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F Baas

Publications and source records attributed to F Baas.

At least 19 recordsLinked to original sources
PubMed2006

Distal myoclonus and late onset in a large Dutch family with myoclonus-dystonia.

We report a large myoclonus-dystonia (M-D) pedigree with a two-base pair deletion in Exon 5 of the epsilon-sarcoglycan gene. Three individuals had onset after age 40 years. Distal myoclonus of the arms was present in all 20 symptomatic mutation carriers. These findings expand the known phenotype of M-D and require revision of the current diagnostic criteria. Five of 14 asymptomatic mutation carriers who inherited the mutation from their mother showed minimal axial dystonia, arguing against a maternal imprinting mechanism.

Adolescent↗
PubMed2006

Results from an in vitro and a clinical/pharmacological phase I study with the combination irinotecan and sorafenib.

PURPOSE: This single-centre, open-label, phase I dose-escalation study was performed to investigate the safety, pharmacokinetics (PK) and efficacy of sorafenib, a multi-kinase inhibitor, combined with irinotecan, a cytotoxic agent, in patients with advanced, refractory solid tumours. PATIENTS AND METHODS: In an initial dose-escalation phase, patients received irinotecan 125 mg/m(2) and sorafenib 100, 200 and 400 mg twice daily (bid) (cohorts 1-3). In an extended phase, colorectal cancer (CRC) patients received fixed-dose irinotecan 140 mg and sorafenib 400 mg bid (cohort 4). RESULTS: Thirty-four patients were treated: 20 in the dose-escalation phase (common tumour types: CRC [45%], ovarian [5%], pancreatic [5%]) and 14 patients in the CRC extension. Frequent drug-related adverse events were gastrointestinal symptoms, dermatological reactions and constitutional symptoms. The maximum tolerated dose was not reached. Generally, concomitant administration of irinotecan had no impact on the PK of sorafenib. Sorafenib 100 or 200 mg bid had no impact on the PK of irinotecan or its metabolite SN38. In contrast, sorafenib 400 mg bid significantly increased irinotecan and SN38 exposures; however, this was not associated with increased toxicities. Stable disease was achieved in 12/20 (60%) evaluable patients in cohorts 1-3, and 10/13 (77%) evaluable patients in cohort 4. A further patient from cohort 4 had a partial response of >200 days. The increase of SN38 exposure might be due to inhibition of formation of the SN38 glucuronide by sorafenib. In vitro, sorafenib strongly inhibited SN38 glucuronidation in human liver microsomes as indicated by a K(i) value of 2.7 micromol/l. CONCLUSION: Sorafenib 400 mg bid can be combined with irinotecan 125 mg/m(2) or 140 mg for the treatment of patients with advanced, refractory solid tumours, although monitoring for toxicity is recommended.

Adult↗
PubMed2006

Charcot-Marie-Tooth disease due to a de novo mutation of the RAB7 gene.

We report a 32-year-old patient with Charcot-Marie-Tooth (CMT2B) including foot ulcerations. Genetic analysis identified a de novo mutation in the small GTP-ase late endosomal RAB7 gene, consisting of a c.471G>C, p.Lys157Asn missense mutation. This observation strongly supports the hypothesis that RAB7 mutations are responsible for CMT2B.

Acyltransferases↗
PubMed2006

Phenotype-genotype correlation in Dutch patients with myoclonus-dystonia.

The epsilon-sarcoglycan (SGCE) gene is an important cause of myoclonus-dystonia (M-D), although the majority of cases with an M-D phenotype test negative. Seven of 31 patients with the M-D phenotype carried a mutation in the SGCE gene. Positive family history and truncal myoclonus were independent prognostic factors. Early disease onset, onset with both myoclonus and dystonia, and axial dystonia were detected significantly more often in the mutation carriers.

Age of Onset↗
PubMed2006

Late onset axonal Charcot-Marie-Tooth phenotype caused by a novel myelin protein zero mutation.

A late onset axonal Charcot-Marie-Tooth phenotype is described, resulting from a novel mutation in the myelin protein zero (MPZ) gene. Comparative computer modelling of the three dimensional structure of the MPZ protein predicts that this mutation does not cause a significant structural change. The primary axonal disease process in these patients points to a function of MPZ in maintenance of the myelinated axons, apart from securing stability of the myelin layer.

Adult↗
PubMed2006

Always around, never the same: pathways of amyloid beta induced neurodegeneration throughout the pathogenic cascade of Alzheimer's disease.

There is an increasing amount of evidence showing the importance of intermediate aggregation species of amyloid beta (Abeta) in the pathogenic cascade of Alzheimer's disease (AD). Different Abeta assembly forms may mediate diverse toxic effects at different stages of the disease. Mouse models for AD suggest that intraneuronal accumulation of Abeta oligomers might be involved in AD pathogenesis at a very early stage of the disease. The detrimental effect of oligomeric Abeta on synaptic efficacy is suggested to be an early event in the pathogenic cascade. Also early neuronal responses as activation of the unfolded protein response are processes likely to be associated with the increased occurrence of oligomeric or low fibrillar Abeta in AD pathology. In later stages of AD pathology, the fibrillarity of Abeta increases, concomitantly with a neuroinflammatory response, followed by tau related neurofibrillary changes in end stage pathology. We will review recent findings in in vitro cell models, in vivo mouse models, and post mortem AD brain tissue in view of the effects of different Abeta peptide species on neurodegeneration during AD pathogenesis. Insight into the role of different Abeta species during AD pathogenesis is essential for the development of disease modifying drugs and therapeutical strategies.

Alzheimer Disease↗
PubMed2005

Lack of association between VEGF polymorphisms and ALS in a Dutch population.

Sequence alterations in the promoter region of the vascular endothelial growth factor (VEGF) gene have been implicated in increasing the risk of developing ALS. VEGF promoter haplotypes were determined in 373 patients with sporadic ALS and 615 matched healthy controls in The Netherlands. No significant association between the previously reported at-risk haplotypes and ALS was found. Pooling our results with the previously studied population still showed a significant association with the AAG haplotype.

Adult↗
PubMed2005

[From gene to disease; Charcot-Marie-Tooth disease or the hereditary motor and sensory neuropathies].

Charcot-Marie-Tooth disease is a clinically and genetically heterogeneous group of inherited neuropathies. The common clinical symptoms include distal muscle weakness, wasting and impaired distal sensation, more in the legs than in the arms, and reduced or absent reflexes. Moreover, foot and hand deformities are often encountered. A distinction between a primarily demyelinating or axonal neuropathy is often possible by means of nerve conduction studies. The major groups of inheritance are the autosomal dominant CMT1 (demyelinating), CMT2 (axonal) and the X-linked type (CMTX), but there are also autosomal recessive demyelinating (CMT4) and axonal (AR-CMT2) forms. The number of genes and loci is steadily increasing, with genes encoding proteins involved in myelin maintenance and axonal function, but also with genes encoding proteins, the function of which in peripheral nerve maintenance is notyet clear. Despite the increase in the number of known genes, especially for CMT2, there are many patients in whom no mutation can yet be found.

Charcot-Marie-Tooth Disease↗
PubMed2005

The unfolded protein response is activated in Alzheimer's disease.

Alzheimer's disease (AD) is, at the neuropathological level, characterized by the accumulation and aggregation of misfolded proteins. The presence of misfolded proteins in the endoplasmic reticulum (ER) triggers a cellular stress response called the unfolded protein response (UPR) that may protect the cell against the toxic buildup of misfolded proteins. In this study we investigated the activation of the UPR in AD. Protein levels of BiP/GRP78, a molecular chaperone which is up-regulated during the UPR, was found to be increased in AD temporal cortex and hippocampus as determined by Western blot analysis. At the immunohistochemical level intensified staining of BiP/GRP78 was observed in AD, which did not co-localize with AT8-positive neurofibrillary tangles. In addition, we performed immunohistochemistry for phosphorylated (activated) pancreatic ER kinase (p-PERK), an ER kinase which is activated during the UPR. p-PERK was observed in neurons in AD patients, but not in non-demented control cases and did not co-localize with AT8-positive tangles. Overall, these data show that the UPR is activated in AD, and the increased occurrence of BiP/GRP78 and p-PERK in cytologically normal-appearing neurons suggest a role for the UPR early in AD neurodegeneration. Although the initial participation of the UPR in AD pathogenesis might be neuroprotective, sustained activation of the UPR in AD might initiate or mediate neurodegeneration.

Adult↗
PubMed2004

[From gene to disease: amyotrophic lateral sclerosis].

Amyotrophic lateral sclerosis is a progressive neurological disorder. It is characterised by selective motor-neuron degeneration in the cortex, brainstem, and spinal cord. Consequently, patients suffer from muscle weakness and usually die within 3-5 years after diagnosis from respiratory insufficiency. About 5-10% of the patients have a family history of ALS, the remaining are classified as sporadic ALS. There is only limited information about genetic susceptibility factors in sporadic ALS. Some patients with familial ALS have mutations in the gene encoding for copper/zinc superoxide dismutase, a protein involved in scavenging superoxide radicals. This results in a toxic gain of function. Mutations in the gene coding for alsin, ALS2, have been shown to be responsible for an autosomal recessive form of juvenile ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2004

Plasminogen activator inhibitor-1 4G allele in the 4G/5G promoter polymorphism increases the occurrence of cerebral ischemia after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: In several acute life-threatening diseases, the 4G-allele in the 4G/5G-promotor polymorphism in the plasminogen activator inhibitor-1 (PAI-1) gene is associated with higher PAI-1 levels and increased poor outcome, probably by promoting the formation of microthrombi. The aim of the present study was to investigate whether the PAI-1 4G/5G polymorphism is associated with the occurrence of cerebral ischemia, rebleeding, and other events, and clinical outcome after aneurysmal subarachnoid hemorrhage. METHODS: DNA was collected and analyzed in 126 patients with aneurysmal subarachnoid hemorrhage admitted to the Academic Medical Centre Amsterdam and University Medical Centre Utrecht in the Netherlands. All episodes of deterioration were classified according to predefined criteria. Causes of poor outcome and functional outcome were assessed 3 months after the initial bleeding according to the 5-point Glasgow Outcome Scale (GOS). RESULTS: Secondary ischemia occurred more often in patients with the 4G genotype than in patients homozygous for the 5G allele (RR: 3.3; 95% CI: 1.1 to 10.0). No significant differences were found between the groups for rebleeding or other events. Patients with the 4G genotype tended to have a higher risk for poor outcome than patients with the 5G/5G genotype (RR 1.2; 95% CI 0.7 to 2.2). CONCLUSIONS: The 4G allele in the PAI-1 gene increases the risk for cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH) and probably also the risk for poor outcome. After early aneurysm occlusion, treatment aimed at enhancing fibrinolysis might be effective to prevent and treat cerebral ischemia in patients with aneurysmal SAH.

Alleles↗
PubMed2004

Hereditary motor and sensory neuropathy (HMSN) IA, developmental delay and autism related disorder in a boy with duplication (17)(p11.2p12).

We present a 6-year-old boy with moderate developmental delay, gait disturbance, autism related disorder and mild dysmorphic features. He was seen for evaluation of his retardation since the age of 2.8 years. At first sight, a cytogenetic analysis showed a normal 46,XY karyotype. Neurological examination at the age of 5.5 years revealed a motor and sensory polyneuropathy. A quantitative Southern blot with probes PMP22 and VAW409 specific for Charcot-Marie-Tooth type 1 (CMT1) disclosed a duplication which confirmed the diagnosis HMSN Ia. Subsequently, GTG banded metaphases were re-evaluated and a small duplication 17p was seen on retrospect. Additional FISH with probe LSISMS (Vysis) specific for the Smith-Magenis region at 17p11.2 again showed a duplication. Both parents had a normal karyotype and the duplication test for CMT1 showed normal results for both of them. The boy had a de novo 46,XY,dup(17)(p11.2p12) karyotype. The present observation confirms previous findings of mild psychomotor delay, neurobehavioural features and minor craniofacial anomalies as the major phenotypic features of dup(17)(p11.2) and dup(17)(p11.2p12); in cases of duplications comprising the PMP22 locus HMSN1 is associated. A recognizable facial phenotype emerges characterized by a broad forehead, hypertelorism, downslant of palpebral fissures, smooth philtrum, thin upper lip and ear anomalies.

Autistic Disorder↗
PubMed2003

Killing cancer by targeting genes that cancer cells have lost: allele-specific inhibition, a novel approach to the treatment of genetic disorders.

Oligonucleotide-based drugs are now rapidly establishing themselves as an important tool in both research and treatment of genetic disorders. In the past many problems were encountered in using antisense oligonucleotides. Our expanding knowledge and new oligonucleotide chemistries are giving us the chance to treat serious genetic disorders such as cancer in novel, elegant and effective ways not previously possible. In addition, recent knowledge about RNA interference may add to these new approaches for disease treatment with oligonucleotide-based drugs. In this review we discuss one such novel therapeutic strategy against cancer called allele-specific inhibition (ASI). ASI is an approach where cancer cells are attacked at one of the few widely occurring and consistently weak points: the loss of large segments of DNA. Oligonucleotide-based drugs may provide the required selectivity for this therapeutic approach.

Alleles↗
PubMed2002

Two amino-acid substitutions in the myelin protein zero gene of a case of Charcot-Marie-Tooth disease associated with light-near dissociation.

Charcot-Marie-Tooth disease caused by mutations of the myelin protein zero gene demonstrates considerable phenotypical variability. We describe a 45-year-old female with a peripheral neuropathy with demyelinating and axonal features, pes cavus and pupillary light-near dissociation. She was heterozygous for two mutations in the myelin protein zero gene (His81Tyr and Val113Phe), both present on the same allele. Our patient shows a less severe phenotype than previously described patients with a His81Arg mutation. Multiple mutations in the myelin protein zero gene, as well as Charcot-Marie-Tooth with pupillary abnormalities have previously been described in rare instances. However, concurrent occurrence of both phenomena is a novel finding.

Adult↗
PubMed2001

cAMP is involved in the differentiation of human teratocarcinoma cells.

The generation of fully differentiated post-mitotic human neuronal cells from stem cells (human teratocarcinoma (hNT2) cells) might enable the development of a co-culture model of human neurons with human Schwann cells (SCs). This co-culture model is an important tool to study formation of myelin sheaths. However, the thin process of the post-mitotic human neuronal cells formed under known culture conditions do not provide a good substrate for human SCs to start myelination. We optimized the culture conditions of these cells to obtain axons with a larger diameter. Western blotting and immunofluorescence studies were performed to confirm the neuronal status of the cells and diameter of the processes. In this study, we show that addition of cAMP-inducing factors to hNT2 cells resulted in rapid morphological changes including the development of processes with a larger diameter.

1-Methyl-3-isobutylxanthine↗
PubMed2001

GOA, a novel gene encoding a ring finger B-box coiled-coil protein, is overexpressed in astrocytoma.

Serial analysis of gene expression (SAGE) was used to identify a gene named GOA (gene overexpressed in astrocytoma), which codes for a novel Ring finger B-box coiled-coil (RBCC) protein. Northern blot hybridization showed overexpression of GOA in 9 of 10 astrocytomas. Except for kidney, in which high expression was found, expression levels in normal tissues were low and comparable to normal brain. Immunohistochemistry demonstrated presence of GOA, with prominent nuclear staining, in astrocytoma tumor cells and astrocytes of fetal brain, but virtual absence in mature astrocytes. Overexpression was not due to amplification, since amplification of GOA was only found in one of 65 astrocytomas. GOA was localized to 17q24-25, a region that is frequently gained or amplified in a number of other tumor types. GOA contains two LXXLL motifs, which are thought to be important for nuclear receptor binding. Our data suggest an important role of GOA in the process of dedifferentiation that is associated with astrocytoma tumorigenesis and possibly with that of other tumor types as well.

Amino Acid Motifs↗
PubMed2001

[Clinical algorithm for cerebrospinal fluid test of 14-3-3 protein in diagnosis of Creutzfeldt-Jacob disease].

OBJECTIVE: To study whether an algorithm that includes additional diagnostic information could increase the specificity of the 14-3-3 protein testing in patients suspected to suffer from Creutzfeldt-Jakob disease (CJD). DESIGN: The development of a diagnostic algorithm. METHOD: The 14-3-3 protein was tested in the cerebrospinal fluid from 69 consecutive patients suspected of having CJD. On the basis of a former study and literature research, a diagnostic algorithm was constructed, which restricted the indication for performing the 14-3-3 protein test. RESULTS: By taking into consideration the findings of neuroimaging and routine cerebrospinal fluid examination prior to 14-3-3 testing, the specificity increased to 97% (95%-CI: 85.5-99.9) thus changing the prior probability of having CJD of 35% to a posterior probability of 75-100%, in the case of a positive test result. CONCLUSION: Determining the presence of 14-3-3 protein is a highly sensitive and specific marker for sporadic CJD when used in combination with imaging and cerebrospinal fluid examination.

14-3-3 Proteins↗