A Metalloproteinase Cocktail from the Venom of Cleaves Amyloid Beta Peptides at the α-Cleavage Site.

A disintegrin and metalloproteinase (ADAM) family proteins are a major class of membrane-anchored multidomain proteinases that are responsible for the shedding of cell surface protein ectodomains, including amyloid precursor protein (APP). Human ADAM 9, 10, and 17 proteolyze APPs and produce non-amyloid-genic p3 peptides, instead of neurotoxic amyloid-β peptides (Aβs; Aβ40 and Aβ42), which form fibrils and accumulate in the brain of patients with Alzheimer's disease (AD). The ADAM family is closely related to snake venom metalloproteinases (SVMPs), which are derived from ancestral ADAMs but act as soluble proteinases.

A review of the fate of inhaled α-quartz in the lungs of rats.

The distribution of dust particles within the lungs and their excretion are highly associated with their pulmonary toxicity. Literature was reviewed to discern pulmonary translocation pathways for inhaled α-quartz compared to those for inhaled TiO. Accordingly, it was hypothesized α-quartz particles in the alveoli were phagocytized by alveolar macrophages but silica-containing macrophages remained in the alveoli for longer time in contrast to the rapid elimination from the alveoli seen for TiO-containing macrophages.

A mechanistic review of particle overload by titanium dioxide.

Chronic exposure to titanium dioxide (TiO) induces slight but significant pulmonary inflammation in experimental animals, and among potential mechanisms, particle overload is likely. Although mechanisms of particle overload are poorly understood, excess accumulation of dust particles in dust containing macrophages (dust cells) can impair their mobility, resulting in reduced clearance ability. Accordingly, retention half-times of inhaled TiO increase linearly with lung burden in rodents, and mathematical (Michaelis-Menten-like) models for pulmonary clearance rates of TiO as a function of lung burden have suggested an alternative mechanism for particle overload, involving excess accumulation of macrophages in the translocation pathway due to the narrow exit to the ciliated airway region, and leading to reduced pulmonary TiO clearance rates.

A mechanistic review of silica-induced inhalation toxicity.

Crystalline forms of silica have been proposed as positive control material for the toxicity test of inhaled particulate/fibrous matter, although mechanism of silica-induced inhalation toxicity has not yet been established. Inhalation exposure of α-quartz to rodents induces severe lung inflammation and fibrosis only after a certain period of latency, despite strong surface reactivity. The delayed occurrence of inhalation toxicity by α-quartz may be largely attributed to the sequestration of α-quartz particles by alternatively activated (M2) macrophages that express abundant levels of scavenger receptors but are relatively insensitive to inflammatory stimuli.

Interstitial duplication of 2q32.1-q33.3 in a patient with epilepsy, developmental delay, and autistic behavior.

Duplications of the 2q33 region are rare; to date, only 13 patients have been reported to have this chromosomal abnormality. The reported duplications are of varying size, and the patients shared developmental delay and minor dysmorphic findings. In this study, we identified a duplication of 2q32.

Research strategies for safety evaluation of nanomaterials, part VIII: International efforts to develop risk-based safety evaluations for nanomaterials.

The use of nanotechnology in consumer and industrial applications will likely have a profound impact on a number of products from a variety of industrial sectors. Nanomaterials exhibit unique physical/chemical properties and impart enhancements to engineered materials, including better magnetic properties, improved electrical activity, and increased optical properties. The United States, Europe, and Japan have each initiated comprehensive programs to promote and expand the utility of nanotechnology for commercial applications.

Estimating health risk from exposure to 1,4-dioxane in Japan.

Exposure to 1,4-dioxane from the atmosphere around high-emission plants and from consumer products used in daily life that contain the substance may have adverse health effects; however, its emission into the atmosphere is not regulated. In this study, the health risk posed by 1,4-dioxane is assessed to investigate whether measures should be undertaken to reduce exposure to 1,4-dioxane. The notion of the margin of exposure (MOE), given by the ratio of no observed adverse effect level (NOAEL) to actual or projected exposure level, is used to assess risk.

Impact of cytidine deaminase activity on intrinsic resistance to cytarabine in carcinoma cells.

Cytarabine (araC) is a highly active antimetabolite against hematological malignancy while the agent shows limited activity against carcinomas. In this study, we focused on cellular transport and catalysis of the nucleoside in order to elucidate the mechanism of intrinsic resistance to araC in carcinomas. Activities of two metabolizing enzymes for araC, deoxycytidine kinase (DCK) and cytidine deaminase (CDA), and cellular transport of the agent were examined in 9 carcinoma cell lines.

Fever as a risk factor causing delayed elimination of methotrexate in pediatric patients receiving high doses of cancer chemotherapy.

Purpose: Delayed elimination of methotrexate (MTX) has been reported to be caused by a number of factors. In order to identify these causes, we retrospectively investigated the risk factors for delayed elimination in pediatric patients who received high doses of MTX.

Subjects And Methods: The study included 69 courses of therapy involving 22 patients who received more than 1000 mg/m(2) of MTX.

Recent advances in the treatment of infant acute myeloid leukemia.

Infant acute myeloid leukemia (AML) of less than 12 months old is generally characterized by a high incidence of acute monoblastic or myelomonoblastic leukemia with hyperleukocytosis and extramedullary involvement. Most of the leukemic cells have 11q23 translocations, which lead to the MLL gene rearrangements. The MLL gene rearrangements occur at a high frequency in monoblastic subtype, hyperleukocytosis or young age in infant AML.

Risk-directed treatment of infant acute lymphoblastic leukaemia based on early assessment of MLL gene status: results of the Japan Infant Leukaemia Study (MLL96).

We studied the effectiveness of risk-directed therapy for infants younger than 13 months of age with acute lymphoblastic leukaemia (ALL). Fifty-five infants were assigned to different treatment programs (from December 1995 to December 1998) on the basis of their MLL gene status at diagnosis. Forty-two cases (76.

Increased Deoxycytidine Kinase mRNA Level After Treatment with Interleukin-3.

Pretreatment of IL-3 to Kasumi-1 human acute myeloid leukemia cells enhanced 1-B-D-arabinofuranosyl cytosine (ara-C) cytotoxicity 1.2. to 1.