Biomedical subjects
Publications and source records attributed to E C Alvord.
Incubation with specific antigen, myelin basic protein, greatly enhances the ability of guinea pig peritoneal exudate cells to transfer experimental allergic encephalomyelitis. Reproducibly successful transfers are obtained with 10(7) cells. With this relatively small number of cells, in vitro studies to determine the immunologic mechanisms involved in the disease process are now possible.
Autosensitization to some central nervous system antigen still remains one of the best hypotheses for the continuing pathogenesis of multiple sclerosis (MS). Enough is now known about the cause, pathogenesis, and treatment of experimental allergic encephalomyelitis (EAE) to test this hypothesis. Reports of therapeutic failure of the encephalitogen myelin basic protein (BP) in the treatment of MS have their counterparts in similar therapeutic failures in EAE. Only highly inbred strain 13 guinea pigs respond consistently to BP therapy, and this only when BP is administered in relatively high doses. Noninbred guinea pigs respond much less well to simple BP therapy, and monkeys hardly at all. In both strains of monkeys so far studied, a nonspecific adjunctive factor--an antibiotic in Macaca mulatta and a steroid in Macaca fascicularis--is also required. Accordingly, human trials of the therapeutic efficacy of BP in MS should include its administration in large concentrations together with an adjunctive agent.
Treatment of experimental allergic encephalomyelitis (EAE) in two strains of monkeys with large amounts of myelin basic basic protein (BP) fails unless an adjunct is also used. In both strains the adjunct by itself is more effective than BP by itself, but in the one strain which could be investigated sufficiently, the combination can be made almost totally effective in reversing EAE. The adjunct varies with the strain of monkey, an antibiotic in Macaca mulatta and a steroid in Macaca fascicularis. Similar adjunctive treatments should be considered in the management of multiple sclerosis, for EAE remains one of the best studied models.
Cerebrospinal fluid contains several proteolytic enzymes that can degrade myelin basic protein (BP) under physiological conditions into peptide fragments of various sizes which still contain antigenic determinants capable of binding antibodies to BP. These enzymes are optimally active in either acid (pH 4) or nuetral (pH 7 to 8) conditions and can be characterized by the nature of the BP peptide fragments produced. Proteinases resembling cathepsin D, thrombin, plasmin (fibrinolysin), or kallikrein are present in variable amounts in CSF. No relationship to any particular disease has yet been established.
Evaluation of the neuropathologic alterations occurring in 170 consecutive autopsies in premature infants dying of the idiopathic respiratory distress syndrome (IRDS) reveals two large groups, hemorrhagic and nonhemorrhagic. Hemorrhages occurred in all possible sites and formed the single largest group. Such hemorrhages appeared to be related to the early death of many premature infants. The nonhemorrhagic group was quite variable, with the largest category of associated lesions being periventricular leukomalacia, the frequency of which increased with increasing age. We suggest that the nonhemorrhagic group may be an important factor in the morbidity of survivors.
Spleen cells from myelin basic protein (BP)-sensitized donor rats appear to be incapable of adoptively transferring experimental allergic encephalomyelitis (EAE) directly to normal recipients. It has been reported that in vitro incubation with concanavalin A (Con A) activates rat spleen cells so that they are capable of transferring EAE. We report here that incubation with specific antigen, BP, also permits transfer of disease with spleen cells. Data are presented in which activation of EAE spleen cells by Con A is compared with activation by BP. Cellular proliferation does not appear to be necessary for in vitro activation with specific antigen.
Explore the source record for details and available documents.
Microcephaly and mental retardation have been principal features of the fetal alcohol syndrome. This article describes the neuropathologic findings in four human neonates who were exposed to large quantities of ethanol at frequent intervals during gestation. The findings suggest that intrauterine exposure to ethanol can result in structural abnormalities of the brain. All four brains displayed similar malformations stemming from errors in migration of neuronal and glial elements. Hydrocephalus was one consequence of the malformations in two of the infants. Futhermore, the brain alterations may be the only distinct abnormality produced by in utero ethanol exposure. Only two of the four subjects were diagnosed as having the fetal alcohol syndrome from external criteria.
Various modes of therapy, alone or in combination, have had little effect in improving the survival of patients with glioblastoma multiforme. Recently, in a pilot study, 34 patients with glioblastoma were treated by fast-neutron-beam irradiation of the whole brain. Following treatment, the patients became steroid-dependent and pursued a gradual downhill course with increasing obtundation. Although there was no improvement in the length or quality of survival of these patients, neuropathological studies in the 13 patients who came to autopsy showed the following: 1) extensive coagulative necrosis of much of the tumor mass; 2) dense infiltration by collagenous connective tissue; 3) minimal phagocytic reaction; 4) marked reduction in the amount of viable tumor; 5) abnormal astrocytic proliferation, which may represent either astrocytoma or a radiation-induced bizarre gliosis, and 6) areas of gliosis and white matter degeneration in the brain stem, remote form the tumor site. These observations suggest that continued efforts to further refine this mode of therapy for glioblastoma are warranted.
Synthetic galactodihydrocerebrosides with widely different fatty acid components can evoke myelination-inhibiting antibodies in rabbits. Whether these are the only such haptens involved in experimental immunizations of other species or in spontaneous human diseases is not yet known.
Although the human brain stem is considered relatively invulnerable to ischemic anoxia, evaluation of 16 cases of a single acute asphyxial episode either at or following birth indicates that such involvement is a frequent and characteristic aspect of anoxic encephalopathy in the infant. Ischemic cell change, neuronal loss, and nuclear or reticular formation gliosis were present in the brain stem of all but one infant. At least two topographic patterns of anoxic encephalopathy exist: (1) a rostrocaudal pattern of decreasing vulnerability, with the cerebral cortex being most sensitive and the brain stem least sensitive, and (2) a pattern of brain stem and thalamic damage. Of the two, the latter pattern appears to follow most acute asphyxial episodes in the human neonate and infant.
Consideration of the most likely method of growth of epidermoid tumors, either congenital or traumatic in origin, suggests that they grow linearly, at rates approximately those reported for normal human skin, rather than exponentially, as most tumors do. Such a linear rate of growth would be expected of tumors derived from a single layer of basal germinal cells spread out over a surface area.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Experimental allergic encephalomyelitis (EAE) is a cell-mediated autoimmune response directed toward a component of central nervous system (CNS) tissue, myelin basic protein (BP). Injection of animals with either whole CNS tissue or purified BP in complete Freund's adjuvant (CFA) induces severe and usually fatal disease. Preimmunization of animals with BP in incomplete Freund's adjuvant (IFA) prevents EAE. We have examined the relative abilities of whole guinea pig BP and its fragments to protect guinea pigs from subsequent EAE induction. The data suggest that the presence of the intact encephalitogenic site (residues 113-121) in the molecules used for preimmunization is necessary but may not be sufficient for complete protection against EAE induction.
Young rats 6 to 22 days of age are extremely susceptible to the neurotoxic effects of hexachlorophene given as a daily bath of undiluted antiseptic detergent containing 3% hexachlorophene (pHiso-Hex). At this age, most rats are clinically and histologically damaged by as few as two daily baths. Younger rats are relatively resistant, probably because they have less myelin to be affected; older rats cannot be poisoned by this route, probably because the more mature liver excretes the drug more effectively. Age-dose-response curves in rats are similar to those in humans. This experimental model is potentially useful in defining other characteristics of this drug.
To assess neurotoxic effects of hexachlorophene in the human population previously shown to be most at risk, a blind clinicopathological analysis was made of all premature infants under 1,400 gm birth weight who survived at least four days and were examined by autopsy over a 7.5-year period. Repeated whole-body bathing of premature newborn infants in 3% hexachlorophene-bearing soap (undiluted pHisoHex) shows a significant statistical association with a vacuolar encephalopathy of the brain stem reticular formation. The prevalence of the vacuolar encephalopathy in premature infants on whom we have adequate brain stem histological information appears to be related to the number of exposures to hexachlorophene, the concentration of hexachlorophene, the thoroughness of rinsing, and other factors (including exposure to ultraviolet light).