Recognizing post-polio syndrome.

The disorder consists of fatigue accompanied by new muscle weakness and muscle pain or, for patients whose acute polio had included bulbar involvement, new difficulty in swallowing or change in voice. The epidemiology remains unclear, fueling anxiety among polio survivors. Yet its course is not drastically progressive, and impairment is usually limited.

[Malignant priapism. Curettage of the corpora cavernosa as a palliative measure]. / Priapismo maligno. Legrado de los cuerpos cavernosos como medida paliativa.

A case of malignant priapism is described in a 58-year-old patient with metastatic carcinoma of the bladder. The diagnostic methods and the possibilities of palliative treatment are discussed.

Enteroviral-related antigen in circulating immune complexes of amyotrophic lateral sclerosis patients.

Circulating immune complexes were isolated by polyethylene glycol precipitation from the sera of patients with amyotrophic lateral sclerosis. Rabbits immunized with circulating immune complexes from 3 of 5 amyotrophic lateral sclerosis patients induced antisera that specifically reacted with enterovirus-infected cells by immunofluorescence and enzyme-linked immunosorbent assay. These antisera were nonneutralizing and did not react with purified virus. In addition, peripheral lymphocytes of amyotrophic lateral sclerosis patients produced lymphokine in response to extracts from enterovirus (Coxsackie B4) infected cells. These results suggest both a humoral (circulating immune complex) and a cellular immune response in some patients with amyotrophic lateral sclerosis to enterovirus-coded or -induced antigen.

Activated T lymphocytes, rheumatoid factor and erythrocyte sedimentation rate assays in rheumatoid arthritis.

Activated T lymphocytes (Ia+ T-cells) in peripheral blood are associated with immune stimulation. We found the percentages of these cells significantly increased in 95% of rheumatoid arthritis (RA) patients. Our studies showed no relation between the percentages of these cells in peripheral blood and concurrent erythrocyte sedimentation rates or rheumatoid factor titers. Circulating immune complex titers determined in a small number of patients conjectured an association with Ia+ T-cell levels.

Immunoregulatory and activated T cells in amyotrophic lateral sclerosis patients.

Circulatory immune complexes are increased in amyotrophic lateral sclerosis (ALS) and an autoimmune mechanism has been inferred. Autoimmune diseases may have changes in the percentages of immunoregulatory T cells and increased activated T cells (Ia+ T) in peripheral blood. The latter are also increased with active viral and bacterial infection and immunization. We found no significant changes of the percentages of immunoregulatory T cells and no relation of the individual values to the clinical state. Ia+ T cells were not increased over the normal range but within that range there was significant negative correlation with the ALS clinical score.

Ganglioside patterns in amyotrophic lateral sclerosis brain regions.

In a search for evidence of biochemical disorders in regions of postmortem brain other than the motor cortex in amyotrophic lateral sclerosis (ALS), ganglioside patterns were also examined in the frontal, temporal, and parahippocampal gyrus cortex. In 21 ALS brains studied (20 sporadic, 1 familial), abnormal patterns were found in the frontal cortex (81%), temporal cortex (75%), motor cortex (70%), and parahippocampal gyrus cortex (71%). Patterns were established by measuring the percentage distribution of 12 ganglioside species. Two abnormal patterns were detected. One was based on low proportions of GD1b, GT1b, and GQ1b associated with high proportions of GM2 and GD3 (GM1, GD1a, GD2, and GT1a values were normal). The second abnormality was the appearance of Gx. Neither abnormality was seen in the 13 non-ALS control brains. The first, and predominant, abnormality was found in the frontal cortex in 14 brains, and the second was observed in 13 brains; 10 brains showed both abnormalities. These findings thus constitute evidence that the disease process in ALS extends beyond the motor cortex and involves neurons in several brain areas.

Deposits of IgG and C3 in the spinal cord and motor cortex of ALS patients.

Deposits of IgG and complement were demonstrated by direct immunofluorescent techniques with sections of motor cortex and spinal cord from amyotrophic lateral sclerosis (ALS) patients. Six of 16 ALS patients showed deposits within the spinal cord while 5 of 13 showed similar deposits within the motor cortex. The specificity of this staining was shown by blocking experiments and the use of conjugated F(ab')2. Similar deposits were found in the CNS in disease states associated with possible immune or infectious etiologies and were not found in the CNS of normal controls.

Ganglioside induced surface activity and neurite formation of Neuro-2a neuroblastoma cells.

These studies demonstrate that while microtubules are essential for BBG-mediated neurite initiation and elongation, they are not involved in microfilament-dependent ganglioside-mediated surface activity. Microfilaments may be more directly altered by exogenous gangliosides than microtubules since they are the major structural elements of microvilli and are required for neurite branching. Our studies suggest that normal neuritogenesis requires a delicately balanced interaction between various cytoskeletal elements. Since there is a close relationship between membrane-associated lipid molecules and submembranous cytoskeletal elements, the incorporation of gangliosides into membranes may alter this balance and result in neurite formation. The use of gangliosides to enhance neurite production provides a unique model for the study of nerve development. We have shown that bovine brain gangliosides stimulate an immediate sequence of surface-related changes as well as microtubule and microfilament dependent neurite formation in Neuro-2a cells. However, the precise molecular events by which gangliosides enhance neuritogenesis await further study.

Kinetics of replication of lactate dehydrogenase-elevating virus in age-dependent polioencephalomyelitis.

The kinetics of replication of lactate dehydrogenase-elevating virus (LDV) in age-dependent polioencephalomyelitis was studied in genetically susceptible (C58/J) and resistant (C57BL/6J) mice. The peripheral replication pattern (plasma concentration) for LDV was similar in both strains. However, the concentration of virus within the central nervous system was strikingly different. In nonsusceptible C57BL/6J mice, little or no virus was found within the central nervous system. In the lumbar cord of susceptible C58/J mice, an increase in the concentration of LDV began 5 days postinfection and continued during the preclinical stages of disease. A direct correlation was shown between the concentration of LDV in spinal cord and the appearance of motor neuron disease but not the degree of inflammatory reaction.

HLA frequencies in amyotrophic lateral sclerosis.

Our study of the distribution of HLA-A, -B, and -C in patients with amyotrophic lateral sclerosis (ALS) found no statistically significant deviation. We found a trend, however, toward a decrease in HLA-A9, as we had reported previously, and toward an increase in HLA-Bw35 and -Cw4. The worldwide incidence of ALS is uniform except in Guam and on Japan's Kii peninsula, and published reports from many countries, including Guam, show no consistent deviation in HLA frequencies related to ALS.

Immunological profile of amyotrophic lateral sclerosis patients and their cell-mediated immune responses to viral and CNS antigens.

The 'immunological profile' of amyotrophic lateral sclerosis (ALS) patients was established from standard tests for B- and T-cell function. This showed no significant difference from age and sex-matched other neurological (CNS) disease controls and normal subjects. Immune complex (IC) levels in ALS serum differed significantly from normal controls but not from CNS controls. There was no relation between the various indices of immune activity of IC levels and the clinical disability of the ALS patient or progression of the disease. Distribution of complement-fixing antibodies to poliovirus was similar to sera of ALS and control groups. The in vitro cell-mediated immune responses to poliovirus, however, were significantly greater in ALS patients than in CNS controls and were inversely related to the ALS disability score. Poliovirus has not been demonstrated in the CNS or extra-CNS tissues of ALS patients by conventional means but, if latent or defective poliovirus or related virus were present, this could account for sensitization and a possible autoimmune mechanism. ALS patients exhibited in vitro cellular immunity to ALS and normal CNS subfractions. These responses were not related to the ALS disability score or progression of the disease and probably represent epiphenomena.

Virological studies in amyotrophic lateral sclerosis.

Complement-fixing antibody response to eleven different viruses were measured in amyotrophic lateral sclerosis (ALS) patients, contacts of ALS patients, neurological controls, and normal controls. The normal controls showed a decreased response to adeno-associated virus and an increased response to adenovirus when compared to the other groups. Levels of interferon-like substances also were investigated in sera and cerebrospinal fluids of ALS patients and neurological controls. Responses were of a low titer and were not increased in the ALS group. Explant cultures were established from tissues of 24 ALS autopsy cases. Cultures were investigated directly or following fusion to various indicator cell lines for viral-like agents. Techniques such as interference assays, 5-bromodeoxyuridine (BudR) induction, hemadsorption, and fluorescent antibody staining failed to detect virus. By addition of helper adenovirus to primary explant cultures, adeno-associated virus was isolated from 2 of 11 ALS cases.

Neuron specific in vitro cytotoxicity of sera from patients with amyotrophic lateral sclerosis.

Sera from patients with amyotrophic lateral sclerosis (ALS) were assayed for a neuron-specific cytotoxic effect on long-term organized cultures of neonatal mouse anterior horn segments. Blind studies show that ALS sera when incorporated into the culture media have a greater degree of antineuronal toxicity than sera from patients with other neurological diseases or from family members of ALS patients.

Ganglioside stimulation of axonal sprouting in vitro.

Bovine brain gangliosides were applied to primary and established neuronal cultures to examine the role of gangliosides in neuronal development. Media containing gangliosides enhanced the degree of axonal elongation exhibited by sensory ganglia neurons and increased the length and number of Neuro-2a neuroblastoma cell processes. Ganglioside-supplemented media caused a twofold increase in ornithine decarboxylase activity in both culture systems. These experiments suggest that gangliosides function as acceptor molecules for growth-promoting substances in embryonic and tumor-derived neurons.

Antibody response to arboviruses. Absence of increased response in amyotrophic lateral sclerosis and multiple sclerosis.

Complement fixation and hemagglutination imhibition tests were conducted on the serums of patients with amyotrophic lateral sclerosis and multiple sclerosis using a variety of arboviral antigens. Seventy-eight complement fixation and 15 hemagglutination-inhibition viral antigens were used representing togaviruses, orbiviruses, rhadoviruses, bunyaviruses, arenaviruses, and several ungrouped agents. The serological results did not indicate any relationship between these viruses and either amyotrophic lateral sclerosis or multiple sclerosis.

[Immunological studies demonstrating the enhancing effect of aristolochic acid on immunoreactions (author's transl)]. / Immunologische Untersuchungen zum Nachweis der abwehrsteigernden Wirkung von Aristolochiasäure.

In experimental studies it was shown that aristolochic acid is able to ameliorate or to stimulate immunoreactions. This was studied in vivo with cutaneous delayed hypersensitivity reactions and by measurement of the gamma-globulin formation of treated rabbits; the in vitro system used was the macrophage migration test.