Yoshimichi Imai

A Missense Mutation in the SH3BP2 Gene on Chromosome 4p16.3 Found in a Case of Nonfamilial Cherubism

OBJECTIVE Cherubism is a rare hereditary multilocular cystic disease of the jaws, characterized by its typical appearance. Although nonfamilial cases have been reported, it is difficult to distinguish nonfamilial cherubism from central giant cell granuloma. Recent studies have revealed the point mutations in the SH3BP2 gene on chromosome 4p16.3 in cherubism families. In this article, the SH3BP2 gene in nonfamilial cherubism was examined. PATIENT A 21-year-old Japanese woman with nonfamilial cherubism. INTERVENTIONS Genomic DNA was purified from a blood sample obtained from the patient and used for direct sequencing. In addition, a sample of the lesion, resected during surgery, was used for histologic and immunohistochemical purposes. RESULTS Genomic DNA sequencing found a Pro418Arg mutation in the SH3BP2 gene of the patient. In a histochemical analysis, the multinucleated giant cells proved to be strongly positive for PGM-1, KP-1, and tartrate-resistant acid phosphatase and faintly positive for osteopontin. CONCLUSIONS The missense mutation Pro418Arg was identified in the SH3BP2 gene from a nonfamilial case of cherubism. DNA diagnosis may play a significant role in the identification of cherubism.

Characterization of the Arterial Anatomy of the Murine Hindlimb: Functional Role in the Design and Understanding of Ischemia Models

Rationale Appropriate ischemia models are required for successful studies of therapeutic angiogenesis. While collateral routes are known to be present within the innate vasculature, there are no reports describing the detailed vascular anatomy of the murine hindlimb. In addition, differences in the descriptions of anatomical names and locations in the literature impede understanding of the circulation and the design of hindlimb ischemia models. To understand better the collateral circulation in the whole hindlimb, clarification of all the feeding arteries of the hindlimb is required. Objective The aim of this study is to reveal the detailed arterial anatomy and collateral routes in murine hindlimb to enable the appropriate design of therapeutic angiogenesis studies and to facilitate understanding of the circulation in ischemia models. Methods and Results Arterial anatomy in the murine hindlimb was investigated by contrast-enhanced X-ray imaging and surgical dissection. The observed anatomy is shown in photographic images and in a schema. Previously unnoticed but relatively large arteries were observed in deep, cranial and lateral parts of the thigh. The data indicates that there are three collateral routes through the medial thigh, quadriceps femoris, and the biceps femoris muscles. Furthermore, anatomical variations were found at the origins of the three feeding arteries. Conclusions The detailed arterial anatomy of murine hindlimb and collateral routes deduced from the anatomy are described. Limitations on designs of ischemia models in view of anatomical variations are proposed. These observations will contribute to the development of animal studies of therapeutic angiogenesis using murine hindlimb ischemia models.

Wound healing in skin promoted by inoculation with Pseudomonas aeruginosaPAO1: The critical role of tumor necrosis factor‐α secreted from infiltrating neutrophils

Wound healing is promoted by the presence of replicating microorganisms adhering to the wounded tissue, but the precise mechanism is not fully understood. In the present study, using a rat model with full‐thickness dermal wounds, we examined the effect of Pseudomonas aeruginosa inoculation on wound healing and the role of neutrophils infiltrating the wound site. Within 3 days, inoculation with this bacterium had accelerated re‐epithelialization, epidermal cell proliferation, and neo‐vascularization, as well as the local infiltration of neutrophils, which reached a peak at 24 hours. Tumor necrosis factor (TNF)‐α was detected in the wound tissues on the mRNA and protein levels within 24 hours. Flow cytometry and immunohistochemical analyses detected higher levels of TNF‐α in the infiltrating neutrophils in rats inoculated with P. aeruginosa than in uninoculated rats. Neutropenic rats treated with anti‐neutrophil mAb or cyclophosphamide exhibited significant attenuation in re‐epithelialization, epidermal cell proliferation, neo‐vascularization, and TNF‐α synthesis compared with control; administration of TNF‐α reversed these attenuations. These wound‐healing responses were decelerated in rats treated with anti‐TNF‐α mAb, as was the infiltration of neutrophils. These results indicate that inoculation with P. aeruginosa promotes wound healing by inducing the infiltration of neutrophils, which play a critical role as a major source of TNF‐α.

Midfacial Changes Through Distraction Osteogenesis Using a Rigid External Distraction System With Retention Plates in Cleft Lip and Palate Patients

PURPOSE The purpose of this study was to investigate the changes in and stability of the maxilla and soft tissue profile achieved after the application of distraction osteogenesis (DO) by use of rigid external distraction (RED) with a retention plate system in unilateral cleft lip and palate (UCLP) adult patients. We compared 2 treatment methods in the management of maxillary hypoplasia: Le Fort I osteotomy and DO. MATERIALS AND METHODS Six UCLP adult patients who underwent treatment with the RED retention plate system were examined (DO group). Changes in the positions of soft and hard tissue landmarks were calculated from lateral cephalograms taken before distraction, at the removal of the halo, and 1 year after surgery and were compared with those in 7 other UCLP patients who underwent Le Fort I osteotomy (LF1 group). RESULTS The mean maxillary advancement was significantly larger in the DO group than in the LF1 group after distraction. During the follow-up period, the relapse rate of the maxilla was significantly smaller in the DO group. An undesirable labial inclination of the upper incisors was found in the LF1 group, which may have been due to relapse. The DO group tended to have a higher soft tissue-to-hard tissue anterior movement ratio from the time of distraction to follow-up. CONCLUSIONS The RED retention plate system improved the midfacial profile by advancement of soft and hard tissue and minimized the risk of injury to the upper lip. Using the RED system with retention plates prevented the undesirable labial inclination of upper incisors that was found in the LF1 group.

Biofilm formation on rat skin wounds by Pseudomonas aeruginosa carrying the green fluorescent protein gene

Please cite this paper as: Biofilm formation on rat skin wounds by Pseudomonas aeruginosa carrying the green fluorescent protein gene. Experimental Dermatology 2010; 19:154–156.

IL-17A promotes neutrophilic inflammation and disturbs acute wound healing in skin

In the wound healing process, neutrophils are the first inflammatory cells to move to the wound tissues. They sterilize wounds by killing microbes, and they stimulate other immune cells to protect the host from infection. In contrast, neutrophil‐derived proteases cause damage to host tissues, so neutrophils play dual opposite roles in wound healing. Interleukin‐17A (IL‐17A) is a proinflammatory cytokine that promotes the recruitment of these cells. The role of this cytokine in the wound healing process is not fully clarified. In the present study, therefore, we examined how defect in IL‐17A production affected the wound healing in skin. IL‐17A‐knockout (KO) mice showed promoted wound closure, myofibroblast differentiation and collagen deposition and decreased the neutrophil accumulation compared with wild‐type (WT) mice. In contrast, the administration of recombinant IL‐17A led to delayed wound closure, low collagen deposition and accelerated neutrophilic accumulation. In addition, the treatment of IL‐17A‐administered mice with a neutrophil elastase inhibitor improved the wound repair to the same level as that of WT mice. These results indicated that IL‐17A hampered the wound healing process and suggested that neutrophilic inflammation caused by IL‐17A may be associated with impaired wound healing in skin.

Versatility of chimeric flap based on thoracodorsal vessels incorporating vascularized scapular bone and latissimus dorsi myocutaneous flap in reconstructing lower-extremity bone defects due to osteomyelitis.

To treat lower-extremity osteomyelitis secondary to trauma, bone and soft tissue can be grafted at the same time using microsurgical techniques. We investigate the use of chimeric flaps based on thoracodorsal vessels incorporating vascularized scapular bone and latissimus dorsi myocutaneous flap to reconstruct bone and soft-tissue defects of the lower leg due to osteomyelitis. Ten patients with lower-extremity bone and soft-tissue defects due to osteomyelitis were treated. Vascularized scapular bones were raised on the angular branch of the thoracodorsal artery. Latissimus dorsi myocutaneous flaps were elevated simultaneously to reconstruct the soft tissue defects. All patients tolerated the procedure well. One patient developed an early venous thrombosis, which was successfully treated by thrombectomy. Mean follow-up time was 7 years and 8 months. Bone union without refracture was observed in all patients. The mean time required for bone union after surgery was 13.5 weeks. Donor-site morbidity was minimal. Chimeric flaps based on thoracodorsal vessels incorporating vascularized scapular bone and latissimus dorsi myocutaneous are safe and effective in the repair of lower-extremity bone and soft-tissue defects caused by osteomyelitis.

Treatment of Hypoglossia-Hypodactyly Syndrome without Extremity Anomalies

Three cases of hypoglossia-hypodactyly syndrome without limb deformities are reported. All exhibited different degrees of tongue hypoplasia, micrognathia, retrognathia with a very narrow space between the left and right halves of the mandible, constricted isthmus, and only one lower incisor. Bone lengthening for the midline mandibular hypoplasia and orthodontic treatment were performed in the three cases with satisfactory results.

Rigid external distraction using skeletal anchorage to cleft maxilla united with alveolar bone grafting.

Objective Documentation of the application of maxillary distraction osteogenesis using rigid external distraction (RED) with skeletal anchorage combined with predistraction alveolar bone grafting (ABG) in cleft maxilla. Design Case report. Patient A patient with numerous congenital missing teeth and severe maxillary deficiency related to complete bilateral cleft lip and palate with large alveolar bone defect. Intervention The patient received preoperative orthodontic treatment, predistraction ABG, and maxillary distraction osteogenesis using RED with skeletal anchorage. Results Predistraction ABG completely united the cleft maxilla. The united maxilla was successfully advanced by the RED system with skeletal anchorage, despite unsound dentition with numerous congenital missing teeth. Conclusion The present study demonstrates that the combination of predistraction ABG and RED system with skeletal anchorage is effective for the treatment of severe maxillary deficiency related to complete bilateral cleft lip and palate with large bone defect and numerous congenital missing teeth.

Transfusion-associated graft-versus-host disease in immunocompetent patient: Early diagnosis and therapy

We report a case of transfusion‐associated graft‐versus‐host disease in a previously healthy, 68‐year‐old Japanese man following an emergency surgery for an acute aortic dissection. We confirmed the chimerism of lymphocytes and the effect of drug therapy using DNA polymorphism analysis. This method is a sensitive, convenient, and rapid method that it is also useful for the evaluation of therapy. And the combination therapy with methylprednisolone, cyclosporine, and 15‐deoxyspergualin may be effective in treating transfusion‐associated GVHD. Am. J. Hematol. 58:84–86, 1998.