Search PubMed⌕ Search

Biomedical subjects

G J te Meerman

Publications and source records attributed to G J te Meerman.

At least 19 recordsLinked to original sources
PubMed2006

CARD15 in inflammatory bowel disease and Crohn's disease phenotypes: an association study and pooled analysis.

BACKGROUND: Three major polymorphisms of the Caspase-Activation Recruitment Domain containing protein 15 gene have been described to be associated with Crohn's disease. Genotype-phenotype studies reported in literature provide conflicting data on disease localisation and behaviour. We investigated the relation of Caspase-Activation Recruitment Domain containing protein 15 with inflammatory bowel disease and Crohn's disease phenotypic characteristics in a large Dutch cohort and performed a pooled analysis on inflammatory bowel disease patients and Crohn's disease phenotypic characteristics reported in association studies. METHODS: We genotyped 781 cases and 315 controls for the R702W, G908R and 1007fsinsC variants and for six microsatellite markers in and close to Caspase-Activation Recruitment Domain containing protein 15. In the pooled analysis data of 7201 inflammatory bowel disease patients and 3720 controls from 20 studies were included. RESULTS: Association was found for Crohn's disease with R702W and 1007fsinsC, including several disease characteristics, and not for ulcerative colitis. In the pooled analysis all three common Caspase-Activation Recruitment Domain containing protein 15 variants showed strong association with Crohn's disease (p<0.00001; odds ratio varying from 3.0 for single heterozygotes to 14.7 for compound heterozygotes) and not with ulcerative colitis. Phenotype analysis showed association with small bowel involvement, stricturing and penetrating disease. CONCLUSION: Caspase-Activation Recruitment Domain containing protein 15 is associated with Crohn's disease and not with ulcerative colitis. All three common Crohn's disease-associated variants are associated with small bowel involvement, the G908R and 1007fsinsC alleles also being associated with a complicated disease course.

Adolescent↗
PubMed2006

Susceptibility to Buruli ulcer is associated with the SLC11A1 (NRAMP1) D543N polymorphism.

Similar to other mycobacterial diseases, susceptibility to Buruli ulcer (Mycobacterium ulcerans infection) may be determined by host genetic factors. We investigated the role of SLC11A1 (NRAMP1) in Buruli ulcer because of its associations with both tuberculosis and leprosy. We enrolled 182 Buruli ulcer patients (102 with positive laboratory confirmation) and 191 healthy neighbourhood-matched controls in Ghana, and studied three polymorphisms in the SLC11A1 gene: 3' UTR TGTG ins/del, D543N G/A, and INT4 G/C. Finger prick blood samples from study subjects were dried on filter papers (FTA) and processed. D543N was significantly associated with Buruli ulcer: the odds ratio (adjusted for gender, age, and region of the participant) of the GA genotype versus the GG genotype was 2.89 (95% confidence intervals (CI): 1.41-5.91). We conclude that a genetic polymorphism in the SLC11A1 gene plays a role in susceptibility to develop Buruli ulcer, with an estimated 13% population attributable risk.

Adolescent↗
PubMed2005

Genetic susceptibility to Hodgkin's lymphoma associated with the human leukocyte antigen region.

Based on the presence of an abundant inflammatory infiltrate, expression of a broad spectrum of cytokines and the professional antigen presenting phenotype of Hodgkin Reed-Sternberg cells it can be anticipated that immunological mechanisms play a major role in the pathogenesis of Hodgkin's lymphoma (HL). Genetic susceptibility to HL probably relates to functionality of the immune system and the large number of associations with the human leukocyte antigen (HLA) region in family and population-based studies supports this relation. In Epstein-Barr virus (EBV) positive HL cases, which usually demonstrate HLA class I expression, HRS cells should be able to present EBV derived antigenic peptides and trigger the immune system. This process depends on the affinity of the HLA binding groove for binding immunogenic peptides and thus on the HLA alleles. It can be anticipated that certain combinations of alleles predispose to or protect from the development of EBV positive HL. In EBV negative HL cases other antigenic peptides, related to malignant transformation, in combination with other HLA alleles may be involved. In addition, differential attraction and activation of inflammatory cells may influence HL subtype. In this article, possible roles of HLA in HL pathogenesis are explored and genetic associations of HLA with HL are reviewed and commented on.

Chromosomes, Human, Pair 6↗
PubMed2005

Analysis of the entire HLA region in susceptibility for cervical cancer: a comprehensive study.

BACKGROUND: Infection with human papillomavirus (HPV) is the main cause of cervical cancer and its precursor lesion, cervical intraepithelial neoplasia (CIN). Variability in host immunogenetic background is important in determining the overall cellular immune response to HPV infections. OBJECTIVE: To determine whether the HLA-DQ or HLA-DR genes, or others in their vicinity, are associated with cervical cancer. METHODS: Markers covering the entire HLA region were genotyped in a large sample of CIN and cervical cancer patients and in controls (311 CIN, 695 cervical cancer, 115 family controls, and 586 unrelated controls). RESULTS: Two markers were associated with susceptibility to cervical neoplasia, G511525 and MICA. G511525, close to the region containing the HLA-DQ and HLA-DR genes, was most strongly associated, showing a decrease in frequency of allele 221 from 6.7% to 3.3% in patients with squamous cell cancer (SCC). An association was found for MICA (allele 184) with SCC (odds ratio (OR) = 1.31 (95% confidence interval, 1.13 to 1.53); homozygotes, OR = 1.48 (1.06 to 2.06)). No associations were observed with adenocarcinoma or CIN. CONCLUSIONS: There is an association of the region containing the HLA-DQ and HLA-DR genes with the risk of developing squamous cell carcinoma. An increased risk was observed for carriers of allele 184 at the MICA locus, in particular for homozygotes, suggesting a recessive effect.

Adenocarcinoma↗
PubMed2004

No association between the Arg201Gly polymorphism of the DCC gene and colorectal cancer.

BACKGROUND AND AIMS: In one small study, the DCC Arg201Gly polymorphism has been observed more frequently in colorectal cancer cases compared with controls. We wondered whether these results could be replicated in a much larger study. METHODOLOGY: The DCC Arg201 Gly polymorphism was genotyped in 625 unselected Caucasian colorectal cancer patients and 220 controls. Association analysis was used to search for a difference between patients and controls. Subgroup analyses were performed for site of tumour, gender, age at diagnosis, family history of colorectal cancer and modified Dukes classification. RESULTS: The association analyses revealed no difference in Arg201Gly genotype frequency between patients and controls, neither overall nor for different subgroups according to site of tumour, gender, age at diagnosis, family history of colorectal cancer and modified Dukes classification. CONCLUSION: No association was observed between the Arg201Gly polymorphism of DCC and colorectal cancer risk.

Adult↗
PubMed2003

Immunohistochemical changes induced by repeated footshock stress: revelations of gender-based differences.

As a growing literature has proven, adverse experiences, particularly when severe and persistent, play a pivotal role in the development of neuronal dysfunctions and psychopathology. In the present study, the neurochemical changes induced by acute and repeated footshock exposure were investigated at the molecular and cellular level, using c-fos and phospho-ERK1/2 immunoreactivity and gene expression arrays. Marked gender-related differences were found following both acute and prolonged footshock exposure. Acute aversive conditioning resulted in significant immunohistochemical changes that might be critically involved in the modulation of fear-related responses, especially in males. Prolonged footshock exposure, on the contrary, was associated with sustained hypothalamic-pituitary-adrenal axis hyperactivity, differential gender-related patterns of cortical-limbic activity, and abnormal neuronal plasticity, especially in medial prefrontocortical regions. These data may provide additional insights into the understanding of the neural circuits underlying the effects of acute and repeated footshock exposure as well as clarify some of the mechanisms involved in the development of stress-related neuronal abnormalities.

Animals↗
PubMed2003

IBD and genetics: new developments.

BACKGROUND: Inflammatory bowel disease (IBD) is a complex disorder with an aetiology that is only partly understood. Apart from environmental factors, inheritance contributes to IBD. REVIEW: Family studies show an increased risk among family members of a patient with IBD, particularly among first-degree relatives. In twin studies, concordance for disease type and localization is observed. In genetically isolated groups there is a higher prevalence of IBD. For instance. Ashkenazi Jews carry the highest risk. Further evidence comes from animal species that spontaneously develop IBD. Unlike Mendelian inheritance, in complex genetic diseases like IBD, genes are expected to be low penetrant and therefore less prone to selection, which results in higher expected gene frequencies. NOD2/CARD15, the first gene associated with IBD, is a polymorphic gene involved in the innate immune system. The gene has over 60 variations. Three of these play a role in 27% of patients with CD, with a predilection for patients with ileal disease. CONCLUSION: Genetics plays an important role in unravelling the pathogenesis of IBD leading to possible new therapeutic approaches.

Carrier Proteins↗
PubMed2002

Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility.

This review focuses on genes other than the high penetrance genes BRCA1 and BRCA2 that are involved in breast cancer susceptibility. The goal of this review is the discovery of polymorphisms that are either associated with breast cancer or that are in strong linkage disequilibrium with breast cancer causing variants. An association with breast cancer at a 5% significance level was found for 13 polymorphisms in 10 genes described in more than one breast cancer study. Our data will help focus on the further analysis of genetic polymorphisms in populations of appropriate size, and especially on the combinations of such polymorphisms. This will facilitate determination of population attributable risks, understanding of gene-gene interactions, and improving estimates of genetic cancer risks.

Ataxia Telangiectasia↗
PubMed2001

Haplotype sharing tests of linkage disequilibrium in a Hutterite asthma data set.

The Genetic Analysis Workshop 12 genome scan data set for "strict" asthma in a Hutterite population was analyzed using haplotype sharing analysis (HSA), which tests for differences in mean length of haplotype sharing around each marker for pairs of chromosomes in cases versus controls. The regions of chromosome 1 and 8 where evidence for linkage was observed in published analyses were negative by HSA. HSA yielded positive results on chromosomes 7, 12, 16, 18, and 21 (p = 0.003 on 21q). Although there are reports of support for linkage to asthma in some of these regions, it is not known whether any represent true positives. Further study is needed of the possible role of length-based measures of linkage disequilibrium in recent population isolates.

Adult↗
PubMed2001

Mapping of a susceptibility gene for multiple sclerosis to the 51 kb interval between G511525 and D6S1666 using a new method of haplotype sharing analysis.

Multiple sclerosis (MS) is a complex disease that is partly genetic in origin. Although an association of MS with specific human leukocyte antigen (HLA) types has been known for almost 30 years, the nature of this relationship has remained unclear. Furthermore, genetic resolution sufficient to implicate a specific gene in the HLA region has not been achieved. Many loci in the HLA region have been found to be significantly associated with MS, which is largely explained by the extended haplotype sharing and varying marker informativity of the region. We have determined 248 haplotypes of MS patients from the population of the northern Netherlands and 226 haplotypes of their relatives as controls using a set of 22 microsatellite markers covering the HLA region. The data were analyzed using standard association methods and a new statistical method, haplotype sharing statistics (HSS). Haplotype sharing statistics determines the extent of haplotype sharing for all pairs of haplotypes of patients and of controls and calculates the difference in mean haplotype sharing between patients and controls. Haplotype sharing was found to be significantly greater among patients than among controls in a region of 1.1 Mb between markers G511525 and TNFalpha. The involvement of this region is also supported by association analysis and the transmission/disequilibrium test (TDT). Within this region, HSS, which is largely independent of association and TDT, indicated the interval of 51 kb between G511525 and D6S1666 as that most likely to contain a susceptibility gene for MS. As DQB1 is the sole gene known in this interval at present, the results of our analysis suggest that this gene plays a role in the pathogenesis of MS.

Cluster Analysis↗
PubMed2001

Susceptibility to development of Mycobacterium ulcerans disease: review of possible risk factors.

Mycobacterium ulcerans disease, also known as Buruli ulcer (BU), is a disease of subcutaneous fat tissue. BU is prevalent in riverine and swamp areas of the tropical zone in Africa, Asia and South America, and a few scattered foci in Australia. The mode of transmission of M. ulcerans has not been fully elucidated, but inoculation into the subcutaneous tissues probably occurs through penetrating skin trauma. BU has not been linked with HIV infection. Antimycobacterial drug treatment is ineffective, and treatment is surgical. Patients eventually develop scars and contractures, with resulting disabilities, and the disease imposes a large burden on affected populations. The incidence of BU has dramatically increased in West African countries over the last decade. There is an urgent need for research into host and environmental risk factors for BU in order to develop effective strategies to combat this disease. We review possible genetic host susceptibility factors for BU that are relevant in other mycobacterial diseases: natural resistance-associated macrophage protein-1 (NRAMP-1), HLA-DR, vitamin D3 receptor, mannose binding protein, interferon-gamma (IFN-gamma) receptor, tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1 alpha, 1 beta and their receptor antagonists; and IL-12. Schistosoma haematobium infection is highly endemic in many BU foci in West Africa, with a striking increase in transmission after river dams were constructed. This observation, and the observations from interaction of schistosomiasis and tuberculosis, have fueled our hypothesis that schistosomiasis is a risk factor for BU by driving the host immune response towards a predominantly Th-2 pattern, away from a Th-1 preponderant protection against mycobacterial infection. If the latter hypothesis is confirmed, enhanced schistosomiasis control should impact on BU.

Carrier Proteins↗
PubMed2000

Observer reliability in assessment of mitotic activity and MIB-1-determined proliferation rate in pediatric sarcomas.

In hematoxylin-eosin-stained sections of 20 pediatric sarcomas the mitotic index was assessed by four experienced pathologists and four less-experienced observers without prior instructions. In adjacent sections immunolabeled for MIB-1, the proliferation index was assessed as the estimated percentage of labeled cells in the tumor cell population. ANOVA revealed that the variation between tumors explained 77% of the variation in mitotic indices in the group of experienced observers compared with 49% in the less experienced group. The variation between tumors explained 64% of the variation in proliferation indices in the experienced group and 71% in the less experienced group. The proliferation indices showed less variation between observers than the mitotic indices. No correlation was found between mitotic and proliferation indices. The results suggest that training is an important factor in the reliability of mitotic counting. The use of proliferation markers has a higher reproducibility, especially in less-experienced observers. However, for clinical use it has the disadvantage of being the more expensive, more time-consuming technique; moreover, the biological significance of proliferation has not been established and may differ from that of mitotic activity.

Adolescent↗
PubMed1999

Computer-assisted cytogenetic analysis of 51 malignant peripheral-nerve-sheath tumors: sporadic vs. neurofibromatosis-type-1-associated malignant schwannomas.

Cytogenetic studies in small groups of patients with malignant peripheral-nerve-sheath tumors (MPNST) revealed complex karyotypes with no consistent changes. A computer-assisted cytogenetic analysis using a cytogenetic database was performed to determine recurrent cytogenetic alterations in 51 MPNSTs (44 from the literature and 7 new cases) and to allow direct cytogenetic comparison between NF-1-associated and sporadic MPNSTs. Significant loss (p < 0.05) was observed in the chromosomal regions 9p2, 11p1, 11q2 and 18p1. Also, loss in 1p3, 9p1, 11q1, 12q2, 17p1, 18q1-q2, 19p1, 22q1, X and Y was detected. Gain of chromosomal material was found in chromosome 7, especially 7q1 (p < 0.05). Most involved breakpoints were: 1p13, 1q21, 7p22, 9p11, 17p11, 17q11, 22q11. Cytogenetic differences between NF-1-associated and sporadic MPNSTs included a relative loss of chromosomal material in NF-1-associated MPNSTs in 1p3, 4p1 and 21p1-q2 and a relative gain in 15p1-q1. Differences in breakpoints between the NF-1 associated and the sporadic MPNST group were observed in 1p21-22 (28% of NF-1 vs. 0% of sporadic MPNSTs), 1p32-34 (17% vs. 0%), 8p11-12 (7% vs. 27%) and 17q10-12 (24% vs. 7%). This approach, in which the cytogenetic results of various reports are combined, shows that losses in 9p2 and gains in 7q1 could be of oncogenetic importance in MPNSTs. Loss of 17q1, on which the NF-1 gene has been located (17q11.2), is not a common cytogenetic finding in NF-1-associated MPNSTs. The observed differences between NF-1-associated and sporadic MPNSTs might reflect different oncogenetic pathways.

Adolescent↗
PubMed1999

Difference in volume of X- and Y-chromosome-bearing bovine sperm heads matches difference in DNA content.

BACKGROUND: To investigate the possibilities of sperm head volume as a sorting criterion for gender preselection, we determined the magnitude of the difference in volume of X- and Y-chromosome-bearing bull sperm heads. MATERIALS AND METHODS: Bovine sperm heads were sorted on the basis of their DNA content in X- and Y-chromosome-bearing fractions, using an existing flow-cytometric technique. Images of sperm heads of both populations were recorded using Differential Interference Contrast (DIC) microscopy. After reconstructing the DIC images, the area and the optical thickness of sperm heads of both populations were determined. RESULTS: We found a difference in volume of X- and Y-bearing bovine sperm heads matching the difference in DNA content (3.5-4%). CONCLUSIONS: Our findings indicate that volume can be used as a criterion to distinguish X- and Y-chromosome-bearing sperm, making development of a technique to sort X- and Y-chromosome-bearing sperm based on head volume theoretically possible. A strong advantage of such a technique over the existing technique based on DNA content would be that X- and Y-chromosome-bearing sperm cells could thus be sorted without subjecting them to any staining.

Animals↗
PubMed1999

Difference in sperm head volume as a theoretical basis for sorting X- and Y-bearing spermatozoa: potentials and limitations.

Volume-based sorting of X- and Y-chromosome-bearing sperm cells could be an interesting alternative to the existing technique based on DNA content. Advantages would be that DNA staining and ultraviolet excitation, used in the existing technique, could be avoided. To assess the possibilities and limitations of sperm-head volume as sorting criterion, achievable purity and yield are determined for bull sperm. Two important parameters in this respect are the magnitude of the volume difference and the biological variation within each (X or Y) population. Earlier, we established a difference in volume matching the difference in DNA content (3.8%) between X- and Y-bearing bull sperm heads by comparing thicknesses and areas of high numbers of pre-sorted X- and Y-bearing bull sperm heads by interference microscopy and subsequent image analysis. Unfortunately, despite the high number of measurements, a direct determination of biological variations was not possible due to an unknown contribution of instrumental variations. In this paper, we determine the contribution of instrumental errors by measuring a single sperm head, varying parameters such as location in the image, orientation angle, focusing etc., simulating the behavior of the measuring system. After correction, both for the instrumental variation, and for the fact that the original samples were not pure, biological variations in volume of 5.9 +/- 0.8% were found. Our results indicate that when 10% of the bull sperm are sorted on basis of their head volume, a theoretical enrichment of 80% could be achieved. Expected purity and yield are lower than what is standard for the existing technique. At the moment, a technique to physically separate X- and Y-bearing sperm cells based on volume is not available. However, for applications for which the potential hazards of DNA staining and UV excitation are problematic, the development of such technique should be considered.

Algorithms↗