Preferential production of IgG1, IL-4 and IL-10 in MuSK-immunized mice

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness associated with acetylcholine receptor (AChR), muscle-specific receptor kinase (MuSK) or low-density lipoprotein receptor-related protein 4 (LRP4)-antibodies. MuSK-antibodies are predominantly of the non-complement fixing IgG4 isotype. The MuSK associated experimental autoimmune myasthenia gravis (EAMG) model was established in mice to investigate immunoglobulin (Ig) and cytokine responses related with MuSK immunity. C57BL/6 (B6) mice immunized with 30 μg of recombinant human MuSK in incomplete or complete Freund's adjuvant (CFA) showed significant EAMG susceptibility (> 80% incidence). Although mice immunized with 10 μg of MuSK had lower EAMG incidence (14.3%), serum MuSK-antibody levels were comparable to mice immunized with 30 μg MuSK. While MuSK immunization stimulated production of all antibody isotypes, non-complement fixing IgG1 was the dominant anti-MuSK Ig isotype in both sera and neuromuscular junctions. Moreover, MuSK immunized IgG1 knockout mice showed very low serum MuSK-antibody levels. Sera and MuSK-stimulated lymph node cell supernatants of MuSK immunized mice showed significantly higher levels of IL-4 and IL-10 (but not IFN-γ and IL-12), than those of CFA immunized mice. Our results suggest that through activation of Th2-type cells, anti-MuSK immunity promotes production of IL-4, which in turn activates anti-MuSK IgG1, the mouse analog of human IgG4. These findings might provide clues for the pathogenesis of other IgG4-related diseases as well as development of disease specific treatment methods (e.g. specific IgG4 inhibitors) for MuSK-related MG.     

An in vitro perspective to cholinesterase inhibitory and antioxidant activity of five Gentiana species and Gentianella caucasea

The dichloromethane (DCM), ethyl acetate (EtOAc), and methanol extracts from the leaves, roots, and flowers of the five species of Gentiana (Gentiana asclepiadea, Gentiana cruciata, Gentiana olivieri, Gentiana septemfida, and Gentiana verna) and Gentianella caucasea were investigated for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and antioxidant effect using 2,2-diphenyl-1-picrylhydrazyl radical scavenging, metal-chelation capacity, and ferric-reducing antioxidant power assays. Total phenol and flavonoid contents of the extracts were determined spectrophotometrically. The presence of some characteristic compounds found in Gentiana species (gentiopicroside, swertiamarin, isoorientin, isovitexin and vitexin) was analyzed in the extracts by thin layer chromatography. The flower DCM extract of G. verna exerted the highest inhibition against AChE (53.65?±?1.03%), whereas the root EtOAc extract of G. cruciata was the most effective in BChE inhibition assay (50.72?±?0.75%) at 100?μg?ml(-?1). The extracts of G. verna were also found to be more active in the antioxidant tests.     

Asperger's disorder and Williams syndrome: a case report

Williams syndrome (WS) is a genetic disorder caused by the hemizygous microdeletion in chromosome 7q11.23. It is characterized by dysmorphic face, cardiovascular disease, idiopathic hypercalcemia, mental retardation, and an uneven profile of cognitive-linguistic abilities and deficits. The presence of autistic features in individuals with WS is a controversial issue. While there are reports that describe them as overly friendly with excessive sociability and good empathic skills, some recent studies focus more on the qualitative impairment of their social abilities. Here, we report the clinical presentation and follow-up of an eight-year-old boy with WS and clear problems in his social interaction, non-verbal communication and circumscribed interests. To our knowledge, this is the first case report on the coexistence of WS and Asperger's disorder. It also differs from previous papers on the comorbidity of WS and autism spectrum disorders, by depicting a highly verbal, nonretarded child followed for seven years through adolescence.     

Benign neurological recovery with low recurrence and low peridural fibrosis rate in pediatric disc herniations after lumbar microdiscectomy

Lumbar disc herniation (LDH) is a very rare clinical entity in the pediatric age group, therefore only a few clinical studies have until now investigated the clinical behavior of pediatric LDH. The natural clinical history, postoperative neurological recovery with radiological follow-up and quality of life related to the disorder continue to be unknown. We prospectively planned and designed two groups of LDH patients scheduled for surgery in this study. The operations were performed by the same surgeon in a randomized fashion. The first group consisted of pediatric patients and the second group of adult patients. Both groups contained 32 cases. Postoperative neurological recovery was assessed using the visual analog scale and Aberdeen Low Back Pain Scale. Postoperative peridural fibrosis was also evaluated in postcontrast magnetic resonance sections. After 3 years of follow-up, all parameters were significantly better in the pediatric LDH group with no recurrence of the disease. The pediatric LDH group was postoperatively better than the adult group both clinically and radiologically. Although LDH seems a catastrophic disease in the pediatric age group, the clinical picture and neurological recovery have a significantly more benign course than in adult patients even in operated cases.     

Diagnostic Imaging of Pulmonary Embolism Using Endobronchial Ultrasound

Endobronchial ultrasound (EBUS) is a new technique that can be used for the diagnostic imaging of central pulmonary thromboembolism (PE). In eight cases at our clinic, EBUS was used because of mediastinal lymphadenopathies or paramediastinal nodular lesions and at the same time images of a PE were obtained by means of EBUS. The PE was diagnosed before the EBUS with computed tomography (CT) of the lungs in all cases (5 women and 3 men). The repletion defects of all the cases compatible with a PE were clarified with CT-angiography. EBUS may be an alternative method for the diagnosis of PE, since it can indicate the presence of a thrombus in the central pulmonary arteries in hemodynamically stable cases.     

Effect of peritonitis on gallbladder smooth muscle contractility in guinea pigs

BACKGROUND: The mechanisms involved in the impaired gallbladder contractile response in peritonitis are unknown. The aim of this study was to determine the effect of peritonitis on the contraction and relaxation responses to different agonists in gallbladder smooth muscle in guinea pig. MATERIALS AND METHODS: Peritonitis was induced by cecal ligation and puncture (CLP) in 10 guinea pigs. Another group of 10 guinea pigs underwent a sham operation and acted as controls. Twenty-four hours after the operation, the guinea pigs were killed, and gallbladder strips were placed in organ bath. The contraction responses to KCl, carbachol, and histamine, and relaxation responses to cyclooxygenase inhibitors (indomethacin, nimesulide, and DFU) on KCl-induced contractions were recorded. RESULTS: There was no significant difference between the contractile responsiveness to KCl, but maximum contractile responses (E(max)) to carbachol and histamine were significantly reduced. Indomethacin, nimesulide, and DFU concentration dependently inhibited on KCl-induced contractions of gallbladder smooth muscle. E(max) values of indomethacin, nimesulide, and DFU were significantly reduced in the peritonitis group compared with controls (P < 0.05). The inhibitor effects of nimesulide and DFU were considerably similar, but inhibitor effect of indomethacin was significantly less than that measured for nimesulide and DFU in both control and peritonitis groups (P < 0.05). CONCLUSIONS: The contraction responses to carbachol and histamine and relaxation responses to COX inhibitors on gallbladder smooth muscle are significantly decreased by peritonitis. Although the mechanism of the decrease in contraction and relaxation responses in CLP-induced peritonitis is completely unknown, we speculate that impaired smooth muscle responses may be related to an alteration in the regulation of receptor/postreceptor excitation-response coupling and/or through changes on Ca(2+) influx.     

Why does post-transplant osteonecrosis develop?

Sir, We read with interest the article by Ekmekci et al. [1], onthe association of thrombophilia and osteonecrosis (ON) of thefemoral head in renal transplant recipients. We previously reporteda case with diffuse ON and severe osteoporosis which was unusualin its presentation in the early post-transplant period, focusingon pre-transplant hormonal changes [2]. Following     

ADL assessment of nondisabled Turkish children with the WeeFIM instrument

OBJECTIVE: To evaluate the WeeFIM instrument's reliability and internal construct validity for the Turkish child population. DESIGN: License was taken from UDSmr to use the WeeFIM instrument. For the reliability and validity studies of the Turkish translation of the WeeFIM instrument, 573 Turkish nondisabled children were included in the study. The reliability of the instrument was assessed by Cronbach's alpha coefficient, intraclass correlation coefficient (ICC), and test-retest reliability. Internal construct validity was assessed by both using Rasch unidimensional measurement model and testing for differential item functioning for age and gender. RESULTS: Cronbach alpha value was 0.99 for motor WeeFIM rating and 0.99 for cognitive WeeFIM rating. ICC was 0.81 for motor WeeFIM rating and 0.92 for cognitive WeeFIM rating. The internal construct validity of the Turkish translation of the WeeFIM instrument was confirmed by excellent fit to the Rasch measurement model. Two subscales were found from the principal component analysis of standardized residual correlation for items. Among the items, bowel management, bladder management, eating, and comprehension showed considerable levels of misfit. CONCLUSIONS: The Turkish translation of the WeeFIM instrument is valid, reliable, and practical for the Turkish child population. Further studies are required to determine the cross-cultural validity of the instrument.