Longitudinal Findings of MRI and PET in West Syndrome with Subtle Focal Cortical Dysplasia.

BACKGROUND AND PURPOSE: Despite the development of neuroimaging, identification of focal cortical dysplasia remains challenging. The purpose of this study was to show the longitudinal changes of MR imaging and FDG-PET in patients with West syndrome and subtle focal cortical dysplasia. MATERIALS AND METHODS: Among 52 consecutive patients with West syndrome, 4 were diagnosed with subtle focal cortical dysplasia on 3T MR imaging. MR imaging and PET findings were evaluated longitudinally at onset and at 12 and 24 months of age. RESULTS: At the onset of West syndrome, MR imaging demonstrated focal signal abnormalities of the subcortical white matter in 2 patients. In the other 2 patients, focal subcortical high-intensity signals became visible on follow-up T2WI as myelination progressed. PET at onset showed focal cortical hypometabolism in 3 patients, with 1 of these patients also having focal hypermetabolism and 1 having normal findings. On PET at 24 months, hypometabolism persisted in 2 patients and disappeared in 1, and hypermetabolism disappeared in 1. In 1 patient with normal MR imaging and PET findings at onset, focal hyperintensity and hypometabolism first appeared at 24 months of age. The findings on MR imaging and PET in these patients evolved differently with brain maturation and the clinical course. CONCLUSIONS: Subtle focal cortical dysplasia can be undetectable on MR imaging at the onset of West syndrome and is not always accompanied by hypometabolism or hypermetabolism on PET. Longitudinal MR imaging and PET studies may be useful for detecting such lesions. Even in West syndrome with a congenital structural abnormality, PET findings evolve differently with brain maturation and the clinical condition.

Synthesis and structural characterization of the first neptunium based metal-organic frameworks incorporating {Np6O8} hexanuclear clusters.

Successful synthesis of the first transuranium metal-organic frameworks (TRU-MOFs) involving tetravalent Np4+ is reported. These compounds were obtained from the controlled hydrolysis of Np4+ in the presence of dicarboxylate ligands. The final structures contain the [Np6O4(OH)4(H2O)6]12+ unit, which were never crystallized before with tetravalent neptunium, associated with ditopic ligands.

Predominant area of brain lesions in neonates with herpes simplex encephalitis.

OBJECTIVE: Nonspecific manifestations and a varied distribution of brain lesions can delay the diagnosis of herpes simplex encephalitis (HSE) in neonates. The aim of this study was to report predominant brain lesions in neonatal HSE, and then to investigate the association between pattern of predominant brain lesions, clinical variables and neurodevelopmental outcome. STUDY DESIGN: A multicenter retrospective study was performed in neonates diagnosed with HSE between 2009 and 2014. Magnetic resonance (MR) images, including diffusion-weighted images, were obtained in the acute and chronic phase. RESULTS: Three predominant areas of brain injury could be defined based on characteristic MRI findings in 10 of the 13 infants (77%). The inferior frontal/temporal pole area was involved in five (38%) patients. The watershed distribution was present in six (46%) patients. Four (31%) infants involved the corticospinal tract area. No significant association was found between any predominant distribution of brain lesion pattern and sex, country, viral type or viral load. However, the corticospinal tract involvement was significantly associated with motor impairment (P=0.045). CONCLUSION: Three predominant areas of brain lesion could be recognized in neonatal HSE. Recognition of those areas can improve prediction of neurodevelopmental outcome.

The specific sorption of Np(V) on the corundum (α-Al2O3) surface in the presence of trivalent lanthanides Eu(III) and Gd(III): A batch sorption and XAS study.

The sorption of pentavalent neptunium, Np(V), on corundum (α-Al2O3) was investigated in the absence and presence of trivalent europium or gadolinium as a competing element under CO2-free conditions. The objective of this study was to investigate how a trivalent metal ion with a higher charge than that of the neptunyl(V) ion would affect the sorption of Np(V) when allowed to adsorb on the mineral surface before the addition of Np(V). Batch sorption experiments conducted as a function of pH (pH-edges) and as a function of Np(V) concentration (isotherms) in the absence and presence of 1×10(-5)M Eu(III) showed no sign of Eu being able to block Np sorption sites. Surface complexation modelling using the diffuse double layer model was applied to the batch data to obtain surface complexation constants for the formed Np(V) complexes on corundum. To account for potential changes occurring in the coordination environment of the neptunium ion in the presence of a trivalent lanthanide, X-ray absorption spectroscopy (XAS) measurements were carried out on the samples containing only Np(V) and Np(V)+Gd(III). The results reveal the presence of a bidentate Np(V) edge-sharing complex on the corundum surface in the absence of Gd(III), while the coordination environment of Np(V) on the corundum surface could be changed when Gd(III) is added to the sample before the sorption of Np(V).

Accumulation of plutonium in mammalian wildlife tissues following dispersal by accidental-release tests.

We examined the distribution of plutonium (Pu) in the tissues of mammalian wildlife inhabiting the relatively undisturbed, semi-arid former Taranaki weapons test site, Maralinga, Australia. The accumulation of absorbed Pu was highest in the skeleton (83% ± 6%), followed by muscle (10% ± 9%), liver (6% ± 6%), kidneys (0.6% ± 0.4%), and blood (0.2%). Pu activity concentrations in lung tissues were elevated relative to the body average. Foetal transfer was higher in the wildlife data than in previous laboratory studies. The amount of Pu in the gastrointestinal tract was highly elevated relative to that absorbed within the body, potentially increasing transfer of Pu to wildlife and human consumers that may ingest gastrointestinal tract organs. The Pu distribution in the Maralinga mammalian wildlife generally aligns with previous studies related to environmental exposure (e.g. Pu in humans from worldwide fallout), but contrasts with the partitioning models that have traditionally been used for human worker-protection purposes (approximately equal deposition in bone and liver) which appear to under-predict the skeletal accumulation in environmental exposure conditions.

Characterization of human multicentric osteosarcoma using newly established cells derived from multicentric osteosarcoma.

PURPOSE: Human multicentric osteosarcoma (HMOS) is a rare, aggressive variant of osteosarcoma, and its etiology is not clear. We used newly established HMOS cells, which were derived from primary (HMOS-A) and secondary (HMOS-P) lesions, respectively, to perform a basic study analyzing the cellular biology and gene expression of HMOS. METHODS: We performed a cell growth assay, an invasion assay, DNA microarray analysis, quantitative real-time RT-PCR (Qrt-PCR), and a telomerase assay and compared the results between HMOS-A, HMOS-P, and human osteosarcoma (HOS) cell lines (MNNG-HOS and Saos-2). RESULTS: The cell biological analysis revealed that HMOS-A and HMOS-P had similar characteristics to Saos-2, and the invasion assay showed that they had similar characteristics to MNNG-HOS. The DNA microarray study showed that the gene expression profiles of HMOS-A and HMOS-P were similar to that of MNNG-HOS, but the overexpression of MMP-2, MMP-9, and MT1-MMP was observed in HMOS-A and HMOS-P, which was correlated with the invasiveness of the extracellular matrix, and collagen type-4 (COL-4) and VEGF were also detected. HMOS-A and HMOS-P showed low telomerase activity similar to Saos-2, which are known to be telomerase negative, but a similar telomere length and telomerase protein to MNNG-HOS. CONCLUSIONS: HMOS-A and HMOS-P demonstrated strong invasive ability, and their gene expression profiles correlated with the invasiveness of the extracellular matrix. Their telomerase activity was low, but they did not shown the typical features of alternative lengthening of telomeres (ALT). HMOS-A and HMOS-P are useful models for further study of various biological aspects and therapeutic manipulation of HMOS.

An increased dose of insulin detemir improves glycaemic control and reduces body weight of Japanese patients with diabetes.

AIMS: The aim of study was to evaluate the safety and efficacy of insulin detemir as a basal insulin switching from neutral protamine Hagedorn insulin (NPH) and insulin glargine in patients with diabetes on an intensive insulin therapy regimen. METHODS: This 6-month multicentre, prospective, treat-to-target [glycosylated haemoglobin (HbA(1c) ) less than 6.5%] trial included 92 people with diabetes (61 type 1, 29 type 2 and two unknown diabetes types). Detemir was administered first with fixed dose and injection times and then adapted to optimal dose after 3 months. RESULTS: Mean HbA(1c) (%) of all the subjects at months 4 to 6 of the study was improved compared with month 0 (7.34 ± 0.87, 7.28 ± 0.88, 7.25 ± 0.93 vs. 7.55 ± 1.18; p < 0.05 paired t-test). However, significant improvement was seen only among the patients who had previously used NPH as a basal insulin. Twice-daily injection of basal insulin increased among people in the type 1 previously injected insulin glargine. Total insulin dose increased in the type 1 glargine group. The mean body weight change in the highest quartile body mass index (BMI) group was from 70.7 to 69.3 kg over the 6 months. Quality of life (QoL) relating to the patients' glycaemic control tended to improve without a change in frequency of hypoglycaemia. CONCLUSIONS: The results suggest that insulin detemir has a greater effect on glycaemic control in subjects with poor glycaemic control using NPH; can reduce or maintain body weight in obese patients; and obtains perceptive stability for patients with unstable glycaemic control.

Is driving a car a risk for Legionnaires' disease?

Legionnaires' disease (LD) is a major cause of severe community-acquired pneumonia but the source and mode of transmission are not always apparent, especially in sporadic cases. We hypothesized that LD can be acquired from the air-conditioning systems of motor cars. Swabs were taken from the evaporator compartments of the air-conditioning system of scrapped cars. Healthy subjects who were mainly employees of regional transportation companies were tested for antibody to Legionella pneumophila serogroups 1-6; they also completed a questionnaire. Legionella species were detected in 11/22 scrapped cars by the loop-mediated isothermal amplification method. The prevalence of microplate agglutination titres > or =1:32 was significantly higher in subjects who sometimes used car air-conditioning systems. Although we did not prove a direct link between Legionella spp. in the car evaporator and LD, our findings point to a potential risk of car air-conditioning systems in LD, which needs further investigation.

Dermatomyositis associated with Sjögren's syndrome: VEGF involvement in vasculitis.

Two patients with dermatomyositis complicated with Sjögren's syndrome (SjS), are reported. Both patients exhibited sensory-dominant polyneuropathy, compatible with neurologic involvement in SjS. Vascular endothelial growth factor (VEGF) levels were increased in their plasma. Histological examination demonstrated vasculitic changes in biopsied specimens of muscle and salivary glands from the patients, and VEGF was overexpressed in the vasculitic lesions. These findings suggest that VEGF overexpression was associated with the development of vasculopathy in skeletal muscle and salivary glands and possibly in the peripheral nervous system.

Functional characterization of three human cytochrome p450 2E1 variants with amino acid substitutions.

1. Cytochrome p450 (p450) 2E1 is a hepatic enzyme of importance for the metabolism of xenobiotics such as drugs and environmental toxicants. Genetic polymorphisms of CYP2E1 in 5'-flanking and coding regions have been found previously in Caucasian and Chinese populations. 2. In order to investigate the effects of amino acid substitutions on the function of CYP2E1, the enzymes of all known CYP2E1 variants in the coding region (CYP2E1.2, CYP2E1.3 and CYP2E1.4) with Arg76His, Val389Ile and Val179Ile substitutions, respectively, as well as the wild-type CYP2E1 (CYP2E1.1) were expressed in COS-1 cells, and their chlorzoxazone 6-hydroxylation and 4-nitrophenol 2-hydroxylation activities were determined. 3. The protein level of CYP2E1.2 was reduced to 29% compared with that of CYP2E1.1. The profiles of the level of activity relative to CYP2E1.1 for chlorzoxazone 6-hydroxylation (300 microM substrate) and 4-nitrophenol 2-hydroxylation (150 microM substrate) were very similar. 4. Although the K(m) values were not significantly different among wild-type and variant CYP2E1s in any oxidation metabolism, the V(max) and V(max)/K(m) of CYP2E1.2 on the basis of the CYP2E1 protein level were 2.7-3.0-fold higher than those of CYP2E1.1. In contrast, the levels of CYP2E1 protein and catalytic activity of CYP2E1.3 and CYP2E1.4 were not affected by the corresponding amino acid substitutions. 5. The findings suggest that Arg76 is closely associated with the function of CYP2E1, and that the genetic polymorphism of CYP2E1 is one cause of interindividual differences in the toxicity of xenobiotics.

Asymmetric autocatalysis of a pyrimidyl alkanol induced by chiral monosubstituted [2.2]paracyclophanes.

[figure: see text] Monosubstituted[2.2]paracyclophanes 3a-c with planar chirality were found to act as chiral initiators in an enantioselective addition of diisopropylzinc to 2-alkynylpyrimidine-5-carbaldehyde 1 to afford 2-alkynylpyrimidyl alkanol 2 with up to 97% ee.

The in vivo activity of olamufloxacin (HSR-903) in systemic and urinary tract infections in mice.

The in vivo activity of olamufloxacin (HSR-903), a new fluoroquinolone, was evaluated and compared with ciprofloxacin, sparfloxacin and levofloxacin. Olamufloxacin was active against systemic infection in mice inoculated with both Gram-positive and -negative bacteria. Olamufloxacin had equal efficacy for experimental urinary tract infections in mice caused by Pseudomonas aeruginosa.

[Changes of infections due to drug resistant bacteria and its control].

The development and use of antibiotics for the chemotherapy of bacterial infections was one of the most remarkable accomplishments in medicine of the 20th. However, antibiotic-resistant bacteria were found in clinical isolates soon after the introduction of the earliest antimicrobial agents into the market. Significant increases in prevalence of resistance to antimicrobial agents have been observed in common pathogens of humans in the worldwide and problems of resistance are still presently serious among the immunocompromised host. The most important of these organisms are methicillin-resistant Staphylococcus aureus penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant Enterococcus, and certain gram-negative bacilli due to extended-spectrum beta-lactamase production. These antibiotic resistances have made antimicrobial therapy of many infections extremely difficult or virtually impossible in some instances. In this article, we reviewed the history of antibiotic-resistance and discussed on the future.

[Vancomycin-resistant enterococci(VRE)].

The incidence of Enterococcal nosocomial infection has increased since 1980s. Most Enterococci are intrinsically resistant to many kinds of antibiotics, therefore, therapeutic drugs for enterococal infectious disease are limited to a few antibiotics such as ampicillin, gentamicin and vancomycin. However, since the first report of penicillinase producing E. faecalis in 1983, ampicillin-resistant strains have been increasing, furthermore, these strains often associated with high-level resistance to aminoglycosides. The yearly usage of vancomycin increased because vancomycin was only effective drug against such resistant strains and worldwide spread of multidrug-resistant MRSA which vancomycin is only effective. However, High-level vancomycin-resistance strains of E. faecium were first isolated in England in 1986. In 1990s, VRE have been spreading all over the world, especially, the emergency of multidrug-resistant strains, which are resistant to high concentrations of ampicillin or gentamicin or to vancomycin in USA, brought serious therapeutic dilemmas. This review focuses on the background in emergence of VRE, the relation with use of avoparcin, is used for growth promotion in farm animals, the mechanism of resistance, and the prevention of the spread of vancomycin resistance.

NAD/NADH models with axial/central chiralities: superiority of the quinoline ring system.

Precursors of NAD model compounds 1c and 3a,b were successfully resolved into their atropisomers with respect to carbamoyl rotation. Atropisomers of quinoline derivatives are much more stable than pyridine derivatives as determined by cyclic voltammetry and X-ray crystallography. The 1,4-reduction of NAD model compound 4 was successfully achieved, affording novel NADH model compound 5. The rotational properties of the side chain of 5 were investigated by means of dynamic NMR. The rotational rate and syn/anti ratio, which indicate the orientation between carbonyl oxygen and hydrogen at the 4-position, are significantly affected by addition of magnesium ion. In the rotational transition state, the double-bond character of the C(carbonyl)-N(amide) bond is disrupted judging from the activation parameters. The oxidation of chiral 5 with p-benzoquinone in the presence of magnesium ion catalyst gave predominantly one enantiomer of 4. On the other hand, oxidation of 5 with p-chloranil (tetrachloro-p-benzoquinone) in the absence of magnesium ions affords the opposite enantiomer of 4 as the major product. The product enantiomer ratio is parallel to the syn/anti ratio in the starting material, indicating the importance of ground state conformation to stereochemistry of the reaction.