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Biomedical subjects

C L Koski

Publications and source records attributed to C L Koski.

At least 37 records · Page 2Linked to original sources
PubMed1995

Electrophysiological studies in Guillain-Barré syndrome: correlation with antibodies to GM1, GD1B and Campylobacter jejuni.

A retrospective study of 50 patients with Guillain-Barré syndrome (GBS) correlated analysis of serial motor nerve conduction studies with the presence of antibodies to Campylobacter jejuni, GM1 and GD1b, determined by ELISA. GBS patients with antibodies to C. jejuni (n = 8), GM1 (n = 4), or GD1b (n = 4) showed electrophysiological features suggestive of demyelination with prolonged distal motor latencies and temporal dispersion/conduction block similar to GBS patients without these specific antibodies. Three of 50 GBS patients had poor recovery with inability to walk at 1 year after onset of symptoms. All three patients had antibodies to C. jejuni, but not to GM1 or GD1b. Although later on in the clinical course distal motor responses were absent in two of these patients, reflecting extensive axonal degeneration, early nerve conduction studies showed findings suggestive of demyelination. We suggest that demyelination of peripheral nerve may be the initial disease mechanism in GBS independent of the presence of antibodies to C. jejuni, GM1 or GD1b.

Adult↗
PubMed1995

Complement depletion affects demyelination and inflammation in experimental allergic neuritis.

The effect of systemic complement depletion by cobra venom factor (CVF) on experimental allergic neuritis (EAN) was studied in rats immunized with variable amounts of bovine peripheral nerve myelin. Low-dose myelin EAN rats treated with CVF i.p. (n = 10) had lower clinical scores (0.3 +/- 0.7 vs. 1.1 +/- 1.1), less demyelination (0.4 +/- 0.8 vs. 1.9 +/- 1.1) and inflammation (0.6 +/- 1.2 vs. 2 +/- 1) than EAN animals treated with i.p. saline (n = 10). Endoneurial infiltrates had fewer ED1-positive (phagocytic) macrophages (0.4 +/- 0.5 vs. 1.6 +/- 1.1) and CD11bc-positive (expressing iC3b receptor or CR3) cells (1 +/- 0.8 vs. 2.5 +/- 0.8) (mean +/- S.D.) detected by immunocytochemistry. This effect was partially abrogated by immunizing animals with a higher dose of myelin. Our studies suggest that complement may play a role in the recruitment of macrophages into the endoneurium and in opsonizing myelin for phagocytosis.

Animals↗
PubMed1994

Adherence-mediated T cell activation in multiple sclerosis and other neurological disorders.

Peripheral blood T cells were isolated from chronic progressive multiple sclerosis patients using a stepwise protocol of density gradient centrifugation, erythrocyte rosetting and adherent cell depletion, after which T cells were cultured with no added stimulus. These cultures exhibited as much as 10-fold higher 'background' proliferative activity (designated hyperactivity) than similarly prepared cultures from normal healthy control individuals. Hyperactivity was also found with T cell cultures from patients with other neurological disorders, i.e. namely, Guillain-Barré syndrome, acute stroke, myasthenia gravis or seizures. Characterizing the hyperactivity, kinetic studies showed that it was not evident until 6 days and became maximal in 8-10 day cultures; it occurred concomitantly with an increase in activated cells; and it was inhibited by anti-HLA-DR antibody, implicating the role of CD4+ T cells. Taken together, these results suggest that the hyperactivity was the result of in vitro stimulation. In further support of this view, hyperactivity was dependent on the adherence step used in the T cell isolation procedure. Although the T cell stimulus and the mechanism underlying the adherence effect is currently speculative, the hyperactivity appears to be the result of a feature common to the diseases in which it was found. The possible roles of inflammatory events in vivo and an autologous mixed lymphocyte response in vitro are discussed.

Antigens, CD↗
PubMed1994

Antibody of patients with Guillain-Barré syndrome mediates complement-dependent cytolysis of rat Schwann cells: susceptibility to cytolysis reflects Schwann cell phenotype.

We previously observed that demyelination of dissociated dorsal root ganglion cultures by acute phase serum of some Guillain Barré syndrome (GBS) patients was associated with cytolysis of rat Schwann cells (SC) not committed to myelination. In this study, to determine if SC cytolysis was antibody (Ab) and complement-dependent and if SC at various stages of differentiation were uniformly susceptible, sciatic nerve SC from 1-2-day-old (SC/2d) or 6-day-old (SC/6d) Sprague Dawley rats were sensitized with IgM from GBS patients or normal controls and incubated at 37 degrees C for 60 min with 25% guinea pig serum complement. Cytolysis was detected by vital dye exclusion. IgM Ab of 11 GBS patients induced complement-mediated cytolysis of 10.7-64.1% SC/2d (38.3 +/- 18.8; mean +/- SD) which was significantly higher than cytolysis of SC/6d (8.5-32%) or that by normal controls (15.0 +/- 15.2 SC/2d; 8.3 +/- 3.3 SC/6d mean +/- SD, n = 11). Culture of SC/6d increased their cytolysis by IgM plus complement to the levels similar to that of SC/2d. FACS analysis suggested that the greater sensitivity of SC/2d to cytolysis did not reflect greater antibody binding since 2.6-fold less GBS IgM was required to initiate SC/2d lysis compared to SC/6d. This suggested that the less differentiated SC were more susceptible to complement-mediated cytolysis.

Animals↗
PubMed1993

Serologic evidence of previous Campylobacter jejuni infection in patients with the Guillain-Barré syndrome.

OBJECTIVE: To determine if patients with the Guillain-Barré syndrome are likely to have had Campylobacter jejuni infection before onset of neurologic symptoms. DESIGN: A case-control study. SETTING: Several university medical centers. PATIENTS: Case patients met clinical criteria for the Guillain-Barré syndrome between 1983 and 1990 and had a serum sample collected and frozen within 3 weeks after onset of neurologic symptoms (n = 118). Disease controls were patients with other neurologic illnesses (n = 56); healthy controls were hospital employees or healthy family members of patients (n = 47). MEASUREMENTS: Serum IgA, IgG, and IgM antibodies to C. jejuni were determined by enzyme-linked immunosorbent assays. Assays were done in a blinded manner. RESULTS: Optical density ratios > or = 2 in two or more immunoglobulin classes were seen in 43 (36%) of patients with the Guillain-Barré syndrome and in 10 (10%) of controls (odds ratio, 5.3; 95% CI, 2.4 to 12.5; P < 0.001). Increasing the optical density ratio or the number of immunoglobulin classes necessary to yield a positive result increased the strength of the association. The number of patients with the Guillain-Barré syndrome who had positive serologic responses was greatest from September to November (P = 0.02). Male patients were three times more likely to have serologic evidence of C. jejuni infection (P = 0.009); the proportion of patients with the syndrome who had a positive serologic response increased with age. CONCLUSIONS: Patients with the Guillain-Barré syndrome are more likely than controls to have serologic evidence of C. jejuni infection in the weeks before onset of neurologic symptoms. Campylobacter jejuni may play a role in the initiation of the Guillain-Barré syndrome in many patients.

Adolescent↗
PubMed1993

Anti-peripheral nerve myelin antibodies and terminal activation products of complement in serum of patients with acute brachial plexus neuropathy.

OBJECTIVE: To determine if complement-fixing antibodies to peripheral nerve myelin (anti-PNM antibodies) and terminal complement activation products were increased in serum of patients with brachial plexus neuropathy compared with normal controls. DESIGN: Case series. SETTING: University medical center. PATIENTS: Three patients (aged 6, 39, and 51 years) with acute brachial plexus neuropathy were studied during the acute and recovery phase of their disease. METHODS: Anti-PNM antibodies were measured in serum samples obtained from three patients and 25 normal controls with the C1 fixation and transfer assay. Soluble terminal complement activation products, SC5b-9, were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples of one patient with brachial plexus neuropathy and of five normal controls. RESULTS: Both serum anti-PNM antibodies and soluble terminal complement activation products were increased in the acute phase of brachial plexus neuropathy compared with normal control values and decreased several months later during clinical recovery. CONCLUSION: Complement dependent, antibody-mediated demyelination may participate in the peripheral nerve damage of brachial plexus neuropathy.

Acute Disease↗
PubMed1993

Serum antibodies to GM1, GD1b, peripheral nerve myelin, and Campylobacter jejuni in patients with Guillain-Barré syndrome and controls: correlation and prognosis.

Serum antibodies to monosialoganglioside (GM1), disialoganglioside (GD1b), and Campylobacter jejuni, measured by enzyme-linked immunosorbent assay and serum antibodies to peripheral nerve myelin, measured by the C1 fixation and transfer assay, were studied in 58 acute-phase patients with Guillain-Barré syndrome (GBS), 42 disease controls, and 29 normal controls. Anti-peripheral nerve myelin antibodies were elevated in 57 of 58 patients with GBS compared with controls, whereas only 8.6% had increased antibody titers to GM1 and 10.3% to GD1b. Only low antibody titers (GM1) or no antibodies (GD1b) were found in controls. More GBS patients (17.2%) than controls (7%) had antibodies to C jejuni. Poor recovery with inability to walk at 1 year after onset of symptoms was seen in 3 (5%) of the patients with GBS. All 3 patients had serological evidence of recent C jejuni infection but no antibodies to GM1 or GD1b. GBS patients with antibodies to GM1 or GD1b had excellent recovery. Our data indicate that antibodies to GM1 or GD1b do not necessarily mediate the extensive axonal damage seen in these severely affected patients.

Acute Disease↗
PubMed1992

Electrophysiologic studies in the Guillain-Barré syndrome: effects of plasma exchange and antibody rebound.

Nerve conduction studies (NCS) and antiperipheral nerve myelin antibody (A-PNM Ab) titers were measured serially in 29 patients with Guillain-Barré syndrome (GBS), of whom 21 were treated with plasmapheresis. Data were obtained from 3 to 6 days until 1 to 2 years after onset of symptoms. Within 3 to 6 days, mean NCS were abnormal. They improved some by 1 week and became maximally abnormal by 4 to 8 weeks, during which time A-PNM Ab fell to low levels. In 5 patients plasmapheresed, A-PNM Ab fell and then increased at 4 to 8 weeks, followed by significant deterioration of NCS (P = 0.01) compared with those without antibody rebound at 18 weeks. These results suggest that, in monophasic GBS, there may be two mechanisms of conduction dysfunction such as early paranodal retraction and later demyelination. In some patients plasmapheresed, A-PNM Ab may rebound associated with further conduction dysfunction. These patients may benefit from further plasmapheresis.

Adolescent↗
PubMed1992

Humoral mechanisms in immune neuropathies.

Antibody and complement are implicated in the pathogenesis of a number of human, primarily demyelinating neuropathies. The ability of serum and purified, primarily IgM, antibodies to mediate demyelination was demonstrated in both in vitro and in vivo model systems. Complement activation to produce channel-forming terminal complement complexes, C5b-8 and C5b-9, was required for demyelination in vitro. Antibodies implicated in the demyelination of peripheral nerve of GBS patients and patients with monoclonal gammopathy-associated neuropathy bind carbohydrate epitopes on various neutral or acidic glycolipids and glycoproteins of peripheral nerve. In acute monophasic GBS, antibodies of multiple specificities may be induced to different infectious agents. These Ab, following penetration of a damaged blood-nerve barrier, are proposed to bind determinants of human peripheral nerve and participate in demyelination of nerve through activation of complement. These antibodies correlate with the clinical course, the generation of complement activation products, and the response to plasmapheresis. The mechanism by which the blood-nerve barrier is broken in GBS and other inflammatory demyelinating neuropathies and the extent of the role of the cellular immune system remain to be determined. Recent experiments demonstrated that T cells, antibody, and complement could synergistically contribute to central nervous system demyelination in naive rats. A similar synergism would be an attractive hypothesis for demyelination in the peripheral nervous system.

Autoantibodies↗
PubMed1991

Kinetics of anti-peripheral nerve myelin antibody in patients with Guillain-Barré syndrome treated and not treated with plasmapheresis.

Serial anti-peripheral nerve myelin antibody titers were determined in 28 consecutive patients with Guillain-Barré syndrome during the course of their illness. Eighteen patients were treated with plasmapheresis and 10 were not. Anti-peripheral nerve myelin antibody titers in the group treated with plasmapheresis declined significantly more rapidly than in the group not treated with plasmapheresis. Five patients treated with plasmapheresis who showed initial clinical improvement, with a concurrent decline in anti-peripheral nerve myelin antibody titer, had one or two recurrences of clinical symptoms during a 2- to 8-week period associated with an increase in anti-peripheral nerve myelin antibody titer. Recurrent weakness was severe enough to prompt additional courses of plasmapheresis. The data suggest that serial determinations of antiperipheral nerve myelin antibody in patients with Guillain-Barré syndrome may identify patients with antibody rebound associated with recurrence of clinical symptoms and prolonged recovery in whom further plasmapheresis should be considered.

Adolescent↗
PubMed1991

In vitro demyelination by serum antibody from patients with Guillain-Barré syndrome requires terminal complement complexes.

Serum from 7 patients who had acute-phase Guillain-Barré syndrome with high anti-peripheral nerve myelin antibody activity (54 to 210 units/ml) was compared with serum from 3 patients in the recovery phase (0 to 17 units/ml) and serum from 7 disease control subjects (0 to 24 units/ml) and 7 normal control subjects (0 to 7 units/ml) for its ability to demyelinate rodent dorsal root ganglion cultures. The demyelinating capacity of each serum was quantitated by counting the percent of damaged internodal segments in each of four cultures. All sera from patients in the acute phase GBS caused 50 to 78% demyelination, in contrast with 6 to 19% by the sera from all 3 patients in the recovery phase and all other control subjects. The degree of demyelination correlated with anti-peripheral nerve myelin antibody activity of the sera and demyelination was complement-dependent. Further, cultures were treated with an immunoglobulin M (IgM) fraction of an acute-phase Guillain-Barré syndrome plasma plus normal human serum depleted of complement component C7. Only those cultures treated with IgM and C7-depleted human serum reconstituted with purified C7 resulted in 50.8% demyelination, which was significantly greater than the 14.2 to 16.2% demyelination observed in the presence of heat-inactivated, C7-depleted human serum plus purified C7 or in the absence of C7 or antibody. In summary, our work suggests that anti-peripheral nerve myelin antibody in Guillain-Barré syndrome mediated complement dependent-demyelination of rodent dorsal root ganglion cultures. Further, this in vitro demyelination required generation of activation complexes of the terminal complement cascade.

Acute Disease↗
PubMed1990

Characterization of complement-fixing antibodies to peripheral nerve myelin in Guillain-Barré syndrome.

Complement-fixing antibodies to peripheral nerve myelin (anti-PNM Ab) can be detected in the serum of patients with Guillain-Barré syndrome (GBS). Kinetics of these antibodies can be correlated with the changing clinical course; the appearance of activation products of the terminal complement cascade in cerebrospinal fluid, serum, and peripheral nerve of patients with GBS; and the ability of GBS serum to mediate complement-dependent demyelination of myelinating cultures of rodent dorsal root ganglion. Some of the anti-PNM Ab in all GBS serum tested thus far bind a neutral glycolipid of human PNM and cross react with Forssman antigen, a cross-species antigen found in many infectious agents. Studies suggest that an IgM antibody in GBS patients that could be triggered by multiple infectious agents binds a surface determinant of a Forssman-like lipid of human PNM and participates in demyelination of peripheral nerve through the activation of complement.

Autoantibodies↗
PubMed1989

Anti-peripheral nerve myelin antibodies in Guillain-Barre syndrome bind a neutral glycolipid of peripheral myelin and cross-react with Forssman antigen.

During acute-phase illness, serum of patients with Guillain-Barre syndrome (GBS) contain complement-fixing antibodies (Ab) to peripheral nerve myelin (PNM). We investigated PNM lipids as putative antigens for these Ab since GBS serum retained significant reactivity to PNM treated with protease. Ab binding to specific lipids was studied with a C1 fixation and transfer (C1FT) assay using fractions of PNM lipid reincorporated into liposomes as antigen targets or to lipids on HPTLC plates with peroxidase-labeled goat Ab to human IgM. Reactivity was detected to a neutral glycolipid (NGL) of human PNM with a similar number of carbohydrates residues to that of Forssman hapten (Forss). Anti-NGL Ab titers in GBS patients (50-220 U/ml) were significantly elevated over disease and normal controls (0-5 and 0-6 U/ml). We studied possible antigenic cross-reactivity of these Ab with Forss by first quantitating Ab activity with C1FT assay and liposomes containing Forss. All 12 GBS sera tested showed titers (54-272 U/ml) significantly elevated over 11 disease controls (0-22 U/ml) and 25 normal controls (0-11 U/ml). GBS serum Ab reacted with Forss isolated from dog nerve or sheep erythrocytes on HPTLC plates. Further, absorption of 80-100% of anti-NGL Ab activity and 17-97% of anti-PNM Ab activity from eight GBS patient serums was accomplished with liposomes containing Forss but not with control liposomes. In seven GBS patients anti-NGL Ab activity represented only a portion of anti-PNM Ab activity. These results suggest that a glycolipid with antigenic cross-reactivity to Forssman hapten may be responsible for some of the anti-PNM Ab activity in GBS.

Antibodies↗
PubMed1988

Autonomic dysfunction in Lambert-Eaton myasthenic syndrome.

Autonomic symptoms were observed in 6 patients with clinically and electrophysiologically documented Lambert-Eaton myasthenic syndrome (LEMS). Of the 6 patients, 2 were extensively investigated in the laboratory. In contrast to previous reports which recognized only cholinergic dysautonomia, abnormalities of sympathetic as well as parasympathetic function were evident. Of the 6 patients, 4 had small cell lung cancer (SCLC). In one male patient, chemotherapy for SCLC resulted in an early improvement of autonomic dysfunction and the electrophysiological defect, documenting simultaneous regression of dysautonomia and LEMS. In addition, the patients with SCLC and LEMS had a survival thus far of 3-13 years suggesting that a subgroup of SCLC patients have a better prognosis.

Adult↗
PubMed1987

Detection of activated terminal complement (C5b-9) in cerebrospinal fluid from patients with central nervous system involvement of primary Sjogren's syndrome or systemic lupus erythematosus.

We have examined cerebrospinal fluid (CSF) and serum from patients with Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE) for evidence of activation of the terminal pathway of complement. Fluid phase terminal complement complexes (SC5b-9), quantitated by ELISA, were detected in the CSF of 14 of 16 patients with SS and focal central nervous system (CNS) disease. Five of six SS patients without focal CNS disease but with psychiatric disease or cognitive dysfunction had detectable CSF SC5b-9, whereas two other SS patients without focal CNS or neuropsychiatric disease had no detectable CSF SC5b-9. Six of seven patients with SLE or SLE overlap syndrome with CNS involvement had CSF SC5b-9, whereas two patients with SLE without CNS involvement had no CSF SC5b-9. A subset of SS and SLE patients with CNS disease had SC5b-9 detected in CSF but not in serum. SC5b-9 was generally absent from the CSF of patients with noninflammatory CNS diseases. These findings demonstrate intrathecal activation of terminal complement in patients with CNS SS or CNS SLE, and suggest a role for terminal complement activation in the pathophysiology of CNS involvement in both SS and SLE.

Complement Membrane Attack Complex↗