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Biomedical subjects

P K Coyle

Publications and source records attributed to P K Coyle.

At least 19 recordsLinked to original sources

Increased levels of beta 2-microglobulin, soluble interleukin-2 receptor, and soluble CD8 in patients with subacute sclerosing panencephalitis.

We measured beta 2-microglobulin (beta 2-M), soluble interleukin-2 receptor (sIL-2R), and soluble CD8 (sCD8) antigen levels in paired cerebrospinal fluid (CSF) and sera from patients with subacute sclerosing panencephalitis (SSPE), multiple sclerosis (MS), and other neurological diseases (OND) using enzyme-linked immunosorbent assay. beta 2-M was significantly increased in CSF of the SSPE group compared to the MS or the OND group. Similarly, beta 2-M in the MS versus OND group was significantly increased in CSF. Although serum levels of beta 2-M were similar in the three groups, the CSF/serum ratios were higher in SSPE versus the MS group and in the MS versus the OND group. Levels of sIL-2R and sCD8 were higher in SSPE CSF than OND CSF; however, there were no differences between levels in SSPE and MS CSF. The levels of sIL-2R were increased in SSPE sera compared to those of MS or the OND group, whereas levels of sCD8 in serum from the three groups were similar. The findings of increased CSF/serum ratio of beta 2-M and higher levels of serum sIL-2R and CSF sCD8 in SSPE patients are consistent with those seen in patients with acute and chronic viral infections. When the levels between the initial and follow-up CSF and serum samples from SSPE patients were compared, the data showed that CSF levels of sCD8 elevated during periods of clinical worsening and decreased during clinical improvement. In contrast, serum beta 2-M decreased during periods of worsening and increased during improvement. The measurement of serum beta 2-M and CSF sCD8 may be useful in SSPE patients as markers to monitor disease activity.

Adolescent

Cognitive functioning in late Lyme borreliosis.

Lyme borreliosis, a tick-borne multisystem disease, may cause a variety of neurologic complications, including meningoencephalitis and encephalopathy. To evaluate neurobehavioral function following treated Lyme borreliosis, 15 patients with Lyme disease and complaints of persistent cognitive difficulty a mean of 6.7 months following antibiotic treatment underwent neuropsychological evaluation and were compared with 10 healthy controls, matched in aggregate for age and education, who underwent the identical neuropsychological assessment. Compared with controls, patients with Lyme disease exhibited marked impairment on memory tests and particularly on selective reminding measures of memory retrieval. The memory impairment did not correlate with serum or cerebrospinal fluid anti-Borrelia burgdorferi antibody titers and was not explained by magnetic resonance imaging findings or depression. The cause of this encephalopathy is currently unknown; however, indirect effects of systemic infection or other toxic-metabolic factors may be partly responsible.

Adult

Increased free light chains in the urine from patients with multiple sclerosis.

We quantitated free kappa (kappa) and lambda light (L) chains in coded urine specimens from subjects with clinically definite multiple sclerosis (MS) (N = 56), other neurologic diseases (OND) (N = 30), and age-matched normal controls (N = 28). Urine from MS patients showed statistically significant increases in free L chains compared with the other groups, although there was overlap between MS patients and OND patients. The ratio of kappa/creatinine was significantly greater in the relapsing-remitting MS group than in patients with clinically stable MS, OND, and normal controls. Elevated free L chains were usually independent of urinary albumin and beta 2-microglobulin levels. Serial studies showed that urinary free kappa/creatinine ratios were elevated during periods of clinical worsening in seven of eight MS patients and subsequently decreased during clinical recovery. The measurement of free L chains in urine obtained at intervals from MS patients may be useful as a marker to monitor disease activity.

Albuminuria

Sequestration of antibody to Borrelia burgdorferi in immune complexes in seronegative Lyme disease.

To find out whether apparent seronegativity in patients strongly suspected of having Lyme disease can be due to sequestration of antibodies in immune complexes, such complexes were isolated and tested for antibody to Borrelia burgdorferi. In a blinded analysis the antibody was detected in all 10 seronegative Lyme disease patients with erythema chronicum migrans (ECM), in none of 19 patients with other diseases, and in 4 of 12 seronegative patients who probably had Lyme disease but had no ECM. These findings were confirmed by western blot, which also showed that immune complex dissociation liberated mainly antibody reactive to the 41 kD antigen and sometimes antibody to an approximate 30 kD antigen. Complexed B burgdorferi antibody was also found in 21 of 22 (95%) of seropositive patients with active disease, 3 additional seronegative but cell mediated immune reactive patients, and 3 other seronegative patients who eventually became seropositive. Apparent B burgdorferi seronegativity in serum immune complexes may thus be due to sequestration of antibody in immune complexes.

Adolescent

Cerebrospinal fluid immune complexes in patients exposed to Borrelia burgdorferi: detection of Borrelia-specific and -nonspecific complexes.

We analyzed cerebrospinal fluid (CSF) from 32 patients with neurological symptoms and evidence of Borrelia burgdorferi infection (29 were seropositive as determined by enzyme-linked immunosorbent assay, 2 were cell-mediated immune positive, and 1 had been seropositive as shown by enzyme-linked immunosorbent assay 9 months previously). CSF immune complexes were found in 22 (69%) of 32 patients; in 18, there was sufficient sample to isolate immune complexes. By enzyme-linked immunosorbent assay, isolated immune complexes from 10 of these 18 patients contained antibody specific for B. burgdorferi antigens. The isotypes were IgG (n = 8), IgM (n = 3), and IgA (n = 2). By immunoblot, these antibodies were directed against B. burgdorferi 41-kDa antigen and occasionally against the 33- and 17-kDa antigens. Anti-B. burgdorferi IgM was present in patients with acute neurological symptoms, was predominantly complexed rather than free, and decreased with clinical recovery in the one serial study. Three patients were nonreactive for free CSF antibodies, but had complexed antibodies to the organism. The preliminary finding of specific B. burgdorferi components in immune complexes in CSF suggests an active process triggered by the organism, even in the absence of other CSF abnormalities.

Adolescent

Drug-induced meningitis.

Meningitis is usually produced by an infectious agent, but there are multiple noninfectious causes. Medications may produce both acute and recurrent meningitis. We present a patient with 3 episodes of aseptic meningitis due to trimethoprim-sulfamethoxazole, and then review the topic of drug-induced meningitis.

Adult

Spirochetal infection of the central nervous system.

Four spirochetal diseases frequently involve the central nervous system: syphilis, leptospirosis, relapsing fever, and Lyme borreliosis. In particular, syphilis and Lyme borreliosis are increasing problems. During the spirochetemic phase there is seeding of the nervous system. After a quiescent latent period, there may be late disease flareups producing a variety of neurologic syndromes. Cerebrospinal fluid examination is very helpful in these infections.

Central Nervous System Diseases

Molecular analysis of IgA in multiple sclerosis.

IgA plays an important role in immune-mediated and anti-viral responses, and is the major antibody in external mucosal secretions. We used enzyme-linked immunosorbent assay (ELISA) and immunoblot to examine IgA in tears and parotid saliva of 21 multiple sclerosis (MS) patients and 19 normal controls. No significant difference in absolute levels were noted and both groups showed a wide range in values. However, 16 of 21 MS patients had detectable changes in molecular form of their IgA. Monomeric IgA was found in 52% of MS tears (P less than 0.001) and 45% of MS parotid saliva (P less than 0.05). Among normals, monomeric IgA was noted in only two saliva samples. IgA in secretions consisted of both A1 and A2 subclasses, although 14% of the monomeric MS IgA samples were restricted to a single subclass. Free secretory component was found in the secretions of all subjects with the exception of a single MS patient. However, immunoblot staining of secretory component was decreased in MS patients compared to controls. This study notes changes in IgA in two distinct external secretions in MS patients compared to controls. These changes are consistent with local mucosal inflammation. Impaired mucosal barriers have important implications in MS with regard to susceptibility to infectious agents, environmental antigen processing, and lymphocyte activation.

Adult

Immune-reactive cells in multiple sclerosis mucosal secretions.

External secretions from multiple sclerosis (MS) patients show immunoglobulin abnormalities consistent with mucosal inflammation. In this study we collected tears and parotid saliva from ten normal subjects and ten MS patients to examine for free-floating inflammatory cells. We found lymphocytes, macrophages, and plasma cells at low numbers in normal secretions, but at much higher numbers in MS secretions. Using an immunobead rosette technique, most of the lymphocytes were null cells. However, we found increased T lymphocytes in the secretions of clinically active MS patients. The extensive mucosal surfaces of the MS patient could provide a peripheral source for activated lymphocytes that subsequently enter brain.

Adult

Borrelia burgdorferi antibodies in multiple sclerosis patients.

Lyme disease is said to produce a late syndrome resembling multiple sclerosis. We analyzed serum antibodies to Borrelia burgdorferi in 100 patients referred for possible MS. All lived in an area endemic for Lyme disease. Only 1 of 89 definite MS patients and 2 of 11 non-MS patients were antibody positive. Infection with Borrelia burgdorferi is rare in MS, and Lyme disease is unlikely to play a significant role in the differential diagnosis of MS.

Adult

Electrophoresis combined with immunologic identification of human tear proteins.

The protein content of normal human tears from five subjects was examined by molecular weight separation using SDS-polyacrylamide gel electrophoresis (PAGE) and by charge separation using agarose isoelectric focusing (IEF) gels. After separation, specific proteins were identified by immunoblot and immunofixation. Tear proteins examined included albumin, IgA, IgG, prealbumin, lactoferrin, lysozyme, secretory component and transferrin. These techniques required 1 to 14 microliters unconcentrated tears. We found SDS-PAGE superior to agarose IEF to examine total tear protein pattern, and silver stain almost ten-fold more sensitive than Coomassie blue stain. Immunologic staining markedly enhanced protein detection in all tear samples and appeared to offer the definitive method to probe for a specific protein in tears. In this study prealbumin and a portion of the IgG were present in normal tears at higher than expected molecular weight, suggesting they were present in complexed form. Prealbumin and secretory component staining showed marked variability between subjects. These techniques should be applicable to examine tear proteins in a variety of ocular disease states.

Adult

Eales' disease presenting as stroke in the young adult.

Eales' disease is an uncommon idiopathic disorder characterized by retinal perivasculitis and recurrent vitreous hemorrhages in young males. Associated neurological involvement is rare. We report a 38-year-old man who presented with stroke attributed to Eales' disease.

Adult

Viral antibodies in normal tears.

Viruses are a common cause of eye infection. The local mucosal response, with production of antibodies released into tears, is believed to provide an important immune defense against these agents. However very little information exists on the viral specificity of normal tear immunoglobulins. In this study we obtained tears, parotid saliva and serum from 40 normal subjects without eye disease. Samples were examined by enzyme linked immunosorbent assay (ELISA) for antibodies to seven common viruses which invade mucosa: cytomegalovirus (CMV), Epstein Barr (EBV), herpes simplex type I (HSVI), measles, mumps, rubella and varicella zoster virus (VZV). The majority of normal tears contained antibodies to HSVI (73%) and EBV (65%), occasionally to mumps (30%), rubella (30%), and VZV (20%), and rarely to CMV (5%). Tear viral antibodies were mainly IgA class, but it was not unusual to find IgG antibodies to HSVI, VZV, rubella and measles. Tear and parotid saliva immunoglobulins from the same individual had entirely different viral reactivity. In most cases tear viral antibodies were reflected in serum viral antibodies, although the immunoglobulin class might differ. However, 15% of normal tears had antibodies to HSVI without detectable serum antibodies. From this study we conclude that normal tear immunoglobulins contain antibodies to common viruses, in particular to HSVI and EBV. These tear antibodies are mainly IgA, but can consist of IgG. Viral antibodies in tears are independent of the antibodies present in parotid saliva, suggesting that there is preferential homing of committed B lymphocytes to different mucosal surfaces.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Increased monomeric immunoglobulin A levels in tears from multiple sclerosis patients.

Mucosal immunity and the secretory antibody are known to be important defense mechanisms against many common viruses. Tears were selected as a representative mucosal fluid, and immunoglobulin A (IgA) was examined by enzyme-linked immunosorbent assay and immunoblot. Tears from 38 normal controls and patients with systemic or ocular diseases contained almost exclusively polymeric IgA. In contrast, almost 75% of 23 patients with multiple sclerosis had detectable monomeric IgA in addition to polymeric IgA. The functional importance of this alteration in the molecular form of secretory IgA remains to be determined.

Adolescent

Detection and isolation of immune complexes in multiple sclerosis cerebrospinal fluid.

Immune complexes were studied in the cerebrospinal fluid (CSF) of 20 multiple sclerosis (MS) and 20 other neurological disease (OND) patients using polyethylene glycol precipitation; ten samples from each group were also examined using gel chromatography followed by ELISA. Polyethylene glycol detected predominantly IgG and IgM complexes in 13 of 20 MS samples and four of 20 OND samples. Intact MS complexes ranged in size from 230 to 340 kDa and contained 64 and 53 kDa antigens. Gel chromatography detected IgA complexes in eight of ten MS samples and one of ten OND samples; these complexes appeared to consist of polymeric IgA rather than true antigen. Chromatography detected IgG complexes in nine of ten MS and four of ten OND samples. Intact MS complexes ranged from 240 to 320 kDa and contained 200 and 150 kDa antigens. This study suggests that immune complexes are a very frequent finding in the CSF of MS patients and are in sufficient quantity to visualize on gel electrophoresis.

Adult