Up-regulation of matrix metallopeptidase 12 in motor neurons undergoing synaptic stripping.

Axotomy of the rodent facial nerve represents a well-established model of synaptic plasticity. Post-traumatic "synaptic stripping" was originally discovered in this system. We report upregulation of matrix metalloproteinase MMP12 in regenerating motor neurons of the mouse and rat facial nucleus. Matrix metalloproteinases (matrix metallopeptidases, MMPs) are zinc-binding proteases capable of degrading components of the extracellular matrix and of regulating extracellular signaling networks including within synapses. MMP12 protein expression in facial motor neurons was enhanced following axotomy and peaked at day 3 after the operation. The peak of neuronal MMP12 expression preceded the peak of experimentally induced synaptic plasticity. At the same time, MMP12 redistributed intracellularly and became predominantly localized beneath the neuronal somatic cytoplasmic membrane. Both findings point to a role of MMP12 in the neuronal initiation of the synaptic stripping process. MMP12 is the first candidate molecule for such a trigger function and has potential as a therapeutic target. Moreover, since statins have been shown to increase the expression of MMP12, interference with synaptic stability may represent one mechanism by which these widely used drugs exert their side effects on higher CNS functions.

Computers in total quality management. Statistical process control to expedite stats.

We developed a system of computer programs to gather and then display data on turnaround time for stat tests. The data were those generated by the testing process itself so that no additional data entry was necessary. The system provided daily as well as longitudinal data for statistical process control implemented in the laboratory. The median and 90th percentile turnaround times were calculated for high-volume tests (complete blood cell count and Chem6 [six chemical serum component concentrations, ie, sodium, potassium, chloride, carbon dioxide, glucose, and urea nitrogen]), and a graphic display was automatically generated. These parameters and visual aids permitted evaluation of stat processing in the laboratory. The impact of management decisions on the stat process could be measured. Intralaboratory processing procedures were modified, and phlebotomy personnel were repositioned. Our various measurements showed which decisions improved stat turnaround time.

Primary meningeal mesenchymal chondrosarcoma.

A primary meningeal mesenchymal chondrosarcoma initially resembled an angioblastic meningioma because the typical chondroid islands were not demonstrable. Cartilage was seen only in an intracerebral recurrence and in subsequent extracranial metastases. Ultrastructural examination of noncartilaginous regions of the tumor demonstrated mesenchymal cells with features suggestive of cartilaginous differentiation, viz, scalloped cell membranes, sac-like distension of abundant rough endoplasmic reticulum, and a matrix containing fibrillary and finely granular material. Features of meningeal or pericytic cells were not seen.

Effects of beta-mercaptoethanol and chelating agents on the stability and activation of creatine kinase in serum.

We investigated the effects of sulfhydryl compounds on the stability of creatine kinase (CK) in unfrozen human serum and found that both beta-mercaptoethanol and N-acetylcysteine led to accelerated loss of the endogenous serum enzyme activity. This is in contrast to the results of others who have either studied the stability of exogenous enzyme added to human serum or studied endogenous enzyme in frozen serum. The addition of cation chelators to serum markedly improved the stability of the endogenous CK activity. The enhanced stability was independent of chelation of calcium, iron, manganese, copper, or zinc. In addition, cation chelators caused a 16% increase in the CK activity of fresh samples. This latter effect was independent of the activation of CK by BME and could be accounted for by chelation of calcium ions during the assay. The data suggest that addition of cation chelators prior to storage may be useful in enhancing the stability of CK in serum whereas sulfhydryl compounds should be added prior to assay rather than prior to storage.