Fucosidosis: four new mutations and a new polymorphism

Fucosidosis is a rare lysosomal storage disease due to a nearlycomplete deficiency of -L-fucosidase (EC 3.2.1.51 [EC] ). In thisstudy, all 8 exons of the -L-fucosidase structural gene (FUCA-1)were amplified by PCR methods, and the amplified products weresubcloned and sequenced. Five patient groups with fucosidosiswere selected according to their ethnic backgrounds and haplotypesfor RFLPs in FUCA-1. Four presumptive disease causing mutationswere detected: 1) A major deletion of DNA containing the lasttwo exons of FUCA-1 in two Algerian siblings. 2) A G to T mutationin exon 6 resulting in an in-frame termination codon (E375X)in eight Hispanic patients from Colorado and New Mexico. 3)A G to A mutation (G60D) in exon 1 in four Italian patientsand in three related French-American (Cajun) patients. ThisG60D mutation creates a unique site for Afl III. 4) A frameshiftmutation resulted from a two-base deletion in exon 2 (K151fs)in an Italian patient. This deletion obliterates a unique BstXIsite and creates a new BpmI site, and was found in only thispatient and in only one allele. The rationale for proposingthese defects as disease causing mutations includes pedigreeanalysis and the predicted consequences of each defect uponthe activity and the concentration of the enzyme. An A to Gtransition (Q281R) in exon 5 was found to be present in homozygousform in affected patients and also in normal subjects; it appearsto be a newly identified polymorphism. It causes a charge changeand may be responsible for the electrophoretic variant phenotypeof fucosidosis. This polymorphism is inherited concordant withthe RFLP PvuII—BglI haplotype 2 – 2, 2 – 2.The 4 new mutations identified here comprise 70% of allelesof the 25 fucosidosis patients in our study.     

Pharmacological Profile of the Vascular Responses to Dopamine in the Canine External Carotid Circulation*

Abstract: The present study investigated the effects of dopamine on the canine external carotid circulation. One min. intracarotid artery (i.c.) infusions of dopamine (10–310 μg min.^?1) produced dose‐dependent decreases in the canine external carotid conductance without affecting blood pressure or heart rate. This effect was mimicked by the D_1/2‐like receptor agonist apomorphine (1–310 μg min^?1), but not by the D₂‐like receptor agonist, bromocriptine (31–310 μg min.^?1). In contrast, fenoldopam (1–310 μg min.^?1, intracarotid), a D₁‐like receptor agonist, produced dose‐dependent increases in external carotid conductance. The vasoconstrictor response to dopamine was abolished after intravenous administration of the antagonists, phentolamine (α_1/2; 2000 μg kg^?1) or rauwolscine (α₂; 100 μg kg^?1), but remained unaffected after prazosin (α₁; 100 μg kg^?1) or haloperidol (D₂‐like; 1000 μg kg^?1). Interestingly, after phentolamine not only were the vasoconstrictor responses to dopamine abolished, but even a dose‐dependent vasodilator component was unmasked. These vasodilator responses to dopamine remained unchanged after intravenous haloperidol or propranolol (1000 μg kg^?1 each). On the other hand, the vasodilator responses to fenoldopam, which remained unchanged after intravenous saline (0.1 ml kg^?1), propranolol (1000 μg kg^?1) or vagosympathectomy, were abolished by the D₁‐like receptor antagonist, SCH‐23390 (10 μg kg^?1). Lastly, the responses to dopamine and fenoldopam were not significantly altered after intraperitoneal pretreatment with reserpine (5 mg kg^?1; ?24 hr). The above results suggest that the canine external carotid vasoconstrictor responses to dopamine: (i) are mainly mediated by α₂‐adrenoceptors; and (ii) overshadow a vasodilator component, which involves vascular D₁‐like receptors.     

Nasal ciliary beat frequency is age independent

Objectives: Evaluate the age-dependency of ciliary beat frequency (CBF) in biopsies after ciliogenesis in culture. Study Design: Retrospective analysis of CBF and ciliary ultrastructure in biopsies and after ciliogenesis from 203 individuals, aged 3 months to 74 years. Methods: All patients with successful culture were included. Ciliogenesis was obtained using the sequential monolayer-suspension culture technique for dissociated nasal epithelial cells. CBF was measured using computerized microscope photometry. Secondary ultrastructural abnormalities were evaluated in transmission electron microscopy. Results: There was no correlation between age and CBF, in either the biopsies (7.0 ± 2.6 Hz; n = 113) or after ciliogenesis in culture (8.1 ± 1.3 Hz; n = 203). Even in individuals older than 70 years, CBF was normal in bioptic material (6.7 ± 1.7 Hz) and after ciliogenesis in culture (7.9 ± 1.0 Hz). Also, in individuals less than 1 year of age CBF was normal in biopsies as well as after ciliogenesis. CBF correlated inversely with the percentage of secondary ultrastructural abnormalities in the biopsies as seen with transmission electron microscopy: 8.1 ± 1.8 Hz when ciliary ultrastructure was normal and 3.5 ± 3.3 Hz in cases of severe secondary ciliary dyskinesia. After ciliogenesis in culture, ciliary ultra-structure was always normal, as was CBF. Conclusion: CBF is age independent but correlates with secondary ultrastructural abnormalities. CBF after ciliogenesis in culture is the intrinsic one.     

An arachnoid cyst presenting as an intramedullary tumour

A case of thoracic intradural extramedullary arachnoid cyst is presented in which an intramedullary low grade glioma was suspected preoperatively. The cyst was widely fenestrated and postoperatively, the patient experienced considerable improvement in her symptoms. As postoperative MRI studies also showed resolution of the intramedullary changes we regard the intramedullary changes as a result of the cyst, without the existence of primary medullary pathology. To our knowledge an arachnoid cyst, to date, has not been described as the cause of syringomyelia. As radiological findings can be misleading, extramedullary pathology, located more cranially, should be ruled out when treating cystic medullary changes.     

Risk assessment of dietary acrylamide intake in Flemish adolescents.

Acrylamide has recently been found in a range of heat treated food items. As it is a neurotoxic agent and a probable, human carcinogen (IARC 2A), human exposure to this chemical might constitute an important public health issue. The purpose of the study was to estimate the acrylamide intake in Flemish adolescents (based on 7-day food record) and to evaluate the possible health risks due to the exposure. The Belgian Federal Agency for the Safety of the Food Chain collected 150 food items from different supermarkets and restaurants to analyse the acrylamide level. The limit of quantitation was 30 microg acrylamide/kg foodstuffs. Exposure modelling was based on Monte Carlo simulations. The estimated dietary intake of acrylamide per person given as the 5th, 50th and 95th percentile were 0.19, 0.51 and 1.09 mircog/kg bw/d. Bread, despite its low acrylamide content, is relevant as a source of acrylamide exposure at the lower percentiles. At higher percentiles the contribution of French fries and crisps is more important. It must be emphasised that the exposure assessment has several limitations. Risk of neurotoxicity seems negligible. The relevance of current intake levels in terms of cancer risk remains a subject of debate.     

Negative Stress and the Outcome of Treatment for Binge Eating

This study investigated the ability of negatively versus positively perceived stress to predict outcome of treatment for binge eating disorder (BED). Participants were 62 obese women satisfying the DSMIV research criteria for BED. Stress was measured using an instrument based on the Recent Life Change Questionnaire (RLCQ). Participants experiencing high negative stress during the study period reported a binge eating frequency three times greater than that reported by subjects experiencing low negative stress (2.14 vs. 0.65 binge-days/week). Negative stress predicted how fast an individual would reduce binge eating and demonstrated more predictive power than positive stress.