A G to T mutation at nucleotide position 2128 in the human FGFR3b coding region resulting in a Cys for Gly substitution (G697C) in the tyrosine kinase domain was observed in 62% (44/ 71) of oral squamous cell carcinomas (OSCC) examined. Immunostained FGFR3b was found in the cytoplasm of prickle cells in normal epithelia, and FGFR3b was localized in the cytoplasm and nucleus in non-FGFR3b mutant OSCC. Overexpressed FGFR3b protein on plasma membranes was noted in OSCC bearing the FGFR3b mutation. Enhanced tyrosine kinase activity of G697C FGFR3b was confirmed. Our results indicate that G697C is an activating mutation causing constitutive ligand-independent FGFR3b signaling. This mutation may be involved in the progression of OSCC and thus the FGFR3b coding sequence may have diagnostic or prognostic value for OSCC. ' 2005 Wiley-Liss, Inc.Key words: FGFR3b; oral squamous cell carcinomas; mutationThe fibroblast growth factor (FGF) family currently includes 22 different gene products that bind to 4 distinct FGF receptors (FGFR1-FGFR4). 1,2 The activities of FGF are mediated by high-affinity FGFR located on the cell surface, which share a common structure of 2 or 3 extracellular immunoglobulinlike loops, a transmembrane domain, and an intracellular split tyrosine kinase domain. 3,4 It is believed that FGFR, when activated by bound FGF in the presence of heparin or heparan sulfate proteoglycan, forms a dimer, which undergoes phosphorylation on tyrosine residues, and transduces signals of cell growth and differentiation. 5,6 It was shown recently that mutations in FGFR cause various congenital skeletal and chondral dysplasia. 7 In these congenital diseases, constitutively active tyrosine kinase activity due to ligand-independent receptor dimerization was observed, and the degree of receptor tyrosine kinase activity correlated with the severity of disease. Squamous cell carcinoma (SCC) is a cancer originating from stratified squamous epithelia that mainly cover skin, oral cavity, esophagus, vagina and bronchus. We have reported previously that all 4 FGFR, including FGFR1 (c isoform), FGFR2 (b isoform), FGFR3 (b isoform) and FGFR4 were expressed exclusively in cells derived from normal oral epithelia and oral squamous cell carcinomas (OSCC). 8 The growth of normal epithelial cells was stimulated by FGF whereas OSCC cell proliferation was not. 9 Mutations in FGFR genes have been reported in human bladder, cervical, gastric and colorectal carcinomas, 10,11 however no such mutations have been reported in OSCC.We examined the mutational status of FGFR3b in a series of human OSCC to determine whether FGFR3b is involved in oral squamous tumorigenesis. We found that 44 OSCC DNAs showed band shifts in exon 17 of the FGFR3b gene by SSCP analysis (Fig. 1a). The DNA sequence of exon 17 in each sample was investigated by direct nucleotide sequencing. A heterozygous missense mutation (G2128T) was observed in exon 17 in all cases (44/71) that exhibited a band shift in PCR-SSCP (Fig. 1b). This mutation resulted in a glycine-tocysteine s...

This study aimed to clarify the natural course of positional plagiocephaly using a three-dimensional (3D) scanner and investigate the effectiveness of cranial helmet therapy (CHT). One hundred infants with severe plagiocephaly who visited our institutions between April 2020 and March 2021 were included. Cranial shape was measured using an Artec Eva 3D scanner. A cranial asymmetry (CA) >12 mm was diagnosed as severe plagiocephaly. An infant whose CA subsided to <12 mm was considered to have improved naturally or by CHT. The difference in CA between the second and initial scans was defined as the improvement value (median scan interval was two months). In the natural-course group comprising 56 infants with severe plagiocephaly, 37 (66%) with a median CA of 15.6 mm exhibited no improvement after two months. In the scan age- and evaluation interval-matched case-control study, the CA value in the CHT group improved by three times that in the natural-course group (−4.6 mm [n = 33] vs. −1.55 mm [n = 24], p < 0.001). Severe plagiocephaly did not improve naturally in 66% of the cases. Therefore, CHT should be considered if the CA is >12 mm on the initial evaluation.

Object Holmes' tremor (HT) is generally considered to be a symptomatic tremor associated with lesions of the cerebellum, midbrain, or thalamus. Deep brain stimulation (DBS) therapy for essential tremor and parkinsonian tremor has proved quite successful. In contrast, surgical treatment outcomes for HT have often been disappointing. The use of 2 ipsilateral DBS electrodes implanted in parallel within the thalamus for severe essential tremor has been reported. Since dual-lead stimulation within a single target can cover a wider area than single-lead stimulation, it produces greater effects. On the other hand, DBS of the subthalamic area (SA) was recently reported to be effective for refractory tremor. Methods The authors implanted 2 DBS electrodes (one at the nucleus ventralis oralis/nucleus ventralis intermedius and the other at the SA) in 4 patients with HT. For more than 2 years after implantation, each patient's tremor was evaluated using a tremor rating scale under the following 4 conditions of stimulation: “on” for both thalamus and SA DBS; “off” for both thalamus and SA DBS; “on” for thalamus and “off” for SA DBS; and “on” for SA and “off” for thalamus DBS. Results The tremor in all patients was improved for more than 2 years (mean 25.8 ± 3.5 months). Stimulation with 2 electrodes exerted greater effect on the tremor than did 1-electrode stimulation. Interestingly, in all patients progressive effects were observed, and in one patient treated with DBS for 1 year, tremor did not appear even while stimulation was temporarily switched off, suggesting irreversible improvement effects. The presence of both resting and intentional/action tremor implies combined destruction of the pallidothalamic and cerebellothalamic pathways in HT. A larger stimulation area may thus be required for HT patients. Multitarget, dual-lead stimulation permits coverage of the wide area needed to suppress the tremor without adverse effects of stimulation. Some reorganization of the neural network may be involved in the development of HT because the tremor appears several months after the primary insult. The mechanism underlying the absence of tremor while stimulation was temporarily off remains unclear, but the DBS may have normalized the abnormal neural network. Conclusions The authors successfully treated patients with severe HT by using dual-electrode DBS over a long period. Such DBS may offer an effective and safe treatment modality for intractable HT.

Low-dose dairy protein plus micronutrient supplementation during RE significantly increased muscle mass in older adults but did not further improve physical performance.

This study found that STN stimulation produced significant improvement of overall pain related to PD in patients with advanced PD, and the efficacy continued for at least 1 year. The present results indicate that musculoskeletal pain and dystonic pain responded well to STN stimulation, but patients with back pain (somatic pain) and radicular/peripheral neuropathic pain originating from spinal disease have a potential risk for postoperative deterioration of their pain.