Identification of Physiological and Toxic Conformations in Aβ42 Aggregates

Aggregation of the 42‐residue amyloid β‐protein (Aβ42) plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Despite numerous structural studies on Aβ aggregates, the relationship between tertiary structure and toxicity remains unclear. Our proline scanning and solid‐state NMR studies suggested that aggregates both of wild‐type Aβ42 and of E22K‐Aβ42 (one of the mutants related to cerebral amyloid angiopathy) contain two conformers: a major one with a turn at positions 25 and 26, and a minor one with a turn at positions 22 and 23. To identify the toxic conformer, the derivative Aβ42‐lactam(22K–23E), in which the side chains at positions 22 and 23 were covalently linked, was synthesized as a minor conformer surrogate, along with Aβ42‐lactam(25K–26E) as a major conformer surrogate. The Aβ42‐lactam(22K–23E) showed stronger aggregation, neurotoxicity, radical generation, and oligomerization than wild‐type Aβ42, whereas in Aβ42‐lactam(25K–26E) were weak. The transition from the physiological conformation with a turn at positions 25 and 26 to the toxic conformation with a turn at positions 22 and 23 might be a key event in the pathogenesis of AD.     

Nuclear magnetic ordering in BCC solid 3He

Applying the cluster expansion method to an antiferromagnetic bcc solid ³He, we calculate the Néel temperature T _sc. The result shows that in the case of J ₂/J ₁ 0.3–0.5, K _F/J ₁ 0.5, and J ₁ –0.5 mK, whose values were determined with a Hamiltonian including four-spin exchange to obtain a good fit with the experimental results, the transition to the normal antiferromagnetic phase at about 2 mK, which was anticipated by the molecular field approximation, does not occur. Using the same method, the paramagnetic susceptibility was also calculated.Work supported in part by the Mitsubishi Foundation.     

A comparison between the journals nature and science

In this paper,Nature andScience, the two distinguished multi-disciplinary scientific journals were compared placing emphasis on their internationality. The items investigated were as follows. A general comparison: 1. number of authors per article, 2. distribution of countries to which first authors' institutions belong, 3. distribution of main discplines studied by first authors, 4. time-lag between the date of receipt of an article by the editor and the date of its publication. B. the position with regard to Japanese author: 1. number of Japanese authors, 2. relationship between the ranking of a Japanese author in the list of authors' names and the country where his institution is located, 3. relationship between the time-lag stated in A-4 and the items stated in B-2. As a result, it can be said thatNature is a more highly international journal thanScience.     

Intra-bile duct growth of hepatocellular carcinoma: value of biliary dilatation on CT

In order to evaluate the usefulness of CT in demonstrating biliary invasion by hepatocellular carcinoma, 191 surgically proved cases were studied. Among 191 CT scans performed before surgery, six (3%) showed biliary dilatation. Pathological biliary invasion was found in eight cases (4%). Of these eight cases, four cases (50%) showed biliary dilatation on CT. In six cases with biliary dilatation on CT, pathological biliary invasion was revealed in four cases (67%). In two cases, the large (> or = 6cm) encapsulated tumors located in the hepatic hilum dilated the intrahepatic bile duct without intraductal tumor growth. We concluded that biliary dilatation on CT cannot be a sign of biliary invasion by hepatocellular carcinoma.     

A unique ectonucleotide pyrophosphohydrolase associated with porcine chondrocyte-derived vesicles

Previous studies have shown increased nucleotide pyrophosphohydrolase (EC 3.6.1.8) (NTPPHase) activity in detergent extracts of degenerated human cartilage containing calcium pyrophosphate dihydrate (CPPD) crystals relative to those from osteoarthritis or normal cartilage. NTPPHase was later shown to be an ectoenzyme and its activity was increased in synovial fluid from patients with CPPD crystal deposits relative to fluids from other types of arthritis. We have purified a soluble 61-kD NTPPHase from conditioned media of organ-cultured porcine articular cartilage to electrophoretic homogeneity. Its NH2-terminal sequence through 26 cycles showed < 30% homology to any previously reported protein sequence. An antibody raised to a synthetic peptide corresponding to this sequence reacted with denatured but not native enzyme. This antibody reacted against a sedimentable vesicle-associated 127-kD protein in conditioned media from cultured articular cartilage or from chondrocytes in primary monolayer culture and against a series of soluble proteins in conditioned media supernatant, including a 61-kD protein representing our original isolate. No reactivity was found in 1% SDS extracts of washed cultured chondrocytes, although these contained greater NTPPHase activity than the conditioned media. Antibody to PC-1, another ectoNTPPHase, reacted with 1% SDS extracts of whole chondrocytes but not against those chromatographic fractions containing the major portion of NTPPHase activity. Release of the vesicle-associated 127-kD enzyme into conditioned medium was stimulated three- to sevenfold by TGF beta 1. The antibody also reacted with a series of soluble proteins and with 127-kD sedimentable protein in human synovial fluid. Kinetic studies supported the existence of a unique vesicle-associated NTPPHase; apparent Km (mM) of chondrocyte membrane NTPPHase was 1.5 and 3.0 at pH 7.3 and 9.88, respectively; apparent Km (mM) of vesicle associated NTPPHase was 0.83 and 1.28 at pH 7.3 and 9.88. The data suggest the existence of a unique ecto-NTPPHase associated with vesicles derived from normal articular cartilage.     

Administration of phosphatidylcholine increases brain acetylcholine concentration and improves memory in mice with dementia

Studies on the effect of phosphatidylcholine administration on memory are limited. We administered egg phosphatidylcholine to mice with dementia and to normal mice and compared the differences in memory and serum choline concentration, and choline and acetylcholine concentrations and choline acetyltransferase activities of three forebrain regions (cortex, hippocampus and the remaining forebrain). Mice with dementia were produced by mating sibling mice who had impaired memory for > 20 generations. These mice had poor memory and low brain acetylcholine concentration. We administered 100 mg of egg phosphatidylcholine (phosphatidylcholine group) or water (control group) by gavage to each mouse daily for about 45 d. Control mice with dementia had poorer memory in passive avoidance performance and lower brain choline (cortex and hippocampus) and acetylcholine (hippocampus and forebrain excluding cortex and hippocampus) concentrations and lower cortex choline acetyltransferase activity than the control normal mice (P < 0.05). The administration of phosphatidylcholine to mice with dementia improved memory and generally increased brain choline and acetylcholine concentrations to or above the levels of the control normal mice. In normal mice, phosphatidylcholine treatment did not affect memory or acetylcholine concentrations in spite of the great increase in choline concentrations in the three brain regions. Serum choline concentration in mice treated with phosphatidylcholine increased to a similar level in both strains of mice, indicating that the absorption of phosphatidylcholine was not impaired in mice with dementia. The results suggest that administration of egg phosphatidylcholine to mice with dementia increases brain acetylcholine concentration and improves memory.     

clinical study of balofloxacin on infectious enteritis and assessment of the fecal drug concentration and intestinal microbial flora in patients with inpatients with infectious enteritis. Research group of balofloxacin on infectious enteritis

The efficacy, safety and usefulness of balofloxacin (BLFX) for patients with acute infectious enteritis and the carriers mainly shigellosis, were investigated. The drug was administered at a daily dose of 200 mg twice a day for 3 days to patients with cholera, 7 days to patients with Salmonella enteritis and 5 days to patients with other conditions of infectious enteritis including shigellosis; 1. The efficacy was analyzed in 89 of the 135 patients who received the administration (43 patients with shigellosis, 14 with Salmonella enteritis, 8 with enteropathogenic/ enterotoxigenic Escherichia coli enteritis, 3 with cholera, 7 with enteritis with other pathogenic bacteria, 6 with polymicrobial infectious enteritis and 8 with acute enteritis that was pathogen-negative). 2. In patients bearing symptoms and who thus could be analyzed for drug efficacy, the drug was markedly effective or effective 50/52 (96.2%). 3. Bacteriologically, the drug was effective for Shigella spp. in 41 (100%) of 41, Salmonella spp. in 12 (85.7%) of 14, and enteropathogenic/enterotoxigenic Escherichia coli in 8 of 8 cases. 4. Adverse effects were seen in 5/133 patients (3.8%) receiving the drug, including two cases of skin eruption, one of the numbness of the hands, one of oral aphtha, and one of nausea. In patients for whom laboratory findings were available, 20/115 (17.4%) showed abnormalities, mainly elevations of GOT and/or GPT, but these were slight. 5. In terms of subjective reports of usefulness, 51/82 (62.2%) were markedly satisfied, and 73/82 (89.0%) were either satisfied or markedly satisfied. 6. The influence of administration of BLFX on fecal concentration and intestinal microbial flora was investigated in 2 patients with acute infectious enteritis. Results approximately equivalent to such flora levels in healthy subjects were obtained. These results suggest that BLFX is highly useful for infectious enteritis such as that caused by shigellosis.     

An introduction to Anatomical Image Digitizing System (AIDS)

We designed, constructed, and evaluated a prototype of a digital data management system for anatomical studies and education, named AIDS (Anatomical Image Digitizing System). By implementing the prototype systems, we intended to determine the technical and anatomical parameters required for such a system, and to attempt digital imaging analysis of morphology. We demonstrated that such systems can be used as a new morphological tool on a macroscopic level, particularly in mathematical image analysis, in comparative anatomy by organizing a database and by modifying images with graphic techniques, and in statistical discussions by manipulating large numbers of illustrations quickly. A 512 X 512 X 8 bit matrix is judged to be satisfactory for analyzing images mathematically and producing illustrations of bones, but higher quality tools are required to store anatomical figures with halftones in a good condition, and to prepare fine anatomical illustrations. Classifications of figures and formats of figure legends are necessary to standardize the storage of figures in the form of a database.     

Improvement of alpha-particle-induced soft-error immunity in a GaAsSRAM by a buried p-layer

Alpha-particle-induced soft-error immunity in a 1-kB GaAs SRAM was improved by a buried p-layer, which was formed in isolation regions as well as in FET regions and was designed to be completely depleted. The mean time between failures exceeded 10⁴ at an alpha-particle fluence of about 2.0×10⁴ cm^-2-s^-1 with a 1.0-μCi²⁴¹Am source. The alpha-particle energy had a peak at 4.0 MeV and was distributed from nearly 0 to 4.6 MeV. This value is five orders of magnitude better than that for a conventional SRAM without a buried p-layer. This improvement in the soft-error immunity can be achieved without increasing the access time or the power consumption by depleting the p-layer completely. Also discussed is the possibility of using a conductive p-layer scheme for higher integration of GaAs SRAMs     

Perspective on BiCMOS VLSIs

A high-performance BiCMOS technology (Hi-BiCMOS) and its applications to VLSIs are described. By combining bipolar and CMOS devices in unit circuits of VLSIs, Hi-BiCMOS provides both speed performance competitive with bipolar LSIs and integration density close to that of CMOS LSIs. Hi-BiCMOS technology has been successfully used for static RAMs, dynamic RAMs, and gate arrays. The effectiveness of its applications to some types of processors has also been examined by evaluating test chips