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Biomedical subjects

A R Pachner

Publications and source records attributed to A R Pachner.

At least 55 records · Page 3Linked to original sources
PubMed1989

Central nervous system manifestations of Lyme disease.

We studied six patients with central nervous system manifestations of Lyme disease. Weeks to years after the initial infection, behavioral changes, ataxia, and/or weakness in bulbar or peripheral muscles developed. Four of the six patients had a lymphocytic pleocytosis in the cerebrospinal fluid, and two of them had magnetic resonance imaging scans suggestive of demyelination. In a patient with a subacute encephalitis, a brain biopsy specimen showed microgliosis without an inflammatory infiltrate and spirochetes morphologically compatible with Borrelia burgdorferi. All six patients had elevated antibody titers to B burgdorferi in serum, but none had selective concentration of specific antibody in the cerebrospinal fluid. All six patients were treated with high-dose intravenous penicillin; four had complete recoveries and two did not. Lyme disease may affect the central nervous system causing organic brain disease or syndromes suggestive of demyelination.

Adult↗
PubMed1989

In vitro neutralization by monoclonal antibodies of alpha-bungarotoxin binding to acetylcholine receptor.

In order to develop monoclonal antibodies that would neutralize binding of alpha-bungarotoxin to acetylcholine receptor in vitro, mice were hyperimmunized with native toxin. Frequent small doses of toxin were used. Hybridoma supernatants were screened by ELISA and six monoclonal antibodies isolated and tested. The anti-alpha-bungarotoxin monoclonal antibodies consisted of IgM, IgG1 or IgG2a antibodies. In an in vitro neutralization assay measuring the effect of the antibodies on the binding of iodinated alpha-bungarotoxin to BC3H1 and TE671 (mouse and human cell lines bearing acetylcholine receptor), three of the six monoclonal antibodies were able to neutralize toxin binding. These studies demonstrate the feasibility of using native toxin for the generation of hybridomas, and the potential of using in vitro neutralization assays to screen hybridomas for in vivo neutralization.

Animals↗
PubMed1989

An immunodominant site of acetylcholine receptor in experimental myasthenia mapped with T lymphocyte clones and synthetic peptides.

Myasthenia gravis (MG) is an autoimmune disease of man caused by antibodies directed against the acetylcholine receptor (AChR). In the experimental model of MG in mice, murine experimental autoimmune myasthenia gravis (EAMG), an anti-AChR immune response is induced by immunization with Torpedo AChR, and anti-AChR antibodies. AChR-sensitized T cells, and neuromuscular dysfunction result. The production of antibodies to AChR is thymus-dependent. In order to define the epitopes of the AChR identified by AChR-specific T cells, we generated T cell populations and T cell hybridoma clones and tested their reactivity to synthetic uniform-sized overlapping peptides representing the entire extracellular portion of the alpha-chain of the AChR. The predominant reactivity of the T cell clones and the parent lines was to a peptide corresponding to residues 146-162 of Torpedo AChR. This data is consistent with a highly limited recognition of AChR determinants in murine EAMG by AChR-specific T cells.

Animals↗
PubMed1989

Lyme disease.

Lyme disease is of interest to the neurologist and neuroscientist for a variety of reasons. As more arthropod hosts throughout the world are infected with the causative organism, Borrelia burgdorferi, the illness in humans is becoming more prevalent; in addition, recognition of the disease in humans and susceptible animals is increasing. The neurological manifestations include acute and chronic forms, and it has become clear that B. burgdorferi has joined Treponema pallidum, herpes simplex virus, and human immunodeficiency virus (HIV) as an agent of persistent infection of the brain. Recent strides in the understanding of antigenic variation in Borrelia have provided insights into how this agent may survive in the human host. Preliminary work in animal models has provided information about the relationships between strain-dependent tropisms, spirochetemia, the development of specific antibody, and nervous system invasion. Finally, the history of the development of understanding of the disease has been a fascinating mixture of parental concern, serendipitous discovery, and correlation of clinical syndromes and serological evaluations across continents.

Humans↗
PubMed1989

Anti-acetylcholine receptor antibodies block bungarotoxin binding to native human acetylcholine receptor on the surface of TE671 cells.

We assayed sera from 20 myasthenics of various clinical stages and anti-acetylcholine receptor (AChR) antibody levels for their ability to affect bungarotoxin (BGT) binding to native human AChR on the surface of TE671 cells. Thirty-five percent of sera blocked BGT binding to the AChR, some at a dilution of up to 1:1000. The 7 patients whose sera blocked toxin binding were all generalized myasthenics with particularly severe disease, 6 of whom had had myasthenic crisis at some point in their course. No ocular myasthenics had blocking antibody. Blockade of toxin binding by myasthenic antibody to TE671 cells resembled blockade produced by unlabeled toxin in being irreversible with washing. There was little correlation between ability to block toxin binding and amplitude of the AChR binding antibody. These data are consistent with the hypothesis that patients with more aggressive generalized myasthenia preferentially have anti-AChR antibody that blocks toxin binding.

Adult↗
PubMed1988

Borrelia burgdorferi in the nervous system: the new "great imitator".

There are many obvious similarities between Lyme disease and syphilis. The major ones are their spirochetal etiology, the ability of the spirochetes to stay alive in human tissue for years, occurrence of clinical manifestations in stages, early disease in the skin and later disease in the brain, and susceptibility to antibiotic treatment. Thus, one can assume that many of the same lessons learned from the centuries of experience with syphilis will apply to Lyme disease. One of these lessons that should be constantly borne in mind is that spirochetal disease of the brain can mimic many other neurological diseases. Thus, the "effective clinician" must take special care to consider Lyme disease primarily because of the excellent response to antibiotics early in its course in relationship to some of the diseases it mimics. Lyme meningitis, occurring in the "second stage" of the disease, usually is fairly easily recognized because it occurs in the summer or early fall, often is associated with ECM or a recent history of it, and has a characteristic clinical picture of lymphocytic meningoradiculoneuritis. Many patients with Lyme meningitis or ECM have very mild symptoms, and it is likely that a large percentage of patients go undiagnosed and untreated. The frequency of progression of these patients to third-stage disease is unknown but may be quite high. This can be inferred from a similar situation in the other major late manifestation of Lyme disease: Lyme arthritis. A large number of patients present with joint involvement as their only manifestation of Lyme disease. Similarly, patients may present with symptoms of third-stage Lyme disease affecting the CNS, but they may not be recognized because of the lack of earlier stages usually associated with the disease. Thus, serology has become a very important tool for identifying patients exposed to B. burgdorferi. At the present time, serologic tests are the key to diagnosis of Lyme disease in its later stages, since, as in neurosyphilis, cultures and tests for antigen have not proven useful. Lyme arthritis and acrodermatitis atrophicans (ACA) both are associated with quite high antibody titers to the organism, while the test is understandably unreliable for identification of patients with ECM. Antibody titers in Lyme meningoradiculoneuritis are generally positive but often are not as high as those in ACA or arthritis. The antibody response in serum in CNS Lyme disease seems to be related to the presence of other manifestations; patients who have had both arthritis and CNS disease have quite high titers, while those with only CNS disease sometimes do not.(ABSTRACT TRUNCATED AT 400 WORDS)

Borrelia Infections↗
PubMed1987

Treatment of Lyme disease.

We compared phenoxymethyl penicillin, erythromycin, and tetracycline, in each instance 250 mg four times a day for 10 days, for the treatment of early Lyme disease (stage 1). None of 39 patients given tetracycline developed major late complications compared with 3 of 40 penicillin-treated patients and 4 of 29 given erythromycin (p = 0.07). However, with all three antibiotic agents, nearly half of patients had minor late symptoms. For neurologic abnormalities (stage 2), 12 patients were treated with high-dose intravenous penicillin, 20 million U a day for 10 days. Pain usually subsided during therapy, but a mean of 7 to 8 weeks was required for complete recovery of motor deficits. For the treatment of established arthritis (stage 3), 20 patients were assigned treatment with intramuscular benzathine penicillin (7.2 million U) and 20 patients received saline. Seven of the 20 penicillin-treated patients (35%) were apparently cured, but all 20 patients given placebo continued to have attacks of arthritis (P less than 0.02). Of 20 arthritis patients treated with intravenous penicillin G, 20 million U a day for 10 days, 11 (55%) were apparently cured. Thus, all 3 stages of Lyme disease can be treated with antibiotic therapy, but some patients with late disease may not respond.

Adult↗
PubMed1987

Neuropathy and IgM paraproteinemia: differential binding of IgM M-proteins to peripheral nerve glycolipids.

Two patients with neuropathy and IgM paraproteinemia displayed different immunoreactivity to acidic peripheral nerve glycolipids. In one patient, immunostaining on thin-layer chromatographic plate revealed binding of the IgM to sulfated glucuronosyl paragloboside (SGPG) and sulfated glucuronosyl lactosaminyl paragloboside (SGLPG). The other IgM bound SGPG, SGLPG, and a new third glycolipid. Immunoreactivity of the IgM varies in this syndrome.

Aged↗
PubMed1986

Anti-glycolipid antibodies and their immune complexes in multiple sclerosis.

Antibody titers against myelin constituents in sera and CSF of patients with multiple sclerosis (MS) were examined by a solid-phase radioimmunoassay. Anti-GM4 and anti-galactocerebroside antibody titers were significantly elevated in the CSF of MS patients, but not anti-GM1 and anti-myelin basic protein antibodies. In sera of MS patients, the titers of antibodies against these myelin constituents were not elevated. Total IgG level was also significantly elevated in the CSF, but not in the sera of MS patients. Immune complexes from the CSF of MS patients were dissociated by acid-ultrafiltration and assayed for antibodies to GM4, GM1, and galactocerebroside. Anti-GM4 and antigalactocerebroside antibody titers were significantly enhanced after acid dissociation and ultrafiltration. These data suggest that antibodies of the IgG class against GM4 and galactocerebroside are present in CSF of MS patients, and a significant number of them exist as immune complexes with their corresponding glycolipid antigens.

Antibody Specificity↗
PubMed1986

Anti-idiotypic antibodies to anti-acetylcholine receptor antibody: characterization by ELISA and immunoprecipitation assays.

The idiotype network is important both as a means of autoregulation of immune mechanisms and a potential tool for manipulation of abnormal responses. In the autoimmune disease myasthenia gravis the acetylcholine receptor (AChR) is the target of an aberrant immune response. In this study we compare 2 widely used methods of antibody determination--immunoprecipitation radioimmunoassay (IPRA) and enzyme-linked immunoassay (ELISA)--for their ability to detect both anti-AChR antibodies (polyclonal and monoclonal) and anti-idiotypic antibodies raised against polyclonal anti-AChR antibodies. Although the IPRA is considerably more sensitive for the detection of monoclonal anti-AChR antibodies, the 2 methods produce similar results in the detection of anti-idiotypic antibodies to the anti-AChR immune response. The 2 techniques also demonstrated specificity of the reagents for idiotypes associated with the anti-AChR response and absence of effect on an idiotype associated with the control antigen, ovalbumin. The results demonstrate that the idiotypic repertoire of the polyclonal anti-AChR response in C57B1/6 mice is sufficiently restricted that antigen-specific blocking anti-idiotypic antibodies can be raised in rabbits by immunization with anti-AChR antibodies.

Animals↗
PubMed1986

Clinical manifestations of Lyme disease.

Lyme disease typically begins with a unique skin lesion, erythema chronicum migrans (ECM) (stage 1). Patients with this lesion may also have headache, meningeal irritation, mild encephalopathy, multiple annular secondary lesions, malar or urticarial rash, generalized lymphadenopathy and splenomegaly, migratory musculoskeletal pain, hepatitis, sore throat, non-productive cough, conjunctivitis, periorbital edema, or testicular swelling. After a few weeks to months (stage 2), about 15% of patients develop frank neurologic abnormalities, including meningitis, encephalitis, cranial neuritis (including bilateral facial palsy), motor or sensory radiculoneuritis, mononeuritis multiplex, or myelitis. At this time, about 8% of patients develop cardiac involvement--AV block, acute myopericarditis, cardiomegaly, or pancarditis. Throughout this stage, many patients continue to experience migratory musculoskeletal pain in joints, tendons, bursae, muscle, or bone. Months to years after disease onset (stage 3), about 60% of patients develop frank arthritis, which may be intermittent or chronic. Recently evidence suggests that Lyme disease may also be associated with chronic neurologic or skin involvement. Thus, Lyme disease occurs in stages with different clinical manifestations at each stage, but the course of the illness in each patient is highly variable.

Borrelia↗
PubMed1986

The treatment of passively transferred experimental myasthenia with anti-idiotypic antibodies.

Experimental autoimmune myasthenia gravis (EAMG) was induced in chickens by passive transfer of a monoclonal antibody (mcAb) specific for the cholinergic binding site of the acetylcholine receptor (AChR). Specific anti-idiotypes raised in rabbits against this antisite mcAb (5.5) were demonstrated to prevent the induction of EAMG by a subsequent injection of mcAb 5.5. Also, administration of anti-idiotypes against mcAb 5.5 to chickens in which EAMG has been induced by mcAb 5.5 led to a recovery from myasthenic symptoms. These results suggest that passive transfer of the appropriate anti-idiotypes may have potential in the regulation of myasthenia.

Animals↗
PubMed1986

Spirochetal diseases of the CNS.

The neurotropism of the spirochete is evident from the above discussions of syphilis, Lyme disease, leptospirosis, and relapsing fever. In all of these diseases, the organism very likely enters the CNS very early in the course of the disease. The fate of the organism then depends on the virulence of the spirochete, the host defenses, and any antibiotic treatment administered. Why Treponema pallidum lays dormant in the CNS and then somehow reactivates is a mystery; the same mystery occurs in Lyme disease. Leptospirosis and relapsing fever seem to be infections much more limited in time, and are not reported to cause these long-term sequelae. The treatment of these last two infections seems to be fairly straightforward. However, the appropriate treatment for the various stages of the disease in both syphilis and Lyme disease in order to prevent long-term sequelae is not universally accepted. At this time, it seems that high-dose intravenous penicillin is the treatment of choice for each of these infections shown to be active in the nervous system.

Central Nervous System Diseases↗
PubMed1985

Helper T-cell lines specific for the acetylcholine receptor: induction, characterization, and in vitro effects.

A strong immune response to the acetylcholine receptor (AChR), involving both cell-mediated and humoral immunity, underlies both myasthenia gravis and its experimental models. A central cell in this response and in its regulation is the helper-proliferative T-cell specific for the AChR. We have produced long-lived lines of these cells derived from mice immunized with AChR. These cells proliferate in an antigen-specific manner to the AChR, bear the Lyl and Thy markers, and lack the Ly23 antigen. Finally, these cells and their supernatants help primed B cells make anti-AChR antibody. These cells will provide us with a necessary tool for the dissection of mechanisms regulating the immune response to the AChR.

Animals↗
PubMed1985

The triad of neurologic manifestations of Lyme disease: meningitis, cranial neuritis, and radiculoneuritis.

We studied 38 patients with Lyme meningitis, a newly recognized spirochetal infection. The patients characteristically had intermittent attacks of severe headache, mild meningismus, and a predominantly lymphocytic pleocytosis. In addition to meningitis, 11 patients experienced subtle encephalitic signs, 19 had cranial neuritis, most commonly unilateral or bilateral facial palsy, and 12 developed peripheral radiculoneuritis, plexitis, or mononeuritis multiplex. Without antibiotic therapy, the duration of neurologic involvement was 3 to 18 months. Although sometimes incomplete, the triad of neurologic manifestations of Lyme disease--meningitis, cranial neuritis, and radiculoneuritis--presents a unique clinical picture.

Adolescent↗
PubMed1985

Antigen-specific proliferation of CSF lymphocytes in Lyme disease.

The neurologic manifestations of Lyme disease include meningitis, radiculoneuritis, and cranial neuritis. In two patients, we investigated the proliferative response of CSF and peripheral blood lymphocytes to protein antigens derived from the Lyme disease spirochete. The response of CSF lymphocytes was 5 to 10 times greater than that of peripheral blood lymphocytes. In contrast, in the one patient studied, lectin-induced proliferation was less in CSF than in peripheral blood. These findings show that the CSF of patients with Lyme meningitis is an enriched source of antigen-specific proliferative lymphocytes.

Epitopes↗