Biomedical subjects

Leonard H Van den Berg

Publications and source records attributed to Leonard H Van den Berg.

5 recordsLinked to original sources

PubMed2007

The association between H63D mutations in HFE and amyotrophic lateral sclerosis in a Dutch population.

BACKGROUND: Mutations in HFE, a gene defect that can disrupt iron metabolism, have been implicated in increasing the risk of developing amyotrophic lateral sclerosis (ALS). OBJECTIVE: To further establish the association between ALS and HFE mutations by investigating whether HFE mutations are associated with an increased risk of developing ALS in a population in The Netherlands and by pooling our results with those from previous studies. DESIGN: Retrospective study. SETTING: Tertiary referral center for neuromuscular disorders. PARTICIPANTS: Genotyping for 2 common HFE mutations was performed in 289 patients with ALS and 5886 population-based controls in The Netherlands between January 1, 2000, and December 31, 2004. MAIN OUTCOME MEASURES: Development of ALS and clinical phenotype were compared among the different HFE genotypes, adjusting for known prognostic factors such as age at onset and sex. RESULTS: Homozygosity for H63D was associated with an increased risk of developing ALS (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.1-4.1). After pooling our results with those from previous studies, a positive association between H63D homozygotes (OR, 2.7; 95% CI, 1.7-4.4), heterozygotes (OR, 1.5; 95% CI, 1.0-2.1), and mutation carriers (OR, 1.7; 95% CI, 1.1-2.5) was found. Within the patient group, heterozygosity for the H63D mutation was associated with a higher age at onset. CONCLUSIONS: These findings suggest that H63D mutations in HFE play a role in the pathogenesis of ALS in various populations. This association might involve a later-onset subset of ALS.

Adult↗

PubMed2005

Multifocal motor neuropathy.

Multifocal motor neuropathy (MMN) is an immune-mediated disorder characterised by slowly progressive, asymmetrical weakness of limbs without sensory loss. The clinical presentation of MMN mimics that of lower-motor-neuron disease, but in nerve-conduction studies of patients with MMN motor-conduction block has been found. By contrast with chronic inflammatory demyelinating polyneuropathy, treatment with prednisolone and plasma exchange is generally ineffective in MMN and even associated with clinical worsening in some patients. Of the immunosuppressants, cyclophosphamide has been reported as effective but only anecdotally. Various open trials and four placebo-controlled trials have shown that treatment with high-dose intravenous immunoglobulin leads to improvement of muscle strength in patients with MMN. Although clinical, pathological, imaging, immunological, and electrophysiological studies have improved our understanding of MMN over the past 15 years, further research is needed to elucidate pathogenetic disease mechanisms in the disorder.

Clinical Trials as Topic↗

PubMed2004

The future of motor neuron disease: the challenge is in the genes.

Adult-onset motor neuron disease (MND) includes sporadic and familial forms of amyotrophic lateral sclerosis (ALS), lower motor neuron disease including progressive and segmental spinal muscular atrophy (LMND) and primary lateral sclerosis (PLS). ALS/MND can be considered to be a spectrum of neurodegenerative diseases characterised by a preferential degeneration of upper and/or lower motor neurons. ALS and LMND have a complex multifactorial aetiology and a large clinical variability. This combination warrants an increasing genomics approach in future research. Genomics is the structural and functional study of genomes--i. e. the complete set of chromosomes and the genes they contain. Several methods may help to understand gene functions, and every method has led to its own "omics". The study of the complex relationship between on the one hand genomics data, transcriptomics data, proteomics data, and interactomics data and on the other hand the phenotype, is called "phenomics". In phenomics, the extensive and detailed phenotyping by the clinician is a prerequisite for meaningful associations. As a consequence, in ALS/MND clinicians have the task to agree about different clinical subtypes in order to make these associations and hence to gain further insight into the complex pathogenesis and identification of diagnostic markers in ALS/MND. Also, several new approaches in the treatment of ALS/MND are here discussed, including the viral delivery of protective compounds, RNA-interference, and stem cell therapy. Further, we argue that a future challenge is to allow for patients to have early access to multidisciplinary centres with specialist knowledge of ALS/MND. These centres can apply specific models of care for people with ALS/MND, but must be designed in a patient-centred format. Ultimately, these models should be assessed according to their outcomes.

Forecasting↗

PubMed2003

Expansion of human gammadelta T cells after in vitro stimulation with Campylobacter jejuni.

Campylobacter jejuni is currently the prime cause of food-borne bacterial gastro-enteritis. An important complication of C. jejuni enteritis is Guillain-Barré syndrome (GBS), an immune-mediated disorder of peripheral nerve tissue. Because little is known about T cell reactivity to C. jejuni, we have analyzed the in vitro immune response of normal individuals against five isolates of C. jejuni representing five different serotypes. We found a preferential expansion of peripheral blood gammadelta T cells after exposure to crude sonicates of all five C. jejuni serotypes. Expansion of gammadelta T cells was dependent on the presence of CD4+/alphabeta+ T cells in the cultures or addition of exogenous IL-2 or IL-15. C. jejuni stimulation was mediated via the TCR and appeared to be induced by a non-proteinaceous bacterial antigen, most likely of phosphoantigenic origin.

Adjuvants, Immunologic↗

PubMed2002

Campylobacter DNA is present in circulating myelomonocytic cells of healthy persons and in persons with Guillain-Barré syndrome.

Campylobacter jejuni is the prime cause of foodborne bacterial gastroenteritis. An important complication of C. jejuni enteritis is Guillain-Barré syndrome (GBS), an immune-mediated disorder of the peripheral nerve. The presence of C. jejuni DNA in peripheral blood mononuclear cells (PBMC) of patients with GBS, patients with C. jejuni enteritis, and healthy subjects was studied. Two target genes, the flagellin and the ceuE genes, were used for polymerase chain reaction (PCR) identification of Campylobacter species in DNA extracted from PBMC. Approximately 30% of the healthy subjects and 50% of the patients with GBS had PBMC containing C. jejuni DNA as verified by Southern blot analysis or sequencing of the PCR products. Cell sorting revealed that Campylobacter DNA was present in CD14(+) and CD33(+) populations, indicating that cells from the myelomonocytic lineage are the Campylobacter DNA-carrying cells. These findings show that Campylobacter DNA is present in blood cells of healthy humans, although viable bacteria could not be demonstrated.

Campylobacter jejuni↗