PubMed Health⌕ Search

Biomedical subjects

S H Appel

Publications and source records attributed to S H Appel.

At least 127 records · Page 7Linked to original sources
PubMed1990

IgG reactivity in the spinal cord and motor cortex in amyotrophic lateral sclerosis.

The spinal cord and motor cortex of patients with amyotrophic lateral sclerosis (ALS) were examined with immunohistochemical methods for the presence of IgG. In 13 of 15 spinal cords, a population of motoneurons stained positively for IgG in a granular pattern, characteristic of binding to the rough endoplasmic reticulum. In 6 of 11 motor cortices, a proportion of pyramidal cells also stained positively for IgG. No such reactivity was noted in motoneurons of control human tissues, although positive IgG staining was present in astrocytes of ALS and control specimens. Reactive microglia and/or macrophages were detected in the territory of degenerating pyramidal tracts and ventral horns. The surface of most of these cells stained positively for IgG, and 50% stained positively for HLA-DR. The accumulation of IgG in motoneurons and the presence of immunologically active macrophages provide additional evidence for the participation of immunologic factors in the pathogenesis of ALS.

Adult↗
PubMed1990

Increased MEPP frequency as an early sign of experimental immune-mediated motoneuron disease.

Intracellular recordings of miniature end-plate potentials were performed in extensor digitorum longus muscles from guinea pigs with experimental immune-mediated motoneuron destruction. In the early stages of the disease, the miniature end-plate potential frequency was elevated compared to that in control and normal animals. The amplitude and time course of the miniature end-plate potentials as well as the resting potential of the muscle fibers were not altered, which implies integrity of the postjunctional membrane. The increase in frequency of miniature end-plate potential reflects an increase of basal acetylcholine release and documents dysfunction of the presynaptic terminal of the neuromuscular junction. The increased frequency was associated with high levels of antimotoneuronal IgG in the blood and the presence of IgG at motor end-plates. These data suggest that the presynaptic terminal of the neuromuscular junction may be involved in the immune attack in animal models of motoneuron degeneration.

Animals↗
PubMed1990

Motor neuron reactivity of sera from animals with autoimmune models of motor neuron destruction.

To determine whether mammalian upper and lower motoneurons share common epitopes, we assessed the immunohistochemical reactivity of serum IgG of two animal models, experimental autoimmune motor neuron disease with destruction of lower motoneurons (EAMND) and experimental autoimmune gray matter disease with destruction of both lower and upper motoneurons (EAGMD). EAMND serum IgG reacted with the cytoplasm of guinea pig spinal motoneurons in a patchy granular pattern paralleling the in vivo localization in the guinea pig model. The EAMND serum IgG also reacted with human upper and lower motoneurons. EAGMD serum IgG reacted with the cytoplasm and subsequently the external membranes of upper and lower motoneurons of guinea pig and human tissues, also paralleling the in vivo localization. IgG was detected in ipsilateral ventral horn following hind limb injections of EAMND and EAGMD serum, thereby suggesting retrograde transport to the motoneuron cell body. The presence of shared epitopes in upper and lower human motoneurons, and the ability of IgG to reach the motoneuron cell body by retrograde transport from the periphery provides evidence for the potential role of autoimmune mechanisms in motoneuron diseases.

Animals↗
PubMed1990

Motor neuron destruction in guinea pigs immunized with bovine spinal cord ventral horn homogenate: experimental autoimmune gray matter disease.

Guinea pigs immunized with bovine spinal cord ventral horn homogenate develop muscle weakness with electromyographic and morphologic evidence of denervation. Pathological examination demonstrates a loss of motoneurons and scattered inflammatory foci primarily localized to the spinal cord. Immunohistochemical techniques document the presence of immunoglobulin G at the motor end plate and around the external membrane and within the cytoplasm of motoneurons. This syndrome of experimental autoimmune gray matter disease (EAGMD) differs from experimental autoimmune motor neuron disease induced by inoculation with purified motoneurons and also differs from experimental autoimmune encephalomyelitis. The existence of two different forms of immune-mediated motoneuron destruction suggests that a number of cytoplasmic and membrane antigens may give rise to an immunologically based attack on the motor system.

Animals↗
PubMed1989

Comparison of antibody response with delayed hypersensitivity in severely injured patients.

Twenty-seven severely injured patients had antibody response to gram-negative organisms measured of whom 25 also had skin testing. Twenty-three patients (92%) were anergic at admission. Injury Severity Scores were greater in patients who remained anergic for three weeks compared with patients whose skin tests became positive. Patients with major infection had longer anergy duration than uninfected patients. Twenty-two (81%) of 27 anergic patients mounted antibody responses. Initial bacterial contamination determined the clinical outcome and antibody response. Six of eight patients with moderate contamination mounted IgM responses to all organisms and/or an IgG response to Escherichia coli, and they remained uninfected. Of the other two patients, one died, and the other developed chronic infection. Seven of eight patients with heavy contamination developed major sepsis despite mounting several antibody responses. Six patients without contamination mounted no antibody responses and remained uninfected.

Antibodies, Bacterial↗
PubMed1989

Experimental autoimmune motoneuron disease.

An animal model of disease of the lower motoneurons has been developed by inoculating guinea pigs with bovine motoneurons. Four of 9 immunized female animals and 4 of 5 immunized male animals developed symptoms of neuromuscular degeneration marked by weakness, evidence of denervation by electromyographic and morphological criteria, and a loss of motoneurons within the spinal cord. No inflammatory foci were noted within parenchyma or meninges of the central nervous system. The immunized guinea pigs developed high serum titers of IgG class antibodies to motoneurons. Immunohistochemical studies demonstrated the presence of IgG within spinal cord motoneurons and at the end-plates of immunized animals. This experimental autoimmune motoneuron disease may provide important insights into the cause and pathogenesis of amyotrophic lateral sclerosis, a human motoneuron disease.

Animals↗
PubMed1989

Identification of basic fibroblast growth factor as a cholinergic growth factor from human muscle.

Dissociated embryonic chick ciliary ganglion cells in culture were used as a bioassay to isolate a cholinergic growth-promoting protein from extracts of autopsied adult human muscle. An active protein was purified after acid and salt precipitation of extract, cation exchange, molecular sieving, heparin affinity chromatography, and in some cases, SDS-PAGE. This protein increased levels of choline acetyltransferase activity and ACh synthesis with time in culture. The protein was identified as basic FGF by several criteria. It shared the high affinity for heparin and was the same approximate molecular weight, 18 kD, as basic FGF. Activity was removed from solution by antibodies specific for basic FGF. Recombinant human basic FGF was equally effective in stimulating CAT activity, but was not additive with our purified protein at saturating concentrations. Basic FGF was also found in extracellular matrix and conditioned medium from cultured embryonic chick muscle. The activity could be released from extracellular matrix by treatment with heparinase or high salt extraction. Basic FGF stimulates neurite outgrowth as well as the capacity for transmitter synthesis. Thus, basic FGF is present in embryonic and adult muscle and capable of acting as a growth regulator for cholinergic neurons.

Acetylcholine↗
PubMed1989

Experimental and clinical significance of endotoxin-dependent HLA-DR expression on monocytes.

For much of the last decade, an increasing number of surgeons have been interested in objective assessment of cellular contributors to host defense function. In order to study many of these processes, it is apparently desirable that the cells be isolated to the extent feasible for the purpose of analyzing a more or less pure population of cellular elements. The purpose of this paper is to describe the physiologic activation of mononuclear cells that occurs as a result of the isolation process. Therefore, it follows logically that such cells are therein intrinsically less responsive to further physiologic manipulation in vitro. Analyses of such data without an awareness of this intrinsic aberration will undoubtedly lead to misinterpretation of the capacity of such cells for further modulation by immunostimulants or by the intrinsic processes related to injury, anesthesia, and operation. Furthermore, it may indicate that certain agents, e.g., cytokines, are unable to stimulate cellular function when, in fact, the defense function of the cell has been initially stimulated by the isolation procedure. Fractionation of human peripheral blood over Hypaque-Ficoll and subsequent purification of monocytes by adherence to plastic lead to an increase in the relative density of HLA-DR on monocytes. This increase occurred when carried out in endotoxin lipopolysaccharide (LPS)-contaminated or LPS-depleted reagents. LPS, added experimentally to whole blood, enhanced HLA-DR expression on monocytes without further manipulation. Monocyte HLA-DR expression measured in whole blood was reduced in patients with major sepsis (n = 19) compared to normal subjects (n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMed1989

The effect of tumor necrosis factor-alpha and interferon-gamma on neutrophil function.

Tumor necrosis factor-alpha (TNF) and interferon-gamma (IFN-gamma) have been shown to regulate cell-mediated immunity and act as effective modifiers of immune function; however, their influence on neutrophil (PMN) function is not well defined. This study investigated the effect of these cytokines on PMN phagocytosis, respiratory burst, and complement receptor (C3b) expression. Human citrated whole blood was incubated with either phosphate-buffered saline (control), 20 micrograms Escherichia coli lipopolysaccharide (LPS), TNF (1, 10, or 100 units), or IFN-gamma (1, 10, or 100 units). Synergy was also assessed between TNF and IFN-gamma. Phagocytosis and respiratory burst were assayed by sequential incubation of blood with dichlorofluorescein diacetate followed by labeled Staphylococcus aureus. C3b receptor expression was assayed by labeled anti-CR3 monoclonal antibody. Measurements were expressed as the mean channel fluorescence of 2000 PMNs counted by flow cytometry. IFN-gamma alone at all doses had no effect on any of the parameters measured. TNF 1 unit/ml increased phagocytosis (666 +/- 47 vs 542 +/- 19), respiratory burst (326 +/- 33 vs 258 +/- 17), and C3b (374 +/- 42 vs 157 +/- 14; all P less than 0.05) over those of control. TNF also demonstrated dose-dependent PMN activation. The combination of TNF + IFN-gamma increased both respiratory burst and C3b compared to either agent alone. These data indicate that TNF enhances PMN function and cytokine interaction may be important in PMN activation.

Humans↗
PubMed1989

The use of a new assay for detecting antibody to Staphylococcus aureus in severely injured patients.

Investigation of the antibody response to Staphylococcus aureus infection has been hindered by lack of a simple and specific assay. We report an enzyme-linked immunosorbent assay (ELISA) using a strain of S. aureus devoid of Protein A, a frequent cause of false positive results in ELISAs, and have used this assay to study antibody responses of 23 severely injured patients. This IgM ELISA had a diagnostic sensitivity for major Staphylococcal infection of 70% (seven of ten patients with major infection) and a specificity of 92% (12 of 13 patients without major infection). Of three patients with major Staphylococcal infections who mounted no IgM response, two died and the other developed severe chronic Staphylococcal infection, and hence prompt initiation of appropriate therapy was necessary. Furthermore, the ability to mount IgM response to Staphylococcal infections appears to contribute to an orchestrated host defense response against this organism.

Antibodies, Bacterial↗
PubMed1989

Purification and characterization of a central cholinergic enhancing factor from rat brain: its identity as phosphoethanolamine.

A compound that can enhance the apparent synthesis of acetylcholine in cultured explants of the medial septal nucleus has been purified from rat brain and identified as phosphoethanolamine. Acetylcholine synthesis is stimulated two- to threefold in cultures grown for 5 days in the presence of phosphoethanolamine, ethanolamine, or cytidine 5'-diphosphoethanolamine at concentrations above 100 microM. This effect appears to result from an increase in the accumulation of choline via the high-affinity, sodium-dependent uptake mechanism. The development of choline acetyltransferase activity is not affected. Phosphoethanolamine and ethanolamine seem to enhance the ability of developing cholinergic neurons to utilize choline accumulated via the sodium-dependent high-affinity choline uptake mechanism for the preferential production of acetylcholine without increasing the general metabolism of the cultures. Choline itself and its related derivatives are not stimulatory for these effects.

Acetylcholine↗
PubMed1989

Trophic effects of skeletal muscle extracts on spinal cord cultures.

A soluble extract of newborn rat muscle was added to cultures of dissociated embryonic spinal cord cells in order to determine the effect on their morphology. The processes per cell ratio, and the length of neurites were all enhanced by the presence of extract in ventral cord cell cultures, but not in dorsal cord cell cultures. It is possible that muscle-derived neurotrophic factors regulate the in vivo phenomenon of neuronal cell death. Interference with neuron-muscle trophic communication, either directly or indirectly, might lead to excessive loss of motor neurons. This mechanism may be important in the pathogenesis of amyotrophic lateral schlerosis.

Animals↗
PubMed1989

Interferon-gamma treatment increases HLA-DR expression on monocytes in severely injured patients.

Traumatic injury and sepsis reduce HLA-DR expression on monocytes. This study assessed the effect of interferon-gamma (IFN-gamma) on the expression of HLA-DR on monocytes taken from severely injured patients. The mononuclear layer of each blood sample was incubated with either 500 units IFN-gamma or control media. The mean baseline HLA-DR expression of the trauma group (n = 11) was 32%, significantly less than the mean HLA-DR expression of 91% for the control group (n = 10). In the trauma group, HLA-DR expression after culturing with IFN-gamma was 81%, significantly greater than both the mean baseline HLA-DR expression (32%). In the control group, HLA-DR expression after culturing with IFN-gamma was 94%, similar to the mean baseline HLA-DR expression of 91%. These data confirm that HLA-DR on monocytes of severely injured patients is markedly reduced and show that it can be increased significantly in vitro by IFN-gamma.

Cells, Cultured↗