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Biomedical subjects

J McGrath

Publications and source records attributed to J McGrath.

At least 19 recordsLinked to original sources
PubMed2004

Expression and glycosylation of MUC1 in epidermolysis bullosa-associated and sporadic cutaneous squamous cell carcinomas.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is particularly problematic in certain patient groups, including patients with dystrophic or junctional epidermolysis bullosa (DEB/JEB). Theoretically, vaccination against a cell surface antigen which is expressed on this type of tumour could prevent SCC development, as well as treat primary and metastatic disease in this patient group. Preliminary studies have suggested that MUC1, a transmembrane glycoprotein, is overexpressed in sporadic cutaneous SCCs, and MUC1 has been used with some success as a target antigen for vaccine development in breast cancer, where it is expressed on > 50% of neoplastic cells in approximately 50-80% of tumours. Furthermore, aberrant glycosylation of MUC1 has been detected in this and other cancer types; however, the glycosylation status of MUC1 in cutaneous SCC is not known. OBJECTIVES: To investigate the expression and glycosylation status of MUC1 in SCCs arising in patients with DEB and JEB, and for comparison in sporadic SCCs and sporadic Bowen's disease. METHODS: Immunohistochemical analysis of MUC1 in 30 SCCs from subjects with DEB/JEB, 55 sporadic SCCs and 30 sporadic lesions of Bowen's disease was carried out using four separate monoclonal antibodies which recognize different isoforms of MUC1. RESULTS: Expression of MUC1 was detected in 100% of SCCs arising in patients with DEB and JEB; > 50% of neoplastic cells stained positive for MUC1 in 57% of DEB/JEB SCCs, with over 95% of tumour cells immunopositive in 33% of cases. MUC1 expression was also observed in 95% of sporadic SCCs and 97% of Bowen's disease, with 36% of sporadic SCCs immunopositive for MUC1 in > 50% of tumour cells. Investigation of the glycosylation status showed that MUC1 was predominantly hyperglycosylated in the DEB/JEB and sporadic tumours. CONCLUSIONS: The results demonstrate that a significant proportion of DEB/JEB and sporadic SCCs express MUC1 in > 50% of tumour cells. Therefore, MUC1 may be a suitable candidate antigen against which to develop a tumour vaccine for these patient groups.

Bowen's Disease↗
PubMed2003

Lithium for schizophrenia.

BACKGROUND: Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used, among them lithium. OBJECTIVES: To review the effects of lithium for the treatment of schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: The reviewers searched the Cochrane Schizophrenia Group's register (March 2002). This register is compiled by methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. We also contacted pharmaceutical companies and authors of relevant studies to identify further trials and to obtain original patient data. SELECTION CRITERIA: All randomised controlled trials comparing lithium to antipsychotics or to placebo (or no intervention), whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted independently by at least two reviewers. Dichotomous data were analysed using relative risks (RR) and the 95% confidence interval (CI) estimated. Where possible the number needed to treat (NNT) or number needed to harm statistics were calculated. Continuous data were analysed using weighted mean differences (WMD). MAIN RESULTS: The review currently includes 20 studies with a total of 611 participants. Most studies were small, of short duration and incompletely reported, but a number of authors were willing to share their data with us. Three studies comparing lithium with placebo as the sole treatment showed no difference in any of the outcomes we analysed. In eight studies comparing lithium with antipsychotic drugs as the sole treatment more participants in the lithium group left the studies early (n=270, RR 1.8, CI 1.2 to 2.9, NNT 9, CI 5 to 33). Several of the outcomes relating to these studies suggested that lithium is less effective than antipsychotic drugs, but it was difficult to summarise the data, because a variety of rating scales were used in the studies. Eleven studies examined whether the augmentation of antipsychotic drugs with lithium salts is more effective than antipsychotic drugs alone. More participants who received lithium augmentation had a clinically significant response (n=244, RR 0.8, CI 0.7 to 0.96, NNT 8, CI 4 to 33). However, statistical significance became borderline when participants with schizoaffective disorders were excluded in a sensitivity analysis (n=120, RR 0.8, CI 0.6 to 1.0, p=0.07). Furthermore, more participants in the lithium augmentation groups left the studies early (n=320, RR 2.0 CI 1.3 to 3.1, NNT 7, CI 4 to 14), suggesting a lower acceptability of lithium augmentation compared to those on antipsychotics alone. No superior efficacy of lithium augmentation in any specific aspect of the mental state was found. While based on very little data, there were no differences between groups for adverse events. REVIEWER'S CONCLUSIONS: There is no randomised trial based evidence that lithium on its own is an effective treatment for people with schizophrenia. The evidence available on augmentation of antipsychotics with lithium is inconclusive, but it justifies further, large, simple and well-designed trials. These should concentrate on two target groups: 1) people with no affective symptoms, so that trialists can determine whether lithium has an effect on the core symptoms of schizophrenia, 2) people with schizoaffective disorders for whom lithium is widely used in clinical practice, although there is no evidence to support this use.

Antipsychotic Agents↗
PubMed2003

Vitamin D3 and brain development.

Evidence for the presence of the vitamin D receptor in brain implies this vitamin may have some function in this organ. This study investigates whether vitamin D(3) acts during brain development. We demonstrate that rats born to vitamin D(3)-deficient mothers had profound alterations in the brain at birth. The cortex was longer but not wider, the lateral ventricles were enlarged, the cortex was proportionally thinner and there was more cell proliferation throughout the brain. There were reductions in brain content of nerve growth factor and glial cell line-derived neurotrophic factor and reduced expression of p75(NTR), the low-affinity neurotrophin receptor. Our findings would suggest that low maternal vitamin D(3) has important ramifications for the developing brain.

Animals↗
PubMed2003

Searching for schizophrenia in ancient Greek and Roman literature: a systematic review.

OBJECTIVE: The aim of this study was to systematically examine ancient Roman and Greek texts to identify descriptions of schizophrenia and related disorders. METHOD: Material from Greek and Roman literature dating from the 5th Century BC to the beginning of the 2nd Century AD was systematically reviewed for symptoms of mental illness. DSM IV criteria were applied in order to identify material related to schizophrenia and related disorders. RESULTS: The general public had an awareness of psychotic disorders, because the symptoms were described in works of fiction and in historical accounts of malingering. There were isolated instances of text related to psychotic symptoms in the residents of ancient Rome and Greece, but no written material describing a condition that would meet modern diagnostic criteria for schizophrenia. CONCLUSION: In contrast to many other psychiatric disorders that are represented in ancient Greek and Roman literature, there were no descriptions of individuals with schizophrenia in the material assessed in this review.

Bipolar Disorder↗
PubMed2003

Fish odour syndrome with features of both primary and secondary trimethylaminuria.

We report a patient with the fish odour syndrome who has both primary and secondary trimethylaminuria. The diagnosis was made using biochemical and genetic analysis in the apparent absence of any characteristic smell. Differentiation of primary and secondary trimethylaminuria is usually made on urinary analysis of trimethylamine and its metabolite trimethylamine N-oxide, with different, characteristic patterns of both compounds in primary and secondary trimethylaminuria. Our patient had biochemical analysis consistent with a diagnosis of secondary trimethylaminuria, while analysis of the flavin-containing mono-oxygenase 3 gene, the causative gene in primary trimethylaminuria, demonstrated three sequence polymorphisms, two of which are known to reduce enzyme activity. The patient showed temporary clinical and biochemical response to treatment with metronidazole and neomycin. It is important to be aware of this diagnosis in patients without obvious clinical signs, and of the subjective benefits of treatment.

Biomarkers↗
PubMed2001

Urban birth and migrant status as risk factors for psychosis: an Australian case-control study.

BACKGROUND: Urban birth and migrant status have been identified as risk factors for psychosis in North American and European studies. The aim of this study was to explore these variables in an Australian case-control study. METHOD: Country of birth of subjects and their parents, and place of birth of Australian-born subjects, were examined in individuals with psychosis drawn from a prevalence study (n = 310) and well controls recruited from the same catchment area (n = 303). RESULTS: Migrant status was associated with a significantly decreased odds of having a psychotic disorder. For those born in Australia, neither migrant status of parents nor urban birth was associated with having a psychotic disorder. CONCLUSIONS: The lack of effect for urban birth and second-generation migrant status may help generate candidate environmental risk factors that operate in Europe but not in Australia.

Adolescent↗
PubMed2001

Adjunctive testing for cervical cancer in low resource settings with visual inspection, HPV, and the Pap smear.

OBJECTIVE: To test whether the performance of visual inspection using acetic acid (VIA) could be improved through adjunctive testing and to determine whether the combination of visual inspection of the cervix and HPV testing could prove useful for identifying those at highest risk of cervical precancer. METHODS: Between October 1995 and August 1997, 2199 women willing to be screened for cervical cancer in peri-urban clinics in Harare, Zimbabwe received VIA, Pap smear and HPV as screening tests. The presence or absence of (pre)cancer was confirmed via colposcopy with biopsy as indicated for >97% of all women. Computerized simulations of sequential testing scenarios provided estimates of the joint (net) test qualities of different paired combinations of the three tests and allowed for comparisons with the individual test qualities. RESULTS: Using HGSIL/CIN II-III as the reference threshold of disease, the net sensitivity and specificity of VIA and HPV when used sequentially were 63.6 and 81.9%, respectively, compared to 43.3 and 91%, respectively, when Pap smears were followed by HPV testing. VIA followed by the Pap smear yielded a net sensitivity of 37.5% and net specificity of 94.3%. CONCLUSIONS: For programs with limited resources but with the capacity for HPV testing, sequential testing involving the use of VIA followed by HPV could yield fewer false positives than the use of VIA alone at a cost of relatively few additional false negatives.

Acetates↗
PubMed2001

Working memory in schizophrenia and mania: correlation with symptoms during the acute and subacute phases.

OBJECTIVE: The aims of this study were to examine working memory in the acute subacute phase of schizophrenia and mania and to examine correlations between working memory and specific symptom domains. METHOD: Visuospatial working memory and symptom profiles were assessed in three groups (schizophrenia group, n= 19; mania, n= 12; controls, n= 19) on two occasions separated by 4 weeks. RESULTS: Both patient groups had significant deficits on working memory compared to the well controls and the schizophrenia and mania groups were equally impaired. All groups showed equivalent improvement over time. In the patient groups, impaired working memory was significantly correlated with the presence of both negative symptoms and positive thought disorder. CONCLUSION: Impaired working memory is found in both schizophrenia and mania during the acute subacute phases. Further research is required in order to clarify the neurocognitive mechanisms linking impaired working memory with both negative symptoms and positive thought disorder.

Acute Disease↗
PubMed2001

Corneodesmosin expression in psoriasis vulgaris differs from normal skin and other inflammatory skin disorders.

SUMMARY: Corneodesmosin (Cdsn) is a late differentiation epidermal glycoprotein putatively involved in keratinocyte adhesion. The Cdsn gene lies within the susceptibility region on chromosome 6p21.3 (PSORS1) for psoriasis, a common chronic disfiguring skin disease. A particular allelic variant of Cdsn has a strong association with psoriasis. Therefore, genetically and biologically, Cdsn is a possible candidate gene for psoriasis susceptibility. To investigate a potential role for Cdsn in psoriasis pathogenesis, protein expression studies were performed by quantitative immunohistochemistry on normal skin, psoriatic skin (lesional and nonlesional), and other skin disorders using monoclonal antibodies (G36-19 and F28-27). In normal and nonlesional skin, Cdsn was expressed in stratum corneum and one or two layers of superficial stratum granulosum. In lesional psoriasis, there was a significant increase in Cdsn expression, which was observed in multiple layers of stratum spinosum and in stratum corneum. The expression pattern varied from granular, cytoplasmic immunoreactivity to cell surface labeling with weakly immunoreactive cytoplasm. In chronic atopic dermatitis, lichen planus, mycosis fungoides, and pityriasis rubra pilaris, Cdsn immunoreactivity was confined to stratum corneum and upper stratum granulosum with no stratum spinosum immunoreactivity. Immunoelectron microscopy of normal and lesional psoriatic skin demonstrated Cdsn release concomitant with involucrin incorporation into cell envelopes and completed before mature envelope formation. Extracellular release of Cdsn occurred at a lower level of the epidermis in psoriasis than normal skin. These protein expression studies provide evidence of altered Cdsn expression in psoriasis consistent with a role of Cdsn in disease pathogenesis. Further functional and genetic studies of Cdsn are justified to determine its role as a potential psoriasis-susceptibility factor.

Chromosomes, Human, Pair 6↗
PubMed2001

Does 'imprinting' with low prenatal vitamin D contribute to the risk of various adult disorders?

Hypovitaminosis D is a candidate risk-modifying factor for a diverse range of disorders apart from rickets and osteoporosis. Based on epidemiology, and on in vitro and animal experiment, vitamin D has been linked to multiple sclerosis, certain cancers (prostate, breast and colorectal), insulin-dependent diabetes mellitus and schizophrenia. I hypothesise that low pre- and perinatal vitamin D levels imprint on the functional characteristics of various tissues throughout the body, leaving the affected individual at increased risk of developing a range of adult-onset disorders. The hypothesis draws from recent advances in our understanding of the early origin of adult disease and proposes a 'critical window' during which vitamin D levels may have a persisting impact on adult health outcomes. Methods to test the hypothesis are outlined. If correct, the hypothesis has important implications for public health. Careful attention to maternal vitamin D status could translate into diverse improvements in health outcomes for the following generation.

Adult↗
PubMed2000

Seasonality of first admissions for schizophrenia in the Southern Hemisphere.

Northern Hemisphere studies of first admissions for schizophrenia have shown an excess of summer admissions (June, July and August) compared to other times of the year. The within-year fluctuations in first admissions could be related to meteorological factors that fluctuate between seasons (e.g. temperature, photoperiod) and/or social factors (e.g. holidays, religious events). If meteorological factors were primarily responsible for the fluctuation, then Southern Hemisphere studies should find excess first admissions in December, January and February. This paper presents the first season of first admission study of schizophrenia in the Southern Hemisphere. The month and year of first admission for schizophrenia (ICD 8/9) for 4487 male and 3252 female, Australian-born individuals were extracted from a Queensland mental health register. Spectral analysis showed a strong annual periodicity of first admissions for males with the peak in August (Southern Hemisphere winter) and a trough in the summer months (December to February). The pattern for females also displayed annual periodicity. These results correspond to the Northern Hemisphere reports of excess of schizophrenia first admissions in terms of the month of the year but not the season of excess. Further work is needed in order to clarify the impact of latitude and meteorological factors on the month of first admission for schizophrenia.

Adult↗
PubMed2000

Carbamazepine for schizophrenia and schizoaffective psychoses.

BACKGROUND: A sizeable minority of people with schizophrenia do not have complete remission of symptoms. A variety of adjunctive treatments have been used to treat schizophrenia, carbamazepine being one. OBJECTIVES: To review the effects of carbamazepine and its derivatives for the treatment of schizophrenia and schizoaffective psychoses. SEARCH STRATEGY: Biological Abstracts (1980-1998), The Cochrane Library (Issue 3, 1998), The Cochrane Schizophrenia Group's Register of Trials (August 1998), EMBASE (1980-1998), MEDLINE (1966-1998), PsycLIT (1886-1998) and PSYNDEX (1974-1998) were searched. Citations from included trials were also inspected and relevant companies and authors contacted for additional data. SELECTION CRITERIA: All randomised controlled trials comparing carbamazepine, or compounds of the carbamazepine family, to placebo or no intervention, whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizoaffective psychoses. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted independently by at least two reviewers. Dichotomous data were analysed using Peto odds ratio (OR) and the 95% confidence interval (CI) estimated. Where possible the number needed to treat (NNT) or number needed to harm statistics were calculated. MAIN RESULTS: There is no clear effect of carbamazepine as the sole maintenance treatment for those with schizophrenia. Eight trials provided very limited data on the value of carbamazepine as an adjunct to antipsychotics. Studies were small and poorly reported. Currently no published data provides convincing evidence that adjunctive carbamazepine has an effect on global functioning, mental state, side effects or acceptability of treatment. REVIEWER'S CONCLUSIONS: Based on currently available randomised trial-derived evidence, carbamazepine cannot be recommend for routine clinical use for treatment or augmentation of antipsychotic treatment of schizophrenia. However, for those with a past history of being responsive to carbamazepine, or for those with associated EEG abnormalities, a trial of the drug may be warranted. More data is expected from trialists and the results of this review may be changed by their inclusion. At present large, simple well designed and reported trials are justified especially if focusing on those with both schizophrenia and EEG abnormalities or violent episodes and people with schizoaffective disorders.

Antimanic Agents↗
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↗