The usefulness of basic fibroblast growth factor for radiation-exposed tissue.

A high dose of ionizing external radiation damage to the skin and soft tissue results in changes in function as well as in the general body condition. Once radiation surpasses the tissue safety or survival level, progressive alteration in the damaged tissue results in tissue loss and then flap loss. Local expression and action of stem cells or local growth factors in the irradiated tissue is mitigated, and external administration is sought to investigate the possibility of skin and soft tissue survival after an elevating flap. Basic fibroblast growth factor (bFGF) is primarily considered as a potent angiogenic growth factor. In burns, resurfacing with a dermal component is required, and bFGF stimulates wound healing and enhances human skin-derived mesenchymal stem cells under serum-free conditions in a dose-dependent manner. Thirty-five male, 4- to 8-week-old CLAWN miniature pigs received radiation exposure to assess the effectiveness of bFGF in terms of the progressive clinical course relevant to human skin and soft tissue. At 2 weeks following 10-Gy irradiation, tissue was preserved in the group receiving subcutaneous placement of a round-type tissue expander and bFGF. The expander plus bFGF group demonstrated significantly greater dermo-epidermal proliferation than the radiation alone, radiation plus bFGF, or expander plus radiation plus vehicle-solution groups, and new blood vessel formation was significantly increased in the expander tissue with bFGF after irradiation (p < 0.01). Electron microscopy revealed that tissue with expander and bFGF maintained more stable skin adnexae with preserved intact epidermis and dermis. Thus, bFGF improved and maintained the tissue viability after immediate irradiation in the skin and soft tissue.

No evidence of association between 8q24 and susceptibility to nonsyndromic cleft lip with or without palate in Japanese population.

OBJECTIVE: Recent genome-wide association studies identified susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL±P) on 8q24.21, 10q25.3, 13q31.1, 15q13.3, 17q22, and 18q22 in populations of European origin. The purpose of this study was to determine, using DNA samples, whether 8q24.21 was a susceptibility locus for the development of NSCL±P in Japanese patients. METHODS: We used DNA from 167 Japanese NSCL±P patients (45 cleft lip without cleft palate and 122 cleft lip with cleft palate patients) and 190 Japanese unaffected control individuals. We performed an association study using 13 single nucleotide polymorphisms (SNPs) selected on the 8q24.21 locus. Genotyping of each SNP was carried out by direct sequencing of genomic DNA. Additionally, a haplotype block was constructed using the selected SNPs. RESULTS: The 13 selected SNPs were successfully genotyped in 357 individuals. The p values obtained were not low enough to indicate a significant association between the haplotypes and the development of NSCL±P in this population. CONCLUSIONS: Our results suggest that the 8q24.21 locus is not associated with susceptibility to NSCL±P in Japanese patients and provide further evidence that ethnicity is a strong factor in determining susceptibility loci, albeit using a limited number of samples. Further studies are needed to identify regions involved in the development of NSCL±P in the Japanese population.

A type of familial cleft of the soft palate maps to 2p24.2-p24.1 or 2p21-p12.

Cleft of the soft palate (CSP) and the hard palate are subtypes of cleft palate. Patients with either condition often have difficulty with speech and swallowing. Nonsyndromic, cleft palate isolated has been reported to be associated with several genes, but to our knowledge, there have been no detailed genetic investigations of CSP. We performed a genome-wide linkage analysis using a single-nucleotide polymorphism-based microarray platform and successively using microsatellite markers in a family in which six members, across three successive generations, had CSP. A maximum LOD score of 2.408 was obtained at 2p24.2-24.1 and 2p21-p12, assuming autosomal dominant inheritance. Our results suggest that either of these regions is responsible for this type of CSP.

Two missense mutations of the IRF6 gene in two Japanese families with popliteal pterygium syndrome.

Mutations in the interferon regulatory factor 6 gene (IRF6) cause either popliteal pterygium syndrome (PPS) or Van der Woude syndrome (VWS), allelic autosomal dominant orofacial clefting conditions. To further investigate the IRF6 mutation profile in PPS, we performed mutation analysis of patients from two unrelated Japanese families with PPS and identified mutations in IRF6: c.251G>T (R84L) and c.1271C>T (S424L). We also found R84L, which together with previous reports on R84 mutations, provided another line of evidence that both syndromes could result from the same mutation probably under an influence of a modifier gene(s). This supports the idea that the R84 residue in the DNA binding domain of IRF6 is a mutational hot spot for PPS. A luciferase assay of the S424L protein in the other family demonstrated that the mutation decreased the IRF6 transcriptional activity significantly to 6% of that of the wild-type. This finding suggests that the C-terminus region of IRF6 could have an important function in phosphorylation or protein interaction. To our knowledge, this is the first report of mutations observed in Japanese PPS patients.

Parotid gland atrophy after conservative treatment of a post-traumatic parotid fistula in a two-year-old boy.

A parotid fistula is a rare complication following parotid gland and duct injury. A two-year-old boy with a previous parotid fistula after parotid injury due to a dog bite was successfully treated with pressure-dressing therapy, which is generally non-invasive and tolerable by young children. During follow-up, ultrasonography revealed atrophy of the parotid gland. This finding is consistent with the healing mechanism previously assumed in adult patients with a parotid fistula. Consideration should be paid to the possibility of oral environmental changes associated with reduced saliva secretion from parotid gland atrophy after conservative treatment of parotid fistula.

Cranioplasty with auto-purified bone flap after infection.

Cranioplasty of cranial bone defects can generally be accomplished with autogeneous bones as well as with nonbiological materials. Autologous living-bone grafts are ideal but require sacrifice of donor bone, and synthetic materials might have possible exposure of the materials, delayed infection, and/or allergic reaction. The authors report cranioplasty with a bone graft after auto-purification by subcutaneous preservation of the contaminated bone fragment. A 47-year-old man was given a frontal cranioplasty with a split parietal bone and rib. Epidural abscess ensued, and debridement was performed to control the infection. The largest bone fragment was subcutaneously preserved in the chest wall and reused for cranioplasty. Subcutaneous preservation of bone is a promising strategy for cranioplasty after neurosurgery. The condition of the bone fragment can be inferred from the condition of the site at which it is preserved. If the bone flap is contaminated, it can be purified by the patient's immune system.