Diabetic muscle infarction: a new perspective on pathogenesis and management.

Two patients with insulin dependent diabetes mellitus developed recurrent episodes of focal muscle pain and swelling. Clinical evaluation, magnetic resonance imaging (MRI) and muscle biopsy confirmed the diagnosis of recurrent hemorrhagic muscle infarctions. Our studies suggest that muscle infarction occurred because of hypercoagulability and associated vascular endothelial damage. Based on these findings we recommend long-term anticoagulation to prevent recurrent infarction.

Family of human neuronal external surface epitopes defined by Torpedo monoclonal antibodies.

We are employing a library of monoclonal antibodies (MAbs) that were made to Torpedo cholinergic synaptosomes to identify conserved, physiologically vital epitopes of the neuronal surface. Our particular interest is in those epitopes that are present on some but not all neurons. In the present study we screened this library on different cell lines, the neuronal cell lines PC12, NG108, MC-IXC, and SY5Y, and the endocrine cell lines GH-3 and HIT. Of these cell lines, only SY5Y cells bind MAbs that define neuronal surface subsets. Utilizing its parent cell line, SK-N-SH, we verified that six MAbs, Tor 25, Tor 103, Tor 190, Tor 201, Tor 219, and Tor 233, bind the external neuronal surface. The cytolocalization of all six MAbs is very similar: the membrane of the cell body and its processes are finely outlined in a punctate distribution. Western blot analyses of Torpedo electric organ homogenates, a highly enriched source of antigenic material, revealed that each MAb identifies multiple polypeptides, two of which have the relative mobilities of 180 kD and 67 kD. In a screen of peripheral nerves from cases of amyotrophic lateral sclerosis (ALS), we found that all these MAbs revealed surface alterations; some displayed a decrease in binding, while others displayed an increase. The combined data provide evidence that these epitopes belong to an important, complex family of polypeptides of the external neuronal surface.

Torpedo monoclonal antibodies react with components of the human peripheral nervous system.

A panel of 141 monoclonal antibodies, generated to the Torpedo ray cholinergic nerve terminal preparation, were tested for binding to components of human nerve and muscle. Tested by immunofluorescence, 13 of the antibodies reacted with components of the human intercostal nerve, and 9 bound either muscle or blood vessels in a diversity of staining patterns. Results indicate that the antibodies identify a spectrum of different antigens. Some of the antibodies that cross react with the human nervous system have been studied in the ray and rat. In the human peripheral nerve and muscle, their cytochemical distribution is consistent with what has been observed in these other species. These antibodies, therefore, are likely to identify components of the neuromuscular junction that have been conserved in evolution from elasmobranchs to humans. The antibodies identified here are potentially useful tools for a molecular examination of human nerves and muscles in pathological conditions.

Quantitative axon terminal and end-plate morphology in amyotrophic lateral sclerosis.

An axon-end-plate double stain yielded more synaptic detail than the older methylene blue stain of the muscle biopsy specimen. Application of the double stain to amyotrophic lateral sclerosis confirmed earlier and well-known findings of denervation, abnormal end-plates, and axonal sprouting. Little new data emerged, however, and the sprouting index seemed to mislead. As in several previous investigations, muscle from normal human subjects showed evidence for at least past if not current denervation, substantiating the need for continued rigorous controls in such studies.

End-plate morphology in amyotrophic lateral sclerosis.

Intercostal muscle end-plates were measured in patients with amyotrophic lateral sclerosis (ALS) and more benign motor neuron disease (MND). The length of the intact end-plates in ALS and MND was not different from the controls. Segmented end-plates were increased in both ALS and benign MND, and the end-plate length was greatest in ALS. In individual ALS cases, no correlation was found between the end-plate abnormalities and relevant clinical variables.