Prevalent morphometric vertebral fractures as a risk factor for subsequent clinical vertebral fractures after shortfusion surgery in older Japanese women with degenerative spondylolisthesis.

STUDY DESIGN: A retrospective cohort study using the Kaplan-Meier method with propensity-score matching. PURPOSE: To evaluate whether the presence of prevalent morphometric vertebral fractures (VFs) poses a risk for subsequent clinical VFs after short-fusion surgery in women aged ≥60 years with degenerative spondylolisthesis. OVERVIEW OF LITERATURE: VFs are common osteoporotic fractures and are associated with a low quality of life. Subsequent VFs are a complication of instrumented fusion in patients with degenerative lumbar disorders. Thus, risk factors for subsequent VFs after fusion surgery must be analyzed. Population-based studies have suggested that prevalent morphometric VFs led to a higher incidence of subsequent VFs in postmenopausal women; however, no studies have investigated whether prevalent morphometric VFs are a risk factor for subsequent VFs after fusion surgery in patients with degenerative spondylolisthesis. METHODS: The study enrolled a total of 237 older female patients: 50 and 187 patients had prevalent morphometric VFs (VF [+] group) and nonprevalent morphometric VFs (VF [-] group), respectively. The time to subsequent clinical VFs after fusion surgery was compared between the two groups using the Kaplan-Meier method. Moreover, 40 and 80 patients in the VF (+) and VF (-) groups, respectively, were analyzed and matched by propensity scores for age, follow-up duration, surgical procedure, number of fused segments, body mass index, and number of patients treated for osteoporosis. RESULTS: Kaplan-Meier analysis indicated that the VF (+) group had a higher incidence of subsequent clinical VFs than the VF (-) group, and Cox regression analysis showed that the presence of prevalent morphometric VFs was an independent risk factor for subsequent clinical VFs before matching. Kaplan-Meier analysis demonstrated comparable results after matching. CONCLUSIONS: The presence of prevalent morphometric VFs may be a risk factor for subsequent clinical VFs in older women with degenerative spondylolisthesis who underwent short-fusion surgery.

Association between ligamentous stenosis at spondylolisthetic segments before fusion surgery and symptomatic adjacent canal stenosis at follow-up in patients with degenerative spondylolisthesis.

STUDY DESIGN: A retrospective case-control propensity score-matching study. PURPOSE: This study aimed to longitudinally evaluate whether preoperative ligamentous stenosis at the spondylolisthetic segments could affect the incidence of symptomatic adjacent canal stenosis following one-segment fusion surgery. OVERVIEW OF LITERATURE: Several risk factors for symptomatic adjacent canal stenosis following fusion surgery have been assessed. Patients with lumbar canal stenosis mainly due to ligamentum flavum (LF) hypertrophy (ligamentous stenosis) also have LF hypertrophy in other segments. METHODS: In total, 76 patients participated in this case-control study (neurologically symptomatic adjacent canal stenosis, n=33; neurologically asymptomatic cases at follow-up, n=43). Their risk factors during surgery and magnetic resonance (MR) images before the surgery and at follow-up were evaluated. Data from the two groups (n=25 each) were matched using propensity scores for age, sex, time to MR imaging at follow-up, surgical procedure, and LF hypertrophy in adjacent segments before the surgery and analyzed. RESULTS: Compared with the asymptomatic group, the symptomatic adjacent canal stenosis group had a significantly larger LF area/spinal canal area in the spondylolisthetic segments before the surgery. During the follow-up periods (in months), they had a larger LF area/ spinal canal area in the adjacent segments: the two values were significantly correlated. The sensitivity, specificity, and positive and negative predictive values for determining symptomatic adjacent canal stenosis were high compared with on the cutoff value for the LF area/spinal canal area at the spondylolisthetic segments before the surgery. These results were the same after matching. CONCLUSIONS: Symptomatic adjacent canal stenosis is mainly caused by LF hypertrophy. Ligamentous stenosis at the spondylolisthetic segments before fusion surgery might be strongly associated with symptomatic adjacent canal stenosis at follow-up.

Vertebral Osteomyelitis and Infective Endocarditis Co-Infection.

Many cases of vertebral osteomyelitis (VO) and infective endocarditis (IE) co-infection have been reported, and it has been recognized that attention should be paid to the possibility of both diseases co-existing during diagnosis and treatment. However, the incidence, clinical status, and outcomes of IE in patients with VO remain unclear. For this study, the eligibility criteria for patient recruitment included all cases of VO at the five medical university hospitals. Patients with a history of spinal surgery were excluded from this study. Echocardiography was routinely performed for all patients with VO. IE was diagnosed according to the modified Duke criteria for definite endocarditis. We analyzed demographic data, underlying conditions, clinical features, laboratory data, echocardiography, radiologic images, treatments, and outcomes. VO was diagnosed in 59 patients and IE was diagnosed in seven patients (12%). There were no significant differences in the clinical features, microorganisms, or radiographic status between the VO-IE co-infection and VO-only groups. In this study, using routine echocardiography for VO, the IE prevalence was 12%. The lack of specific clinical features and laboratory findings may hamper the diagnosis of IE. Therefore, clinicians are always required to suspect IE in patients with VO.

Is Arthroscopic Hip Labral Repair/Reconstruction Surgery Effective for Treating Femoroacetabular Impingement in the Presence of Osteoarthritis?

OBJECTIVE: To investigate clinical outcomes after arthroscopic labral preservation surgery for femoroacetabular impingement (FAI) in the presence of osteoarthritis (OA) compared with FAI without significant OA. DESIGN: Retrospective case-control study. SETTING: Department of Orthopaedic Surgery and Sports Medicine, Hospital of Academic Institute. PATIENTS: Femoroacetabular impingement patients (n = 97; ≥35 years) undergoing arthroscopic FAI correction with labral preservation surgery from March 2009 to April 2014 were enrolled in this study. INTERVENTIONS: Patients were divided into 2 groups: FAI group (79 patients), with Tonnis grade 0 or 1, and FAI + OA group (18 patients), with Tonnis grade 2 or 3. MAIN OUTCOME MEASURES: We examined the clinical outcomes using the Modified Harris Hip Score (MHHS), Nonarthritic Hip Score (NAHS), and the conversion rate to total hip arthroplasty (THA). RESULTS: No significant differences existed between the 2 groups with respect to age, sex, follow-up period, or preoperative MHHS or NAHS. The mean MHHS and NAHS at the final follow-up were significantly lower in the FAI + OA group than in the FAI group. There was a significant difference in the rate of conversion to THA and failure between the 2 groups (THA 5% vs 50%) (failure 15% vs 67%). CONCLUSION: Patients with FAI in the presence of OA did not improve after arthroscopic labral preservation surgery and had a high conversion rate to THA. LEVEL OF EVIDENCE: Level III.

A Diagnostic Approach to Myelopathy Based on Prognostic Factors in Patients With Lower Extremity Symptoms.

STUDY DESIGN: Case-control study. OBJECTIVE: We aimed to identify predictors for latent myelopathy and to develop a diagnostic protocol based on these factors. SUMMARY OF BACKGROUND DATA: There is no diagnostic protocol for latent myelopathy to avoid misdiagnosis in patients complaining only of lower extremity symptoms. METHODS: This case-control study identified 791 patients discussed at conferences from April 2006 to August 2012. Overall, 460 patients complaining only of lower extremity symptoms and who underwent spine surgery were included as participants; 54 underwent surgery involving the cervical and thoracic vertebrae and were assigned to the cervical-thoracic group (C-T group); 406 underwent lumbar surgery and were assigned to the lumbar group (L group). RESULTS: By univariate analysis, age ≥67 years, patellar tendon (PT) hyperreflexia, Achilles tendon (AT) hyperreflexia, spastic gait, and gait inability were more common in the C-T group than in the L group. By multivariate analysis, age ≥67 years (OR, 8; P = 0.001), AT hyperreflexia (OR, 20.5; P < 0.001), spastic gait (OR, 225; P < 0.001), and gait inability (OR, 64; P < 0.001) were significant predictive factors. In patients with age ≥67 years, PT hyperreflexia, and/or AT hyperreflexia, the sensitivity for myelopathy diagnosis was 98%. In patients with spastic gait or gait inability, the specificity of myelopathy diagnosis was 96%. CONCLUSIONS: We analyzed factors that predict latent myelopathy in patients complaining only of lower extremity symptoms. We believe a diagnostic protocol based on the predictors shown in this study would contribute to the accurate diagnosis of latent myelopathy. LEVEL OF EVIDENCE: 4.

Attenuation of Post-Traumatic Osteoarthritis After Anterior Cruciate Ligament Injury Via Inhibition of Hedgehog Signaling.

We aimed to investigate whether post-traumatic osteoarthritis (PTOA) progression is appropriately represented by a PTOA mouse model using a unique climbing cage to add mechanical loading after anterior cruciate ligament (ACL) transection and to determine how Hedgehog signaling inhibition prevents PTOA progression by observing time-dependent morphological changes. This controlled laboratory study histologically compared mice with surgically-induced ACL transection (ACLT) and those with voluntary increased activity in a climbing cage from 1 week postoperatively (ACLT + climbing). We generated conditional knockout (cKO) mice with a deleted Smoothened (Smo) gene. Time-dependent histopathological, immunohistochemical, and gene expression analyses were performed. The ACLT + climbing group showed more severe cartilage defects and massive osteophyte formation than the ACLT group. Smo deletion significantly suppressed PTOA progression. The time-dependent assessment revealed cartilaginous processes of equivalent size at the posterior tibial margin in the Smo cKO and control mice at 4 weeks postoperatively. However, at 8 weeks postoperatively, mature ossifying lesions were detected in the controls but not in Smo cKO mice. In the articular cartilage, ADAMTS5 and RUNX2 expression were observed in hypertrophic chondrocytes near the defective cartilage in controls but not in Smo cKO mice. Climbing exercise after ACLT accelerated PTOA progression more severely not only through increasing joint instability induced by ACLT but also through mechanical loading force induced by climbing exercise. Hedgehog signaling inhibition attenuated PTOA progression by suppressing chondrocyte hypertrophy induced by mechanical loads, to which ACL-deficient athletes are usually exposed. Thus, Hedgehog signaling inhibition may be a therapeutic option to prevent arthritic changes in athletes. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:609-619, 2020.

Findings as a starting point to unravel the underlying mechanisms of in vivo interactions involving Wnt10a in bone, fat and muscle.

Wnt10a is a member of the WNT family. Although deficiency of this gene causes symptoms related to teeth, hair, nails, and skin, we recently demonstrated a new phenotype of Wnt10a knockout (KO) mice involving bone and fat. The in vivo effect of the Wnt10a gene on bone and fat is unclear, and the relationship between bone/fat and muscle in Wnt10a signaling is also interesting. We aimed to evaluate the tissue changes in Wnt10a KO mice compared to wild-type mice and show the findings as a starting point to unravel the underlying mechanisms of in vivo interactions involving Wnt10a in bone, fat and muscle. Trabecular bone loss in the lower limbs of Wnt10a mice and decreased bone mineralization were observed. The adipose tissue in bone marrow was also decreased, and adipocyte differentiation was reduced. The body fat mass in Wnt10a KO mice was decreased, and white adipocytes in subcutaneous fat were converted to beige adipocytes. The muscle weight of the lower limbs was not decreased despite trabecular bone loss, but Gdf8/myostatin expression was reduced in the subcutaneous fat and gastrocnemius muscles of Wnt10a KO mice. Thus, in vivo deletion of Wnt10a inhibited osteogenic activity, promoted beige adipogenesis of white adipocytes and maintained muscle mass. These results suggest that regulation of Gdf8 by Wnt10a may help maintain the muscle mass of Wnt10a KO mice. This study was the first to histologically evaluate the bone, fat and muscle phenotypes of Wnt10a KO mice. The results of this study, which were obtained by investigating the three tissues together, could influence the understanding of in vivo interactions involving the Wnt10a gene.

Systemic bone loss, impaired osteogenic activity and type I muscle fiber atrophy in mice with elastase-induced pulmonary emphysema: Establishment of a COPD-related osteoporosis mouse model.

Although it is suggested that chronic obstructive pulmonary disease (COPD) and bone are related, almost all of the pathological mechanisms of COPD-related osteoporosis remain unknown. There is a mouse model showing a deterioration of bone quality after cigarette smoke exposure; however, in smoking exposure models, various factors exist that affect bone metabolism, such as smoking and body weight loss (muscle and fat mass loss). We considered it appropriate to use an elastase-induced emphysema model to exclude factors influencing bone metabolism and to investigate the influence of pulmonary emphysema on bone metabolism. The purpose of this study was to establish a COPD/emphysema-related osteoporosis mouse model by using the elastase-induced emphysema model. The lumbar vertebrae and femurs/tibiae exhibited trabecular bone loss and impaired osteogenic activity in 24-week-old male elastase-induced emphysema model mice. In addition, the model mice showed atrophy of type I muscle fibers without atrophy of type II muscle fibers. We believe that the mice described in this experimental protocol will be accepted as a COPD/emphysema-related osteoporosis mouse model and contribute to further investigations.

Arthroscopic treatment for symptomatic lateral discoid meniscus: The effects of different ages, groups and procedures on surgical outcomes.

BACKGROUND: There is a paucity of literature regarding the results of arthroscopic saucerization, with or without stabilization, for lateral discoid meniscus (LDM) in children, and differences in clinical outcomes between adults and children. The purpose of this study was to compare the clinical outcomes following arthroscopic treatment of symptomatic LDM in children versus adults. Secondly, outcomes of different surgical procedures (saucerization only and saucerization with repair or centralization) were also compared. METHODS: Fifty-two consecutive patients with LDM were evaluated and divided into two groups. Group 1 had 16 patients (18 knees; nine males, seven females) aged <13 years; Group 2 had 36 patients (38 knees; 19 males, 17 females) aged ≥13 years. All patients were arthroscopically treated with saucerization only, or saucerization with repair or centralization for LDM. They had a mean follow-up of 30 months (range 24-72). Clinical outcomes were compared preoperatively and at final follow-up (minimum two years) after surgery using patient-reported outcome scores, International Knee Documentation Committee (IKDC) scores, and Lysholm scores. Radiographic evaluation was also performed for degenerative changes using Kellgren-Lawrence classification. RESULTS: The IKDC scores at final follow-up in Group 1 demonstrated better clinical outcomes when compared with those in Group 2 (91.1 ±â€¯9.49 vs. 73.7 ±â€¯16.4, P = 0.001). No significant intergroup difference was noted at the follow-up for radiographic osteoarthritic grade according to Kellgren-Lawrence classification. Similarly, no differences were found at final follow-up between saucerization only and saucerization with repair or centralization. There were no significant differences in IKDC score of repair and centralization at final follow-up. CONCLUSIONS: Clinical outcomes in children aged <13 years was significantly better than those aged ≥13 years. Arthroscopic saucerization only or saucerization with repair or centralization for discoid meniscus was effective in improving knee function and preventing early degenerative changes during short-term follow-up periods.

A Comparison of Clinical Outcome Between Athletes and Nonathletes Undergoing Hip Arthroscopy for Femoroacetabular Impingement.

OBJECTIVE: To compare the clinical outcome of arthroscopic surgery for femoroacetabular impingement (FAI) between athlete and nonathlete patients. DESIGN: Retrospective case-control study. Level of Evidence III. PATIENTS AND METHODS: Seventy-four patients who underwent arthroscopic FAI correction from March 2009 to April 2012 were enrolled in this study. The patients were divided into 2 groups, according to their sports participation (47 in the athlete group and 27 in the nonathlete group). MAIN OUTCOME MEASURES: We reviewed clinical and radiographic data for all patients, up to a minimum of 2 years after surgery. We used analysis of covariance to compare the mean patient reported outcome scores including modified Harris hip score (MHHS) and the nonarthritis hip score (NAHS) preoperatively, at 6, 12, and 24 months after surgery. RESULTS: The mean age at the time of surgery in the athlete group was significantly lower than that in the nonathlete group. Although there was no significant difference in preoperative MHHS and NAHS, the mean NAHS at 6, 12, and 24 months postoperatively and the mean MHHS at 24 months postoperatively in athletes were significantly higher than that in nonathletes (P < 0.05). CONCLUSIONS: Although arthroscopic FAI correction and labral preservation surgery is generally beneficial, it appears to provide a better clinical outcome in athletes than in nonathletes.

Total or partial vertebrectomy for lung cancer invading the spine.

BACKGROUND: Surgery for lung cancer invading the spine remains challenging associated with high morbidity and mortality. However, recent advances in surgical techniques as well as in perioperative care may improve outcomes of lung cancer surgery with vertebrectomy. We describe our surgical approach and assess the outcome lung cancer invading the spine. METHODS: We retrospectively reviewed our recent experiences of lung cancer with vertebral invasion, in which we have performed total or partial vertebrectomy from January 2011 through April 2015. RESULTS: We experienced eight patients who were treated with partial or total vertebrectomy for lung cancer. Vertebral invasion was evaluated by chest CT and MRI findings. All cases were no distant metastasis. N factors were all patients N0 revealed by chest CT and PET-CT. Two patients were treated preoperative induction therapy (CDDP + TS-1, Radiation 50 Gy). For the surgery, total vertebrectomy was performed two patients, hemi vertebrectomy was two patients, transverse-process resection was four patients. In all of eight cases, complete resection were perfomed with total or partial vertebrectomy. Morbidity was observed in six patients (75%); no mortality occurred. Six patients (75%) were survived after surgery (range: 12-62 months) and four patients (50%) were no recurrence. Five years overall survival rate was 71.4%. CONCLUSIONS: In our experience, Lung cancer surgery combined with vertebrectomy is highly aggressive surgery associated with high morbidity. But, this procedure is a promising treatment option for selected patients, for example N0M0 disease with lung cancer invading the spine.

Total vertebrectomy (Th2) and dissection of the subclavian artery for a superior sulcus tumor invading the spine: A case report.

INTRODUCTION: Surgery for primary lung cancer invading the spine remains challenging. Here, we present a case of superior sulcus tumor (SST) with vertebral invasion, successfully resected with total vertebrectomy (Th2) and dissection of involved apical chest wall and the subclavian artery (SCA). PRESENTATION OF CASE: A 62-year-old man was referred with the diagnosis of lung squamous cell carcinoma originating from left upper lobe (clinical stage IIIA/T4N0M0) involving the thoracic vertebrae (Th2) as well as the apical chest wall including three ribs (1st, 2nd and 3rd) and SCA. After induction concurrent chemo-radiotherapy, we achieved complete resection by three-step surgical procedures as follows: first, the anterior portion of involved chest wall including SCA was dissected through the trans-manubrial approach (TMA); next, the posterior portion of involved chest wall including ribs was dissected and left upper lobectomy with nodal dissection was performed through posterolateral thoracotomy; finally, total vertebrectomy (Th2) was performed through posterior mid-line approach. DISCUSSION: This tumor was existence of anterior and posterior position in pulmonary apex region. So that, it is very important for complete resecting this complicated tumor to work out operation's strategy. CONCLUSION: Surgery may be indicated for SST invading the spine, when complete resection is expected.

Intratumoral hemorrhage because of primary spinal mixed germ cell tumor presenting with atypical radiological features in an adult.

BACKGROUND CONTEXT: Germ cell tumors are known to arise in the central nervous system, usually in the intracranial regions. However, primary spinal mixed germ cell tumors are extremely rare. PURPOSE: This is the first reported case of intratumoral hemorrhage because of a primary spinal mixed germ cell tumor consisting of germinoma and immature teratoma in the conus medullaris of an adult patient that presented with rapid changes on magnetic resonance image (MRI). We report this rare case and discuss the clinical manifestations of an intramedullary spinal mixed germ cell tumor in adult. STUDY DESIGN: A case report. METHODS: A 42-year-old woman experienced buttock numbness, and a spinal cord tumor was observed on the conus medullaris on MRI. The patient was scheduled for an operation in 1 month, but she developed sudden-onset neurologic deterioration. Rapid progression of the tumor was observed on follow-up MRI. The tumor was removed by emergency surgery and was identified as a primary mixed germinoma and immature teratoma. RESULTS: The patient received adjuvant chemotherapy and radiotherapy after gross total resection. The neurologic deficit of the patient was relieved, and recurrence of the tumor was not observed 26 months after the surgery. CONCLUSIONS: We present this rare case and emphasize the necessity of precise diagnosis and early treatment of primary spinal germ cell tumor. Close observation on MRI is required after surgery, and adjuvant chemotherapy and radiotherapy should be considered according to the pathologic features.

Total vertebrectomy for non-small cell lung cancer.

We present a case who had left upper lobectomy with total vertebrectomy after arterial embolization in preparation for intraoperative bleeding. A 35-year-old man complained of left back pain. Chest CT revealed a tumor in S1+2 of the left lung, invading the third thoracic vertebra. As no nodal or distant metastasis was detected, we performed left upper lobectomy and lymph node dissection (ND2a-2) after embolization of the vessels feeding the tumor in order to reduce intraoperative bleeding. In addition, the team of orthopedics performed en bloc resection of the third thoracic vertebra and parts of the left third and fourth ribs. Histological examination of the tumor revealed pleomorphic carcinoma (pT4N0M0, stage IIIA).

Cre-mediated recombination can induce apoptosis in vivo by activating the p53 DNA damage-induced pathway.

Cre-mediated apoptosis has been observed in many contexts in mice expressing Cre-recombinase and can confound the analysis of genetically engineered conditional mutant or transgenic alleles. Several mechanisms have been proposed to explain this phenomenon. We find that the degree of apoptosis induced correlates roughly with the copy number of loxP sites present in the genome and that some level of increased apoptosis accompanies the presence of even only a few loxP sites, as occurs in conditional floxed alleles. Cre-induced apoptosis in this context is completely p53-dependent, suggesting that the apoptosis is stimulated by p53 activation in response to DNA damage incurred during the process of Cre-mediated recombination.

IGF-1R signaling in chondrocytes modulates growth plate development by interacting with the PTHrP/Ihh pathway.

Systemic derangements and perinatal death of generalized insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R) knockout mice preclude definitive assessment of IGF-1R actions in growth-plate (GP) chondrocytes. We generated cartilage-specific Igf1r knockout ((Cart) Igf1r(-/-)) mice to investigate local control of chondrocyte differentiation in the GP by this receptor. These mice died shortly after birth and showed disorganized chondrocyte columns, delayed ossification and vascular invasion, decreased cell proliferation, increased apoptosis, and increased expression of parathyroid hormone-related protein (Pthrp) RNA and protein in their GPs. The increased Pthrp expression in the knockout GPs likely was due to an increase in gene transcription, as determined by the increased activity of a LacZ reporter that was inserted downstream of the endogenous PTHrP promoter and bred into the knockout mice. To circumvent the early death of (Cart) Igf1r(-/-) mice and investigate the role of IGF-1R during postnatal growth, we made tamoxifen (Tam)-inducible, cartilage-specific Igf1r knockout ((TamCart) Igf1r(-/-)) mice. At 2 weeks of age and 7 to 8 days after Tam injection, the (TamCart) Igf1r(-/-) mice showed growth retardation with a disorganized GP, reduced chondrocyte proliferation, decreased type 2 collagen and Indian Hedgehog (Ihh) expression, but increased expression of PTHrP. Consistent with in vivo observations, in vitro knockout of the Igf1r gene by adenoviral expression of Cre recombinase suppressed cell proliferation, promoted apoptosis, and increased Pthrp expression. Our data indicate that the IGF-1R in chondrocytes controls cell growth, survival, and differentiation in embryonic and postnatal GPs in part by suppression of Pthrp expression.

A role for the mesenchymal T-box gene Brachyury in AER formation during limb development.

During limb development, several signaling centers organize limb pattern. One of these, the apical ectodermal ridge (AER), is critical for proximodistal limb outgrowth mediated by FGFs. Signals from the underlying mesoderm, including WNTs and FGFs, regulate early steps of AER induction. Ectodermal factors, particularly En1, play a critical role in regulating morphogenesis of a mature, compact AER along the distal limb apex, from a broad ventral ectodermal precursor domain. Contribution of mesodermal factors to the morphogenesis of a mature AER is less clear. We previously noted that the chick T gene (Brachyury), the prototypical T-box transcription factor, is expressed in the limb bud as well as axial mesoderm and primitive streak. Here we show that T is expressed in lateral plate mesoderm at the onset of limb bud formation and subsequently in the subridge mesoderm beneath the AER. Retroviral misexpression of T in chick results in anterior extension of the AER and subsequent limb phenotypes consistent with augmented AER extent and function. Analysis of markers for functional AER in mouse T(-/-) null mutant limb buds reveals disrupted AER morphogenesis. Our data also suggest that FGF and WNT signals may operate both upstream and downstream of T. Taken together, the results show that T plays a role in the regulation of AER formation, particularly maturation, and suggest that T may also be a component of the epithelialmesenchymal regulatory loop involved in maintenance of a mature functioning AER.