New MRI Findings in Fukuyama Congenital Muscular Dystrophy: Brain Stem and Venous System Anomalies.

BACKGROUND AND PURPOSE: Leptomeningeal glioneuronal heterotopia of the brain stem and cerebral migration abnormality were pathologically reported in Fukuyama congenital muscular dystrophy, but the radiologic assessments of the brain stem and cerebral venous system (which may be involved in the development of the anomaly) were insufficient. Here, we evaluated the brain stem and cerebral veins on MR imaging in patients with Fukuyama congenital muscular dystrophy. MATERIALS AND METHODS: We retrospectively reviewed the MR imaging findings of 27 patients with Fukuyama congenital muscular dystrophy. We visually assessed the hypoplasia, superficial structures, and signal intensity of the brain stem on T2WI, FLAIR, and double inversion recovery images and the cerebral, superficial, and deep veins with and without hemorrhage on T2WI and SWI. RESULTS: Brain stem fluffy structures were seen in 96.3% of the cases on T2WI. Superficial high signal intensity on T2WI and FLAIR images was seen in 96.3% and 92.6%, respectively. Abnormally located superficial vessels beneath the cortex were seen in 11.1% on T2WI. Hypoplasia of the superficial cerebral veins was noted in all patients who underwent SWI. Dilated and tortuous subependymal veins were seen in 40.0% on SWI. Hemorrhages were seen in 11.1% on T2WI and in 60.0% on SWI. CONCLUSIONS: Superficial brain stem structural and signal abnormalities would be useful MR imaging findings to diagnose Fukuyama congenital muscular dystrophy as well as venous system abnormalities. Clinicians must keep in mind that this disease has a high risk of hemorrhage.

Different X-linked KDM5C mutations in affected male siblings: is maternal reversion error involved?

Genetic reversion is the phenomenon of spontaneous gene correction by which gene function is partially or completely rescued. However, it is unknown whether this mechanism always correctly repairs mutations, or is prone to error. We investigated a family of three boys with intellectual disability, and among them we identified two different mutations in KDM5C, located at Xp11.22, using whole-exome sequencing. Two affected boys have c.633delG and the other has c.631delC. We also confirmed de novo germline (c.631delC) and low-prevalence somatic (c.633delG) mutations in their mother. The two mutations are present on the same maternal haplotype, suggesting that a postzygotic somatic mutation or a reversion error occurred at an early embryonic stage in the mother, leading to switched KDM5C mutations in the affected siblings. This event is extremely unlikely to arise spontaneously (with an estimated probability of 0.39-7.5 × 10(-28) ), thus a possible reversion error is proposed here to explain this event. This study provides evidence for reversion error as a novel mechanism for the generation of somatic mutations in human diseases.

Deformation-driven p-wave halos at the drip line: 31Ne.

The halo structure of 31Ne is studied using 1n-removal reactions on C and Pb targets at 230 MeV/nucleon. A combined analysis of the cross sections of these nuclear and Coulomb dominated reactions that feed directly the 30Ne ground-state reveals 31Ne to have a small neutron separation energy, 0.15(-0.10)(+0.16) MeV, and spin-parity 3/2-. Consistency of the data with reaction and large-scale shell-model calculations identifies 31Ne as deformed and having a significant p-wave halo component, suggesting that halos are more frequent occurrences at the neutron drip line.

Operation status of the electron cyclotron resonance ion source at Gunma University.

An ECR ion source of Gunma University Heavy Ion Medical Center, so-called KeiGM [M. Muramatsu, A. Kitagawa, Y. Sakamoto, S. Sato, Y. Sato, H. Ogawa, S. Yamada, H. Ogawa, Y. Yoshida, and A. G. Drentje, Rev. Sci. Instrum. 76, 113304 (2005)], has been operated for cancer therapy and physical/biological experiment since 2010. KeiGM produces typically 230 µA of 10 keV/u C(4+) ions from CH4 gases. The vacuum pressure is kept between 1.2 × 10(-4) and 1.7 × 10(-4) Pa so as to suppress the pulse-to-pulse current fluctuation within ±10%. The extraction electrode is cleaned every 6-8 months in order to remove deposited carbon, which increases the leak current and discharge. In order to investigate the possibility of long-term operation without such maintenances, oxygen aging for the cleaning of the extraction electrode has been tested in the test bench. The same-designed ion sources at National Institute of Radiological Sciences and SAGA Heavy Ion Medical Accelerator in Tosu (SAGA-HIMAT) are also operated with stable C(4+) current, which are suitable for the continuous operation for cancer therapy.

Evaluation of different fluoride concentrations supplemented with trimetaphosphate on enamel de- and remineralization in vitro.

Trimetaphosphate (TMP) effects on demineralized bovine enamel were studied after 15 days of pH cycling. Treatments included 30 wt% (weight percent) dilutions of 0, 500, 1,500 or 3,000 µg F/g aqueous NaF solutions with or without 3% TMP. Treated specimens were assessed by transverse microradiography. With the exception of the 3,000 µg F/g case, 3% TMP addition provided significant additional overall remineralization compared with F alone. Mineral content profiles differed significantly between corresponding F and F + TMP groups. Fluoride alone resulted in more remineralization in the original demineralized zone, whereas F + TMP caused less demineralization in the underlying, originally sound enamel.

Effect of rinsing with water immediately after neutral gel and foam fluoride topical application on enamel remineralization: An in situ study.

OBJECTIVE: The aim of this study was to evaluate, in situ, the effect of rinsing with water immediately after neutral fluoride foam application (Foam) or fluoride gel application (Gel). DESIGN: Ten volunteers wore acrylic palatal appliances containing 4 enamel blocks selected by surface hardness with artificial caries. Five experimental regimes of 3 days each were set according to treatment: placebo; Gel and Foam followed by no rinsing or consuming of liquids or solids for the next 30min; Gel and Foam followed by immediately washing with water jet. After each phase, surface hardness was again measured for analysis of mineral gain, evaluated through percentage of surface hardness recovery (%SHR) and integrated loss of subsurface hardness (ΔKHN). The concentration of loosely bound fluoride (CaF2) and firmly bound fluoride (FA-like) formed and retained were also determined. RESULTS: Fluoride treatments produced greater remineralization (%SHR and ΔKHN) compared to placebo group (p<0.05). There was no difference in the ability to promote remineralization and in the concentration of fluoride formed and retained, in each analysis, between Gel and Foam (p>0.05). CONCLUSION: The data suggest that rinsing with water immediately after topical application does not seem to have an influence on the ability of fluoride to promote remineralization.

Observation of a large reaction cross section in the drip-line nucleus 22C.

Reaction cross sections (sigma(R)) for 19C, 20C and the drip-line nucleus 22C on a liquid hydrogen target have been measured at around 40A MeV by a transmission method. A large enhancement of sigma(R) for 22C compared to those for neighboring C isotopes was observed. Using a finite-range Glauber calculation under an optical-limit approximation the rms matter radius of 22C was deduced to be 5.4+/-0.9 fm. It does not follow the systematic behavior of radii in carbon isotopes with N < or = 14, suggesting a neutron halo. It was found by an analysis based on a few-body Glauber calculation that the two-valence neutrons in 22C preferentially occupy the 1s(1/2) orbital.

Spectroscopy of 32Ne and the "Island of Inversion".

We report on the first spectroscopic study of the N=22 nucleus 32Ne at the newly completed RIKEN Radioactive Ion Beam Factory. A single gamma-ray line with an energy of 722(9) keV was observed in both inelastic scattering of a 226 MeV/u 32Ne beam on a carbon target and proton removal from 33Na at 245 MeV/u. This transition is assigned to the deexcitation of the first Jpi=2+ state in 32Ne to the 0+ ground state. Interpreted through comparison with state-of-the-art shell-model calculations, the low excitation energy demonstrates that the "island of inversion" extends to at least N=22 for the Ne isotopes.

Development of large deformation in 62Cr.

The structure of neutron-rich isotopes 60Cr and 62Cr was studied via proton inelastic scattering in inverse kinematics. The deformation lengths (delta) for 60Cr and 62Cr were extracted as 1.12(16) and 1.36(14) fm, respectively, providing evidence for enhanced collectivity in these nuclei. An excited state at 1180(10) keV in 62Cr was identified for the first time. We adopted 4;{+} as its spin and parity, leading to the rapid increase of the Ex(4;{+})/E_{x}(2;{+}) ratio, which indicates the development of large deformation in 62Cr near N=40. Importance of the admixture of the gd-shell component above N=40 is also discussed by comparing with a modern shell model calculation.

In vitro evaluation of dentifrice with low fluoride content supplemented with trimetaphosphate.

One way to reduce dental fluorosis is by reducing the fluoride (F) concentration in dentifrice, but low-F dentifrice should be as effective as a standard dentifrice. This study evaluated in vitro whether the supplementation with sodium trimetaphosphate (TMP) of a dentifrice with low F content (500 microg/g) would provide a similar effect to that of a standard dentifrice. Bovine enamel blocks were submitted to a pH cycling regime incorporating daily exposures to a slurry of dentifrice: a low-F dentifrice with or without 0.1-3.0% TMP; an F-free, phosphate-free dentifrice (negative control), or a dentifrice with 1,100 microg/g F (positive control). The addition of TMP to dentifrice with or without F was associated with higher surface hardness and decreased loss of integrated subsurface hardness after pH cycling. The combination of 1% TMP and 500 microg F/g had a greater effect than the positive control dentifrice. It is concluded that the addition of TMP to the 500-microg F/g dentifrice allowed a similar or larger effect as compared with a standard dentifrice in this in vitro model.

Halo structure of the island of inversion nucleus 31Ne.

The cross sections for single-neutron removal from the very neutron-rich nucleus 31Ne on Pb and C targets have been measured at 230 MeV/nucleon using the RIBF facility at RIKEN. The deduced large Coulomb breakup cross section of 540(70) mb is indicative of a soft E1 excitation. Comparison with direct-breakup model calculations suggests that the valence neutron of 31Ne occupies a low-l orbital (most probably 2p(3/2)) with a small separation energy (S(n) approximately < 0.8 MeV), instead of being predominantly in the 1f(7/2) orbital as expected from the conventional shell ordering. These findings suggest that 31Ne is the heaviest halo system known.

Decay pattern of pygmy states observed in neutron-rich 26Ne.

Coulomb excitation of the exotic neutron-rich nucleus (26)Ne on a (208)Pb target was measured at 58 MeV/u in order to search for low-lying E1 strength above the neutron emission threshold. This radioactive beam experiment was carried out at the RIKEN Accelerator Research Facility. Using the invariant mass method in the 25Ne+n channel, we observe a sizable amount of E1 strength between 6 and 10 MeV excitation energy. By performing a multipole decomposition of the differential cross section, a reduced dipole transition probability of B(E1)=0.49+/-0.16e(2) fm(2) is deduced, corresponding to 4.9+/-1.6% of the Thomas-Reiche-Kuhn sum rule. For the first time, the decay pattern of low-lying strength in a neutron-rich nucleus is measured. The extracted decay pattern is not consistent with several mean-field theory descriptions of the pygmy states.

Prediction of lateral pelvic node involvement in low rectal cancer by conventional computed tomography.

BACKGROUND: The clinical significance of lateral pelvic lymphatic spread in rectal cancer remains unknown. The present study aimed to assess the accuracy of preoperative computed tomography (CT) for prediction of lateral node involvement in patients with low rectal cancer and to determine the prognostic significance of extended lateral node dissection. METHODS: A total of 109 patients with primary low rectal cancer were enrolled in this prospective cohort study. The preoperative CT findings were compared with the histopathological results and with follow-up data. RESULTS: CT diagnosed lateral lymph node status with high accuracy (sensitivity 95 per cent, specificity 94 per cent), in marked contrast to mesorectal node status. Of 68 patients who had R0 resection without lateral node dissection, only two developed pelvic wall recurrence during median follow-up of 4.1 years. Metastatic nodes in the lateral pelvic region were significantly larger than those in the mesorectum (P < 0.001). CONCLUSION: CT accurately predicted lateral lymph node status in low rectal cancer, allowing preoperative identification of patients who might benefit from extended lateral node dissection.

Vanishing N = 20 shell gap: study of excited states in (27,28)Ne.

This Letter reports on the (1)H((28)Ne, (28)Ne) and (1)H((28)Ne, (27)Ne) reactions studied at intermediate energy using a liquid hydrogen target. From the cross section populating the first 2(+) excited state of (28)Ne, and using the previously determined BE(2) value, the neutron quadrupole transition matrix element has been calculated to be M(n)=13.8 +/- 3.7 fm(2). In the neutron knockout reaction, two low-lying excited states were populated in (27)Ne. Only one of them can be interpreted by the sd shell model while the additional state may intrude from the fp shell. These experimental observations are consistent with the presence of fp shell configurations at low excitation energy in (27,28)Ne nuclei caused by a vanishing N=20 shell gap at Z=10.

Anomalously hindered E2 strength B(E2;2+(1)-->0+) in 16C.

The electric quadrupole transition from the first 2(+) state to the ground 0(+) state in 16C is studied through measurement of the lifetime by a recoil shadow method applied to inelastically scattered radioactive 16C nuclei. The measured mean lifetime is 77+/-14(stat)+/-19(syst) ps. The central value of mean lifetime corresponds to a B(E2;2+(1)-->0(+)) value of 0.63e(2) fm(4), or 0.26 Weisskopf units. The transition strength is found to be anomalously small compared to the empirically predicted value.

Cholesteryl ester transfer protein polymorphism associated with macroangiopathy in Japanese patients with type 2 diabetes.

A polymorphism in the gene for cholesteryl ester transfer protein (CETP) has been reported to be associated with serum cholesterol levels and risk for atherosclerotic vascular diseases, and to clarify the relationship between the gene polymorphism for CETP and macroangiopathy in diabetes mellitus, a cross-sectional study was performed. The subjects of the study were182 Japanese (age: 59.6+/-8.6 years) with type 2 diabetes and no signs of renal dysfunction, 24 of whom had macroangiopathy, and 158 of whom did not. The genotype of the subjects for the TaqIB polymorphism of CETP in intron one was analyzed by using polymerase chain reaction - restriction fragment length polymorphism. Serum CETP levels were significantly higher in the B1/B1 genotype than in the other genotypes (P<0.05). The serum CETP levels were correlated with the serum LDL cholesterol levels (P<0.01), but not with the HDL cholesterol levels. Macroangiopathy was more frequently observed in subjects with the B1/B1 genotype than in the other genotypes (odds ratio=2.953, 95% confidence interval=1.250-6.977, P=0.0136). Logistic regression analysis revealed that the CETP genotype was independently associated with macroangiopathy. The exact mechanism underlying the association remains unknown, but differences in serum CETP levels may be involved.

[Morphology and immunophenotyping in hematological malignancies].

We evaluated 443 outpatients and inpatients in Keio University Hospital between 1994 and 1999. Morphologic features from peripheral blood and bone marrow aspiration were evaluated in our hematology laboratory, using Wright-Giemsa, peroxidase staining films and other cytochemistry. Immunophenotype was determined by cell surface antigen analysis by laser flow cytometry, FACscan, using various monoclonal antibodies. Information on cytogenetic and molecular genetic characteristics can be also integrated for diagnosis. One hundred fifty patients were diagnosed with acute leukemia, in which 59 cases were ALL and 91 cases were AML. Seventy-four cases were MDS, 76 cases were myeloproliferative disorders, 21 cases were CLL related disorders, 104 patients were malignant lymphoma, and 18 cases were multiple myeloma. The ratio of male to female was 1.7. The probability of diagnostic rate by Immunophenotyping was estimated by Discriminant analysis in 189 patients, using multivariate analysis of immunophenotype compared to morphology. The average probability by immunophenotypic analysis for diagnostic rate was 91.7%, in which the probability for NHL was very high of 97.1%. Thus, morphologic and immunophenotypic analysis is most essential and basic approach in laboratory hematology, from the perspective of rapid and precise diagnostic methods. Recent advance appreciates the rapid contribution for diagnosis by immunophenotypic analysis. Furthermore, Tele-hematology would contribute the standardization for morphologic method in the near future.

Activated factor XII levels are dependent on factor XII 46C/T genotypes and factor XII zymogen levels, and are associated with vascular risk factors in patients and healthy subjects.

Coagulation factor XII (FXII) is activated on contact with various biologic surfaces, including subendothelial tissues and lipoprotein particles. Thus, the plasma level of activated FXII (XIIa) might represent vascular lesions or be a marker of abnormal lipid metabolism. A 46C/T polymorphism was recently described in the FXII gene close to the ATG translation initiation codon, which was associated with inter-individual variation of plasma FXII zymogen levels. The present paper reports the association of the 46C/T polymorphism with plasma XIIa levels in apparently healthy subjects, and in patients with ischemic cerebrovascular disease (CVD) and arteriosclerosis obliterans (ASO). XIIa levels were not significantly different between patients and controls, but were strongly dependent on XII 46C/T genotypes (2.07 +/- 0.81, 1.65 +/- 0.63, and 0.93 +/- 0.41 ng/ml for C/C, C/T, and T/T genotypes, respectively; P < 0.0001). This association was evident for each group studied (P < 0.0001 for CVD and controls; P= 0.0007 for ASO). There were positive correlations between plasma FXII clotting activity and XIIa levels. In a univariate analysis, XIIa correlated with total cholesterol, triglycerides, plasminogen activator inhibitor-1, and C-reactive protein (CRP), although the presence of conventional cardiovascular risk factors (male sex, smoking, hypertension, hypercholesterolemia, diabetes) did not significantly increase XIIa. Stepwise regression analyses revealed that the XII clotting activity had the strongest association with XIIa. In conclusion, XIIa levels depended on XII 46C/T genotype and correlated with some cardiovascular risk factors. Thus, the FXII genotype should be taken into consideration for interpretation of plasma XIIa levels.

Angiotensin converting enzyme insertion/deletion polymorphism is associated with plasma antigen levels of plasminogen activator inhibitor-1 in healthy Japanese population.

Plasminogen activator inhibitor-1 (PAI-1) has a central role in the regulation of the fibrinolytic enzyme system. An elevated plasma PAI-1 level is associated with thrombotic disorders. In vitro and in vivo studies indicate that the renin-angiotensin system is involved in the regulation of PAI-1. A 287-bp insertion/deletion (I/D) polymorphism in the gene-encoding angiotensin converting enzyme (ACE) is associated with cardiovascular disorders. We evaluated the association between the ACE I/D polymorphism and plasma PAI-1 antigen levels in 110 healthy Japanese male subjects. Subjects with the D-allele of the gene-encoding ACE had higher levels of PAI-1 (26.3 +/- 14.7 ng/ml, mean +/- standard deviation) compared with those without (21.0 +/- 12.0; P = 0.0491). A multiple linear regression model with independent variables (age, body-mass index, total cholesterol level, triglyceride level, ACE I/D genotype, and PAI-1 genotype due to a single guanine I/D polymorphism in the PAI-1 gene) demonstrated that the triglyceride level (P = 0.0059) and ACE I/D genotype (P = 0.0372) were independent predictors of plasma PAI-1 antigen levels in a subset of the subjects without diabetes mellitus that were not taking lipid-lowering drugs. These findings suggest that the ACE I/D polymorphism is a genetic factor for the regulation of plasma PAI-1 antigen levels in the healthy Japanese population.