Incidence of fibroblast growth factor receptor 3 gene (FGFR3) A248C, S249C, G372C, and T375C mutations in bladder cancer

Bladder cancer is the most frequent cancer of the urinary system. Fibroblast growth factor receptors (FGFR) belong to the tyrosine kinase family and have important roles in cell differentiation and proliferation and embryogenesis. FGFR3 is located on chromosome 4p16.3, and missense mutations of FGFR3 are associated with autosomal dominant human skeletal disorders and have some oncogenic effects. We examined the incidence of FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C, and in exon 10, G372C and T375C, and their correlation with clinical-pathological parameters in bladder carcinoma patients. Fifty-six paraffin-embedded specimens of transitional cell carcinoma of the urinary bladder were included in this study. Analysis of FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C, and in exon 10, G372C and T375C, was performed by PCR- restriction fragment length polymorphism (RFLP) analysis and DNA sequencing. FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C, and in exon 10, G372C and T375C, were detected in 33 of the 56 patients (heterozygous mutant). Among the 56 transitional cell carcinomas, missense point mutations were detected in seven of them at codon A248C, 28 of them at codon S249C, and three of them at codon T375C, similar to data from previous reports. When the results of the FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C and in exon 10, G372C and T375C, were analyzed one by one or as a group, despite the findings of previous research reports, our data suggest that these mutations are detected homogenously regardless of the tumor classification and tumor grade. © FUNPEC-RP

CRTC Potentiates Light-independent timeless Transcription to Sustain Circadian Rhythms in Drosophila

Light is one of the strongest environmental time cues for entraining endogenous circadian rhythms. Emerging evidence indicates that CREB-regulated transcription co-activator 1 (CRTC1) is a key player in this pathway, stimulating light-induced Period1 (Per1) transcription in mammalian clocks. Here, we demonstrate a light-independent role of Drosophila CRTC in sustaining circadian behaviors. Genomic deletion of the crtc locus causes long but poor locomotor rhythms in constant darkness. Overexpression or RNA interference-mediated depletion of CRTC in circadian pacemaker neurons similarly impairs the free-running behavioral rhythms, implying that Drosophila clocks are sensitive to the dosage of CRTC. The crtc null mutation delays the overall phase of circadian gene expression yet it remarkably dampens light-independent oscillations of TIMELESS (TIM) proteins in the clock neurons. In fact, CRTC overexpression enhances CLOCK/CYCLE (CLK/CYC)-activated transcription from tim but not per promoter in clock-less S2 cells whereas CRTC depletion suppresses it. Consistently, TIM overexpression partially but significantly rescues the behavioral rhythms in crtc mutants. Taken together, our data suggest that CRTC is a novel co-activator for the CLK/CYC-activated tim transcription to coordinate molecular rhythms with circadian behaviors over a 24-hour time-scale. We thus propose that CRTC-dependent clock mechanisms have co-evolved with selective clock genes among different species.ope

Mast cells and eosinophils in invasive breast carcinoma

<p>Abstract</p> <p>Background</p> <p>Inflammatory cells in the tumour stroma has gained increasing interest recently. Thus, we aimed to study the frequency and prognostic impact of stromal mast cells and tumour infiltrating eosinophils in invasive breast carcinomas.</p> <p>Methods</p> <p>Tissue microarrays containing 234 cases of invasive breast cancer were prepared and analysed for the presence of stromal mast cells and eosinophils. Tumour infiltrating eosinophils were counted on hematoxylin-eosin slides. Immunostaining for tryptase was done and the total number of mast cells were counted and correlated to the proliferation marker Ki 67, positivity for estrogen and progesterone receptors, clinical parameters and clinical outcome.</p> <p>Results</p> <p>Stromal mast cells were found to correlate to low grade tumours and estrogen receptor positivity. There was a total lack of eosinophils in breast cancer tumours.</p> <p>Conclusion</p> <p>A high number of mast cells in the tumours correlated to low-grade tumours and estrogen receptor positivity. Eosinophils are not tumour infiltrating in breast cancers.</p

Motor cortical thresholds and cortical silent periods in epilepsy

We studied motor cortical thresholds (TIs) and cortical silent periods (SPs) evoked by transcranial magnetic stimulation (TMS) in 110 epileptic patients. Sixty-two had primary generalised, 48 had partial type seizures. Fifteen out 110 patients were analysed both before and after anticonvulsant medication. Our aims were to evaluate the TI levels and the duration of SPs in patients with epilepsy and to determine the reliability of TMS in patients with epilepsy. There was no negative effect of TMS on the clinical status and EEG findings in patients with epilepsy. TIs obtained from patients with partial epilepsy were higher than those obtained from both controls and primary epileptics. The duration of SPs in patients with primary epileptics was more prolonged than those obtained from controls. There was no correlation between EEG lateralisation and both SP duration and TI values. In de novo patient group, SP duration was significantly prolonged after anticonvulsant medication. We concluded that TMS is a reliable electrophysiological investigation in patients with epilepsy. The analysis of SP duration may be an appropriate investigation in monitoring the effect of anticonvulsant medication on the cortical inhibitory activity. (C) 2003 BEA Trading Ltd. Published by Elsevier Ltd. All rights reserved

Cutaneous silent periods of the vastus medialis evoked by the stimulation of lateral femoral cutaneous nerve

WOS: 000229984300011PubMed ID: 15978495Objective: Cutaneous silent period (CSP), which is a spinal reflex mediated by A-delta cutaneous afferents, is transient suppression of the electromyographic activity. In this study, our aim is to investigate CSPs of vastus medialis muscle (vm-CSP) evoked by the stimulation of the lateral femoral cutaneous nerve (LFCN) in healthy controls and in patients with meralgia paresthetica (NIP). Methods: Twenty-one patients with MP (17 unilateral, 4 bilateral) and 27 healthy controls were included. Nerve conduction studies of LFCN and vm-CSP were analyzed in all subjects. A stimulus train consisting of five electrical shocks was applied to the skin at the anterolateral side of the thigh for recording of the vm-CSP. Results: Nerve conduction abnormalities of LFCN were observed in all patients with NIP. Mean duration of vm-CSP was 69.7 +/- 9.2 ins, and mean onset latency was 44.7 +/- 6.9 in healthy controls. Onset latency of vm-CSP was significantly prolonged and the duration of vm-CSP was significantly shortened in patients with MP. Vm-CSP abnormalities were observed in 20/25 extremities with MP. Conclusions: Dysfunction of A-delta afferents may cause these findings in patients with MP. Additionally, spinal modulation of pain may also play a role in the explanation of our findings. Significance: The present study demonstrates the CSP alterations in the patients with entrapment neuropathy of a cutaneous nerve. (c) 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved

Sensory nerve conduction in branches of common interdigital nerves: A new technique for normal controls and patients with Morton's neuroma

PubMed ID: 20479659In this article, a new electrodiagnostic approach is described for patients with Morton's neuroma. The new method is based on the anatomic fact that the two branches of the common plantar interdigital nerves innervate the lateral side of one toe and the medial side the next one. This study included 20 normal subjects (aged 28-58 years, 10 men and 10 women) and 4 patients with Morton's neuroma (aged 44-52 years, 4 women). The branches of adjacent common plantar interdigital nerves that innerve one toe were stimulated superficially and separately with half of one toe covered with a piece of medical tape. The recordings were obtained on the posterior tibial nerve at the medial malleolus with needle electrodes. Thus, the difference in latencies of obtained sensory nerve action potentials on the posterior tibial nerve with needle electrode was measured. From normal subjects' data, it was determined that a latency difference value of above 0.17 milliseconds (mean ± 2.5 SD) in one toe was abnormal. All of the patients with Morton's neuroma showed abnormal interlatency difference values. This new method, which we have developed, is more sensitive, simple to use, does not require extra equipment, and does not cause excessive pain. We suggest that interlatency difference between branches of the common plantar interdigital nerves is a useful and sensitive method for the diagnosis of Morton's neuroma. Copyright © 2010 by the American Clinical Neurophysiology Society

Association of macrophages, mast cells and eosinophil leukocytes with angiogenesis and tumor stage in non-small cell lung carcinomas (NSCLC).

The association between inflammatory cells, including tumor associated macrophage (TAM), mast cell (MC) and eosinophil Leucocyte (EL) densities and angiogenesis, as well as the relation of TAM, MC and EL densities and angiogenesis to tumor stage were investigated in specimens of 63 non-small cell lung carcinoma (NSCLC). Fifteen cases were in stage I, 12 were in stage II, 33 were in stage III and 3 were in stage IV. ELs and MCs were identified by hematoxilen-eosin and toluidine-blue histochemical stains, respectively. TAMs were shown by immunohistochemistry for CD68. Microvessets demonstrated by immunohistochemistry for CD31 were quantified by a stereotogical method and vascular surface density (VSD) and microvessel number (NVES) were calculated. There was not any statistically significant correlation between tumor's stage and VSD, TAM and EL counts. MC count and NVES were found to be higher, in early stages. VSD and NVES were not associated with EL, MC and TAM counts. The lack of consistent correlation of angiogenesis to the stage of disease in this study supports the view that tumor angiogenesis is not a significant prognostic factor in NSCLCs. The absence of correlation between MCs, ELs and TAM counts and angiogenesis and absence of any relation between ELs and TAMs and tumor stage are discordant with the results of some of the previous studies in NSCLCs and in other tumors. The differing results may be due to wide variations in methodologies which were used for demonstration of inflammatory cells and vessels and variations in the degree of activation and complexity of functions of these cells. (C) 2003 Elsevier Ireland Ltd. All rights reserved