Characterization of p16(INK4A) expression in multiple myeloma and plasma cell leukemia

Loss of p16(INK4A) (p16) expression is frequently associated with the development of epithelial and lymphoid malignancies. However, the frequency and significance of p16 abnormalities in multiple myeloma (MM) and the more aggressive phase of plasma cell leukemia (PCL) have not been well defined. Accordingly, the goal of this study was to define the expression and function of p16 in fresh samples of MM and PCL. We found that p16 protein was highly expressed in primary MM cells, although it was undetectable in fresh samples of PCL. Additionally, p16 protein was also absent in four of four MM-derived cell lines. To determine the mechanism for p16 underexpression in PCL and MM-derived cell lines, we performed PCR analysis to evaluate both gene deletion and the presence of methylation. Interestingly, the p16 gene was present and methylated in all patient PCL cells and MM cell lines, whereas it was unmethylated in patient MM cells and normal B cells. Furthermore, treatment with the demethylating agent 5-deoxyazacytidine or p16 retrofection restored p16 protein expression and induced G1 growth arrest in patient PCL cells and MM cell lines. These results suggest that inactivation of the p16 gene by methylation may be associated with decreased growth control and the development of PCL in a subset of patients with MM.     

Skeletal muscle fiber degeneration in mdx mice induced by electrical stimulation

We present an in vitro model in which mouse skeletal muscle fibers undergo degeneration by increasing the current strength of tetanic stimulation. To understand the mechanisms of muscle fiber necrosis in Duchenne muscular dystrophy patients, the process of fiber degeneration was compared between mdx and control mice. The process consisted of four steps, beginning with muscle fiber contraction and extending to onset of myofibril disruption. The four processes were not observed in fibers in Krebs-HEPES (-Ca2+) buffer, nor in the presence of L-type Ca2+ channel blockers. These results suggest that this degenerative phenomenon is regulated by intracellular Ca2+, which moved into fibers mainly through voltage-dependent L-type Ca2+ channels. With the exception of myofibril disruption, mdx mice also exhibited the three other steps, but at a significantly lower current strength than in the fibers in the control mice. We postulate that excess Ca2+ flux occurs in fibers, mainly through abnormal L-type Ca2+ channels, and that the excessively accumulated calcium results in premature degeneration of the fibers by tetanic contraction. This study would provide a clue to investigate and prevent the degeneration processes in Duchenne muscular dystrophy.     

Low-energy unstable nuclear beam channel “SLOW” at the RIKEN ring cyclotron

A new type of low-energy radioactive nuclear beam channel “SLOW” has been constructed at the RIKEN ring cyclotron facility, intended not only for the study of emission mechanisms of various low-energy radioactive as well as stable isotope ions from a characterized surface of the primary target, but also for the generation of useful radioactive ion beams for surface-physics studies of the secondary target.

In the commissioning experiment of the SLOW beam channel, the reaction products of a heavy-ion induced nuclear reaction have been observed after surface ionization at a hot tungsten target.     

Not Oligomers but Amyloids are Cytotoxic in the Membrane‐Mediated Amyloidogenesis of Amyloid‐β Peptides

The formation of neurotoxic aggregates by amyloid‐β peptide (Aβ) is considered to be a key step in the onset of Alzheimer's disease. It is widely accepted that oligomers are more neurotoxic than amyloid fibrils in the aqueous‐phase aggregation of Aβ. Membrane‐mediated amyloidogenesis is also relevant to the pathology, although the relationship between the aggregate size and cytotoxicity has remained elusive. Here, aggregation processes of Aβ on living cells and cytotoxic events were monitored by fluorescence techniques. Aβ formed amyloids after forming oligomers composed of ≈10 Aβ molecules. The formation of amyloids was necessary to activate apoptotic caspase‐3 and reduce the ability of the cell to proliferate; this indicated that amyloid formation is a key event in Aβ‐induced cytotoxicity.     

Antiambipolar Transistor: A Newcomer for Future Flexible Electronics

An antiambipolar transistor exhibits a steep increase and decrease in drain current within a certain range of gate bias voltage. This unique feature is brought about by a partially stacked pn‐heterointerface formed around the center of the transistor channel. First, this review discusses recent topics related to the antiambipolar transistor, including the constituent materials, operation mechanism, and factors controlling device performance. Then, novel functional applications, such as optoelectronics and multivalued logic circuits, are introduced. The transistor channels of antiambipolar transistors consist largely of 2D atomically thin films or organic semiconductors. These materials are mechanically flexible. Therefore, antiambipolar transistors have the potential to enable advances to be made in the field of flexible electronics.     

The composition of particulate phosphorus: A case study of the Grand River,Canada

We examined the fractions of particulate phosphorus (PP) in the lower reaches of the Grand River, Canada, to test the hypothesis that the river is a source of both particulate-bound orthophosphate and labile species of PP. At the mouth of the Grand River, the proportion of particulate organic P (POP) was, on average, 57.7% of total PP, which was significantly higher than the proportion of particulate inorganic P (PIP) in PP. Analysis with ³¹P nuclear magnetic resonance (NMR) spectroscopy showed that the proportion of P species other than orthophosphate in the NaOH- EDTA extract was 1.75 times greater than that of orthophosphate. Labile P species (e.g. nucleotides and pyrophosphate) were present in the NMR spectrum; whereas, refractory organic P (myo-inositol hexakisphosphate) was absent. These results suggest that during winter and spring, the Grand River supplies primarily bioavailable phosphorus species in organic forms to Lake Erie, rather than inorganic orthophosphate. These results suggest that labile organic P is contained in PP rather than alkaline extractable inorganic P. Future studies should examine POP species in other rivers of the Lake Erie watershed.     

Preparation of nickel-based amorphous alloys with finely dispersed lead and lead-bismuth particles and their superconducting properties

The application of the melt-quenching technique to Ni-Si-B-Pb, Ni-P-B-Pb, Ni-Si-B-Pb-Bi and Ni-P-B-Pb-Bi alloys containing immiscible elements such as lead and bismuth has been tried and it has been found to result in the formation of a new type of material consisting of fine fcc Pb or hcp (Pb-Bi) + bct X(Pb-Bi) particles dispersed uniformly in the nickelbased amorphous matrix. The particle size and interparticle distance were 1 to 3 and 1 to 4 µm, respectively, for the lead phase, and less than 0.2 to 0.5 µm and 0.2 to 1.0 µm for the Pb-Bi phase. The uniform dispersion of such fine particles into the amorphous matrix was achieved in the composition range below about 6at% Pb and 7at% (Pb + Bi). Additionally, these amorphous alloys have been found to exhibit a superconductivity by the proximity effect of f c c Pb or (Pb-Bi) superconducting particles. The transition temperatureT _c was in the range 6.8 to 7.5 K for the Ni-Si(or P)-B-Pb alloys and 8.6 to 8.8 K for the Ni-Si (or P)-B-Pb-Bi alloys. The upper critical fieldH _c2 and the critical current densityJ _c for (Ni_0.8 P_0.1 B_0.1)₉₅ Pb₃ Bi₂ at 4.2 K were, respectively, about 1.6T and of the order of 7 X 10⁷ A m^–2 at zero applied field. Melt quenching of amorphous phase-forming alloys containing an immiscible element has thus been demonstrated, enabling us to produce amorphous composite materials exhibiting unique and useful characteristics which cannot be obtained in homogeneous amorphous alloys.     

Graft frequency of graft copolymers by chain transfer of growing polymer radicals to trunk polymers containing nitro groups

The relationship between the chain transfer constant, extent of monomer conversion, and number of branches was derived for the graft copolymerization through chain transfer of growing polymer radicals to the pendent aromatic nitro groups on the trunk polymer. The equation derived enables us to predict the number of branches for a given monomer trunk polymer. The relationship obtained is compared with the experimental data previously reported for the graft copolymerization of styrene onto poly(vinyl p-nitrobenzoate). The value of α′, the ratio of nitro groups with branches to those which are attacked by polystyrene radicals, is less than unity except for the graft copolymers obtained with high initiator concentrations and at early stages of the reaction. This lowering of α′ is attributed to the steric hindrance of branches already formed on the trunk polymer which prevents the attack of polystyrene radicals on the nitro groups and side reactions, such as reaction of the nitroso groups formed as an intermediate with styrene.     

Short-term effects of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor on cholesterol and bile acid synthesis in humans

Competitive inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase improve hypercholesterolemia. However, reports about the effects of these agents on bile acid synthesis, the metabolic pathway of cholesterol, are conflicting. We studied the short-term effect of one of these agents, pravastatin, on bile acid synthesis. Six male volunteers were given 40 mg of pravastatin. Plasma mevalonate level (which reflects cholesterol synthesis) and 7α-hydroxy-4-cholesten-3-one level 9which reflects bile acid synthesis) were measured every 2 h for 8 h. These plasma levels were compared to those of the same volunteers without pravastatin. Plasma mevalonate level after 2 h was lower than control (3.0 ± 1.1 ng/ml vs. 6.7 ± 2.5, mean ±SD; P<0.05). This decrease continued for 8 h (2.5 ± 0.8 vs. 5.2 ± 1.5; P<0.05). On the other hand, plasma 7α-hydroxy-4-cholesten-3-one level did not change until after 6 h; then at 8 h it was lower than control (15.7 ± 11.8 ng/mL vs. 24.7 ± 16.9; P <0.05). According to three-way layout analysis of variance, mevalonate level was influenced by both pravastatin treatment (P<0.01) and time-course (P<0.01). On the other hand, the 7α-hydroxy-4-cholesten-3-one level was affected by both individual difference (P<0.01) and time course (P<0.01), but pravastatin treatment did not influence this compound. This indicates that bile acid synthesis was not influenced by pravastatin, although cholesterol synthesis was inhibited. The shortterm inhibition of cholesterol synthesis did not affect bile acid synthesis.