DBA/2J Genetic Background Exacerbates Spontaneous Lethal Seizures but Lessens Amyloid Deposition in a Mouse Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is a leading cause of dementia in the elderly and is characterized by amyloid plaques, neurofibrillary tangles (NFTs) and neuronal dysfunction. Early onset AD (EOAD) is commonly caused by mutations in amyloid precursor protein (APP) or genes involved in the processing of APP including the presenilins (e.g. PSEN1 or PSEN2). In general, mouse models relevant to EOAD recapitulate amyloidosis, show only limited amounts of NFTs and neuronal cell dysfunction and low but significant levels of seizure susceptibility. To investigate the effect of genetic background on these phenotypes, we generated APP^swe and PSEN1^de9 transgenic mice on the seizure prone inbred strain background, DBA/2J. Previous studies show that the DBA/2J genetic background modifies plaque deposition in the presence of mutant APP but the impact of PSEN1^de9 has not been tested. Our study shows that DBA/2J.APP^swePSEN1^de9 mice are significantly more prone to premature lethality, likely to due to lethal seizures, compared to B6.APP^swePSEN1^de9 mice—70% of DBA/2J.APP^swePSEN1^de9 mice die between 2-3 months of age. Of the DBA/2J.APP^swePSEN1^de9 mice that survived to 6 months of age, plaque deposition was greatly reduced compared to age-matched B6.APP^swePSEN1^de9 mice. The reduction in plaque deposition appears to be independent of microglia numbers, reactive astrocytosis and complement C5 activity.     

Some comments on the aerobiology of fungus spores

While exposure/symptom relationships are relatively well-defined for pollen allergens, such relationships have not been clearly established for airborne fungus spores due to a lack of clearly defined seasonal patterns, prevalence of world-wide cosmopolitan fungi, and serious problems with sampling and identification. Ascospores and basidiospores have been least studied with respect to aerobiology, although both are clearly allergenic. Preliminary data on allergenicity and diurnal and seasonal prevalence patterns for selected ascospore and basidiospore types are presented.     

Association of beta-glucosidase with intact cells of Thermoactinomyces.

The location of the B-glucosidase activity in a whole culture broth of the thermophilic organism Thermoactinomyces has been studied. Little beta-glucosidase activity was found in the culture filtrate, while the culture solids contained the major part of the activity of the whole culture broth. The activity does not appear to be adsorbed to the culture solids; rather there is evidence that it is an intracellular soluble enzyme(s). The pH and temperature optima for a crude beta-glucosidase preparation were determined to be pH 6.5 and 50--55 degrees C. Enzyme activity studies indicate that the same enzyme(s) accounts for the beta-glucosidase and the cellobiase activities. The validity of using the filter paper activity of culture filtrates from Thermoactinomyces to predict the total saccharification of cellulosic materials to glucose is discussed.     

Oxidation of certain cyclic carbonyl compounds with alkaline hydrogen peroxide

The following cyclic compounds were oxidized at 4° by means of aqueous sodium peroxide in large excess: 2,3,4,6/5-pentahydroxycyclohexanone (1); xylo-pentahydroxy-2-cyclohexen-l-one (2); xylo-trihydroxycyclohexane-1,2,3-trione (3); reductic acid (4); and ninhydrin (5). On oxidation, 1, 2, and 3 gave carbon dioxide, formic acid, and oxalic acid; in addition, 1 yielded DL-glucaric acid, and 2 and 3 afforded xylaric acid. Compound 4 gave almost equimolecular quantities of carbon dioxide and succinic acid. In addition to a small amount of formic acid, compound 5 gave carbon dioxide and phthalic acid in yields of 92 and 95%, respectively. Reaction mechanisms are proposed.     

Prostaglandin inhibition of cyclic-AMP accumulation and rate of lipolysis in fat cells

A direct relationship between the rate of cyclic AMP accumulation for 2 minutes and the rate of free fatty acid mobilization for 20 minutes was found in rat isolated fat cells stimulated with norepinephrine or theophylline. The concentration-dependent inhibition of cAMP accumulation by prostaglandin E₂ was reflected in proportional inhibition of lipolysis. These data suggest that the anti-lipolytic mechanism of action of prostaglandin E₂ is mediated by inhibition of the early rate of cAMP accumulation rather than the total production of cAMP.     

Localization of cytochrome P450 CYP2S1 expression in human tissues by in situ hybridization and immunohistochemistry.

CYP2S1 is a recently discovered dioxin-inducible member of the cytochrome P450 superfamily. It has been shown to be involved in the metabolism of some aromatic hydrocarbons as well as retinoic acid, suggesting a role in biotransformation of both exogenous and endogenous compounds. In this study, we used mRNA in situ hybridization and immunohistochemistry to investigate the cellular localization of CYP2S1 in various human tissues using tissue microarrays. High expression levels were observed mainly in epithelial cell types, especially in the epithelia frequently exposed to xenobiotics. In the respiratory tract, the expression was strong in nasal cavity, bronchi, and bronchioli, whereas it was low in the alveolar lining cells. Similarly, CYP2S1 was highly expressed in the epithelial cells throughout the gastrointestinal tract. Strong epithelial expression was also observed in uterine cervix, urinary bladder, and skin. In many exocrine glands (e.g., adrenal gland and pancreas), secretory epithelial cells showed moderate to strong expression levels. In the liver, the expression was low. CYP2S1 was highly expressed in epithelial cells that are major targets for carcinogen exposure and common progenitor cells to tumor development. Indeed, we found strong CYP2S1 expression in many tumors of epithelial origin.