Search PubMed⌕ Search

Biomedical subjects

J McGrath

Publications and source records attributed to J McGrath.

At least 37 records · Page 2Linked to original sources
PubMed2000

Green fluorescent protein: A novel viability assay for cryobiological applications.

Assessment of tissue viability following the application of a freezing protocol is challenging due to the paucity of viability assays that can be used dynamically, in situ. Cells transfected with a green fluorescent protein (GFP) vector actively produce GFP, which is retained intracellularly. Because of its constitutive and heritable expression, GFP fluorescence of transfected cells may have significant utility as a viability assay for cells within tissues. As a first step toward application to tissues, this work seeks to establish the validity of this GFP-based assay in cell suspensions by comparing the results to other accepted measures of viability. To the authors' knowledge, this is the first use of GFP in cryobiology applications. Intracellular GFP fluorescence was evaluated following slow freezing. Nontransfected and GFP-transfected rat 3230 adenocarcinoma (R3230AC) cells were frozen at 1 degrees C/min to minimum temperatures between -5 and -30 degrees C and then immediately thawed in a 37 degrees C water bath. Samples were assayed using the common viability indicators trypan blue and ethidium bromide (EtBr). A regression analysis of recovery measured with the GFP assay as a function of recovery measured with a trypan blue assay gave a correlation coefficient of 0.97. A similar correlation coefficient, 0.95, was determined for recovery assessed by the GFP assay as a function of recovery measured by an EtBr assay. Nontransfected and GFP-transfected cells responded similarly to slow freezing, indicating that GFP transfection did not significantly alter the response of cells to typical freezing conditions. The excellent correlation of GFP assay results with those of two common viability assays suggests that the GFP-based assay is valid for cells and that further development of a tissue viability assay based on transfection is appropriate.

Animals↗
PubMed2000

Low-temperature recovery strategies for the isolation of bacteria from ancient permafrost sediments.

Permafrost represents a unique ecosystem that has allowed the prolonged survival of certain bacterial lineages at subzero temperatures. To better understand the permafrost microbial community, it is important to identify isolation protocols that optimize the recovery of genetically diverse bacterial lineages. We have investigated the impact of different low-temperature isolation protocols on recovery of aerobic bacteria from northeast Siberian permafrost of variable geologic origin and frozen for 5000 to 3 million years. Low-nutrient media enhanced the quantitative recovery of bacteria, whereas the isolation of diverse morphotypes was maximized on rich media. Cold enrichments done directly in natural, undisturbed permafrost led not only to recovery of increased numbers of bacteria but also to isolation of genotypes not recovered by means of liquid low-temperature enrichments. On the other hand, direct plating and growth at 4 degrees C also led to recovery of diverse genotypes, some of which were not recovered following enrichment. Strains recovered from different permafrost samples were predominantly oligotrophic and non-spore-forming but were otherwise variable from each other in terms of a number of bacteriological characteristics. Our data suggest that a combination of isolation protocols from different permafrost samples should be used to establish a culture-based survey of the different bacterial lineages in permafrost.

Bacteria↗
PubMed2000

The androgen receptor exon 1 trinucleotide repeat does not act as a modifier of the age of presentation in breast cancer.

The CAG repeat in exon 1 of the androgen receptor (AR) genes has been postulated as both a susceptibility allele and phenotypic modifier in BRCA1-associated breast cancers. We have analysed this repeat in a set of 178 breast cancer cases who have been selected only for age of presentation at 65 years or less. No effect of repeat length on age of presentation was found and there was no association between repeat length and family history. In combination with the data from other workers, our findings suggest that the androgen receptor repeat does not act as a modifier gene or susceptibility locus outside the context of the hereditary breast/ovarian cancer syndrome.

Adult↗
PubMed2000

Awareness and unawareness of thought disorder.

OBJECTIVE: There is little systematic evidence to determine if patients with thought disorder are aware of their impaired communication. Awareness versus unawareness of deficit has important implications for neurocognitive models of thought disorder. The aims of this study were to assess awareness of impaired communication in patients prone to thought disorder, and to explore associations between degree of awareness of thought disorder, objective measurement of thought disorder and performance on tests sensitive to impaired executive ability. METHOD: Thirty-one patients with schizophrenia, 16 patients with mania and 20 well controls were included. Subjects completed a new instrument to assess awareness of thought disorder, the Communication Awareness Scale (CAS). Thought disorder was rated from free speech samples scored with Andreasen's Scale for the Assessment of Thought Language and Communication. Four tests sensitive to impaired executive ability were administered. RESULTS: Subjects with higher levels of positive thought disorder had significantly higher CAS scores. Unexpectedly, those with lower scores on executive ability had significantly higher scores on the CAS. CONCLUSIONS: The significant correlation between objective levels of positive thought disorder and higher scores on the CAS suggests that, overall, patients with thought disorder are aware of their deficit. A neurocognitive model of thought disorder is described that involves a dissociation between the ability to monitor errors (required for accurate awareness of deficit) and the ability to correct errors (required for the production of efficient communication).

Adolescent↗
PubMed2000

Universal interventions for the primary prevention of schizophrenia.

OBJECTIVE: To speculate on the role of universal (population-based) interventions designed to prevent schizophrenia. METHOD: A nonsystematic review of candidate risk factors for schizophrenia, with particular emphasis on the quality of the evidence, effect size of the risk factor, population attributable risk and potential for population-based intervention. RESULTS: In order to design population-based interventions for the prevention of schizophrenia, we need to identify weak but prevalent risk factors. Based on current knowledge, the leading risk factors for schizophrenia include genes, season and place of birth, obstetric complications, prenatal exposure to viruses and prenatal nutrition. For the nongenetic exposures, we need to consider if potential interventions are effective, safe, cheap and acceptable. CONCLUSIONS: Vaccinations and interventions related to improving prenatal nutrition and antenatal care appear to be the most plausible options for universal prevention.

Female↗
PubMed2000

Psychotic disorders in urban areas: an overview of the Study on Low Prevalence Disorders.

OBJECTIVE: This paper reports on a study designed within the framework of the National Survey of Mental Health and Wellbeing to: estimate the prevalence of psychoses in urban areas of Australia; identify profiles of symptomatology, impairments and disabilities; collect information on services received and needed; and explore quality of life issues in a broadly representative sample of people with psychotic illnesses. METHOD: The study was conducted over four areas in the Australian Capital Territory, Queensland, Victoria and Western Australia, as a two-phase survey: (i) a census and screening for psychosis of all individuals who made contacts with mental health services during a period of 1 month in 1997; and (ii) interviews with a stratified random sample (n=980) of the screen-positive individuals (n=3800) using a standardised instrument. RESULTS: The point prevalence (1 month) of psychotic disorders in the urban population aged 18-64 is in the range of 4-7 per 1000 with a weighted mean of 4.7 per 1000. People with psychotic disorders experience high rates of functional impairments and disability, decreased quality of life, persistent symptoms, substance-use comorbidity and frequent side effects of medication. Although the utilisation of hospital-based and community mental health services, as well as of public and non-governmental helping agencies, is high, the majority live in extreme social isolation and adverse socioeconomic circumstances. Among the many unmet needs, the limited availability of community-based rehabilitation, supported accommodation and employment opportunities is particularly prominent. CONCLUSIONS: The so-called 'low-prevalence' psychotic disorders represent a major and complex public health problem, associated with heavy personal and social costs. There is a need for a broad programmatic approach, involving various sectors of the community, to tackle the multiple dimensions of clinical disorder, personal functioning and socioeconomic environment that influence the course and outcome of psychosis and ultimately determine the effectiveness of service-based intervention.

Activities of Daily Living↗
PubMed2000

Automated quantitation of circulating neutrophil and eosinophil activation in asthmatic patients.

BACKGROUND: Asthma has been associated with eosinophil activation, measured in serum, sputum, bronchoalveolar lavage (BAL) fluid, and urine. A whole blood automated method was developed to assess eosinophil and neutrophil activity in terms of peroxidase content and cell morphology using the Bayer haematology analyser. The method was applied to an in vitro stimulation model when fMLP was added to whole blood and the samples were then analysed for changes in granularity and shape. In addition, cells stimulated with interleukin (IL)-8 were examined by electron microscopy. METHODS: A cross sectional analysis was performed on venous blood from non-atopic, non-asthmatic normal subjects (n = 37), mild (n = 46) and symptomatic (n = 22) asthmatic patients on inhaled beta(2) agonist only, and more severe asthmatic patients (n = 17) on inhaled and oral corticosteroid therapy. Samples were analysed by the haematology analyser and peroxidase leucograms gated using the WinMDI software program. RESULTS: There were significant differences in the amount of light scatter by the neutrophil populations in the symptomatic (p = 0.007) and severe asthmatic (p = 0.0001) groups compared with the control group. However, abnormalities in eosinophil populations were not observed. In vitro activation of whole blood with fMLP caused similar changes in neutrophil light scatter, suggesting that neutrophil activation is present in peripheral blood of symptomatic asthmatic patients. IL-8 caused a change in shape of the neutrophils seen using transmission electron microscopy. CONCLUSIONS: Evidence of neutrophil activation can be seen in whole blood from patients with asthma using a novel automated method. This may potentially be applied to other inflammatory diseases.

Adult↗
PubMed2000

Predicting the revolving door phenomenon among patients with schizophrenic, affective disorders and non-organic psychoses.

OBJECTIVE: The aim of the study was to identify the variables that predict the revolving door phenomenon in psychiatric hospital at the moment of a second admission. METHODS: The sample consisted of 3,093 patients who have been followed during 5 to 24 years after their first hospital admission due to schizophrenia, and affective or psychotic disorders. Those who had had four or more admissions during the study period were considered as revolving door patients. Logistic regression analyses were used to assess the impact of gender, age, marital status, urban conditions, diagnosis, mean period of stay on the first admission, interval between the first and second admissions on the patterns of hospitalization. RESULTS: The variables with the highest predictive power for readmission were the interval between first and second admissions, and the length of stay in the first admission. CONCLUSIONS: These data may help public health planners in providing optimal care to a small group of patients with more effective utilization of the available services.

Adolescent↗
PubMed2000

Heterogeneity in schizophrenia; mixture modelling of age-at-first-admission, gender and diagnosis.

OBJECTIVE: Identifying and explaining sources of heterogeneity in schizophrenia would help elucidate its aetiology and course. In this paper we examine heterogeneity in terms of age-at-first-admission, diagnosis and gender by decomposing a large dataset using mixture modelling. METHOD: Using the Queensland Mental Health Statistics System, we first extracted age-at-first-admission data for schizophrenia (ICD8/9 295) to represent a 'narrow' definition of schizophrenia (N= 7651); we then added paraphrenia (297) and other non-organic psychoses (298) for a 'broad' definition (N= 10 199). Mixture models were fitted to these narrowly and broadly defined distributions for both males and females. RESULTS: For narrowly defined schizophrenia a three-component model best fitted both male and female distributions. While the mean ages of these components were very similar for both males and females, the ratios of males to females crossed from an excess of males in the 'youngest' component to an excess of females in the 'oldest' component. When using the broad definition, four components best fitted the underlying distributions. While the first three were similar to those found for narrowly defined schizophrenia, the additional fourth component reverted to a male excess; however, the mean age for males was 10 years younger than for females. CONCLUSION: Our findings suggest that subtypes based on age-at-first-admission can be identified, although the number identified depends on how inclusively schizophrenia is defined. While there appear to be the same number with similar mean ages for both genders, there are differences in the proportions of males to females. Further work to fully characterize their nature is warranted.

Adult↗
PubMed1999

Hypothesis: is low prenatal vitamin D a risk-modifying factor for schizophrenia?

The central nervous system is increasingly being recognised as a target organ for vitamin D via its wide-ranging steroid hormonal effects and via the induction of various proteins such as nerve growth factor. This paper proposes that low maternal vitamin D may impact adversely on the developing foetal brain, leaving the affected offspring at increased risk of adult-onset schizophrenia. The hypothesis can parsimoniously explain diverse epidemiological features of schizophrenia, such as the excess of winter births, increased rates of schizophrenia in dark-skinned migrants to cold climates, the increased rate of schizophrenia births in urban versus rural setting, and the association between prenatal famine and schizophrenia. Studies that will allow rejection of the hypothesis are proposed.

Adult↗
PubMed1999

Altered adhesion, proliferation and death in neural cultures from adults with schizophrenia.

The causes of schizophrenia are unknown, but there is evidence linking subtle deviations in neural development with schizophrenia. Embryonic brain development cannot be studied in an adult with schizophrenia, but neurogenesis and early events in neuronal differentiation can be investigated throughout adult life in the human olfactory epithelium. Our past research has demonstrated that neuronal cultures can be derived from biopsy of the human adult olfactory epithelium. In the present study, we examined mechanisms related to neurogenesis and neuronal differentiation in adults with schizophrenia versus well controls. Forty biopsies were collected under local anaesthesia from ten individuals with DSM III-R schizophrenia and ten age- and sex-matched well controls. All patients, except one, were receiving antipsychotic medication at the time of the biopsy. Immunostaining for neuronal markers indicated that neurogenesis occurred in the biopsies from both patients and controls since all contained cells expressing tubulin and/or olfactory marker protein. The major findings of this study are: 1. biopsies from patients with schizophrenia showed a significantly reduced ability to attach to the culture slide: 29.9% of patient biopsies attached compared to 73.5% of control biopsies; 2. biopsies from patients with schizophrenia had a significantly greater proportion of cells undergoing mitosis: 0.69% in the patients compared to 0.29% in the controls; and 3. dopamine (10 microM) significantly increased the proportion of apoptotic cells in the control cultures but significantly decreased the proportion in patients' cultures.

Adult↗
PubMed1999

Electrodermal responses to sensory stimuli in individuals with fragile X syndrome: a preliminary report.

The fragile X mutation and fragile X syndrome are associated with hyperarousal, hyperactivity, aggression, and anxiety. These may be related to strong reactions to auditory, tactile, visual, and olfactory stimuli [Hagerman, 1996b; Hagerman and Cronister, 1996]. However, almost no data exist describing hyperarousal and sensory sensitivity in individuals with the fragile X mutation. This study establishes a reliable laboratory paradigm for examining reactions to sensory stimuli. We found the pattern of electrodermal responses (EDRs) to stimulation in one sensory modality predicted the pattern of EDRs in four other sensory systems. In addition, the EDR pattern of individuals with the fragile X mutation was related to their FMR-protein expression. Finally, EDRs in individuals with fragile X syndrome were significantly different from those of normal controls, demonstrating greater magnitude, more responses per stimulation, responses on a greater proportion of trials, and lower rates of habituation. The findings support the theory that individuals with fragile X syndrome have a physiologically based enhancement of reactions to sensations. Because electrodermal activity indexes sympathetic nervous system activity, the data suggest that the over-arousal to sensation may involve the sympathetic system.

Adolescent↗
PubMed1999

Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction.

The lats gene has been identified as a tumour suppressor in Drosophila melanogaster using mosaic screens. Mosaic flies carrying somatic cells that are mutant for lats develop large tumours in many organs. The human LATS1 homologue rescues embryonic lethality and inhibits tumour growth in lats mutant flies, demonstrating the functional conservation of this gene. Biochemical and genetic analyses have revealed that LATS1 functions as a negative regulator of CDC2 (ref. 3). These data suggest that mammalian LATS1 may have a role in tumorigenesis. To elucidate the function of mammalian LATS1, we have generated Lats1-/- mice. Lats1-/- animals exhibit a lack of mammary gland development, infertility and growth retardation. Accompanying these defects are hyperplastic changes in the pituitary and decreased serum hormone levels. The reproductive hormone defects of Lats1-/- mice are reminiscent of isolated LH-hypogonadotropic hypogonadism and corpus luteum insufficiency in humans. Furthermore, Lats1-/- mice develop soft-tissue sarcomas and ovarian stromal cell tumours and are highly sensitive to carcinogenic treatments. Our data demonstrate a role for Lats1 in mammalian tumorigenesis and specific endocrine dysfunction.

Animals↗
PubMed1999

Topographical distribution of blood supply to the anal canal.

BACKGROUND: It has been suggested that anal fissure is an ischaemic ulcer caused by a combination of poor blood supply to the posterior midline of the anal canal and spasm of the internal anal sphincter. This study investigated the topographical distribution of blood supply to quadrants of the anal canal above and below the dentate line. METHODS: Cadaveric anal canals were removed and 1-cm blocks were cut above and below the dentate line. Blocks were sectioned at 10 microm and every 25th section was mounted. Using the technique of systematic random sampling, fields in the subanodermal space and the internal anal sphincter in posterior, lateral and anterior quadrants of the anal canal were chosen. The numbers of small arterioles in each field were counted. Mean counts were compared for both subanodermal space and internal anal sphincter between quadrants and levels above and below the dentate line using Page's L test for trends. RESULTS: Anal canals from eight cadavers were examined. There was a significant trend to an increasing number of arterioles from posterior to anterior in the subanodermal space at all levels and at two of three levels in the internal anal sphincter. CONCLUSION: The arteriolar density is less in the posterior quadrant throughout the anal canal. It may be that this poor blood supply predisposes to the development of anal fissures at their most common site in the posterior midline.

Anal Canal↗