Early detection of Niemann-pick disease type C with cataplexy and orexin levels: continuous observation with and without Miglustat.

STUDY OBJECTIVES: Niemann-Pick type C (NPC) is an autosomal recessive and congenital neurological disorder characterized by the accumulation of cholesterol and glycosphingolipids. Symptoms include hepatosplenomegaly, vertical supranuclear saccadic palsy, ataxia, dystonia, and dementia. Some cases frequently display narcolepsy-like symptoms, including cataplexy which was reported in 26% of all NPC patients and was more often recorded among late-infantile onset (50%) and juvenile onset (38%) patients. In this current study, we examined CSF orexin levels in the 10 patients of NPC with and without cataplexy, which supports previous findings. METHODS: Ten patients with NPC were included in the study (5 males and 5 females). NPC diagnosis was biochemically confirmed in all 10 patients, from which 8 patients with NPC1 gene were identified. We compared CSF orexin levels among NPC, narcoleptic and idiopathic hypersomnia patients. RESULTS: Six NPC patients with cataplexy had low or intermediate orexin levels. In 4 cases without cataplexy, their orexin levels were normal. In 5 cases with Miglustat treatment, their symptoms stabilized or improved. For cases without Miglustat treatment, their conditions worsened generally. The CSF orexin levels of NPC patients were significantly higher than those of patients with narcolepsy-cataplexy and lower than those of patients with idiopathic hypersomnia, which was considered as the control group with normal CSF orexin levels. DISCUSSION: Our study indicates that orexin level measurements can be an early alert of potential NPC. Low or intermediate orexin levels could further decrease due to reduction in the neuronal function in the orexin system, accelerating the patients' NPC pathophysiology. However with Miglustat treatment, the orexin levels stabilized or improved, along with other general symptoms. Although the circuitry is unclear, this supports that orexin system is indeed involved in narcolepsy-cataplexy in NPC patients. CONCLUSION: The NPC patients with cataplexy had low or intermediate orexin levels. In the cases without cataplexy, their orexin levels were normal. Our study suggests that orexin measurements can serve as an early alert for potential NPC; furthermore, they could be a marker of therapy monitoring during a treatment.

Polymerization of room-temperature ionic liquid monomers by electron beam irradiation with the aim of fabricating three-dimensional micropolymer/nanopolymer structures.

A novel method for fabricating microsized and nanosized polymer structures from a room-temperature ionic liquid (RTIL) on a Si substrate was developed by the patterned irradiation of an electron beam (EB). An extremely low vapor pressure of the RTIL, 1-allyl-3-ethylimidazolium bis((trifluoromethane)sulfonyl)amide, allows it to be introduced into the high-vacuum chamber of an electron beam apparatus to conduct a radiation-induced polymerization in the nanoregion. We prepared various three-dimensional (3D) micro/nanopolymer structures having high aspect ratios of up to 5 with a resolution of sub-100 nm. In addition, the effects of the irradiation dose and beam current on the physicochemical properties of the deposited polymers were investigated by recording the FT-IR spectra and Young's modulus. Interestingly, the overall shapes of the obtained structures were different from those prepared in our recent study using a focused ion beam (FIB) even if the samples were irradiated in a similar manner. This may be due to the different transmission between the two types of beams as discussed on the basis of the theoretical calculations of the quantum beam trajectories. Perceptions obtained in this study provide facile preparation procedures for the micro/nanostructures.

3-D Finite element analysis of all-ceramic posterior crowns.

The purpose of this study was to evaluate the stress distribution under various loading conditions within posterior all-ceramic crowns. A three-dimensional finite element model representing a lower first molar was constructed. Variations of the model had two types of single layer all-ceramic crowns (Dicor and Empress) and two types of double layer all-ceramic crowns (In-Ceram and Empress2) cemented. A load of 600 N, simulating the maximum bite force, was applied vertically to the crowns. Loads of 225 N, simulating masticatory force, were applied from three directions (vertically, at a 45 degrees angle, and horizontally). In the test simulating maximum bite force, the maximum tensile stresses on all crowns (17.4-19.4 MPa) concentrated around the loading points. In the masticatory force simulation test, the specimens experienced maximum tensile stresses of 19.7-27.0 MPa under a horizontal load and 10.8-10.9 MPa under a vertical load. When the load was applied horizontally, the maximum tensile stress was observed around the loading points on the surface in the case of the single layer crowns, and of the cervical area of the inner core of the double layer crowns. Within the limitation of this study, it was found that the strength of occlusal contact points is important to the integrity of posterior all-ceramic crowns and that bite forces applied from the horizontal direction are a critical factor.

Fracture resistance of pressable glass-ceramic fixed partial dentures.

The aim of the present study was to evaluate the mechanical strength of the Empress2 system, which is based on the use of a high-strength glass--ceramic core of lithium disilicate, and the fracture resistance of fixed partial dentures fabricated with this material. To evaluate mechanical strength, four types of ceramic materials were tested for four-point flexural strength and diametral tensile strength: Empress2 core material, Empress2 layering porcelain, conventional Empress material and Dicor. Then, using Empress2, conventional Empress and Dicor, actual clinical type anterior fixed partial dentures were fabricated for fracture testing. The results showed that the Empress2 core material, at 329 MPa, has more than twice the flexural strength of conventional materials and at 271 MPa, more than four times the diametral tensile strength of conventional materials. Furthermore, fixed partial dentures fabricated with Empress2 had a fracture resistance of 1424 N. That is, they were more than twice as fracture resistant as fixed partial dentures made with conventional materials.

Ecdysone-inducible foreign gene expression in stably-transformed lepidopteran insect cells.

Cultured cell lines that can be stably transformed with inducible gene constructs could prove extremely valuable for the continuous and economical production of recombinant proteins. Toward this goal, we have established 11 clones (designated NISES-BoMo-DK1 to 11) from a previously reported silkworm cell line, NISES-BoMo-DZ. Nine of these clonal lines showed a distinct morphological change. i.e., cell aggregation, in response to treatment with 1 microM 20-hydroxyecdysone (20E). DK10 cells transfected with various reporter assay plasmids under optimal conditions (i.e., 20-30% transfection efficiency) showed inducibility of gene expression by 20E. The 20E treatment of the prototypical DK10 cells resulted in a simultaneous, transient increase of the nuclear ecdysone (E) receptor levels. Further, this inducibility was also observed in a DK10 cell line stably transformed with the reporter plasmid that carries the hygromycin-resistance gene. This offers an opportunity to achieve efficient, continuous production of recombinant proteins. It could also allow high throughput screening for potential E agonists.

Stress analysis of metal-free polymer crowns using the three-dimensional finite element method.

PURPOSE: The purpose of this study was to evaluate the stress distribution under various loading conditions within posterior metal-free crowns made of new composite materials. MATERIALS AND METHODS: A three-dimensional finite element model representing a mandibular first molar was constructed. Variations of the model had crowns of two types of composite, a glass ceramic, and porcelain fused to metal. A load of 600 N, simulating the maximum bite force, was applied vertically to the crowns. Loads of 225 N, simulating masticatory force, were applied from three directions (vertically, at a 45-degree angle, and horizontally). RESULTS: The stress distributions in both types of composite crown were similar to that of the glass-ceramic crown. In the test simulating maximum bite force, the maximum tensile stresses on all crowns (17.9 to 18.3 MPa) concentrated around the loading points. In the masticatory force-stimulation test, the specimens experienced maximum tensile stresses of 20.3 to 26.6 MPa under a horizontal load and 10.9 to 11.0 MPa under a vertical load. When the load was applied horizontally, the maximum tensile stress was observed around the loading points on the surface in the case of composite and glass-ceramic crowns, and in the cervical area of the metal coping in the porcelain-fused-to-metal crowns. CONCLUSION: It would appear that the strength of occlusal contact points is important to the integrity of posterior metal-free crowns made of new composite materials and that bite forces applied from the horizontal direction are a critical factor determining success and failure.

[Higher cortical dysfunctions and image diagnosis in a 9-year-old girl with complex partial epilepsy caused by focal neural migration disorder].

A 9-year-old right-handed girl was admitted because of complex partial seizures, left-right disorientation and finger agnosia. At the age of 2 years, she began to have seizures, which were exacerbated by carbamazepine and diazepam. Subsequently she was treated with phenytoin and phenobarbital, and remained seizure-free for four years. After age 7, she began to have attacks of alteration of consciousness, which lasted 10 seconds and occurred every two or three months. At age 9, neuropsychological testing revealed borderline intellectual functioning (WISC-R:FSIQ 83, VIQ 94, PIQ 73), but selective deficits were found in tests of calculation and spatial-figural relationships. Axial spin echo (3,000/22) image showed an abnormal high signal intensity in the left temporo-parieto-occipital lobe, in which interictal IMP-SPECT demonstrated decreased cerebral blood flow. These results seemed to explain the relationship between clinical findings and focal migration disorder. It is important to detect a focal migration disorder in patients with intractable focal epilepsy or higher cortical dysfunctions.