Biomedical subjects

Arnoldo Frigessi

Publications and source records attributed to Arnoldo Frigessi.

10 recordsLinked to original sources

PubMed2007

Effects of alcohol consumption and antipsychotic medication on brain morphology in schizophrenia.

Magnetic resonance imaging (MRI) studies have shown smaller volumes of grey matter (GM) and white matter (WM) both in schizophrenia and among patients with alcohol abuse or dependence. The effect of alcohol consumption in non-clinical alcohol consumers, i.e. subjects not recruited as having alcohol use disorders is less studied. In the present study, we investigated the effects of alcohol consumption, antipsychotic medication and a diagnosis of schizophrenia on variation in brain volumes among patients recruited for having schizophrenia and a group of age and gender matched control subjects. A total of 69 patients with schizophrenia (n=56), schizoaffective disorder (n=12) and schizophreniform disorder (n=1) and 97 control subjects were included. Alcohol Use Disorder Identification Test (AUDIT) was used to estimate alcohol consumption. In the entire group of patients and controls higher AUDIT score was significantly related to smaller volumes of WM. When ten patients and six control subjects who met lifetime diagnostic criteria for alcohol use disorders were excluded only a trend level association between AUDIT score and WM volumes was found. Having a diagnosis of schizophrenia was related to smaller volumes of total, frontal and temporal WM, total and temporal GM, and larger volumes of total, frontal and temporal cerebrospinal fluid (CSF). A diagnosis of schizophrenia remained a significant factor for smaller WM volumes even when the effect of alcohol consumption was taken into account. Antipsychotic medication was related to larger volumes of temporal CSF. This study demonstrates that alcohol consumption is an important factor for variation in WM volumes, and this effect should be taken into account in all studies evaluating brain volumes from MR images.

Adult↗

PubMed2006

BDNF gene variants and brain morphology in schizophrenia.

The objective was to investigate putative associations between brain-derived neurotrophic factor gene (BDNF) polymorphisms and brain morphology in patients with schizophrenia and healthy control subjects. Four BDNF polymorphisms were genotyped and analyzed versus 39 brain volume measures in 96 patients with schizophrenia or schizoaffective disorder and 104 healthy subjects. In all subjects, quantitative data on segmented gray, white, and cerebrospinal fluid (CSF) tissue class volumes of total brain and major cerebral lobes including ventricular CSF were obtained using magnetic resonance imaging (MRI). In a randomly selected subset of this population (n = 101-122), MR volumes from cerebellar tonsil, hemispheres, and vermis subregions, striatal structures, hippocampus, and corpus callosum were also measured. The BDNF 11757 G/C polymorphism was highly significantly associated with frontal gray matter volume variation in patients alone and in patients and control subjects combined. In patients only, the 270 C/T polymorphism was associated with total caudate volume. Significant associations were demonstrated between the BDNF 11757 G/C and Val66Met polymorphisms and a global haplotype estimate of four BDNF polymorphisms and the posterior superior cerebellar vermis volume in the controls as well as in the combined group, but not in the patients. The 11757 G/C polymorphism was associated with cerebellar hemisphere white and gray matter volumes in the combined group. The BDNF -633 T/A polymorphism was associated with gray matter of the putamen in the controls. Trends for associations between several polymorphisms/haplotype estimates and MRI volumes were found. BDNF gene variation may influence brain morphology. The effects may be different in patients with schizophrenia and healthy subjects.

Adult↗

PubMed2006

Brain-derived neurotrophic factor gene (BDNF) variants and schizophrenia: an association study.

Polymorphisms in the brain-derived neurotrophic factor (BDNF) gene have been suggested to be associated with schizophrenia. In a replication attempt, Swedish patients with schizophrenia (n=187) and control subjects (n=275) were assessed for four BDNF gene polymorphisms. There were no significantly different allele, genotype or haplotype frequencies between cases or controls. Neither were there any differences when schizophrenic patients were sub-divided with regard to a number of different clinical variables, although a small group of psychotic patients with prominent affective features displayed higher frequencies of the less common alleles of the Val66Met and 11757 G/C polymorphisms compared to controls. The present Swedish results do not verify previous associations between putative functional BDNF gene polymorphisms and schizophrenia. However, when combined with previous studies meta-analyses indicated that the BDNF 270 T-allele and the Val66Met homozygous state were associated with the disorder. Thus, the BDNF gene may confer susceptibility to schizophrenia. Additional studies are warranted to shed further light on this possibility.

Adult↗

PubMed2006

Incidence and clinical presentation of IBD in children: comparison between prospective and retrospective data in a selected Norwegian population.

OBJECTIVE: The results of recent research suggest that there is an increasing incidence of inflammatory bowel disease (IBD) among children. Newly diagnosed IBD was compared between two consecutive 6-year periods in the same catchment area of southeastern Norway. MATERIAL AND METHODS: Children subjected to endoscopy from 1993 to 2004 were recorded retrospectively in the first 6-year period and prospectively for the subsequent period. The mean size of the child population under 16 years in the area was 70,500. The study reports on incidence numbers, age at diagnosis, disease distribution and clinical presentation at diagnosis. RESULTS: There were 23 incident cases of IBD in the first period and 25 in the subsequent period. The rates of Crohn's disease (CD) for the two periods were, respectively, 1.95 and 3.64, and for ulcerative colitis (UC) 3.67 and 2.05/100,000 children/year. Total incidence rates of IBD for the two periods were 5.6 and 5.7, respectively, similar to the findings of the IBSEN study of 1990-94. The change in CD and UC rates from the first to the second period can be explained by better methods of diagnosis. CONCLUSIONS: The total incidence of IBD was not changed between time periods, whereas a trend towards an increase in CD and a reduction in UC was recorded. The incidence rates are in accordance with previously reported national and international data from the past decade. The extent of disease in CD and UC may indicate a serious prognosis of IBD among children.

Child↗

PubMed2005

The influence of missing value imputation on detection of differentially expressed genes from microarray data.

MOTIVATION: Missing values are problematic for the analysis of microarray data. Imputation methods have been compared in terms of the similarity between imputed and true values in simulation experiments and not of their influence on the final analysis. The focus has been on missing at random, while entries are missing also not at random. RESULTS: We investigate the influence of imputation on the detection of differentially expressed genes from cDNA microarray data. We apply ANOVA for microarrays and SAM and look to the differentially expressed genes that are lost because of imputation. We show that this new measure provides useful information that the traditional root mean squared error cannot capture. We also show that the type of missingness matters: imputing 5% missing not at random has the same effect as imputing 10-30% missing at random. We propose a new method for imputation (LinImp), fitting a simple linear model for each channel separately, and compare it with the widely used KNNimpute method. For 10% missing at random, KNNimpute leads to twice as many lost differentially expressed genes as LinImp. AVAILABILITY: The R package for LinImp is available at http://folk.uio.no/idasch/imp.

Algorithms↗

PubMed2005

Genome-wide estimation of transcript concentrations from spotted cDNA microarray data.

A method providing absolute transcript concentrations from spotted microarray intensity data is presented. Number of transcripts per microg total RNA, mRNA or per cell, are obtained for each gene, enabling comparisons of transcript levels within and between tissues. The method is based on Bayesian statistical modelling incorporating available information about the experiment from target preparation to image analysis, leading to realistically large confidence intervals for estimated concentrations. The method was validated in experiments using transcripts at known concentrations, showing accuracy and reproducibility of estimated concentrations, which were also in excellent agreement with results from quantitative real-time PCR. We determined the concentration for 10,157 genes in cervix cancers and a pool of cancer cell lines and found values in the range of 10(5)-10(10) transcripts per microg total RNA. The precision of our estimates was sufficiently high to detect significant concentration differences between two tumours and between different genes within the same tumour, comparisons that are not possible with standard intensity ratios. Our method can be used to explore the regulation of pathways and to develop individualized therapies, based on absolute transcript concentrations. It can be applied broadly, facilitating the construction of the transcriptome, continuously updating it by integrating future data.

Bayes Theorem↗

PubMed2005

Effects of anastrozole on the intratumoral gene expression in locally advanced breast cancer.

Intratumoral levels of E1 (oestrone), E1S (oestrone sulphate) and E2 (oestradiol) are significantly reduced by treatment with the aromatase inhibitor anastrozole regardless of treatment response. The purpose of the present pilot study was to look for additional markers of biochemical response to aromatase inhibitors on mRNA expression level. Whole genome expression was studied using microarray analysis of breast cancer tissue from 12 patients with locally advanced tumors, both before and following 15 weeks of treatment with the aromatase inhibitor anastrozole (Arimidex). Intratumoral mRNA levels for a subset of genes coding for steroid metabolizing enzymes, hormone receptors and some growth mediators involved in cell cycle control were analysed by quantitative RT-PCR. There was a correlation between the two methods for some but not all genes. The mRNA expression levels of the different genes were correlated to each other and to the intratumoral levels of E1, E2 and E1S, before and after the treatment. Notably, a correlation of the E1/E2 metabolic ratio to the mRNA levels of CYP19A1 was observed before treatment (r=0.745, p<0.005). Whole genome expression analysis of these 12 breast cancer patients revealed similar tumor classification to previously published larger studies. Tumors with no or low expression of ESR1 (oestrogen receptor) clustered together and were characterized by a strong basal-like signature highly expressing keratins 5/17, cadherin 3, frizzled and apolipoprotein D, among others. The luminal epithelial tumor cluster, on the other hand, highly expressed ESR1, GATA binding protein 3 and N-acetyl transferase. An evident ERBB2 cluster was observed due to the marked over-expression of the ERBB2 gene and GRB7 and PPARBP in this patient material). Using significance analysis of microarrays (SAM), we identified 298 genes significantly differently expressed between the partial response and progressive disease groups.

Anastrozole↗

PubMed2005

Bayesian population dynamics of interacting species: great gerbils and fleas in Kazakhstan.

We propose a discrete-time Bayesian hierarchical model for the population dynamics of the great gerbil-flea ecological system. The model accounts for the sampling variability arising from data originally collected for other purposes. The prior for the unknown population densities incorporates specific biological hypotheses regarding the interacting dynamics of the two species, as well as their life cycles, where density-dependent effects are included. Posterior estimates are obtained via Markov chain Monte Carlo. The variance of the observed density estimates is a quadratic function of the unknown density. Our study indicates the presence of a density-dependent growth rate for the gerbil population. For the flea population there is clear evidence of density-dependent over-summer net growth, which is dependent on the flea-to-gerbil ratio at the beginning of the reproductive summer. Over-winter net growth is favored by high density. We estimate that on average 35% of the gerbil population survives the winter. Our study shows that hierarchical Bayesian models can be useful in extracting ecobiological information from observational data.

Animals↗

PubMed2004

Analysis of the humoral immune response to immunoselected phage-displayed peptides by a microarray-based method.

We describe a novel approach for high-throughput analysis of the immune response in cancer patients using phage-based microarray technology. The recombinant phages used for fabricating phage arrays were initially selected via the use of random peptide phage libraries and breast cancer patient serum antibodies. The peptides displayed by the phages retained their ability to be recognized by serum antibodies after immobilization. The recombinant phage microarrays were screened against either breast cancer or healthy donor serum antibodies. A model-based statistical method is proposed to estimate significant differences in serum antibody reactivity between patients and normals. A significant tumor effect was found with most of the selected phage-displayed peptides, suggesting that recombinant phage microarrays can serve as a tool in monitoring humoral responses towards phage-displayed peptides.

Amino Acid Sequence↗

PubMedDate not supplied

A genetic and spatial Bayesian analysis of mastitis resistance.

A nationwide health card recording system for dairy cattle was introduced in Norway in 1975 (the Norwegian Cattle Health Services). The data base holds information on mastitis occurrences on an individual cow basis. A reduction in mastitis frequency across the population is desired, and for this purpose risk factors are investigated. In this paper a Bayesian proportional hazards model is used for modelling the time to first veterinary treatment of clinical mastitis, including both genetic and environmental covariates. Sire effects were modelled as shared random components, and veterinary district was included as an environmental effect with prior spatial smoothing. A non-informative smoothing prior was assumed for the baseline hazard, and Markov chain Monte Carlo methods (MCMC) were used for inference. We propose a new measure of quality for sires, in terms of their posterior probability of being among the, say 10% best sires. The probability is an easily interpretable measure that can be directly used to rank sires. Estimating these complex probabilities is straightforward in an MCMC setting. The results indicate considerable differences between sires with regards to their daughters disease resistance. A regional effect was also discovered with the lowest risk of disease in the south-eastern parts of Norway.

Animals↗