Age-associated and cell-type-specific neurofibrillary pathology in transgenic mice expressing the human midsized neurofilament subunit.

Alterations in neurofilaments are a common occurrence in neurons of the human nervous system during aging and diseases associated with aging. Such pathologic changes may be attributed to species-specific properties of human neurofilaments as well as cell-type-specific regulation of this element of the cytoskeleton. The development of transgenic animals containing human neurofilament subunits offers an opportunity to study the effects of aging and other experimental conditions on the human-specific form of these proteins in a rodent model. The present study shows that mice from the transgenic line NF(M)27, which express the human midsized neurofilament subunit at low levels (2-25% of the endogenous NF-M), develop neurofilamentous accumulations in specific subgroups of neurons that are age dependent, affecting 78% of transgenic mice over 12 months of age. Similar accumulations do not occur in age-matched, wild-type littermates or in 3-month-old transgenic mice. In 12-month-old transgenic mice, somatic neurofilament accumulations resembling neurofibrillary tangles were present predominantly in layers III and V of the neocortex, as well as in select subpopulations of subcortical neurons. Intraperikaryal, spherical neurofilamentous accumulations were particularly abundant in cell bodies in layer II of the neocortex, and neurofilament-containing distentions of Purkinje cell proximal axons occurred in the cerebellum. These pathological accumulations contained mouse as well as human NF subunits, but could be distinguished by their content of phosphorylation-dependent NF epitopes. These cytoskeletal alterations closely resemble the cell-type-specific alterations in neurofilaments that occur during normal human aging and in diseases associated with aging, indicating that these transgenic animals may serve as models of some aspects of the pathologic features of human neurodegenerative diseases.

Diagnosis of disseminated candidiasis based on serum D/L-arabinitol ratios using negative chemical ionization mass spectrometry.

The main objective was to appraise the diagnostic specificity of the serum D/L-arabinitol ratio technique in a patient population biased for renal dysfunction. The D/L ratio (mean +/- S.D.) in normal serum (n = 29) was 1.76 +/- 0.47 (range 0.77-2.75). D/L-Arabinitol greater than 3.18 (mean + 3 S.D.) are considered indicative of disseminated candidiasis. Of 49 patients without candidiasis, but 46% with serum creatinine greater than 1.5 mg/dl, diagnostic specificity was 88%. In confirmed candidiasis (n = 16) sensitivity was 94% (D/L range 3.2-50.1). Switching from positive to negative chemical ionization permits the use of as little as 5 microliters sample (20 microliters used routinely; D/L ratios constant in the 5-200 microliters range) permitting the extension of the technique to pediatric applications. Results can obtained in 2 h. Suggested areas of clinical application include aiding diagnosis, monitoring patients as risk so that treatment could be initiated while fungus load is still small, and following the course of antifungal chemotherapy.

Malignant fibrous histiocytoma of the gastrointestinal tract in a patient with neurofibromatosis.

Malignant fibrous histiocytoma (MFH) of the gastrointestinal tract is extremely rare. A case of MFH of the colon associated with neurofibromatosis is presented. MFH is a high-grade soft-tissue sarcoma of fibroblast cell origin with a strong propensity for metastasis and recurrence. Immunochemical markers help to differentiate MFH from other sarcomas. The most successful treatment of MFH is surgical extirpation. Adjuvant chemotherapy and radiotherapy have not been definitively shown to be of value.

High-temperature structural ceramics.

The unique properties of ceramics based on silicon carbide and silicon nitride make them prime candidates for use in advanced energy conversion systems. These compounds are the bases for broad families of engineering materials, whose properties are reviewed. The relationships between processing, microstructure, and properties are discussed. A review and assessment of recent progress in the use of these materials in high-temperature engineering systems, and vehicular engines in particular, is presented.

Reductive dechlorination and degradation of mirex and kepone with Vitamin B12.

Vitamin B12s effects the reductive dechlorination of mirex (dechlorane) in protic solvent systems, under both catalytic and stoichiometric conditions, mainly to yield compounds of composition C10Cl12-nHn, with n = 1-8, in which the basic dihomocubane cage structure is retained; the formation of cage-opened, reductively dehalogenated derivatives of 4,7-methanoindene occurs only to a very minor extent. The corresponding reactions of kepone (chlordecone), in contrast, occur with predominant formation of indene derivatives. Under certain mild conditions, vitamin B12s induces a fragmentation of kepone leading to the destruction of the dihomocubane moiety and the formation of an isolable organocobalamin having a C3Cl3H2 residue attached to the cobalt atom. In strongly alkaline media, the reaction of kepone with vitamin B12s may in addition yield high-molecular-weight condensation products of unknown constitution. Reactions of this type are of interest as prototypes of soil-decontamination processes.

Coenzyme M and methylcobalamin in methane biosynthesis: results of model studies.

Coenzyme M (2-mercaptoethanesulfonate, HS-CH2CH2SO3-) reacts with methylcobalamin nonenzymatically in the pH-range between 6 and 14 to yield the S-methyl derivative (CH3-S-CH2CH2SO3-). In addition, and also at lower pH, methane is produced by reductive cleavage of the Co-C bond. With methylcobaloximes as the methyl group donors, methane production predominates, with insignificant S-methylation. The initial rates of methane production from methylcobaloximes with coenzyme M as the reductant correlate with the rates of methane production from these substrates with active cell extracts of Methanobacterium M.o.H.