Respiratory muscle dysfunction in facioscapulohumeral muscular dystrophy

Sleep and Breathing -     

Transgenic technology in farm animals--progress and perspectives

Current applications of gene transfer in farm animals include the improvement of product quality and quantity, disease resistance, the production of valuable proteins in the mammary gland or other organs, the genetic modification of pigs for xenotransplantation and the generation of new animal models in cases where rodent models are not sufficient for studying the problem under evaluation. Although DNA microinjection into pronuclei of zygotes from various farm animal species has happened since 1985, the efficiency of this method is low. Further drawbacks are related to the random integration process which may cause mosaicism, insertional mutations and varying expression due to position effects. Sperm-mediated gene transfer is not routinely established yet, although the mechanisms of binding and internalisation of DNA by sperm cells is becoming increasingly clearer. New protocols for the use of retroviral vectors to infect metaphase II oocytes which are subsequently fertilised resulted in efficient production of transgenic cattle. In spite of extensive efforts to establish pluripotent stem cells from farm animal species, no germ-line competent cells have been reported in mammalian species other than mouse so far. However, recent success in cloning sheep, cattle, goats and pigs from cultured cells provides an alternative route for efficient and targeted genetic modifications of farm animals.     

Is There a FADS2-Modulated Link between Long-Chain Polyunsaturated Fatty Acids in Plasma Phospholipids and Polyphenol Intake in Adult Subjects Who Are Overweight?

Dietary polyphenols promote cardiometabolic health and are linked with long-chain polyunsaturated fatty acids in plasma phospholipids (LC-PUFA). The FADS2 polymorphisms are associated with LC-PUFA metabolism and overweight/obesity. This 4-week study examined the link between polyphenol intake, FADS2 variants (rs174593, rs174616, rs174576) and obesity in 62 overweight adults (BMI ≥ 25), allocated to consume 100 mL daily of either: Aronia juice, a rich source of polyphenols, with 1177.11 mg polyphenols (expressed as gallic acid equivalents)/100 mL (AJ, n = 22), Aronia juice with 294.28 mg polyphenols/100 mL (MJ, n = 20), or nutritionally matched polyphenol-lacking placebo as a control (PLB, n = 20). We analyzed LC-PUFA (% of total pool) by gas chromatography and FADS2 variants by real-time PCR. Four-week changes in LC-PUFA, BMI, and body weight were included in statistical models, controlling for gender and PUFA intake. Only upon AJ and MJ, the presence of FADS2 variant alleles affected changes in linoleic, arachidonic, and eicosapentaenoic acid (EPA). Upon MJ treatment, changes in EPA were inversely linked with changes in BMI (β= −0.73, p = 0.029) and weight gain (β= −2.17, p = 0.024). Only in subjects drinking AJ, the link between changes in EPA and anthropometric indices was modified by the rs174576 variant allele. Our results indicate the interaction between FADS2, fatty acid metabolism, and polyphenol intake in overweight subjects.     

Sensorineural deafness in X-linked Charcot-Marie-Tooth disease with connexin 32 mutation (R142Q)

OBJECTIVE: To report a family with X-linked Charcot-Marie-Tooth disease (CMTX) with proven connexin 32 (Cx32) mutation associated with deafness. METHODS: Twelve members of a CMTX family were examined clinically. Electromyography and sensory and motor conduction studies were performed in three men, two women, and a 7-year-old boy. Audiometric testing was carried out in the three men, one woman, and an 8-year-old girl. Molecular genetic analysis was performed in six men and five women. RESULTS: The three men and the 7-year-old boy had the usual sensorimotor deficit and pronounced reduction of motor nerve conduction velocity. A 15-year-old boy was asymptomatic and had only areflexia. The women had impairment of vibratory sensation and slight slowing of nerve conduction velocities. Sensorineural deafness was observed in the three men and in an 8-year-old girl without any motor or sensory deficit. Molecular genetic analysis revealed a new missense mutation located in codon 142 of the Cx32 gene leading to the substitution of an arginine by a glutamine. CONCLUSION: CMTX due to Cx32 mutations often shows interfamilial and intrafamilial phenotypic variation, which is also the hallmark of this family. The sensorineural deafness observed in this family suggests that Cx32 could play an important role in the auditory pathway.     

Adenovirus myelitis and Epstein-Barr myelitis: two unusual viral causes with similar presentations

We report two cases of viral myelitis, one associated with adenovirus and the other with Epstein-Barr virus. The clinical presentation and course were similar, with viral illness, paraplegia with a D4 sensory level, and fever. Spinal magnetic resonance imaging showed a T2 cervico-dorsal high intensity signal. Cerebrospinal fluid examination showed pleocytosis without oligoclonal bands. Both patients recovered after treatment with high-dose methylprednisolone.These two cases suggest a similar clinical and paraclinical pattern in viral transverse myelitis. Moreover, treatment with corticosteroids seems to be useful in viral myelitis.     

Paraplegia episodes revealing tuberculous myelitis

A 38 year-old woman, without previous medical history, presented, since 1993, several paraplegic fits carrying herself progressively through to a severe paraplegia. Diagnoses successively proposed were spinal cord compressions by slipped discs, spinal cord infarct and multiple sclerosis. In November 1998, the patient presented back pain and fever. Spinal cord magnetic resonance imaging (MRI) revealed a mildly enlarged dorsal cord with signal abnormalities. The lesions were isointense on T1-weighted images, hyperintense on T2-weighted images and showed a ringlike contrast enhancement. A lumbar puncture showed a trouble cerebrospinal fluid (CSF) with leucocytes 600/mm(3) (85 p.100 polynuclear), protein 6.7 g/l, glucose 0.26 g/l, chloride 109 mmol/l. The patient was first treated with parenteral unspecific antibiotherapy. Microbiological studies of blood and CSF were negative. CSF examination with polymerase chain reaction (PCR) was positive for Mycobacterium tuberculosis. Clinical (pain and fever) symptoms and CSF abnormalities decreased after antituberculous treatment. However, paraparesis remain severe. Spinal tuberculous localizations often lead to diagnostic and therapeutic errors. Improvement of spinal cord MRI sequences and using of PCR technics in CSF would contribute to reduce these difficulties.     

Spinal cord magnetic resonance imaging in multiple sclerosis: importance of determining degree of atrophy as a marker of disease course

Spinal cord magnetic resonance imaging (MRI) is of particular interest in the management of multiple sclerosis (MS) especially in primary progressive forms. Most of the demyelinating lesions are located in the cervical or dorsal cord. Spinal cord area reduction has been recently correlated with the progression of disability (Losseff et al., 1996, Lycklama a Nijeholt et al., 1998). The aim of this study was to confirm this first result, to assess the reproducibility of this method and to correlate demyelinating lesions with spinal cord area reduction. Fifty two patients were included and compared with 15 controls (normal subjects). T2 Sagittal and axial plane images were performed to localized hypersignal lesions. Spinal cord area was obtained by a volume acquired inversion prepared fast spoiled gradient echo acquisition (MP-Rage) sequence. We compared the mean area value with clinical parameters (age, course of the disease, expanded disability status scale ?EDSS) and with the number and location of demyelinating lesions. Demyelinating lesions were found in 82p.100 of MS patients and in none of controls. Mean spinal cord area was closely similar to Losseff et al. (1996) results and was reduced compared with controls (p<0.001). Spinal cord reduction was correlated with disability, studied by the EDSS. Furthermore, no correlation was found between demyelinating lesions and spinal cord area reduction. This study confirms the interest of spinal cord area mesurement in MS. Spinal cord atrophy is a reliable marker for axonal loss. This method should be of particular interest for the follow-up of axonal loss in thepeutic trials especially in primary progressive MS.