Epigenetic Regulation of Ameloblast Differentiation by HMGN Proteins.

Dental enamel formation is coordinated by ameloblast differentiation, production of enamel matrix proteins, and crystal growth. The factors regulating ameloblast differentiation are not fully understood. Here we show that the high mobility group N (HMGN) nucleosomal binding proteins modulate the rate of ameloblast differentiation and enamel formation. We found that HMGN1 and HMGN2 proteins are downregulated during mouse ameloblast differentiation. Genetically altered mice lacking HMGN1 and HMGN2 proteins show faster ameloblast differentiation and a higher rate of enamel deposition in mice molars and incisors. In vitro differentiation of induced pluripotent stem cells to dental epithelium cells showed that HMGN proteins modulate the expression and chromatin accessibility of ameloblast-specific genes and affect the binding of transcription factors epiprofin and PITX2 to ameloblast-specific genes. Our results suggest that HMGN proteins regulate ameloblast differentiation and enamel mineralization by modulating lineage-specific chromatin accessibility and transcription factor binding to ameloblast regulatory sites.

Modification of LSC spectra of 125I by high atomic number elements.

The 125I pulse-height spectra via a liquid scintillation counter (LSC) displayed notable variations. The counting efficiencies of higher and lower energy peaks increased and decreased, respectively, with the enhancement of the amount of high atomic numbered elements within the cocktails. This tendency was ascribed to the increasing probability of the interaction of photons with the scintillation cocktail. Moreover, it was noted that the shape of a 125I spectrum strongly depends on the amount of high atomic numbered elements.

A functional SNP upstream of the beta-2 adrenergic receptor gene (ADRB2) is associated with obesity in Oceanic populations.

OBJECTIVE: Obesity is a growing health concern in the Oceanic populations. To investigate the genetic factors associated with adult obesity in the Oceanic populations, the association of single nucleotide polymorphisms (SNPs) of the beta-2 adrenergic receptor (ADRB2) gene with obesity was examined in 694 adults living in Tonga and Solomon Islands. RESULTS: A screening for variation in 16 Oceanic subjects detected 17 SNPs in the entire region of ADRB2, of which nine SNPs including two non-synonymous ones, rs1042713 (Arg16Gly) and rs1042714 (Gln27Glu), were further genotyped for all subjects. The rs34623097-A allele, at a SNP located upstream of ADRB2, showed the strongest association with risk for obesity in a logistic regression analysis adjusted for age, sex, and population (P=5.6 × 10(-4), odds ratio [OR]=2.5, 95% confidence interval [CI]=1.5-4.2). The 27Glu was also significantly associated with obesity in the single-point association analysis (P=0.013, OR=2.0, 95%CI=1.2-3.4); however, this association was no longer significant after adjustment for rs34623097 since these SNPs were in linkage disequilibrium with each other. A copy of the obesity-risk allele, rs34623097-A, led to a 1.6 kg/m(2) increase in body mass index (BMI; defined as weight in kilograms divided by height in meters squared) (P=0.0019). A luciferase reporter assay indicated that rs34623097-A reduced the transcriptional activity of the luciferase reporter gene by approximately 10% compared with rs34623097-G. An electrophoretic mobility shift assay demonstrated that rs34623097 modulated the binding affinity with nuclear factors. An evolutionary analysis implies that a G>A mutation at rs34623097 occurred in the Neandertal genome and then the rs34623097-A allele flowed into the ancestors of present-day humans. CONCLUSION: The present results suggest that rs34623097-A, which would lead to lower expression of ADRB2, contributes to the onset of obesity in the Oceanic populations.

[Intractable pneumothorax secondary to pulmonary metastasis of angiosarcoma].

A 68-year-old male suffered from right pneumothorax and was admitted to our hospital. He had a previous history of angiosarcoma of the scalp, and had received local resection and chemoradiotherapy. Chest computed tomography (CT) on admission revealed right pneumothorax and bilateral multiple thin-walled cavities of the lung. We performed partial resection of right lung. Histopathological examination showed a small metastatic lesion around the thin-walled cavities of the lung. Four months after the 1st lung resection, he suffered left pneumothorax. We performed partial resection of the left lung. Ten days after the 2nd lung resection, left pneumothorax recurred. Nine days later, he also developed right pneumothorax. We performed the 3rd operation for right lung. Thoracoscopy demonstrated multiple bullas in right lung and it showed impossibility for radical surgery. Although surgical resection for pneumothorax secondary to metastatic lung cancer is usually efficient, it is very hard to manage the pneumothorax of metastatic angiosarcoma.

The effects of a neutrophil elastase inhibitor on the postoperative respiratory failure of acute aortic dissection.

BACKGROUND: Postoperative respiratory failure is often encountered in patients suffering from acute aortic dissection (AAD) and is believed to be influenced by release of neutrophil elastase after cardiopulmonary bypass. Sivelestat is a specific neutrophil elastase inhibitor, and this study aims to evaluate the effects of sivelestat on postoperative respiratory failure due to AAD. METHODS AND RESULTS: Patients who were operated for AAD from January 2000 to April 2005 and who had less than 300 mmHg initial postoperative PaO (2)/FiO (2) were investigated retrospectively and divided into two groups. Group 1 (n = 9) received intravenous administration of sivelestat immediately after the operation, while Group II (n = 9) received no sivelestat. There were no significant differences between Group I and II with respect to patients' characteristics or background (age, body weight, operating time, cardiopulmonary bypass time, amount of bleeding, preoperative WBC number and initial PaO (2)/FiO (2)). Though patients in Group I showed a subtle improvement in certain parameters such as PaO (2)/FiO (2), A-aDO (2) and respiratory index (RI) over a 3-day observation period compared to those of Group II, there were no significant differences. Neither postoperative mechanical ventilation time nor ICU stay differed between Group I and II. However, Group I showed a significantly greater improvement in the ratio of RI to initial RI on the 3POD compared to that of Group II (61.6 +/- 44.2 % vs. 111.9 +/- 40.9 %, P = 0.02). CONCLUSION: Inhibiting the activity of the neutrophil elastase may attenuate the postoperative respiratory complications of patients with AAD.

Focal T2 hyperintensity in the dorsal brain stem in patients with vestibular schwannoma.

BACKGROUND AND PURPOSE: The vestibular nucleus cannot be visualized on MR imaging, but some patients with vestibular schwannoma show a tiny area of hyperintensity in the dorsal brain stem on T2-weighted images. The aim of this study was to determine whether this tiny area is characteristic of vestibular schwannoma. METHODS: We retrospectively reviewed the postoperative MR images of 53 patients with cerebellopontine angle tumor. MR images were obtained with a 1.5T scanner. Spin-echo pre- and postcontrast 3-mm-thick T1-weighted axial images, 3-mm-thick fast spin-echo (FSE) T2-weighted axial images, and 0.8-mm-thick constructive interference in steady state (CISS) axial images were acquired. Surgical and histopathologic diagnosis was vestibular schwannoma (41/53 = 77%), meningioma (7/53 = 13%), epidermoid cyst (3/53 = 6%), glioma with exophytic growth (1/53 = 2%), and chordoma (1/53 = 2%). RESULTS: A tiny area of hyperintensity was observed at the lateral angle of the fourth ventricle floor in 6 patients (3 men, 3 women; age range, 24-54 years; mean age, 43 years) with vestibular schwannoma larger than 2 cm in maximal diameter on both FSE T2-weighted and CISS images. Preoperative MR images with the same pulse sequences showed the same area of hyperintensity in all these patients. CONCLUSION: Because the location of the area of hyperintensity is coincident with the vestibular nucleus, the hyperintensity may represent degeneration of the nucleus. This hyperintensity should not be confused with a postoperative lesion or a small infarction. If such hyperintensity is seen in a patient with a large cerebellopontine angle tumor, a diagnosis of vestibular schwannoma is suggested.

Chart analysis of body composition change among pre- and postadolescent Japanese subjects assessed by underwater weighing method.

OBJECTIVE: To examine the effect of age on the relationship between fat-free mass (FFM) and fat mass (FM), and fat-free mass index (FFMI) and fat mass index (FMI) by applying body composition chart analysis on pre- and postadolescent Japanese subjects. SUBJECTS AND METHOD: A sample of 516 children (244 boys and 272 girls) ranging in age from 11 to 17 y and 840 adults (288 male and 552 female subjects) ranging in age from 18 to 59 y were studied to determine a body composition by an underwater weighing method. FMI and FM were put on an x- and y-axis in body composition chart 1, and FFMI (FFM/ height(2)) and FMI (FM/height(2)) were taken on an x- and y-axis in body composition chart 2. RESULTS: In body composition chart 1, the plots for male subjects stayed flat from 11 to 14 y and after that a steady growth of FFM concurring with the FM growth was observed. During the adult stage, steady increments of FM and gradual decreases of FFM were observed. In body composition chart 2, steady increases of FFMI and gradual decreases of FMI were indicated in the male preadolescent period. In the adult stage, FFMI decreased year by year, although the FMI continued to increase. In female subjects, a conspicuous increase of FMI was observed throughout all periods of the present subjects. After middle age, the decline of FFMI was characteristically demonstrated in the chart. CONCLUSION: The relationships between FFM and FM are characteristically delineated on the body composition charts demonstrating clear gender differences. The change of body mass index was not reflecting the change of adiposity level in male subjects, although it was occurring along with the changes of the adiposity level in female subjects.

Atrophy of the basal ganglia as the initial diagnostic sign of germinoma in the basal ganglia.

Germ-cell tumors of the central nervous system generally develop in the midline, but the tumors can also occur in the basal ganglia and/or thalamus. However, MR images have rarely been documented in the early stage of the tumor in these regions. We retrospectively reviewed MR images obtained on admission and approximately 3 years earlier in two patients with germinoma in the basal ganglia, and compared them with CT. In addition to hyperdensity on CT, both hyperintensity on T1-weighted images and a small hyperintense lesion on T2-weighted images were commonly seen in the basal ganglia. These findings may be early MRI signs of germinoma in this region, and the earliest and most characteristic diagnostic feature on MRI was atrophy of the basal ganglia, which was recognizable before development of hemiparesis.

MRI of high-grade astrocytic tumors: early appearance and evolution.

The clinical management and prognosis of patients with diffusely infiltrating astrocytomas are dependent on neuropathological grading of the tumors. The characteristics of MR images of high-grade astrocytic tumors are well known, but the early MRI appearance and the MRI evolution of high-grade astrocytic tumors have rarely been examined. We retrospectively reviewed MR images obtained from 4 months to 3 years and 3 months before admission, as well as MR images on admission, for five patients with pathologically proven high-grade astrocytic tumors (two glioblastomas and three anaplastic astrocytomas). In two patients, neoplastic lesions were not detectable on initial MRI, even retrospectively. In the remaining three patients, however, hyperintense areas with little or no mass effect were demonstrated on T2-weighted imaging. These lesions were misinterpreted as non-neoplastic processes, such as ischemic lesion or infarction, or demyelinating processes. All tumors showed gadolinium enhancement on admission, that emerged from the previously existing hyperintense areas on T2-weighted images without gadolinium enhancement, except for one de novo glioblastoma. Development of a small central cyst without gadolinium enhancement was demonstrated in one case before the emergence of an enhancing area.

MRI in essential primary cutis verticis gyrata.

We report MRI findings in four patients with essential primary cutis verticis gyrata (CVG). The patients were all men, aged 49-81 years (mean 65 years). They had no symptoms related to this rare scalp condition, preceding scalp disease or associated systemic disease. Coronal images showed a characteristic corrugated appearance of the thickened scalp at the vertex, diagnostic of CVG. Neuroradiologists should be aware of this condition.

Embryonic development in the eggs of the silkworm, Bombyx mori, exposed to the space environment.

To investigate the effects of cosmic radiation and microgravity on embryogenesis and organogenesis in Bombyx eggs, two different stages of eggs, the early stage after oviposition and the diapause-terminated eggs, were loaded on the US Space Shuttle/Atlantis (STS-84) for a 9 day flight. More than 85% of the early stage eggs hatched in the flight sample and the ground control. In the diapause-terminated eggs, the percentage of unhatched eggs were 43% in the ground control and 56% in the flight sample. In these eggs, uncompleted embryonic reversal was observed two-fold higher percentage in the flight sample than in the ground control. The incidence of abnormality such as the larvae with segmental fusion and the appearance of abnormal crescent marking in the flight sample was significantly higher than that in the ground control. This was also observed in the 1st and 2nd filial generation of the flight sample. From these results, unsuccessful blastokinesis and the abnormal appearance was discussed in relation to cosmic radiation and microgravity.

Intratumoral hemorrhage from a posterior fossa tumor after cardiac valve surgery--case report.

A 53-year-old woman suffered intracranial hemorrhage from a cerebellar tumor several days after aortic valve replacement. Surgical intervention was not performed because the patient refused blood infusion for religious reasons (Jehovah's Witness). Instead, the anticoagulation therapy was interrupted for a week, and the patient was conservatively treated with administration of mannitol and steroid. The anticoagulation therapy was restarted 7 days after the hemorrhage. The intratumoral hemorrhage did not recur, and no systemic embolism occurred. The tumor was treated with gamma knife radiosurgery 6 weeks after the hemorrhage, under the radiological diagnosis of meningioma. Anticoagulation therapy is routinely used for patients following cardiac surgery to decrease the risk of thromboembolic complications, but also increases the risk of hemorrhagic events which often involve the central nervous system. Temporary discontinuation of anticoagulation therapy is an option for intratumoral hemorrhage in patients with replacement heart valves, and patients with known brain tumors should be informed about the risk of intracranial hemorrhage before cardiac surgery.

Sphingosine-1-phosphate and lysophosphatidic acid trigger invasion of primitive hematopoietic cells into stromal cell layers.

A new primitive hematopoietic cell line (THS119), exhibiting Lin(-)/Sca-1(+)/c-Kit(+) a surface phenotype, grew and survived underneath stromal cells (TBR59). The ability of the THS119 cells to invade these stromal cell layers was dependent on the inclusion of serum in the culture medium. This was apparently due to a requirement for lipids contained in serum. Their invasion of the stromal cell layers in serum-free cultures could be triggered by addition of sphingosine-1-phosphate (S1P) or lysophosphatidic acid (LPA) and was dependent on both Rho- and Ras-signaling pathways. Between the 2 possible receptors of S1P and LPA, edg-1 and edg-2, expression of edg-2 only was found to be correlated with immaturity and/or invasive activity of the primitive hematopoietic cells. These results suggest the importance of specific lipids and their specific receptors on the invasive activity of primitive hematopoietic cells in the hematopoietic microenvironment.

Nuclear receptor binding factor-2 (NRBF-2), a possible gene activator protein interacting with nuclear hormone receptors.

A protein named nuclear receptor binding factor-2 (NRBF-2) was identified by yeast two-hybrid screening, as an interaction partner of peroxisome proliferator-activated receptor alpha as well as several other nuclear receptors. NRBF-2 exhibited a gene activation function, when tethered to a heterologous DNA binding domain, in both mammalian cells and yeast.

Isolation of a novel PDZ-containing myosin from hematopoietic supportive bone marrow stromal cell lines.

Stromal cells in bone marrow provide an optimal microenvironment for hematopoiesis. The established stromal cell lines from bone marrow showed various cellular heterogeneities and differed in their hematopoietic supportive ability. By a differential display method, we cloned a gene whose expression levels were correlated with the hematopoietic supportive ability of stromal cells. Its deduced amino acid sequence shows a structure similar to myosins, except that it lacks an actin binding site. Interestingly, it contains a KE-rich sequence and a PDZ domain in the NH(2)-terminal, which are protein-protein interaction domains; therefore we termed this novel myosin Myosin containing PDZ domain (MysPDZ). Western blot analysis showed that its protein levels positively correlated with the supportive ability of stromal cells and immunostaining suggested that MysPDZ was present at cytoskeleton in a filamentous and/or network form. Thus MysPDZ may be involved in the maintenance of the stromal cell architectures required for cell to cell contact.

CT and MR imaging of the "target sign" in metastatic brain disease.

The "target sign" is a common finding in granulomatous infection. A case with the target sign in metastatic brain tumor from small cell lung carcinoma is reported.

Solitary myofibromatosis of the skull.

We present a case of solitary infantile myofibromatosis of the skull in a 3-month-old boy. A right parietal subcutaneous lump was found at birth, and it increased in size over the ensuing 3 months. Surgery was performed, and a diagnosis of myofibromatosis was confirmed histopathologically. Solitary myofibromatosis of the skull is extremely rare. The radiographical, CT, and MR appearances, as well as histopathological findings, are described in this article.

Clinical experience of a vacuum-assisted nonroller extra-corporeal circulation system.

We designed a nonroller extra-corporeal circulation system (NRECC) to minimize space requirements and to improve the safety and ease of cardiopulmonary bypass. The NRECC includes a circuit, a centrifugal pump, and a vacuum regulator. The vacuum regulator has five channels, each of which can control negative pressure independently. Negative pressure is applied to suctions, a vent, and a venous reservoir. Auto Vent-SV and one-way valves were placed between the suctions/vent and the reservoir. The total space required for the NRECC with a heat exchanger was 0.49 m2, which is much smaller than that of our current roller pump system. The maximum volume through the suction/vent was 2.5 L/min at -100 mmHg measured in a simulated system. We used the NRECC for six CABG cases and compared results with those of five CABG cases managed by traditional roller pump extra-corporeal circulation (RECC). The two systems were compared in terms of set-up time and stability/accuracy of the suction/vent. The set-up time of the NRECC (5.3 +/- 1.9 min) was significantly shorter than that of RECC (29 +/- 3.4 min) (p < .01). Stable and accurate blood flow were achieved with the NRECC operating between -15 mmHg and -25 mmHg. In conclusion, NRECC can run a bypass easily and safely and has the benefit of reducing space requirements and shortening set-up time.