Human ROBO1 regulates interaural interaction in auditory pathways

In rodents, the Robo1 gene regulates midline crossing of major nerve tracts, a fundamental property of the mammalian CNS. However, the neurodevelopmental function of the human ROBO1 gene remains unknown, apart from a suggested role in dyslexia. We therefore studied axonal crossing with a functional approach, based on magnetoencephalography, in 10 dyslexic individuals who all share the same rare, weakly expressing haplotype of the ROBO1 gene. Auditory-cortex responses were recorded separately to left- and right-ear sounds that were amplitude modulated at different frequencies. We found impaired interaural interaction that depended on the ROBO1 in a dose-dependent manner. Our results indicate that normal crossing of the auditory pathways requires an adequate ROBO1 expression level.     

Cerebral magnetic fields to lingual stimulation.

We recorded cerebral magnetic fields to electric stimulation of the tongue in 7 healthy adults. The two main deflections of the response peaked around 55 msec (P55m) and 140 msec (N140m). During both of them the magnetic field pattern, determined with a 7- or 24-channel SQUID magnetometer, suggested a dipolar current source. The topography of P55m can be explained by a tangential dipole at the first somatosensory cortex (SI) in the posterior wall of the central sulcus. The equivalent source of N140m is, on average, about 1 cm lateral to the source of P55m. The reported method allows non-invasive determination of the cortical tongue representation area.     

Intensive care management of patients with acute intermittent porphyria: Clinical report of four cases and review of literature

Acute intermittent porphyria (AIP), the most common and the most severe form of acute hepatic porphyria, is an autosomal dominant condition. It results from lower-than-normal levels (less than 50%) of porphobilinogen (PBG) deaminase. Patients may present commonly with gastrointestinal complaints and neuropsychiatric manifestations. Diagnosis may be confirmed with the presence of intermediary metabolites of haem synthesis, amino levulinic acid (ALA) and PBG in urine or with specific enzyme assays. Abdominal pain is the most common symptom (90%). Peripheral polyneuropathy, primarily motor with flaccid paresis of proximal musculature, with or without autonomic involvement, is characteristic. Respiratory failure necessitates ventilator and intensive care support. Avoidance of precipitating factors and the use of haem preparations and intravenous dextrose form the basis of management. Gabapentin and propofol, rather than the conventional antiepileptics appear to be the appropriate choice for seizure control. Here, we present intensive care management of four cases of AIP with varying clinical presentation.     

SADDAN syndrome

Achondroplasia is the most common type of short-limbed dwarfism in children resulting from fibroblast growth factor receptor (FGFR) mutations. Activating mutations of FGFR3 also result in other forms of skeletal dysplasia and craniosynostosis. Acanthosis nigricans is associated with these skeletal dysplasias and we recently encountered a skeletal dysplasia along with acanthosis nigricans in a young boy. We report the case due its unusual nature affecting one of twin brothers.     

Chronic obstructive pulmonary disease is associated with enhanced bronchial expression of FGF-1, FGF-2, and FGFR-1

An important feature of chronic obstructive pulmonary disease (COPD) is airway remodelling, the molecular mechanisms of which are poorly understood. In this study, the role of fibroblast growth factors (FGF-1 and FGF-2) and their receptor, FGFR-1, was assessed in bronchial airway wall remodelling in patients with COPD (FEV1 < 75%; n = 15) and without COPD (FEV1 > 85%; n = 16). FGF-1 and FGFR-1 were immunolocalized in bronchial epithelium, airway smooth muscle (ASM), submucosal glandular epithelium, and vascular smooth muscle. Quantitative digital image analysis revealed increased cytoplasmic expression of FGF-2 in bronchial epithelium (0.35 +/- 0.03 vs 0.20 +/- 0.04, p < 0.008) and nuclear localization in ASM (p < 0.0001) in COPD patients compared with controls. Elevated levels of FGFR-1 in ASM (p < 0.005) and of FGF-1 (p < 0.04) and FGFR-1 (p < 0.001) in bronchial epithelium were observed. In cultured human ASM cells, FGF-1 and/or FGF-2 (10 ng/ml) induced cellular proliferation, as shown by [3H]thymidine incorporation and by cell number counts. Steady-state mRNA levels of FGFR-1 were elevated in human ASM cells treated with either FGF-1 or FGF-2. The increased bronchial expression of fibroblast growth factors and their receptor in patients with COPD, and the mitogenic response of human ASM cells to FGFs in vitro suggest a potential role for the FGF/FGFR-1 system in the remodelling of bronchial airways in COPD.