A systematic review of visual processing and associated treatments in body dysmorphic disorder.

OBJECTIVE: Recent advances in body dysmorphic disorder (BDD) have explored abnormal visual processing, yet it is unclear how this relates to treatment. The aim of this study was to summarize our current understanding of visual processing in BDD and review associated treatments. METHOD: The literature was collected through PsycInfo and PubMed. Visual processing articles were included if written in English after 1970, had a specific BDD group compared to healthy controls and were not case studies. Due to the lack of research regarding treatments associated with visual processing, case studies were included. RESULTS: A number of visual processing abnormalities are present in BDD, including face recognition, emotion identification, aesthetics, object recognition and gestalt processing. Differences to healthy controls include a dominance of detailed local processing over global processing and associated changes in brain activation in visual regions. Perceptual mirror retraining and some forms of self-exposure have demonstrated improved treatment outcomes, but have not been examined in isolation from broader treatments. CONCLUSION: Despite these abnormalities in perception, particularly concerning face and emotion recognition, few BDD treatments attempt to specifically remediate this. The development of a novel visual training programme which addresses these widespread abnormalities may provide an effective treatment modality.

Individualised mindfulness-based stress reduction for head and neck cancer patients undergoing radiotherapy of curative intent: a descriptive pilot study.

People with head and neck cancer (HNC) experience elevated symptom toxicity and co-morbidity as a result of treatment, which is associated with poorer psychosocial and quality-of-life (QoL) outcomes. This Phase I study examined whether an individualised mindfulness-based stress reduction (IMBSR) programme could be successfully used with HNC patients undergoing curative treatment. Primary aims were to explore feasibility, compliance, acceptability and fidelity. Secondary aims were to determine whether (1) participation in the intervention was associated with changes in post-intervention mindfulness and (2) post-intervention mindfulness was associated with post-intervention distress and QoL. Nineteen HNC patients participated in a seven-session IMBSR programme with pre- and post-test outcome measures of psychological distress, depression, anxiety and QoL. Primary aims were assessed by therapists or participants. Mindfulness, distress and QoL were assessed using self-report questionnaires at pre- and post-intervention. Longer time spent meditating daily was associated with higher post-intervention mindfulness. After controlling for pre-intervention mindfulness, there was an association between higher post-intervention mindfulness and lower psychological distress and higher total, social and emotional QoL. This study offers important preliminary evidence than an IMBSR intervention can be administered to HNC patients during active cancer treatment. A randomised controlled trial is warranted to confirm these findings.

Metabolic syndrome in people with a psychotic illness: is cannabis protective?

BACKGROUND: Rates of the metabolic syndrome in people with psychotic illness are high. Emerging evidence suggests that cannabis use may have a positive impact on cardiometabolic risk factors in the general population, but little is known about its impact for people with psychotic illness. Our aim was to investigate whether the rate of the metabolic syndrome in people with psychotic illness was associated with frequency of cannabis use. METHOD: The 2010 Australian psychosis survey used a two-phase design to randomly select a nationally representative sample of 1825 adults with psychotic illness for interview and physical assessment. This study is based on 1813 participants who provided data on cannabis use. Multiple logistic regression was used to model the influence of frequency of cannabis use on the metabolic syndrome, adjusting for potential covariates including antipsychotic medication use, smoking, alcohol use and cognitive function. RESULTS: One-third (33.0%) of participants had used cannabis in the past year. The proportion of non-users, occasional users and frequent users with the metabolic syndrome was 63.0, 51.7 and 43.5%, respectively (p < 0.001). In unadjusted analyses, both occasional use and frequent cannabis use were associated with significantly lower odds of the metabolic syndrome. In the adjusted analyses, the association between the metabolic syndrome and frequent cannabis use remained significant [odds ratio = 0.56, 95% confidence interval (CI) 0.39-0.80], but not the association with occasional use (odds ratio = 0.75, 95% CI 0.49-1.13). CONCLUSIONS: While cannabis use may be detrimental for mental health, these data suggest that it may also have a cardiometabolic protective effect. Further investigation is required to understand the mechanism underlying this paradoxical finding.

Correlates of physical activity in people living with psychotic illness.

OBJECTIVE: In the light of the high prevalence of physical comorbidities in people with psychotic illness, there is a need to explore modifiable risk factors that may contribute to this disease burden. The benefits of physical activity to both physical and mental health have been well established. We aimed to examine the prevalence and correlates of physical activity in a national sample of adults living with psychotic illness. METHODS: Physical activity was assessed in 1801 people using the International Physical Activity Questionnaire. Participants were dichotomised into low and moderate-high physical activity groups and associations between physical activity and a range of sociodemographic, clinical and physical comorbidity variables were examined using logistic regression. RESULTS: More than half the participants were categorised in the moderate-high physical activity group with nearly half of the sample engaged in physical activity every day. There were significant associations between low physical activity and older age, unemployment, educational non-participation, antipsychotic medication use, social dysfunction, self-reported loneliness and obesity. However, there was no significant association between physical activity and sex, psychosis type, illness duration, physical comorbidity or negative symptoms. CONCLUSION: The findings from this study may inform future interventions designed to increase physical activity in people with psychotic illness.

Psychosis prevalence and physical, metabolic and cognitive co-morbidity: data from the second Australian national survey of psychosis.

BACKGROUND: There are insufficient data from nationwide surveys on the prevalence of specific psychotic disorders and associated co-morbidities. METHOD: The 2010 Australian national psychosis survey used a two-phase design to draw a representative sample of adults aged 18-64 years with psychotic disorders in contact with public treatment services from an estimated resident population of 1 464 923 adults. This paper is based on data from 1642 participants with an International Classification of Diseases (ICD)-10 psychotic disorder. Its aim is to present estimates of treated prevalence and lifetime morbid risk of psychosis, and to describe the cognitive, physical health and substance use profiles of participants. RESULTS: The 1-month treated prevalence of psychotic disorders was 3.10 cases per 1000 population aged 18-64 years, not accounting for people solely accessing primary care services; lifetime morbid risk was 3.45 per 1000. Mean premorbid intelligence quotient was approximately 0.5 s.d.s below the population mean; current cognitive ability (measured with a digit symbol coding task) was 1.6 s.d.s below the population mean. For both cognitive tests, higher scores were significantly associated with better independent functioning. The prevalence of the metabolic syndrome was high, affecting 60.8% of participants, and pervasive across diagnostic groups. Of the participants, two-thirds (65.9%) were current smokers, 47.4% were obese and 32.4% were sedentary. Of the participants, half (49.8%) had a lifetime history of alcohol abuse/dependence and 50.8% lifetime cannabis abuse/dependence. CONCLUSIONS: Our findings highlight the need for comprehensive, integrative models of recovery to maximize the potential for good health and quality of life for people with psychotic illness.

Group music therapy for severe mental illness: a randomized embedded-experimental mixed methods study.

OBJECTIVE: Music therapy is an innovative approach to support people with severe mental illness (SMI). The aim of the study was to determine whether group music therapy (GMT) positively impacted on quality of life (QoL), social enrichment, self-esteem, spirituality and psychiatric symptoms of participants with SMI and how they experienced the intervention. METHOD: The primary outcome was QoL; secondary measures assessed social enrichment, self-esteem, spirituality and psychiatric symptoms. The 13-week intervention comprised singing familiar songs and composing original songs recorded in a professional studio. Qualitative data were generated from focus group interviews and song lyric analysis. RESULTS: Ninety-nine adults (57 female) were recruited, with an initial cohort (n = 75) randomized to either: weekly GMT followed by standard care (SC) or SC followed by GMT. Crossover occurred after 13 weeks. Measures were conducted at baseline, 13, 26 and 39 weeks. A second cohort (n = 24) could not be randomized and were assigned to GMT followed by SC. Intention-to-treat analysis showed a significant difference between GMT and SC on QoL and spirituality. This was robust to different assumptions about missing data (listwise deletion, last observation carried forward or multiple imputation). Per-protocol analysis suggested greater benefit for those receiving more sessions. Focus group interview and song lyric analyses suggested that GMT was enjoyable; self-esteem was enhanced; participants appreciated therapists and peers; and although challenges were experienced, the programme was recommended to others. CONCLUSION: Group music therapy may enhance QoL and spirituality of persons with SMI.

A whole-of-population study of the prevalence and patterns of criminal offending in people with schizophrenia and other mental illness.

BACKGROUND: Large epidemiological studies are needed to better understand the prevalence and profile of offending by people with mental illness. This study used a whole-of-population design to examine the prevalence, type and pattern of offending across all psychiatric diagnoses, including schizophrenia, compared to the general population. Method We used whole-of-population longitudinal record-linked data for a cohort of all Western Australians born 1955-1969 to determine arrest history over the period 1985-1996 and to ascertain recorded history of psychiatric illness. Of the cohort, 116 656 had been arrested and 40 478 were on the psychiatric case register. RESULTS: The period prevalence of arrest for people with any psychiatric illness was 32.1%. The highest arrest prevalence, by diagnostic category, was for substance use disorders (59.4%); the prevalence for schizophrenia was 38.7%. Co-morbid substance use disorders significantly increased risk of arrest in people with schizophrenia. The prevalence of mental illness among offenders was 11.1%: 6.5% of offenders had substance use disorders and 1.7% had schizophrenia. For the majority of offenders with a psychiatric illness, first arrest preceded first contact with mental health services; for schizophrenia only, this proportion was increasing over time. The mean percentage annual change in the number of arrests during 1985-1996 rose significantly for offenders with a psychiatric illness other than schizophrenia and dropped significantly for those with no mental illness. Compared to non-psychiatric offenders, offenders with schizophrenia were more likely to offend alone, to offend in open places and to target strangers. CONCLUSIONS: Our findings open the way to an informed approach to the management of offenders with mental illness.

Brain connectivity in body dysmorphic disorder compared with controls: a diffusion tensor imaging study.

BACKGROUND: Several neuroimaging studies have investigated brain grey matter in people with body dysmorphic disorder (BDD), showing possible abnormalities in the limbic system, orbitofrontal cortex, caudate nuclei and temporal lobes. This study takes these findings forward by investigating white matter properties in BDD compared with controls using diffusion tensor imaging. It was hypothesized that the BDD sample would have widespread significantly reduced white matter connectivity as characterized by fractional anisotropy (FA). METHOD: A total of 20 participants with BDD and 20 healthy controls matched on age, gender and handedness underwent diffusion tensor imaging. FA, a measure of water diffusion within a voxel, was compared between groups on a voxel-by-voxel basis across the brain using tract-based spatial statistics within the FSL package. RESULTS: Results showed that, compared with healthy controls, BDD patients demonstrated significantly lower FA (p < 0.05) in most major white matter tracts throughout the brain, including in the superior longitudinal fasciculus, inferior fronto-occipital fasciculus and corpus callosum. Lower FA levels could be accounted for by increased radial diffusivity as characterized by eigenvalues 2 and 3. No area of higher FA was found in BDD. CONCLUSIONS: This study provided the first evidence of compromised white matter integrity within BDD patients. This suggests that there are inefficient connections between different brain areas, which may explain the cognitive and emotion regulation deficits within BDD patients.

Public attitudes towards genomic risk profiling as a component of routine population screening.

Including low penetrance genomic variants in population-based screening might enable personalization of screening intensity and follow up. The application of genomics in this way requires formal evaluation. Even if clinically beneficial, uptake would still depend on the attitudes of target populations. We developed a deliberative workshop on two hypothetical applications (in colorectal cancer and newborn screening) in which we applied stepped, neutrally-framed, information sets. Data were collected using nonparticipant observation, free-text comments by individual participants, and a structured survey. Qualitative data were transcribed and analyzed using thematic content analysis. Eight workshops were conducted with 170 individuals (120 colorectal cancer screening and 50 newborn screening for type 1 diabetes). The use of information sets promoted informed deliberation. In both contexts, attitudes appeared to be heavily informed by assessments of the likely validity of the test results and its personal and health care utility. Perceived benefits included the potential for early intervention, prevention, and closer monitoring while concerns related to costs, education needs regarding the probabilistic nature of risk, the potential for worry, and control of access to personal genomic information. Differences between the colorectal cancer and newborn screening groups appeared to reflect different assessments of potential personal utility, particularly regarding prevention.

Early intervention in psychotic disorders: faith before facts?

This paper reviews the literature on early intervention in psychotic disorders, weighs the cons of this approach, and makes suggestions for clinicians and researchers regarding how to interpret and respond to what is still an embryonic evidence-base, notably in terms of any long-term benefits.

Executive function in body dysmorphic disorder.

BACKGROUND: Body dysmorphic disorder (BDD) is a poorly understood disorder that involves a preoccupation with imagined or minor bodily defects. Only a few studies of neuropsychological function have been conducted. Two previous studies have indicated executive dysfunction in BDD. The current study sought to further define these executive deficits. METHOD: Fourteen DSM-IV BDD patients and 14 age- and sex-matched control participants took part. Because of the high incidence of co-morbidity in BDD, patients with co-morbid Axis I disorders were not excluded. Control participants had no history of psychiatric illness. All participants completed the following executive function (EF) tests: Spatial Span (SS), Spatial Working Memory (SWM) and the Stockings of Cambridge (SOC) task. They also completed the Pattern Recognition (PR) test, a test of visual memory (VM). RESULTS: BDD participants made significantly more between-search errors on the SWM task, an effect that increased with task difficulty. Between-search errors are an example of poor maintenance and manipulation of information. SOC results indicated slower subsequent thinking times (i.e. the time taken to plan) in BDD participants. There were no group differences in SS or PR scores. The severity of BDD, depressive or anxiety symptoms was not correlated with performance on any of the cognitive tasks. CONCLUSIONS: The results of this study indicate that BDD patients have EF deficits in on-line manipulation, planning and organization of information. By contrast, spatial memory capacity, motor speed and visual memory were intact. Considered with evidence from lesion and neuroimaging studies, these results suggest frontal lobe dysfunction in BDD.

The detection of mupirocin resistance and the distribution of methicillin-resistant Staphylococcus aureus at the University Hospital of the West Indies, Jamaica.

OBJECTIVES: The objectives of this study were to determine the susceptibility of Methicillin Resistant Staphylococcus aureus (MRSA) isolates to Mupirocin and other antimicrobial agents and to record the prevalence and distribution of this organism at the University Hospital of the West Indies (UHWI). METHODS: MRSA isolates collected between January 1, 2008 and December 31, 2008, were tested for low and high level resistance to Mupirocin. Susceptibility testing to other antibiotics including cotrimoxazole, minocycline, tetracycline, clindamycin, erythromycin, gentamicin and vancomycin was also done. Laboratory records for all patients from whom MRSA was recovered were reviewed and data on type and source of isolates, clinical diagnosis, history of previous hospitalization and use of mupirocin were extracted. In addition, the laboratory records for 2004 and 2005 were also reviewed to determine prevalence during these periods. RESULTS: Seven per cent of Staphylococcus aureus isolates were resistant to methicillin (MRSA) and of these, 30% and 24% showed low level and high level resistance to mupirocin, respectively. Ninety-four per cent of MRSA strains were resistant to erythromycin while 52% showed resistance to clindamycin. Resistance to tetracycline, co-trimoxazole and minocycline was 27%, 12% and 6%, respectively, while about one-third of the isolates were resistant to gentamicin. There was no resistance to vancomycin. More than half (58%) of the isolates were from skin and soft tissue specimens while isolates from respiratory and urinary tracts and the bloodstream accounted for 19%, 13% and 4%, respectively. There has been a steady increase in prevalence from 4% in 2004 to 5% in 2007 and 7% in 2008. CONCLUSION: Resistance of MRSA to mupirocin appears to be an emerging problem at the UHWI and must be monitored carefully. There is also significant resistance to commonly used antimicrobial agents and strict adherence to antibiotic policy is required to preserve the usefulness of these agents.

Protein sorting and secretion granule formation in regulated secretory cells.

Formation of secretion granules in regulated secretory cells involves packaging a subject of proteins undergoing intracellular transport into specific vesicular carriers that function in stimulus-dependent exocytosis. Recent findings suggest that immature granules are a site of passive sorting, involving condensation of regulated secretory proteins. Proteins that are not condensed are stored to a lesser degree and are enriched in unstimulated, constitutive-like secretion. While these observations have helped to distinguish possible mechanisms of secretory protein sorting, there are only recent hints about the sorting processes that may be required to create the regulated secretory carrier membranes.

Distribution of nosocomial organisms and their resistance patterns in the intensive care unit of the University Hospital of the West Indies, Kingston, Jamaica.

OBJECTIVES: To determine the distribution and antibiotic susceptibility patterns of nosocomial pathogens in the Intensive Care Unit (ICU) at the University Hospital of the West Indies (UHWI). METHODS: A retrospective review of the laboratory records of all ICU patients from 2002-2004 was done. All organisms isolated from blood, urine, sputum, wound swabs and CVP tips were recorded. Sensitivity reports for organisms isolated in 2004 were also obtained. Results were analysed according to source of isolates and type of infection. RESULTS: Gram-negative organisms account for the majority oflCU isolates and show resistance to multiple antibiotics. The common Gram negative pathogens in the ICU are Pseudomonas aeruginosa, Acinetobacter spp and Stenotrophomonas maltophilia while the common Gram positive nosocomial organisms are Group D Streptococcus and coagulase negative Staphylococcus. CONCLUSION: The organisms isolated in the ICU at the UHWI are similar to those isolated in many ICUs all over the world. Surveillance data are necessary to monitor nosocomial pathogens and their resistance patterns to guide empirical antibiotic therapy.

The relationship between physical activity levels and symptoms of depression, anxiety and stress in individuals with alopecia Areata.

BACKGROUND: Alopecia Areata (AA) is an autoimmune condition that is characterised by non-scarring hair loss. Its aesthetic repercussions can lead to profound changes in psychological well-being. Although physical activity (PA) has been associated with better mental health outcomes in diverse populations, the association in individuals with AA has not been established. The aim of this study was to examine the associations between PA and mental health outcomes in individuals with AA to inform intervention strategies for this specific population. METHODS: A cross-sectional study was conducted among individuals who were diagnosed with AA. A total of 83 respondents aged (40.95 ± 13.24 years) completed a self-report questionnaire consisting of International Physical Activity Questionnaire-Short Form (IPAQ-SF) and the Depression and Anxiety Stress Scale (DASS-21). Three-way contingency Chi-square analyses were used to determine the associations between PA, mental health outcomes and participants with hair loss of more than 50% on the scalp. RESULTS: 81.9% of the participants did not meet PA guidelines. Participants with hair loss of more than 50% on the scalp, and who did not meet PA guidelines, were significantly more likely to experience symptoms of severe depression (p = .003), moderate anxiety (p = .04) and mild stress (p = .003) than those who met guidelines CONCLUSION: Findings suggest that increased PA participation in AA individuals with severe hair loss is associated with improved mental health status. Intervention efforts for this specific population should consider barriers and enablers to PA participation as they face challenges that differ from the general population.

Childhood adversity and clinical and psychosocial outcomes in psychosis.

AIMS: Associations between childhood abuse and various psychotic illnesses in adulthood are commonly reported. We aim to examine associations between several reported childhood adverse events (sexual abuse, physical abuse, emotional abuse, neglect and interpersonal loss) among adults with diagnosed psychotic disorders and clinical and psychosocial outcomes. METHODS: Within a large epidemiological study, the 2010 Australian National Survey of Psychosis (Survey of High Impact Psychosis, SHIP), we used logistic regression to model childhood adverse events (any and specific types) on 18 clinical and psychosocial outcomes. RESULTS: Eighty percent of SHIP participants (1466/1825) reported experiencing adverse events in childhood (sexual abuse, other types of abuse and interpersonal loss). Participants reporting any form of childhood adversity had higher odds for 12/18 outcomes we examined. Significant associations were observed with all psychosocial outcomes (social dysfunction, victimisation, offending and homelessness within the previous 12 months, and definite psychosocial stressor within 12 months of illness onset), with the strongest association for homelessness (odds ratio (OR) = 2.82). Common across all adverse event types was an association with lifetime depression, anxiety and a definite psychosocial stressor within 12 months of illness onset. When adverse event types were non-hierarchically coded, sexual abuse was associated with 11/18 outcomes, other types of abuse 13/18 and, interpersonal loss occurring in the absence of other forms of abuse was associated with fewer of the clinical and psychosocial outcomes, 4/18. When adverse events types were coded hierarchically (to isolate the effect of interpersonal loss in the absence of abuse), interpersonal loss was associated with lower odds of self-reproach (OR = 0.70), negative syndrome (OR = 0.75) and victimisation (OR = 0.82). CONCLUSIONS: Adverse childhood experiences among people with psychosis are common, as are subsequent psychosocial stressors. Mental health professionals should routinely enquire about all types of adversities in this group and provide effective service responses. Childhood abuse, including sexual abuse, may contribute to subsequent adversity, poor psychosocial functioning and complex needs among people with psychosis. Longitudinal research to better understand these relationships is needed, as are studies which evaluate the effectiveness of preventative interventions in high-risk groups.

Twins discordant for schizophrenia: psychopathology of the non-schizophrenic co-twins.

OBJECTIVE: Patients with schizophrenia are more likely to suffer from mood and anxiety disorders compared with the general population. We explored the aetiology of this comorbidity using a twin study design. METHOD: We applied an additive genetic + unique environment (AE) random effects model in the analysis of 35 non-schizophrenic co-twins from pairs discordant for schizophrenia, and 131 control twins. RESULTS: Non-schizophrenic co-twins had significantly increased rates of depression (P = 0.006) and anxiety disorders (P = 0.021) compared with the control twins. CONCLUSION: Our results provide evidence for a familial association between schizophrenia and anxiety and depression. This could reflect common aetiological factors contributing to each of the disorders. Future studies should attempt to investigate the relative genetic and environmental contribution to the shared risk factors for schizophrenia, mood and anxiety disorders.

The secretory carrier membrane protein family: structure and membrane topology.

Secretory carrier membrane proteins (SCAMPs) are integral membrane proteins found in secretory and endocytic carriers implicated to function in membrane trafficking. Using expressed sequence tag database and library screens and DNA sequencing, we have characterized several new SCAMPs spanning the plant and animal kingdoms and have defined a broadly conserved protein family. No obvious fungal homologue has been identified, however. We have found that SCAMPs share several structural motifs. These include NPF repeats, a leucine heptad repeat enriched in charged residues, and a proline-rich SH3-like and/or WW domain-binding site in the N-terminal domain, which is followed by a membrane core containing four putative transmembrane spans and three amphiphilic segments that are the most highly conserved structural elements. All SCAMPs are 32-38 kDa except mammalian SCAMP4, which is approximately 25 kDa and lacks most of the N-terminal hydrophilic domain of other SCAMPs. SCAMP4 is authentic as determined by Northern and Western blotting, suggesting that this portion of the larger SCAMPs encodes the functional domain. Focusing on SCAMP1, we have characterized its structure further by limited proteolysis and Western blotting with the use of isolated secretory granules as a uniformly oriented source of antigen and by topology mapping through expression of alkaline phosphatase gene fusions in Escherichia coli. Results show that SCAMP1 is degraded sequentially from the N terminus and then the C terminus, yielding an approximately 20-kDa membrane core that contains four transmembrane spans. Using synthetic peptides corresponding to the three conserved amphiphilic segments of the membrane core, we have demonstrated their binding to phospholipid membranes and shown by circular dichroism spectroscopy that the central amphiphilic segment linking transmembrane spans 2 and 3 is alpha-helical. In the intact protein, these segments are likely to reside in the cytoplasm-facing membrane interface. The current model of SCAMP1 suggests that the N and C termini form the cytoplasmic surface of the protein overlying a membrane core, which contains a functional domain located at the cytoplasmic interface with little exposure of the protein on the ectodomain.

Activation of the mitogen-activated protein kinase pathway in Triton X-100 disrupted NIH-3T3 cells by p21 ras and in vitro by plasma membranes from NIH 3T3 cells.

We describe a novel Triton-disrupted mammalian cell system wherein the pathways for activation of mitogen-activated protein (MAP) kinases (MAPKs) are capable of direct biochemical manipulation in vitro. MAPKs p42mapk and p44mapk are activated in signal transduction cascade(s) initiated by occupancy of plasma membrane receptors for peptide growth factors, hormones, and neurotransmitters. One likely activation pathway for MAPKs consists of sequential activations of c-ras, c-raf-1, and a protein-tyrosine/threonine kinase, MAP kinase kinase. Triton-disrupted cells retained capacity for activation of the pathway by both peptide growth factors and by addition of GTP-loaded p21 rasVal12. Incubation of disrupted cells with an antibody that neutralized the function of c-ras (Y13-259) abolished receptor-mediated stimulation of MAPK as did acute addition of 200 microM azatyrosine. Activation of the pathway was reconstituted in a cell-free system using high-speed supernatants generated from Triton-disrupted cells together with purified plasma membranes from parental cells and as a heterogeneous system using purified plasma membranes from v-ras-transformed cells. These systems will allow biochemical dissection in vitro of the interaction(s) between c-ras and the MAPK pathway in mammalian cells.