Widespread astrogliosis exists in the subcortical white matter in amyotrophic lateral sclerosis (ALS). As revealed by glial fibrillary acidic protein (GFAP) immunostaining, the gliosis has the morphological properties of an active process. It is present in the midfrontal, inferior parietal, temporal, cingulate, and occipital cortices, as well as in the motor cortex. Compared to matched regions from other neurological diseases, the gliosis in ALS does not appear to be the nonspecific result of a progressive, degenerative disease. In cell number and apparent cell size, the gliosis is comparable to that present in neurological diseases known to have white matter gliosis. Cytologically, the gliosis most closely resembles that present in cases of cerebral infarction. The basis for this similarity is unknown.

The distribution of reactive astrocytes was examined in the cortical gray matter of non-motor and motor regions from cases of familial and sporadic amyotrophic lateral sclerosis (ALS) and compared to that of beta-amyloid deposits. By glial fibrillary acidic protein immunocytochemistry, patches of reactive astrocytes, characterized by multiple reactive astrocytes in a circular or patch-like formation, occurred in 12 of 15 ALS cases examined. These patches of reactive astrocytes were not restricted to the motor cortex but were found in the gray matter in ALS in all examined brain regions, including frontal, temporal, inferior parietal, cingulate, occipital, and motor cortices, from both familial and sporadic ALS cases. Reactive astrocytes were also found in the subpial region and at the gray/white matter junction. Because patches of astrocytes can occur in association with senile plaques, beta-amyloid was localized. By immunostaining, beta-amyloid deposits were observed in five of the 15 ALS cases: three cases had only early plaques, two had both early and classic plaques. The number of ALS cases with both astrocyte patches and amyloid plaques was four of 15, but typically astrocyte patches in ALS occurred without any evidence of an association with beta-amyloid deposits. Therefore, the astrocyte patches in ALS are not the result of beta-amyloid deposition. The widespread occurrence of reactive astrocytes, as patches in the cortical gray matter and in the subpial region and at the gray/white matter junction, is evidence of a widespread pathology in ALS cortex in both familial and sporadic forms of the disease.

A library of monoclonal antibodies was generated to the cholinergic synaptosome. The immunogen was a preparation of highly purified synaptosomes from Torpedo electric organ. One hundred forty-one hybridoma cell lines were generated from the fusion of a single mouse. Tests reveal these cells produce antibodies with a vast range of neuronal specificities. The initial screen for specificity of antibody production was solid phase radioimmune binding to the original, highly purified synaptosome preparation. Subsequent tissue specificity tests have indicated that most antibodies are synaptosome-specific amongst the fish tissues tested: brain, liver, and purified synaptic vesicles. Less than 11% cross-react with liver. Many antibodies cross-react with frog and rat CNS. Localization within the frog and rat nervous tissue has revealed a vast array of antibody staining patterns. Some antibodies stain in a synaptic fashion. A few stain a restricted set of mammalian CNS neurons. Others define a broader set of CNS neurons. These Torpedo antibodies promise to be valuable probes with which to describe the molecular cell biology of the nervous system, of neurons in general, and of cholinergic neurons in particular.

No abstract

Antigen and mitogen-induced gamma interferon (gamma-IFN) production was studied in peripheral blood mononuclear cells from 34 leprosy patients. 17 of 18 lepromatous leprosy and borderline lepromatous patients (LL and BL) failed to release gamma-IFN in response to specific antigen (Mycobacterium leprae) and displayed reduced responses to mitogen (concanavalin A) stimulation. In contrast, cells from six tuberculoid and borderline tuberculoid patients (TT and BT) produced considerable levels of gamma-IFN under the same experimental conditions. Normal controls failed to respond to M. leprae and most displayed good responses to concanavalin A. Mid-borderline patients (BB) showed intermediate levels of gamma-IFN release. gamma-IFN release by lepromatous patients could be partially restored with purified interleukin 2 and M. leprae antigen but not with interleukin 2 alone.