Insulin secretion and sensitivity before and after surgical treatment for aldosterone-producing adenoma.

AIM: Primary aldosteronism, which is usually caused by an aldosterone-producing tumour, affects glucose metabolism. The effects of this condition on insulin secretion and insulin sensitivity have remained unclear, however. To gain insight into the influence of primary aldosteronism on glucose tolerance, various parameters related to insulin secretion or insulin sensitivity in patients with an aldosterone-producing tumour were comprehensively analyzed. METHODS: To assess 14 patients with an aldosterone-producing tumour, hyperglycaemic and hyperinsulinaemic-euglycaemic clamp tests as well as oral glucose tolerance tests (OGTTs) were performed before and after tumour excision. Time between presurgical analysis and surgery was 27-559 (194±132) days, and 14-142 (51±38) days between surgery and postsurgical analysis. Various parameters related to insulin secretion or sensitivity as determined by OGTT as well as hyperglycaemic and hyperinsulinaemic-euglycaemic clamp analyses were evaluated. RESULTS: Surgical treatment of tumours ameliorated hypokalaemia and reduced plasma aldosterone levels. First and second phases of insulin secretion during the hyperglycaemic clamp, as well as the insulinogenic index and total insulin secretion measured during OGTT, were also improved after surgery. In addition, the insulin sensitivity index determined during the hyperinsulinaemic-euglycaemic clamp was reduced after surgery. CONCLUSION: Primary aldosteronism impairs insulin secretion.

Efficiency of genomic selection for breeding population design and phenotype prediction in tomato.

Genomic selection (GS), which uses estimated genetic potential based on genome-wide genotype data for a breeding selection, is now widely accepted as an efficient method to improve genetically complex traits. We assessed the potential of GS for increasing soluble solids content and total fruit weight of tomato. A collection of big-fruited F1 varieties was used to construct the GS models, and the progeny from crosses was used to validate the models. The present study includes two experiments: a prediction of a parental combination that generates superior progeny and the prediction of progeny phenotypes. The GS models successfully predicted a better parent even if the phenotypic value did not vary substantially between candidates. The GS models also predicted phenotypes of progeny, although their efficiency varied depending on the parental cross combinations and the selected traits. Although further analyses are required to apply GS in an actual breeding situation, our results indicated that GS is a promising strategy for future tomato breeding design.

AIP mutation identified in a patient with acromegaly caused by pituitary somatotroph adenoma with neuronal choristoma.

Pituitary adenoma with neuronal choristoma (PANCH) is a rare condition that includes ganglion cells and GH-producing tumor that is characterized by sparsely granulated somatotroph cell type. However, the pathophysiology of this condition remains to be elucidated. We report a case of 46-year-old woman with acromegaly caused by PANCH. The patient had a large and invasive macroadenoma that was resistant to preoperative therapy with somatostatin analogue (SSA) and dopamine agonist. Histological examination showed typical diffuse, chromophobe-type adenoma containing ganglion cells, and sparsely granulated somatotroph cell type, which were consistent with PANCH. Genetic analysis showed heterozygous germline missense mutation in the AIP gene that results in Y261X amino acid substitution. The clinical characteristics of acromegaly associated with AIP mutations are reportedly macroadenomas with tumor extension and invasion, lower decreases in GH and IGF-I and less tumor shrinkage with SSA treatment, and sparsely granulated somatotroph cell type, which are comparable with those observed in PANCH. Taken together, the mutation in AIP gene may explain the clinical characteristics and pathogenesis of PANCH.

An in situ hybridization study of the insulin-like growth factor system in developing condylar cartilage of the fetal mouse mandible.

The objective of this study was to investigate the involvement of the insulin-like growth factor (IGF) system in the developing mandibular condylar cartilage and temporomandibular joint (TMJ). Fetal mice at embryonic day (E) 13.0-18.5 were used for in situ hybridization studies using [35S]-labeled RNA probes for IGF-I, IGF-II, IGF-I receptor (-IR), and IGF binding proteins (-BPs). At E13.0, IGF-I and IGF-II mRNA were expressed in the mesenchyme around the mandibular bone, but IGF-IR mRNA was not expressed within the bone. At E14.0, IGF-I and IGF-II mRNA were expressed in the outer layer of the condylar anlage, and IGF-IR mRNA was first detected within the condylar anlage, suggesting that the presence of IGF-IR mRNA in an IGF-rich environment triggers the initial formation of the condylar cartilage. IGFBP-4 mRNA was expressed in the anlagen of the articular disc and lower joint cavity from E15.0 to 18.5. When the upper joint cavity was formed at E18.5, IGFBP-4 mRNA expression was reduced in the fibrous mesenchymal tissue facing the upper joint cavity. Enhanced IGFBP-2 mRNA expression was first recognized in the anlagen of both the articular disc and lower joint cavity at E16.0 and continued expression in these tissues as well as in the fibrous mesenchymal tissue facing the upper joint cavity was observed at E18.5. IGFBP-5 mRNA was continuously expressed in the outer layer of the perichondrium/fibrous cell layer in the developing mandibular condyle. These findings suggest that the IGF system is involved in the formation of the condylar cartilage as well as in the TMJ.

Growth hormone deficiency in 2 siblings associated with combined GH1 gene polymorphisms.

This study was performed to clarify the pathophysiology of familial short stature with moderate GH deficiency.The siblings showed moderate GH deficiency with short stature. Pedigree analysis revealed an accumulation of the history of short stature in father's relatives, although there was no consanguinity.We performed sequencing analysis of GH1 and GHSR gene in the siblings.We detected SNPs in the GH1 gene in the combination of the - 278G, - 57T, +1169T, and +2103C in one allele from the father and the - 278T, - 57G, +1169 A, and +2103T in the other allele from the mother in the siblings. In the previous report, the -278G and - 57T allele are associated with low serum IGF-I levels in patients with isolated GH deficiency and the haplotype of the - 278T, - 57G, +1169 A, and +2103T allele exhibited an impaired GH secretion in vitro.It is suggested that these haplotypes were responsible at least in part for the GH deficiency and short stature in these siblings.

Gliomatosis cerebelli in a Saint Bernard dog.

A 6-year-old, neutered male Saint Bernard dog was presented with a 1-month history of ataxia, hypermetria and head tilt. High-field magnetic resonance imaging revealed a mass in the cerebellar vermis. During necropsy examination, a cream-coloured irregular area was observed in the cerebellar white matter. Microscopically, the mass comprised a diffuse neoplastic proliferation of spindle cells with oval pleomorphic nuclei in the white and grey matter of the cerebellum and pons and in the subpial area. Neoplastic infiltration was not found in the cerebrum. Immunohistochemistry revealed that the neoplastic cells were positive for vimentin and partially positive for glial fibrillary acidic protein. Based on these findings, the neoplastic lesion was diagnosed as gliomatosis cerebelli, without involvement of the cerebrum.

A crucial role of sialidase Neu1 in hyaluronan receptor function of CD44 in T helper type 2-mediated airway inflammation of murine acute asthmatic model.

CD44 is a highly glycosylated cell adhesion molecule that is involved in lymphocyte infiltration of inflamed tissues. We have demonstrated previously that sialic acid residues of CD44 negatively regulates its receptor function and CD44 plays an important role in the accumulation of T helper type 2 (Th2) cells in the airway of a murine model of acute asthma. Here we evaluated the role of sialidase in the hyaluronic acid (HA) receptor function of CD44 expressed on CD4+ T cells, as well as in the development of a mite antigen-induced murine model of acute asthma. Splenic CD4+ T cell binding of HA was examined with flow cytometry. Expression of sialidases (Neu1, Neu2, Neu3 and Neu4) in spleen cells was evaluated by quantitative real-time reverse transcription-polymerase chain reaction. Airway inflammation and airway hyperresponsiveness (AHR) were evaluated in the asthmatic Neu1-deficient mouse strain SM/J model. Splenic CD4+ T cells from asthmatic model mice displayed increased HA receptor activity of CD44 after culture with the antigen, along with characteristic parallel induction of sialidase (Neu1) expression. This induction of HA binding was suppressed significantly by a sialidase inhibitor and was not observed in SM/J mice. Th2 cytokine concentration and absolute number of Th2 cells in the bronchoalveolar lavage fluid, and AHR were decreased in SM/J mice. In conclusion, HA receptor activity of CD44 and acute asthmatic reactions, including Th2-mediated airway inflammation and AHR, are dependent upon Neu1 enzymatic activity. Our observation suggests that Neu1 may be a target molecule for the treatment of asthma.

Evaluation of dural arteriovenous fistulas with 4D contrast-enhanced MR angiography at 3T.

BACKGROUND AND PURPOSE: Four-dimensional contrast-enhanced MR angiography (4D-CE-MRA) at 3T may replace digital subtraction angiography (DSA) for certain diagnostic purposes in patients with intracranial dural arteriovenous fistula (DAVF). The aim of this study was to test the hypothesis that 4D-CE-MRA at 3T enables the same characterization of intracranial DAVFs as DSA. MATERIALS AND METHODS: The study population consisted of 18 consecutive patients with intracranial DAVFs (11 women, 7 men; age range, 35-82 years; mean age, 64.8 years). They underwent 4D-CE-MRA at 3T and DSA. The 4D-CE-MRA series combined randomly segmented central k-space ordering, keyhole imaging, sensitivity encoding, and half-Fourier imaging. We obtained 30 dynamic scans every 1.9 seconds with a spatial resolution of 1 x 1 x 1.5 mm. Two independent readers reviewed the 4D-CE-MRA images for main arterial feeders, fistula site, and venous drainage. Interobserver and intermodality agreement was assessed by kappa statistics. RESULTS: At DSA, 8 fistulas were located at the transverse sigmoid sinus; 8, at the cavernous sinus; and 2, at the sinus adjacent to the foramen magnum. Interobserver agreement was fair for the main arterial feeders (kappa = 0.59), excellent for the fistula site (kappa = 0.91), and good for venous drainage (kappa = 0.86). Intermodality agreement was moderate for the main arterial feeders (kappa = 0.68) and excellent for the fistula site (kappa = 1.0) and venous drainage (kappa = 1.0). CONCLUSIONS: The agreement between 4D-CE-MRA and DSA findings was good to excellent with respect to the fistula site and venous drainage.

Assessment of vascular supply of hypervascular extra-axial brain tumors with 3T MR regional perfusion imaging.

BACKGROUND AND PURPOSE: The vascular supply of extra-axial brain tumors provided by the external carotid artery has not been studied with RPI. The purpose of this work was to determine whether RPI assessment is feasible and provides information on the vascular supply of hypervascular extra-axial brain tumors. MATERIALS AND METHODS: Conventional ASL and RPI studies were performed at 3T in 8 consecutive patients with meningioma. On the basis of MRA results, we performed RPI by placing a selective labeling slab over the external carotid artery. Five patients underwent DSA before surgery. Two neuroradiologists independently evaluated the overall image quality, the degree of tumor perfusion, and the extent of the tumor vascular territory on conventional ASL and RPI. RESULTS: In overall quality of conventional ASL and RPI, no images interfered with interpretation. In comparisons of the vascular tumor territory identified by the conventional ASL and RPI techniques, the territories coincided in 3 cases, were partially different in 4, and completely different in 1. The interobserver agreement was very good (kappa = 0.82). In 5 patients who underwent DSA, the 4 patients in whom the dominant supply was the external carotid artery were scored as coincided or partially different. The 1 patient in whom the vascular supply was from the internal carotid artery was scored as completely different. CONCLUSIONS: RPI with selective labeling of the external carotid artery is feasible and may provide information about the vascular supply of hypervascular extra-axial brain tumors.

Comparison of the added value of contrast-enhanced 3D fluid-attenuated inversion recovery and magnetization-prepared rapid acquisition of gradient echo sequences in relation to conventional postcontrast T1-weighted images for the evaluation of leptomeningeal diseases at 3T.

BACKGROUND AND PURPOSE: The usefulness of contrast-enhanced 3D T2-FLAIR MR imaging for the evaluation of leptomeningeal diseases has not been systematically investigated. The purpose of this study was to assess the value added by contrast-enhanced 3D T2-FLAIR and MPRAGE sequences to conventional postcontrast T1-weighted images in the evaluation of leptomeningeal diseases. We also undertook in vitro studies in attempts to understand the consequences of our patient study. MATERIALS AND METHODS: Twelve patients with confirmed leptomeningeal diseases underwent postcontrast T1-weighted, MPRAGE, and 3D T2-FLAIR imaging at 3T. Two radiologists independently assessed the presence of additional information on postcontrast 3D MR images compared with postcontrast T1-weighted images. The effect of different Gd concentrations and flow velocities on the signal intensity on 3D T2-FLAIR images was investigated in vitro. RESULTS: According to both reviewers, 3D T2-FLAIR images yielded significantly more information than did MPRAGE images (P < .05 and P < .01, respectively). In the in vitro study, 3D T2-FLAIR was more highly sensitive to low Gd concentrations and less sensitive to high Gd concentrations than were T1-weighted or MPRAGE sequences. On 3D T2-FLAIR sequences, at a flow velocity exceeding 1.0 cm/s, the signal intensity of blood-mimicking fluids at concentrations of 0 and 0.1 mmol/L was as low as at 1.3 mmol/L. CONCLUSIONS: For the depiction of leptomeningeal diseases, postcontrast 3D T2-FLAIR provides more additional information than postcontrast MPRAGE imaging. The superiority of the 3D T2-FLAIR sequence is associated with its high sensitivity to flow.

Comparison of survival between anatomic and non-anatomic liver resection in patients with hepatocellular carcinoma: significance of surgical margin in non-anatomic resection.

AIMS: Anatomic resection, i.e., systematic removal of a liver segment confined by portal branches, is theoretically effective in eradicating intrahepatic metastasis of hepatocellular carcinoma (HCC). The procedure may reduce tumour recurrence and enhance survival of HCC patients. To determine the significance of anatomic resection for HCC patients, we retrospectively conducted a comparative analysis between anatomic (AR) and non-anatomic liver resection (NAR) in 113 Japanese HCC patients with a solitary tumour, a tumour located within one segment, absence or invasion of distal to second order branches of the portal vein, and absence or invasion of peripheral branches of the hepatic vein. METHODS: Patients were divided into two groups, AR group (n = 49) and NAR group (n = 64). RESULTS: The prevalence of liver damage Grade B in the NAR group was significantly greater than in the AR group (p < 0.05). Tumour-free and overall survival following liver resection was not significantly different between AR and NAR groups. In the NAR group, tumour-free and overall survival in patients with tumour exposure at the surgical margin was significantly lower than with a surgical margin greater than 0 mm (not exposed) (p < 0.05). Survival between the AR and NAR groups without tumour exposure at the surgical margin was similar. CONCLUSIONS: Anatomic resection is the theoretical aim. In HCC patients with impaired liver functions, limited liver resection without tumour exposure may provide longer tumour-free and overall survival.

Prognostic value of perfusion MR imaging of high-grade astrocytomas: long-term follow-up study.

BACKGROUND AND PURPOSE: Although the prognostic value of perfusion MR imaging in various gliomas has been investigated, that in high-grade astrocytomas alone has not been fully evaluated. The purpose of this study was to evaluate retrospectively whether the tumor maximum relative cerebral blood volume (rCBV) on pretreatment perfusion MR imaging is of prognostic value in patients with high-grade astrocytoma. MATERIALS AND METHODS: Between January 1999 and December 2002, 49 patients (30 men, 19 women; age range, 23-76 years) with supratentorial high-grade astrocytoma underwent MR imaging before the inception of treatment. The patient age, sex, symptom duration, neurologic function, mental status, Karnofsky Performance Scale, extent of surgery, histopathologic diagnosis, tumor component enhancement, and maximum rCBV were assessed to identify factors affecting survival. Kaplan-Meier survival curves, the logrank test, and the multivariate Cox proportional hazards model were used to evaluate prognostic factors. RESULTS: The maximum rCBV was significantly higher in the 31 patients with glioblastoma multiforme than in the 18 with anaplastic astrocytoma (P < .03). The 2-year overall survival rate was 67% for 27 patients with a low (< or =2.3) and 9% for 22 patients with a high (>2.3) maximum rCBV value (P < .001). Independent important prognostic factors were the histologic diagnosis (hazard ratio = 9.707; 95% confidence interval (CI), 3.163-29.788), maximum rCBV (4.739; 95% CI, 1.950-11.518), extent of surgery (2.692; 95% CI, 1.196-6.061), and sex (2.632; 95% CI, 1.153-6.010). CONCLUSION: The maximum rCBV at pretreatment perfusion MR imaging is a useful clinical prognostic biomarker for survival in patients with high-grade astrocytoma.

Magnetic resonance imaging of pilocytic astrocytomas: usefulness of the minimum apparent diffusion coefficient (ADC) value for differentiation from high-grade gliomas.

BACKGROUND: On contrast-enhanced magnetic resonance (MR) images, pilocytic astrocytomas (PAs) are usually well-enhanced tumors that may mimic high-grade gliomas (HGGs). On the other hand, it has been suggested that areas exhibiting minimum apparent diffusion coefficient (ADC) values reflect the sites of highest cellularity within heterogeneous tumors. PURPOSE: To test the hypothesis that the cellularity of PAs is significantly different to the cellularity of HGGs, which should result in significant differences in minimum ADC values. MATERIAL AND METHODS: Between 1999 and 2005, 15 patients (nine males, six females) with histopathologically confirmed PAs underwent pretreatment MR examination including diffusion-weighted (DW) imaging. We reviewed their MR findings with respect to the size, location, morphology, contrast enhancement, and minimum ADC value of the tumors. The minimum ADC values of the 15 PAs were compared with those of 104 HGGs diagnosed during the same period. RESULTS: The diameter of the 15 PAs ranged from 11 to 60 mm (mean 36 mm); all were located around the ventricles, and all contained enhancing components. All except two small (11 and 14 mm) PAs contained cystic components. The minimum ADC values were significantly higher in PAs (median 1.688, range 1.375-1.897 x 10(-3) mm(2)/s) than HGGs (0.997, 0.543-2.024 x 10(-3) mm(2)/s) (P < 0.0001), although there was substantial overlap. Among the tumors with enhancing components, all but one PA were differentiated from the 76 HGGs with enhancing components (0.922, 0.543-1.462 x 10(-3) mm(2)/s) when the minimum ADC cutoff value was set at 1.5 x 10(-3) mm(2)/s. CONCLUSION: The minimum ADC value may be helpful for the differentiation between PAs and HGGs. A tumor with enhancing components should be PA instead of HGG when the minimum ADC value is higher than 1.5 x 10(-3) mm(2)/s.

Differentiation between paraclinoid and cavernous sinus aneurysms with contrast-enhanced 3D constructive interference in steady- state MR imaging.

BACKGROUND AND PURPOSE: Differentiation between paraclinoid and cavernous sinus aneurysms of the internal carotid artery (ICA) is critical when considering treatment options. The purpose of this study was to determine whether contrast-enhanced (CE) 3D constructive interference in steady state (CISS) MR imaging is useful to differentiate between paraclinoid and cavernous sinus aneurysms. MATERIALS AND METHODS: This study included 11 aneurysms in 10 consecutive female patients, ranging from 52 to 66 years of age. All aneurysms were adjacent to the anterior clinoid process. After conventional and CE 3D-CISS imaging on a 1.5T MR imaging unit, all patients underwent surgery, and the relationship between the aneurysms and the dura was confirmed. Two neuroradiologists evaluated the location of the aneurysms on CE 3D-CISS images and classified them as intradural, partially intradural, and extradural aneurysms. Operative findings were used as a reference standard. To understand the imaging characteristics, we assessed the boundary and signal intensity of the cavernous sinus, CSF, and carotid artery on the side contralateral to the lesion. RESULTS: Operative findings disclosed that 5 aneurysms were intradural and 6 were extradural. All except 2 were accurately assessed with CE 3D-CISS imaging. One intradural aneurysm adjacent to a large cavernous aneurysm and 1 cavernous giant aneurysm were assessed as partially intradural. On CE 3D-CISS images, the boundary between the CSF, cavernous sinus, and carotid artery was identified by high signal-intensity contrast in all cases. CONCLUSION: CE 3D-CISS MR imaging is useful for the differentiation between paraclinoid and cavernous sinus aneurysms.

Distribution and frequencies of CDH23 mutations in Japanese patients with non-syndromic hearing loss.

Mutations in the CDH23 gene are known to be responsible for both Usher syndrome type ID (USH1D) and non-syndromic hearing loss (DFNB12), and the molecular confirmation of the CDH23 gene has become important in the diagnosis of these conditions. The present study was performed to find whether the CDH23 mutations are also responsible for non-syndromic hearing loss in patients in the Japanese population. A total of 51 sequence variants were found in 64 Japanese probands with non-syndromic sensorineural hearing impairment from autosomal recessive families. Among them, at least four missense mutations in six patients from five families were confirmed to be responsible for deafness by segregation study. All mutations detected were missense mutations, corroborating the previous reports regarding DFNB12. The present data confirmed that CDH23 mutations are frequently found and significantly responsible in Japanese. Interestingly, the CDH23 mutation spectrum in Japanese is very different from that found in Caucasians. This Japanese spectrum may be representative of those in Eastern Asian populations and its elucidation is expected to facilitate the molecular diagnosis of DFNB12 and USH1D.

Effects of 20-day bed rest with and without strength training on postural sway during quiet standing.

AIM: To examine the effect of unweighting as a possible contributory factor to a reduced calf muscle volume on postural sway during quiet standing, changes in postural sway following bed rest with or without strength training were investigated. METHODS: Twelve young men participated in a 20-day bed-rest study. Subjects were divided into a non-training group (BR-Con) and a strength training group (BR-Tr). For the BR-Tr group, training was comprised of dynamic calf-raise and leg-press exercises to maintain the muscle volume of the plantar flexors. Before and after bed rest, subjects maintained quiet standing in a barefoot position on a force platform with their eyes open or closed. During the quiet stance, foot centre-of-pressure (CoP) and the mean velocity of CoP was calculated. Muscle volume of the plantar flexors was computed using axial magnetic resonance images of the leg. RESULTS: After the bed-rest period, the muscle volume decreased in the BR-Con group but not in the BR-Tr group. The mean velocity of CoP as an assessment of postural sway, however, increased in both groups. These results indicate that the strength training during bed rest cannot counteract the increase in postural sway. CONCLUSION: We concluded that postural sway increases following 20 days of bed rest despite maintenance of the muscle volume of plantar flexors as the main working muscles for the human postural standing.

Folate intakes and folate biomarker profiles of pregnant Japanese women in the first trimester.

OBJECTIVE: To assess the status of dietary folate intake, serum and red blood cell (RBC) folate, and related nutritional biomarkers in healthy Japanese women in early pregnancy. DESIGN: A cross-sectional, observational study. SUBJECTS: Pregnant women in the first trimester, at 7-15 weeks gestation (n=70), who were not consuming any folate supplements or folate fortified foods. METHODS: Three-day dietary records were obtained from each subject to assess dietary folate intake. Blood samples were collected for measurement of biomarkers. Biomarkers and nutrient intake were analyzed in two groups defined by their serum folate concentrations: the low folate group (serum folate < 9 ng/ml) and the high folate group (serum folate > or = 9 ng/ml). RESULT: Mean serum and RBC folate concentrations in all subjects were 10.3 and 519 ng/ml, respectively. These levels were remarkably higher than the reported values from many other countries despite our subjects receiving no folic acids supplements. However, mean folate intake by our subjects from natural foods was 289 microg/day, which is thought to be low according to the Japanese dietary recommendation specified for pregnant women. The intake of spinach and fruits was significantly greater in the high folate group than in the low folate group. CONCLUSION: Folate intake was thought to be adequate to maintain a desirable level of serum folate concentration in Japanese pregnant women in the first trimester, although the intake of folate from natural food was not high enough to meet the recommended daily intake.

Maternal weight gain ranges for optimal fetal growth in Japanese women.

OBJECTIVE: To identify adequate weight gain ranges during pregnancy in Japanese women. METHOD: Obstetric records from 2001 to 2002 for 46,659 term, singleton, vaginally delivered live births was used to estimate IUGR and macrosomia risk. Total maternal weight gain was grouped according to gestational age-specific percentile values of weight gain as follows: "very low" (under the 25th), "low" (25th to 49th), "moderate" (50th to 74th), "high" (75th to 89th), and "very high" (90th and over). RESULTS: About 6% of infants were identified as having IUGR and 0.9% as macrosomia. IUGR risk was elevated with low weight gains. Macrosomia risk was related to high weight gains and previous spontaneous abortions. CONCLUSION: Achieving weight gains between the 50th and 75th percentiles for gestational age was considered adequate for optimal fetal growth in Japanese pregnant women.

Human standing posture control system depending on adopted strategies.

Control of the standing posture of humans involves at least two distinct modes of operation to restore the body balance in the sagittal plane: the ankle strategy and the hip strategy. The objective of the study was to estimate the contribution of vestibular, visual and somatosensory feedbacks to these distinct strategies. The body dynamics was described as the motion of two linked rigid segments that represented the legs and the rest of the body. The posture controller received the inclination angles of the two body segments as inputs and regulated the moments around the ankle and hip joints. The controller had four feedback paths that were characterised by transfer functions connecting the two inputs and the two outputs. To evoke the distinct strategies, the floor conditions were varied by narrowing the support surface under the feet. A continuous pseudo-random external disturbing force was applied to the waist and the thigh independently. The inclination angles of the body segments and the ground reaction force were measured, and the transfer functions of the controller were estimated with the maximum-likelihood system identification procedure. Six healthy male adult subjects participated in the experiment. When the hip strategy became evident under the narrow support surface conditions, the transfer function relating the leg inclination angle and the ankle joint moment decreased its DC gain (16%), whereas the other three transfer functions increased the gains (20-140%) (ANOVA, p < 0.05). Based on a criterion for simplicity in the modification of the posture controller, these changes suggest a new hypothesis that, when posture control becomes difficult, the central nervous system selectively activates the somatosensory feedback paths from the hip joint angle to the moments around the ankle and hip joints.

Runx2-deficient mice lack mandibular condylar cartilage and have deformed Meckel's cartilage.

Runx2 (runt-related transcription factor 2) deficient mice lacked the mandibular condylar cartilage and the mandibular bone. The anlage of the condylar process consisted of mesenchymal condensation, which expressed Type I collagen mRNA and alkaline phosphatase activity, but not Type II collagen and aggrecan mRNAs. Therefore, the differentiation of the mandibular condylar cartilage stopped at the preosteoblast (skeletoblast) stage. The lateral pterygoid muscle was attached to this anlage, and relatively abundant mesenchymal condensations were also formed at the muscle-attaching sites, e.g. the anlage of the mandibular body, the angular and coronoid processes. Three-dimensional reconstruction models showed that each mesenchymal condensation was connected to one another, and roughly outlined the shape of the mandible. Meckel's cartilage in the Runx2-deficient mice had two ectopic cartilaginous processes to which the digastric and myohyoid muscles were attached. These findings indicate that Runx2 is essential for the formation of the mandibular condylar cartilage, as well as for normal development of Meckel's cartilage and that muscle tissues influence mandible morphology.