric and Psychotically Egocentric-Severe. Clusters were compared on Positive and Negative Syndrome Scale ratings and on subscales from the Eysenck Personality Questionnaire. MANOVAs indicated significant differences among clusters. These differences provided further interpretations of cluster membership. Implications for the use of BORRTI profiles for treatment and rehabilitation planning are discussed.

Adult↗

Phyllodes tumors of the breast: correlation of nucleolar organizer regions with histopathological malignancy grading, flow cytometric DNA analysis and clinical outcome.

To examine whether nucleolar organizer regions detected by argyrophilia (Ag-NOR counts) can be used as a prognostic indicator in phyllodes tumors of the breast, and to compare its usefulness with that of DNA flow cytometric analysis, 28 cases of breast phyllodes tumors (including 15 benign, two borderline and 11 malignant tumors) were subjected to Ag-NOR staining and counting as well as DNA flow cytometric analysis. S-phase fraction and DNA ploidy analysis showed useful trends for improving outcome predictions in malignant phyllodes tumors. However, high Ag-NOR counts were significant in predicting survival status (P = 0.013) and reached near statistical significance in predicting survival times (P = 0.07). In predicting survival status, results for Ag-NOR counts were significantly better than those for ploidy analysis (P = 0.02) and S-phase fraction (P < 0.01). Only S-phase fraction was significantly predictive of survival times (P = 0.025). It is concluded that Ag-NOR counts and DNA flow cytometric analysis, easily performed using paraffin sections, give information that can improve predictions made by histopathological classification. Ag-NOR counts are significant in predicting survival in the presence of histopathological features of malignancy.

Adolescent↗

Work rehabilitation in schizophrenia: does cognitive impairment limit improvement?

Cognitive impairments may be an important contributor to disability in schizophrenia and may limit the rate of improvement in work rehabilitation. Thirty-three outpatients with schizophrenia or schizoaffective disorder who participated in a 6-month work rehabilitation program were assessed for symptom severity and administered neuropsychological testing at intake. Their work performance was evaluated biweekly using the Work Behavior Inventory. On each of five domains of work performance, 76 to 91 percent of subjects reached proficiency or improved significantly over 26 weeks. Individual differences in rate of improvement were robustly predicted by neuropsychological variables: Work Habits, r2 = 0.79; Personal Presentation, r2 = 0.73; Cooperativeness, r2 = 0.67; Work Quality, r2 = 0.56; Social Skills, r2 = 0.27; Total, r2 = 0.44. Neuropsychological measures had differential relationships to work domains. Individual differences in improvement were not predicted by symptom measures. These findings link cognitive impairment to disability and suggest that remediating or accommodating such deficits may be necessary for successful rehabilitation.

Adult↗

Nonspecific down-regulation of CD8+ T-cell responses in mice expressing human papillomavirus type 16 E7 oncoprotein from the keratin-14 promoter.

The E7 oncoprotein of human papillomavirus 16 (HPV16) transforms basal and suprabasal cervical epithelial cells and is a tumor-specific antigen in cervical carcinoma, to which immunotherapeutic strategies aimed at cytotoxic T-lymphocyte (CTL) induction are currently directed. By quantifying major histocompatibility complex class I tetramer-binding T cells and CTL in mice expressing an HPV16 E7 transgene from the keratin-14 (K14) promoter in basal and suprabasal keratinocytes and in thymic cortical epithelium, we show that antigen responsiveness of both E7- and non-E7-specific CD8+ cells is down-regulated compared to non-E7 transgenic control mice. We show that the effect is specific for E7, and not another transgene, expressed from the K14 promoter. Down-regulation did not involve deletion of CD8+ T cells of high affinity or high avidity, and T-cell receptor (TCR) Vbeta-chain usage and TCR receptor density were similar in antigen-responsive cells from E7 transgenic and non-E7 transgenic mice. These data indicate that E7 expressed chronically from the K14 promoter nonspecifically down-regulates CD8+ T-cell responses. The in vitro data correlated with the failure of immunized E7 transgenic mice to control the growth of an E7-expressing tumor challenge. We have previously shown that E7-directed CTL down-regulation correlates with E7 expression in peripheral but not thymic epithelium (T. Doan et al., J. Virol. 73:6166-6170, 1999). The findings have implications for the immunological consequences of E7-expressing tumor development and E7-directed immunization strategies. Generically, the findings illustrate a T-cell immunomodulatory function for a virally encoded human oncoprotein.

Animals↗

Object relations and reality testing in early- and late-onset schizophrenia.

One hundred fifty-seven U.S. military veterans with schizophrenia were divided into early-onset (i.e., onset at age 20 or before, n = 36) and late-onset (i.e., onset after age 30, n = 28) groups and completed the Bell Object Relations and Reality Testing Inventory (BORRTI), the Positive and Negative Syndrome Scale, and several representative neuropsychological instruments. Participants were compared on background characteristics and test measures. The early-onset group demonstrated significantly more object-relations and reality-testing deficits than the late-onset group. In contrast, no significant group differences were found on symptom or neuropsychological variables. An a posteriori three-group analysis that included the middle age of onset group (i.e., ages 21 to 30) found that the middle group had mean values that fell between early- and late-onset groups on most variables. No distinct patterns of BORRTI subscale scores distinguished the middle group. The finding that object-relations and reality-testing deficits are more pronounced in early-onset schizophrenia has implications for the treatment and rehabilitation of schizophrenia.

Adult↗

Internal consistency, temporal stability and neuropsychological correlates of three cognitive components of the Positive and Negative Syndrome Scale (PANSS).

Comprehensive models of schizophrenia have increasingly included symptoms of cognitive dysfunction as an important feature of schizophrenia. Factor analytic studies of the Positive and Negative Syndrome Scale (PANSS) have consistently established cognitively disorganized symptoms as a separate domain from positive and negative symptoms. However, the individual symptom composition of the cognitive domain varies from model to model. The present study explores the temporal stability, internal consistency, concurrent validity, and discriminant validity for three published PANSS factor analytically derived cognitive components (Bell et al., 1994a, Psychiatry Res., 52, 295-303; Dollfus et al., 1991. Eur. Psychiatry, 6, 251-259; Kay and Sevy, 1990. Schizophr. Bull., 16, 537-544). Analyses were conducted using PANSS data from 120 patients with DSM-IV diagnoses of schizophrenia or schizoaffective disorder. Results indicate that the Bell et al. and Kay and Sevy models have similar psychometric properties including adequate temporal stability, internal consistency, and discriminant validity. The Kay model demonstrated somewhat better concurrent validity with cognitive test measures, while the Dollfus model demonstrated relatively poor psychometrics. The symptom composition of a narrowly defined cognitively disorganized subtype and a more broadly defined cognitively impaired subtype are discussed in terms of their value for schizophrenia research.

Adult↗

Transfusion practices among patients who did and did not predonate autologous blood before elective cardiac surgery.

BACKGROUND: Preoperative autologous blood donation is commonly used to reduce exposure to allogeneic transfusions among patients undergoing elective cardiac surgery. However, this technique is associated with an overall increase in transfusions (allogeneic or autologous). The authors assessed the impact of transfusion decision-making on the effectiveness of preoperative autologous donation in reducing the frequency of allogeneic transfusions, and its impact on the increased transfusion rate associated with preoperative autologous donation in cardiac surgery. METHODS: This retrospective analysis compared transfusion practices among 176 patients who predonated autologous blood before elective cardiac surgery and 176 matched cardiac surgery patients who did not predonate blood. The impact of decision-making on transfusion exposure was determined using multivariate analyses to account for major perioperative interventions and complications. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for exposure to allogeneic blood transfusion or any transfusion, before and after exclusion of transfusions not conforming with selected transfusion criteria. RESULTS: Exposure to allogeneic transfusion was more likely among patients who did not predonate blood than among those who did predonate blood (OR 14.0, 95% CI 5.8-33.8). This finding was still true after exclusion of transfusions not meeting the transfusion criteria (OR 19.3, 95% CI 6.7-55.7). The autologous blood donors were more likely than the nondonors to receive any transfusion (OR 10.8, 95% CI 5.7-20.3). However, this association was substantially attenuated after exclusion of transfusions not meeting the transfusion criteria (OR 1.9, 95% CI 1.1-3.2). INTERPRETATION: Patients who predonated blood before elective cardiac surgery were at lower risk of receiving allogeneic transfusions than the nondonors. This was not because of a deliberate withholding of allogeneic transfusions from autologous donors. However, more liberal transfusion criteria for autologous blood were largely responsible for the increased transfusion rate among the autologous donors.

Aged↗

Human papillomavirus type 16 E7 oncoprotein expressed in peripheral epithelium tolerizes E7-directed cytotoxic T-lymphocyte precursors restricted through human (and mouse) major histocompatibility complex class I alleles.

Mice which coexpress human papillomavirus type 16 E7 and HLA A2.1 in peripheral squamous epithelium and thymic cortical epithelium are tolerant at the cytotoxic T-lymphocyte (CTL) level to E7 epitopes restricted through HLA A*0201 and H-2(b) (T. Doan, M. Chambers, M. Street, G. J. Fernando, K. Herd, P. Lambert, and R. Tindle, Virology 244:352-364, 1998). Here we used bone marrow-reconstituted radiation chimeras to distinguish whether E7-directed CTL tolerance was mediated peripherally by E7 expression in skin or centrally by E7 expression in thymus. In chimeric mice expressing E7 in skin and reconstituted with E7-naïve bone marrow and E7-naïve thymus, CTL responses to vaccine-administered E7 epitopes were not restored, i.e. , the mice remained tolerant. In contrast, chimeric mice not expressing E7 in skin and reconstituted with E7-naïve bone marrow and E7-expressing thymus had full E7-directed CTL responses. These results demonstrate that E7 protein expression in peripheral squamous epithelium is sufficient to tolerize the E7-directed CTL precursor repertoire. The data have implications for E7-mediated tumorigenesis and for the development of E7-based immunotherapeutic strategies, since peripheral immunological tolerance of tumor-associated antigens may create a barrier to effective immunotherapy.

Animals↗

Personality and psychosocial dysfunction in schizophrenia: the association of extraversion and neuroticism to deficits in work performance.

Research on vocational dysfunction in schizophrenia has as yet only examined associated features of illness. We hypothesized that personality variables may be also associated with work function. We reasoned that higher levels of extraversion and neuroticism would predict poor function by virtue of the social support seeking and passive/avoidant coping styles associated with each. To test this, multiple regressions were conducted in which measures of extraversion and neuroticism predicted work performance among 43 subjects with schizophrenia or schizoaffective disorder. Higher levels of extraversion and neuroticism significantly predicted poorer function, accounting for between 7% and 27% of the variance in global cooperativeness, work quality, work habits and personal presentation measures of work behavior. The potential importance of assessing personality in rehabilitation is discussed.

Adult↗

Affect recognition in deficit syndrome schizophrenia.

This study has three aims: (1) to compare a deficit syndrome schizophrenia sample (n=19) with a non-deficit sample (n=50) on affect recognition; (2) to determine the association between individual deficit criteria and affect recognition performance in the deficit sample; and (3) to compare the deficit syndrome and negative syndrome samples with respect to affect recognition test performance. Results revealed that the deficit sample had significantly lower adjusted mean affect recognition scores than the non-deficit sample. In addition, 17 of the 19 subjects with deficit syndrome had impairments in affect recognition, whereas, non-deficit subjects were only slightly more likely to score in the impaired range than the unimpaired range. Within the deficit sample Diminished Sense of Purpose was the criterion most strongly associated with affect recognition impairment. Finally, a group of subjects classified as having prominent negative symptoms did not demonstrate the same pattern of impairment as shown by the deficit syndrome sample. The relationship between affect recognition, information processing and the deficit syndrome is discussed along with implications for classification in schizophrenia.

Adult↗