Anti-USAG-1 therapy for tooth regeneration through enhanced BMP signaling.

Uterine sensitization-associated gene-1 (USAG-1) deficiency leads to enhanced bone morphogenetic protein (BMP) signaling, leading to supernumerary teeth formation. Furthermore, antibodies interfering with binding of USAG-1 to BMP, but not lipoprotein receptor-related protein 5/6 (LRP5/6), accelerate tooth development. Since USAG-1 inhibits Wnt and BMP signals, the essential factors for tooth development, via direct binding to BMP and Wnt coreceptor LRP5/6, we hypothesized that USAG-1 plays key regulatory roles in suppressing tooth development. However, the involvement of USAG-1 in various types of congenital tooth agenesis remains unknown. Here, we show that blocking USAG-1 function through USAG-1 knockout or anti-USAG-1 antibody administration relieves congenital tooth agenesis caused by various genetic abnormalities in mice. Our results demonstrate that USAG-1 controls the number of teeth by inhibiting development of potential tooth germs in wild-type or mutant mice missing teeth. Anti-USAG-1 antibody administration is, therefore, a promising approach for tooth regeneration therapy.

Lens Epithelial Cell Damage and Apoptosis in Atopic Cataract. Histopathological and Immunohistochemical Studies.

Purpose: To elucidate the relationship between damage of lens epithelial cells and apoptotic cell death in patients with atopic cataract.Methods: Histopathological and immunohistochemical studies were carried out using anterior lens capsules obtained at surgery from 13 patients with atopic cataract and from 25 patients with senile cataract.Results: No specific histopathological findings were found in the lens epithelial cells in atopic cases. However, the frequency and severity of histopathological findings such as flattening, nuclear pyknosis, and loss of cells were more frequent and more severe in atopic cases than in senile cases. The terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP-biotin nick end labelling (TUNEL) method revealed that the mean ratio of cells containing fragmented DNA to whole epithelial cells was almost the same in both atopic and senile cases. However, the mean ratio of Bax-positive cells was significantly higher in atopic cases (mean +/- standard deviation, 29.1 +/- 35.0%) than in senile cases (2.7+/-7.0%) (P<.05). The mean ratio of Bcl-2-positive cells was significantly lower in atopic cases (1.4+/-3.4%) than in senile cases (44.3+/-35.7%) (P<.05).Conclusion: These results suggest that apoptotic cell death may play an important role in the development of lens epithelial cell damage in atopic cataract.

[Lens epithelial cell damage and apoptosis in atopic cataract--histopathological and immunohistochemical studies].

PURPOSE: To elucidate the relationship between damage of lens epithelial cells and apoptotic cell death in patients with atopic cataract. METHODS: Histopathological and immunohistochemical studies were carried out using anterior lens capsules obtained at surgery from 13 patients with atopic cataract and from 25 patients with senile cataract. RESULTS: No specific histopathological findings were found in the lens epithelial cells in atopic cases. However, the frequency and severity of histopathological findings such as flattening, nuclear pyknosis, and loss of cells were more frequent and more severe in atopic cases than in senile cases. The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labelling (TUNEL) method revealed that the mean ratio of cells containing fragmented DNA to whole epithelial cells was almost the same in both atopic and senile cases. However, the mean ratio of Bax-positive cells was significantly higher in atopic cases (mean +/- standard deviation, 29.1 +/- 35.0%) than in senile cases (2.7 +/- 7.0%) (p < 0.05). The mean ratio of Bcl-2-positive cells was significantly lower in atopic cases (1.4 +/- 3.4%) than in senile cases (44.3 +/- 35.7%) (p < 0.05). CONCLUSION: These results suggest that apoptotic cell death may play an important role in the development of lens epithelial cell damage in atopic cataract.

Limb salvage and survival rates among elderly patients with advanced limb ischemia.

The purpose of this study was to clarify the incidence of limb salvage and patient survival rates among elderly patients with advanced leg ischemia. We reviewed the records of 159 patients treated for advanced ischemia over a 15-year period at Aichi Medical University, 74 of whom were aged over 75 years and 85, between 65 and 74 years. There was a collective total of 186 limbs; 82 in the older group and 104 in the younger group. The older group had a greater proportion of women, and a higher incidence of coronary heart disease, pulmonary dysfunction, and acute onset of advanced ischemia than the younger group. Limb salvage was achieved in 73% of the affected limbs in the older group and in 92% of the limbs in the younger group. The poor limb salvage rate in the older group was mainly related to the high initial amputation rate. Early recognition of the sentinel ischemic signs before the ischemia is essential, especially in the elderly. Timely revascularization should be attempted whenever possible, and it should not be abandoned simply because the patient is deemed too old. The 1-, 3-, and 5-year survival rates in the older group were 59%, 28%, and 23%, respectively, which were markedly poorer than the expected survival rates of the age- and sex-matched Japanese population at 1, 3, and 5 years, which were 93%, 79%, and 65%, respectively. Thus, advanced limb ischemia carries a poor prognosis to the point of being life-threatening, and further continuous systemic management with the collaboration of physicians and surgeons must be provided even after the patient has left the hospital.

Benefits of arterial reconstruction in claudication.

We conducted a midterm follow-up of 150 claudicants who underwent surgical reconstruction by assessing cumulative patency, survival, and palliation (graft patency in live patients) rates. Eighty-nine claudicants (group I) underwent direct (in situ) proximal revascularization, 33 (group II) had indirect (ex situ) proximal revascularization, while 28 (group III) had distal revascularization. The secondary patency rates at 3 years were 97.5% in group I, 97.0% in group II, and 75.0% in group III, respectively. Only one patient with limb graft thrombosis required below-knee amputation. There were 3 perioperative deaths (2 in group I and 1 in group II). The survival rates at 3 years were 86.0% in group I, 69.5% in group II, and 95.8% in group III, respectively. The palliation rates at 3 years were 84.8% in group I, 70.0% in group II, and 77.9% in group III, respectively. These findings indicate the midterm benefits of supra- and infrainguinal arterial reconstructions, and also suggest that the preoperative assessment of risks in individual patients, the selection of the appropriate operative procedure and graft material, and intensive postoperative follow-up and management of any associated disease are all important aspects in the treatment of claudicants.