Three-dimensional longitudinal changes in craniofacial growth in untreated hemifacial microsomia patients with cone-beam computed tomography.

INTRODUCTION: The purpose of this study was to evaluate the concept that the affected and contralateral sides do not grow at the same rate in patients with hemifacial microsomia. Changes in the cranial base, maxilla, mandible, and occlusal plane were evaluated on 3-dimensional images from cone-beam computed tomography data in untreated patients. METHODS: Six patients were classified as having mandibular Pruzansky/Kaban type I, IIA, or IIB hemifacial microsomia. Cone-beam computed tomography (MercuRay; Hitachi, Tokyo, Japan) scans were taken before orthodontic treatment during both growth and postpuberty periods. RESULTS: The cranial base as defined by the position of the mastoid process was in a different position between the affected and contralateral control sides. The nasomaxillary length or height was shorter on the affected side for all 6 patients with hemifacial microsomia regardless of its severity, and it grew less than on the contralateral control side in 5 of the 6 patients. The occlusal plane angle became more inclined in 4 of the 6 patients. The mandibular ramus was shorter on the affected side in all patients and grew less on the affected side in 5 of the 6 patients. The mandibular body grew slower, the same, or faster than on the control side. CONCLUSIONS: The cranial base, position of the condyle, lengths of the condyle and ramus, and positions of the gonial angle and condyle can vary between the affected and contralateral control sides of patients with hemifacial microsomia, with the ramus and nasomaxillary length usually growing slower than they grow on the control side. These results suggest that many factors affect the growth rate of the craniofacial region and, specifically, the mandible in patients with hemifacial microsomia.

Regulation of hair regrowth in alopecic site of IFN-gamma-/- mice by macrophages infiltrating into allograft in IFN-gamma+/+ mice.

We previously demonstrated that around 6 weeks of age, most of the interferon-gamma (IFN-gamma)-/- C57BL/6 mice began to lose morphogenesis-derived hairs in their dorsal and occipital areas and that hair regrowth in the alopecic site was induced by intraperitoneal (i.p.) injection of IFN-gamma and allogeneic Meth A cells. Here, we explored the IFN-gamma mRNA expression in the cells infiltrating into allograft in IFN-gamma(+)/(+) mice by RT-PCR and adoptively transferred specific antigen-minus infiltrates into IFN-gamma-/- mice to assess the hair regrowth inducibility. IFN- gamma mRNA was expressed in the infiltrates on days 3-8 after allografting, with a peak on day 3 or 4, and CD4(+) and F4/80(+) cells were the major producers of IFN-gamma. All infiltrates on day 3 induced hair regrowth, whereas those on days 0-2 or 4-8 were ineffective or partially effective, respectively. The removal of F4/80(+) macrophages from all infiltrates failed to induce hair regrowth, whereas the removal of Ly-6C(+) macrophages rather accelerated the hair regrowth. These results showed that F4/80(+), Ly-6C(+), and CD4(+) and F4/80(+) cells were stimulatory, inhibitory, and IFN-gamma-producing cells, respectively, in the regulation of hair regrowth.

Induction of hair regrowth in the alopecia site of IFN-gamma knockout mice by allografting and IFN-gamma injection into the transplantation site.

We previously demonstrated that around 6 weeks of age most of the interferon-gamma (IFN-gamma)(-/-) but none of the IFN-gamma(+/+) C57BL/6 mice began to lose hair in their dorsal or occipital areas or both and that a single s.c. injection of IFN-gamma into IFN-gamma(-/-) mice at 3 but not at 8 weeks of age (or later) could protect all the mice from alopecia. Here, we report hair regrowth in the alopecia site of IFN-gamma(-/-) mice at 8 weeks of age (or later) by the combination of IFN-gamma and allografting. Skin or tumor allografting and IFN-gamma injections into the transplantation site induced hair regrowth in the alopecia site of IFN-gamma(-/-) mice at 8-66 weeks of age, whereas IFN-gamma injections into the hairless site or allografting alone was ineffective in causing the hair regrowth. Histologic findings showed that the hair cycle in the region of alopecia of IFN-gamma(-/-) mice was blocked at the anagen stage and that in the IFN-gamma(-/-) mice treated with IFN-gamma and allografting, the cycle was at the telogen stage. The therapeutic effects were maintained for >1 year.

Cellular origin of IFN-gamma essential for hair cycle in normal skin.

Hair growth abnormalities in mice usually are accompanied by histologic abnormalities as well. Recently, however, we reported a mouse model in which an arrest of the hair cycle and diffuse shedding of the hair without pathologic features induced alopecia in interferon-gamma(-/-) (IFN-gamma(-/-)) C57BL/6 (B6) mice. Here, we explored the cellular origin of IFN-gamma. When bone marrow from IFN-gamma(-/-) B6 mice was transplanted into lethally irradiated IFN-gamma(+/+) B6 mice, the level of IFN-gamma mRNA expression in the skin or peripheral blood mononuclear cells (PBMCs) of recipient mouse was markedly reduced, suggesting that IFN-gamma is normally produced by bone marrow-derived cells. Although severe combined immunodeficiency (SCID) mice lack mature T cells and B cells, IFN-gamma-dependent hair regrowth was induced in SCID mice by depilation, which caused alopecia in IFN-gamma(-/-) B6 mice. Consistently, IFN-gamma mRNA expression in the skin or PBMC from SCID mice was comparable to that from their genetic counterpart (BALB/c mice), suggesting IFN-gamma production by non-T cells. RT-PCR analyses after separation of PBMC from SCID mice into eight fractions by a cell sorter revealed that Mac-1(+) cells were the major origin of IFN-gamma.

Alopecia of IFN-gamma knockout mouse as a model for disturbance of the hair cycle: a unique arrest of the hair cycle at the anagen phase accompanied by mitosis.

Interferon-gamma(-/-) (IFN-gamma(-/-)) and IFN-gamma(+/+) C57BL/6 mice (3 weeks of age) completed the production of morphogenesis-derived hair. Around 6 weeks of age, however, most of the IFN-gamma(-/-) but none of the IFN-gamma(+/+) mice began to lose hairs in the dorsal and occipital areas in the absence of inflammatory reactions, and the alopecia was sustained for at least several 10-week periods of observation. A single subcutaneous injection of IFN-gamma to IFN-gamma(-/-) mice at 3, but not 4, 5, or 8 weeks of age could protect all the mice from alopecia, revealing that the lack of IFN-gamma around 3 weeks of age is directly responsible for the alopecia. Histologic features showed that the hair follicles of the IFN-gamma(+/+) mice passed through the anagen (4-5 weeks of age) and catagen/telogen ( approximately 6 weeks of age) phases, whereas those of IFN-gamma(-/-) mice (5 weeks of age or older) stayed in the anagen phase. TUNEL and bromodeoxyuridine experiments suggested that an arrest with unlimited DNA synthesis of the hair cycle in the anagen phase by the lack of IFN-gamma-dependent apoptosis in the midfollicle region and diffuse shedding of previously formed hair induced alopecia in IFN-gamma(-/-) mice.