Biomedical subjects

Christian Søborg

Publications and source records attributed to Christian Søborg.

5 recordsLinked to original sources

PubMed2006

Influence of candidate susceptibility genes on tuberculosis in a high endemic region.

Genetic susceptibility towards clinical tuberculosis has been proposed in several population studies. We investigated whether polymorphisms in the candidate genes encoding solute carrier 11a1 protein (SLC11A1 formerly NRAMP1), mannose-binding lectin (MBL2) and Vitamin D receptor (VDR) were associated with tuberculosis in an East-African setting. Four hundred and forty-three culture positive pulmonary tuberculosis patients and 426 controls from Mwanza district in the northern part of Tanzania were prospectively included. Polymorphisms in the candidate genes were detected by different PCR-based techniques. A significant association between pulmonary tuberculosis and a microsatellite marker in the 5'(CA)n locus in the SLC11A1 gene compared with controls (38% versus 30% odds ratio 1.45, 95% CI: 1.06-1.9, P=0.014) was observed. The association was apparent only in HIV negative tuberculosis patients. No association with tuberculosis was seen with 3 other SLC11A1 loci investigated, which previously have been associated with tuberculosis in other populations or with MBL2 and VDR polymorphisms. The tuberculosis associated microsatellite marker was situated on different SLC11A1 haplotypes. In this cohort a microsatellite marker in the 5'(CA)n locus situated in the SLC11A1 gene was associated with tuberculosis. The observed association was seen only in HIV negative patients suggesting that this genetic susceptibility for tuberculosis may be surpassed by co-infections.

Adolescent↗

PubMed2005

Increased volume of the pigmented neurons in the locus coeruleus of schizophrenic subjects: a stereological study.

The locus coeruleus is the largest cluster of noradrenaline-producing neurons in the brain and has been involved in regulating attention. The neurotransmitter system contributes to the initiation and maintenance of forebrain activity as well as modulation of the collection and processing of sensory information. This makes locus coeruleus a target of interest in the study of possible structural changes in the brains of subjects with chronic schizophrenia. Uniform sampling and optical disectors were used for estimation of total neuron numbers and the rotator principle for estimation of mean cell volume. This study estimated the bilateral total number of pigmented neurons in the locus coeruleus of schizophrenic and control subjects and found no difference between the two; schizophrenic subjects have 37,400 (coefficient of variation=CV=SD/mean=0.28), control subjects have 35,500 (CV=0.19), p=0.64. The average volume of the cell perikaryon of pigmented neurons was measured in both groups and showed a significant larger cell volume in the locus coeruleus of schizophrenic compared to control subjects; mean locus coeruleus cell volume was 58,400 microm(3) (CV=0.31) in schizophrenic subjects, which is 55% larger than the 37,600 microm(3) (CV=0.33) found in control subjects, a difference of 20,800 microm(3) (p=0.009). The fixation time was significantly longer for the schizophrenic brains with an average of 169 months compared to 88 months for the control brains. No relation was found between total numbers or geometric mean volume of the pigmented cells and fixation time.

Adult↗

PubMed2003

Mannose-binding lectin polymorphisms in clinical tuberculosis.

Mannose-binding lectin (MBL) mediates protection against infections by using the complement system, but certain microorganisms may increase infectivity by exploiting this host defense system. Thus, it has been speculated whether genetically determined low MBL levels may confer partial protection against certain intracellular microorganisms, such as Mycobacterium tuberculosis. We investigated MBL alleles in 109 culture-positive human immunodeficiency virus-uninfected patients with tuberculosis living in Denmark and 250 white control subjects. Patients and control subjects were divided into 3 different groups defined by undetectable, low, and high serum MBL concentrations, which correlates to deficient, low, and high expressing MBL genotypes. A significantly decreased frequency of patients with the low-expressing MBL genotype was observed in white patients compared to control subjects. The same tendency also was observed in patients of other ethnic origin. It may be hypothesized that heterozygosity for MBL variant alleles, which encodes low serum MBL levels, is associated with protection against clinical tuberculosis.

Adult↗

PubMed2003

[Tuberculosis and molecular biology].

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB) hunting millions worldwide, is a challenge to work with in the laboratory. Modern molecular biology has provided extremely useful tools which have changed conventional diagnostic procedures in the TB laboratories. Research in molecular epidemiology is currently expanding our knowledge of the natural history of TB. Access to the genome sequence has opened new avenues for research in drug development and new vaccines. However, we are still awaiting the impact of these efforts in the resource-poor TB endemic countries.

Genetic Techniques↗

PubMed2002

Natural resistance-associated macrophage protein 1 polymorphisms are associated with microscopy-positive tuberculosis.

The natural resistance-associated macrophage protein 1 (NRAMP1) is implicated in the pathophysiology of mycobacterial infections. We investigated by polymerase chain reaction previously published Nramp1 genotypes at 4 loci-INT4, N543D, 3'UTR, and 5'(CA)(n) microsatellite markers-in 104 human immunodeficiency virus-negative patients with tuberculosis and 176 healthy control subjects living in Denmark. No significant difference in genotype frequency was found between white patients with tuberculosis and control subjects (P>.16), but carriage of Nramp1 variant alleles at loci INT4 and 5'(CA)(n) conferred a significantly increased risk of having microscopy-positive compared with microscopy-negative tuberculosis (65% vs. 35% [P=.0004] and 63% vs. 38% [P=.047], respectively). The Nramp1 alleles were not associated with increased risk for the development of cavities seen on chest radiographs, or with extrapulmonary tuberculosis. These results indicate that variant alleles in the Nramp1 gene are associated with increased mycobacterial replication rather than susceptibility for tuberculosis and may thus confer increased risk of severe disease.

Adult↗