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Biomedical subjects

E L Alexander

Publications and source records attributed to E L Alexander.

52 records · Page 3Linked to original sources

Neurologic complications of primary Sjögren's syndrome.

Although peripheral nervous system disease has been well documented in Sjögren's syndrome (SS), central nervous system (CNS) involvement is considered distinctly uncommon. Sixteen patients with primary SS and CNS disorders not attributable to other causes were the subjects of this study. Cerebral manifestations, both focal and diffuse, as well as spinal cord disease, were observed. Peripheral vasculitis occurred in 12 patients (75%), 83% of whom had anti-Ro(SSA) antibodies. The high proportion of patients with concomitant peripheral vasculitis, and the observed association with antibodies to the Ro(SSA) antigen system which, in other studies, has been linked to vasculitis in SS, suggest that an immune vasculopathy may play a role in the pathogenesis of the CNS disease of SS.

Adult↗

Sjögren syndrome: central nervous system manifestations.

We studied eight patients who had primary Sjögren syndrome and central nervous system (CNS) disorders that were not attributable to other causes. Focal cerebral deficits were observed in five patients. Aseptic meningoencephalitis was seen in five patients, recurrent in one. Spinal cord manifestations in three patients took several forms: acute transverse myelitis, chronic progressive myelopathy, and spinal subarachnoid hemorrhage. Precipitating antibodies to the Ro(SSA) cytoplasmic antigen were detected in the sera of seven of eight patients. This may be relevant to the pathogenesis of CNS disease in Sjögren syndrome, because there is a strong correlation between vasculitis and the presence of anti-Ro(SSA) antibodies in this connective tissue disorder.

Adult↗

Human leukocyte Fc (IgG) receptors: quantitation and affinity with radiolabeled affinity cross-linked rabbit IgG.

Quantitative studies have been made of Fc receptors on human leukocytes derived from peripheral blood, thymus, tonsil, and spleen. The relative affinities and average numbers of receptors per cell were determined by measuring the binding of 125I-labeled, affinity cross-linked trimers of rabbit IgG to various populations of cells. In parallel, the sizes of receptor-bearing populations were determined by fluorescence microscopy. Fc receptors could be detected on leukocytes from peripheral blood and spleen, but not from tonsil or thymus. In the peripheral blood, the highest density of receptors was found on polymorphonuclear leukocytes; a subpopulation of lymphocytes had somewhat fewer receptors per cell, and circulating monocytes had the lowest receptor density. Among splenocytes, most of the receptors were found on myeloid cells and monocytes. In all populations, the affinity of Fc receptors for the trimer was about the same. At 0 degrees C the average value for the association constant was 5 x 10(7) M-1.

Adult↗

Quantitation of Fc receptors and surface immunoglobulin is affected by cell isolation procedures using plasmagel and ficoll-hypaque.

When mononuclear leukocytes are isolated directly from whole human blood using Ficoll-Hypaque or Plasmagel, cytophilic immunoglobulin is detected on cell surfaces. Upon incubation at 37 degrees C, this cell-associated immunoglobulin is shed slowly into the medium. However, when cells are prewashed in phosphate-buffered saline prior to isolation, they appear to be free of cytophilic immunoglobulin. Compared to prewashed cells, populations retaining cytophilic immunoglobulin on their surfaces demonstrate a decreased binding of soluble immune complexes and radiolabelled trimeric rabbit IgG. The data suggest that Ficoll-Hypaque and Plasmagel cause serum IgG to bind with abnormally high affinity to human mononuclear leukocytes, probably via Fc receptors. This artifact of preparation can lead to erroneous estimates of the numbers of cells bearing Fc receptors or intrinsic membrane immunoglobulin within a given population of cells and to an inaccurate assessment of the average number of Fc receptors per cell.

Animals↗

Human peripheral lymphocytes bearing surface immunoglobulin do not have readily detectable Fc receptors.

The question of whether human peripheral B lymphocytes have Fc receptors was examined directly by double-label immunofluorescent techniques utilizing assays for detection of Fc receptors, surface immunoglobulin, and complement receptors. Fc receptors were detected by indirect immunofluorescence after incubation with soluble antigen-antibody complexes. Complement receptors were detected by the binding of fluoresceinated bacteria coated with complement. It was demonstrated that most surface immunoglobulin-bearing, complement-receptor positive lymphocytes did not bind soluble antigen-antibody complexes. Conversely, most cells which readily bound soluble complexes did not have surface immunoglobulin or complement receptors. Therefore, most peripheral B lymphocytes do not have easily detectable Fc receptors and most Fc receptor-bearing lymphocytes do not have B cell markers.

Antigen-Antibody Complex↗

F(ab')2 reagents are not required if goat, rather than rabbit, antibodies are used to detect human surface immunoglobulin.

The present report provides evidence that whole goat anti-human immunoglobulin, unlike similar reagents produced in the rabbit, binds both to the same number of and the same individual cells as the F(ab')2 fragments of rabbit or goat anti-human immunoglobulin. These results suggest that goat IgG has a lower affinity for the Fc receptors of human lymphocytes and monocytes than rabbit IgG. Because of this property, whole goat antibodies against human immunoglobulin can be used as simple, convenient relatively inexpensive reagents for the routine detection of immunoglobulin on cell surfaces by immunofluorescence microscopy. The preparation of F(ab')2 fragments of anti-immunoglobulin, which are necessary when rabbit antibodies are used, does not appear to -e required if goat antibodies can be empolyed. This observation has multiple practival applications in cellular immunology.

Animals↗

Human lymphocytes: similarity of B and T cell surface morphology.

When viewed by scanning electron microscopy human lymphocytes fixed in suspension and processed with minimal cell loss appear uniformly covered with short microvilli. Contrary to previous reports, lymphocytes from subpopulations selectively enriched for T cells are villous and indistinguishable from B lymphocytes. Whereas lymphocyte surface architecture can change rapidly and substantially in response to environmental modifications, such as contact with an underlying surface, these alterations are similar for both B and T cells and do not serve to distinguish these subpopulations.

Animals↗

A high-yield technique for preparing cells fixed in suspension for scanning electron microscopy.

Human leukocytes fixed in suspension were allowed to settle onto poly-L-lysine-coated glass coverslips and prepared for observation with the scanning electron microscope (SEM). The coverslips were dehydrated in ethanol, critical point dried with CO2, and coated with gold-palladium. With the aid of a locator grid, several fields were photographed with light microscopy after the cells had settled onto the poly-L-lysine-coated coverslips and again after completion of the processing before SEM observation. Quantitative comparison of the number of cells present after settling with the number retained for final viewing with the SEM revealed a cell yield approaching 100%. This simple, reproducible, high-yield technique for processing cells fixed in suspension for SEM prevents changes in surface architecture induced by collecting live cells onto various substrates before fixation and also avoids potentially selective cell losses. Such a technique should allow quantitative correlations between SEM and other morphological and functional parameters.

Cytological Techniques↗

Ro(SSA) and La(SSB) antibodies in the clinical spectrum of Sjögren's syndrome.

Seventy-five patients with the symptomatic sicca complex were evaluated clinically and classified as having Sjögren's syndrome (SS) alone or the sicca complex associated with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS) or another connective tissue disorder. Their status with respect to anti-Ro(SSA)/La(SSB) antibodies was determined independent of clinical evaluation and categorization. Overall, 33 (44%) were found to have antibodies to Ro(SSA); and 12 (16%) had antibodies to La(SSB). Anti-Ro antibodies occurred in 50% of those with SS alone as well as in SS associated with RA (39%), SLE (58%), and PSS (20%). Furthermore, patients with SLE without the sicca complex demonstrated antibodies to Ro(SSA) (24%) and La(SSB) (5%). A striking association of anti-Ro(SSA) antibodies in SS with vasculitis is described.

Antibodies↗

The coexistence of rheumatoid arthritis with Reiter's syndrome and/or ankylosing spondylitis: a model of dual HLA-associated disease susceptibility and expression.

In a prospective study of 184 patients with ankylosing spondylitis and/or Reiter's disease, we have examined the frequency of concomitant rheumatoid arthritis (RA) and determined the HLA profile of these patients. Five men (2.7%), 3 with ankylosing spondylitis and 2 with Reiter's disease, had coexistent classical RA and 2 of these also had Felty's syndrome. Immunogenetic analysis demonstrated that all 5 patients had either HLA-R27 or another B-7-cross-reactive antigen and that 3 also possessed HLA-DR4. Thus, 2 or more HLA-associated genetic predispositions may occur in the same individual, and, when expressed, result in the dual expression of both a spondylitic disease and RA.

Adolescent↗