Search PubMed⌕ Search

Biomedical subjects

B C Jacobs

Publications and source records attributed to B C Jacobs.

At least 37 records · Page 2Linked to original sources
PubMed2000

Clinical features and response to treatment in Guillain-Barré syndrome associated with antibodies to GM1b ganglioside.

GM1b is a minor ganglioside in human peripheral nerves. Serum anti-GM1b antibodies frequently are present in patients with Guillain-Barré syndrome (GBS). In this collaborative study, we investigated the antecedent infections, clinical features, and response to treatment of GBS patients with anti-GM1b antibodies. Of 132 GBS patients who participated in the Dutch GBS trial that compared the effect of intravenous immunoglobulins and plasma exchange, 25 (19%) patients had anti-GM1b antibodies. IgM antibodies were present in 14, IgG antibodies in 15, and both isotypes in 4 patients. The 25 patients with anti-GM1b antibodies had a clinical pattern distinct from that of the other 107 GBS patients. They more often had an episode of gastrointestinal illness and frequently showed serological evidence of recent infection by Campylobacter jejuni. The anti-GM1b-positive subgroup was marked by more rapidly progressive, more severe, and predominantly distal weakness. Cranial nerve involvement and sensory deficits were less common in the patients with anti-GM1b antibodies. The presence of anti-GM1b antibodies was associated with slower recovery. The clinical manifestations predominantly were associated with anti-GM1b antibodies of the IgG isotype. Fourteen (56%) of the 25 patients with anti-GM1b antibodies also had anti-GM1 antibodies. The group of patients with both antibodies was clinically more homogeneous and had a more rapidly progressive, pure motor neuropathy. The subgroup of anti-GM1b-positive GBS patients responded well to treatment with immunoglobulins but not to plasmapheresis. The distinctive clinical features of the patients with anti-GM1b antibodies show that acute motor neuropathy represents a specific subgroup within GBS and that recognizing these patients may have consequences as to the choice of therapy.

Adolescent↗
PubMed1999

Rapidly progressive, predominantly motor Guillain-Barré syndrome with anti-GalNAc-GD1a antibodies.

OBJECTIVE: To investigate the presence of anti-GalNAc-GD1a antibodies in patients with Guillain-Barré syndrome (GBS) and to determine the relation of anti-ganglioside antibodies with clinical features. BACKGROUND: The GBS is heterogeneous with regard to clinical manifestations, antecedent infections, and the presence and specificity of anti-ganglioside antibodies. Recently, antibodies to minor gangliosides have been identified in serum from GBS patients. METHODS: The authors used ELISA to detect anti-ganglioside antibodies in 132 GBS patients and then correlated results with a database containing information on antecedent infections and clinical parameters. RESULTS: Anti-GalNAc-GD1a antibodies could be detected in 19 (14%) GBS patients. The presence of anti-GalNAc-GD1a antibodies was related to antecedent Campylobacter jejuni infection (p<0.001). GBS patients with anti-GalNAc-GD1a antibodies had a rapidly progressive, more severe, and predominantly distal weakness. Furthermore, they had less sensory loss, paresthesia, and cranial nerve involvement. In most patients, this reactivity was independent of reactivity to GM1. Dividing patients into separate groups based on their reactivity to GalNAc-GD1a and GM1 enabled the authors to delineate more homogeneous subgroups with regard to clinical features. CONCLUSIONS: This study provides further evidence for the hypothesis that antecedent infections and the specificity of subsequent anti-neural antibody responses determine the clinical manifestations in GBS patients.

Adolescent↗
PubMed1999

Miller Fisher anti-GQ1b antibodies: alpha-latrotoxin-like effects on motor end plates.

In the Miller Fisher syndrome (MFS) variant of the Guillain-Barré syndrome, weakness is restricted to extraocular muscles and occasionally other craniobulbar muscles. Most MFS patients have serum antibodies against ganglioside type GQ1b of which the pathophysiological relevance is unclear. We examined the in vitro effects of MFS sera, MFS IgG, and a human monoclonal anti-GQ1b IgM antibody on mouse neuromuscular junctions (NMJs). It was found that anti-GQ1b antibodies bind at NMJs where they induce massive quantal release of acetylcholine from nerve terminals and eventually block neuromuscular transmission. This effect closely resembled the effect of the paralytic neurotoxin alpha-latrotoxin at the mouse NMJs, implying possible involvement of alpha-latrotoxin receptors or associated downstream pathways. By using complement-deficient sera, the effect of anti-GQ1b antibodies on NMJs was shown to be entirely dependent on activation of complement components. However, neither classical pathway activation nor the formation of membrane attack complex was required, indicating the effects could be due to involvement of the alternative pathway and intermediate complement cascade products. Our findings strongly suggest that anti-GQ1b antibodies in conjunction with activated complement components are the principal pathophysiological mediators of motor symptoms in MFS and that the NMJ is an important site of their action.

Animals↗
PubMed1998

Differences in N-acetylmuramyl-L-alanine amidase and lysozyme in serum and cerebrospinal fluid of patients with bacterial meningitis.

N-acetylmuramyl-L-alanine amidase (NAMLAA) specifically degrades peptidoglycan, a major component of bacterial cell walls. Lysozyme degrades peptidoglycan differently by hydrolyzing the aminosugar backbone of peptidoglycan. In another study, it was shown that the two enzymes act synergistically to inactivate the inflammatory properties of peptidoglycan. The presence of lysozyme and NAMLAA was determined in serum and cerebrospinal fluid (CSF) of patients with bacterial meningitis. High concentrations of lysozyme were found in CSF while, surprisingly, NAMLAA was not present. To explain this phenomenon, the degranulation pattern of neutrophils in CSF was compared with that of neutrophils from blood. Specific granules contain lysozyme and the azurophil granules contain both lysozyme and NAMLAA. CD66b expression on the cell surface, indicative for fusion of the specific granules with the cell membrane, was higher in CSF than in blood, while the marker for the azurophil granules was lower.

Adolescent↗
PubMed1998

The spectrum of antecedent infections in Guillain-Barré syndrome: a case-control study.

OBJECTIVE: To determine which antecedent infections are specifically associated with the Guillain-Barré syndrome (GBS). BACKGROUND: Infections with many agents have been reported preceding GBS. Some infections are related to specific clinical and immunologic subgroups in GBS. Most agents were reported in case reports and uncontrolled small series of GBS patients only, and their relation to GBS and its subgroups remains unclear. METHOD: A serologic study for 16 infectious agents in 154 GBS patients and 154 sex- and age-matched controls with other neurologic diseases. Acute phase, pretreatment samples were used from clinically well-defined GBS patients. The seasonal distribution of serum sampling in the GBS and control group was the same. RESULTS: Multivariate analysis showed that in GBS patients, infections with Campylobacter jejuni (32%), cytomegalovirus (13%), and Epstein-Barr virus (10%) were significantly more frequent than in controls. Mycoplasma pneumoniae infections occurred more often in GBS patients (5%) than in controls in univariate analysis. Infections with Haemophilus influenzae (1%), parainfluenza 1 virus (1%), influenza A virus (1%), influenza B virus (1%), adenovirus (1%), herpes simplex virus (1%), and varicella zoster virus (1%) were also demonstrated in GBS patients, but not more frequently than in controls. C. jejuni infections were associated with antibodies to the gangliosides GM1 and GD1b and with a severe pure motor form of GBS. Cytomegalovirus infections were associated with antibodies to the ganglioside GM2 and with severe motor sensory deficits. Other infections were not related to specific antiganglioside antibodies and neurologic patterns. CONCLUSIONS: Recent infections with C. jejuni, cytomegalovirus, Epstein-Barr virus, and M. pneumoniae are specifically related to GBS. The variety of infections may contribute to the clinical and immunologic heterogeneity of GBS.

Adenoviridae Infections↗
PubMed1997

Electrodiagnostic findings related to anti-GM1 and anti-GQ1b antibodies in Guillain-Barré syndrome.

Antibodies against the gangliosides GM1 and GQ1b may induce conduction failure in mice. To investigate their possible site of action in the Guillain-Barré syndrome (GBS), we studied the relation between serum anti-GM1 and anti-GQ1b antibodies and electromyography in 124 GBS patients. Anti-GM1 antibodies were found in 22 (18%) and anti-GQ1b antibodies in 5 (4%) patients. Anti-GM1 antibodies were associated with low distal compound muscle action potential amplitudes and relatively high compound sensory nerve action potential (CSNAP) amplitudes. In none of the patients with anti-GQ1b antibodies could CSNAPs be detected. Patients with anti-GM1 and anti-GQ1b antibodies were heterogenous with respect to electrodiagnostic features exclusive fordemyelination oraxonal degeneration, although the anti-GM1 positive patients tended to have more axonal degeneration. In conclusion, electromyographic studies indicate selective and more severe damage of motor nerves in patients with anti-GM1 antibodies, while patients with anti-GQ1b antibodies have more severe damage of sensory nerves. These antibodies may interfere with the electrophysiologic properties of different nerve fibers and thereby contribute to the clinical heterogeneity in GBS.

Animals↗
PubMed1997

Humoral immune response against Campylobacter jejuni lipopolysaccharides in Guillain-Barré and Miller Fisher syndrome.

In this study we characterized the IgG antibodies against lipopolysaccharides (LPS) of Campylobacter jejuni in serum from patients with Guillain-Barré syndrome (GBS), Miller Fisher syndrome (MFS), C. jejuni enteritis and normal controls. In patients with GBS and MFS long-lasting titers of IgG1 and IgG3 antibodies against LPS from GBS and MFS associated C. jejuni were found. The subclass and course of these antibodies were highly associated with those of antibodies against GM1 and GQ1b in GBS and MFS patients. However, in C. jejuni enteritis and normal controls anti-LPS antibodies were predominantly IgG2. Antibody binding with LPS was reduced after treatment with choleratoxin and sialidases, suggesting that the ganglioside-like epitopes in LPS are immunodominant. These results further indicate that antecedent C. jejuni infections determine the specificity and isotype of anti-ganglioside antibodies in GBS and MFS patients.

Antibodies↗
PubMed1997

Human IgM paraproteins demonstrate shared reactivity between Campylobacter jejuni lipopolysaccharides and human peripheral nerve disialylated gangliosides.

IgM paraproteins from patients with CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, M-protein, agglutination, anti-disialosyl antibodies) react with NeuAc(alpha 2-8)NeuAc epitopes on a wide range of gangliosides including GQ1b, GT1a, GD1b and GD3. The tissue distribution of reactive antigens in human peripheral nerve has not been addressed in detail. In addition, the origin of these antibodies is unknown. Here we report that purified anti-disialosyl paraproteins from two affected patients bind a wide array of human peripheral nerve structures including dorsal root ganglia, dorsal and ventral root axons, femoral and oculomotor nerves. We also show that these paraproteins bind lipopolysaccharides of Campylobacter jejuni isolates from 3/3 cases of Miller Fisher syndrome, and to a less frequent extent, from cases of Guillain-Barré syndrome and enteritis controls. In conjunction with our previous studies, these data provide a possible causal link between the origin and pathogenic effects of anti-disialosyl antibodies in human paraproteinaemic neuropathy.

Agglutination↗
PubMed1997

Guillain-Barré syndrome: multifactorial mechanisms versus defined subgroups.

The clinical spectrum of Guillain-Barré syndrome (GBS) is summarized in relation to antecedent infections and anti-ganglioside antibodies. Associations exist between a pure motor form of GBS, diarrhea, Campylobacter jejuni infection, and anti-GM1 antibodies; between cranial nerve involvement and Miller Fisher syndrome, C. jejuni infection, and anti-GQ1b antibodies; and between variants, such as severe sensory involvement and cytomegalovirus infection. These three clinical variants are suggested to form the extremes of a continuous spectrum; they are discussed in relation to the more pathologically defined patterns of acute motor axonal neuropathy and acute motor-sensory axonal neuropathy. In particular, patients with a clinically pure motor variant of GBS, diarrhea, anti-GM1 antibodies, or C. jejuni infection seem to respond better to early treatment with high-dose immunoglobulins than to plasma exchange.

Autoantibodies↗
PubMed1997

Cross-reactive antibodies against gangliosides and Campylobacter jejuni lipopolysaccharides in patients with Guillain-Barré or Miller Fisher syndrome.

Campylobacter jejuni was isolated from stool specimens of 3 patients with Miller Fisher syndrome (MFS) and 2 patients with Guillain-Barré syndrome (GBS). Anti-GQ1b antibodies in serum from all MFS patients cross-reacted with sialidase-sensitive epitopes in the lipopolysaccharide fraction of C. jejuni from these 3 MFS patients. One GBS patient had anti-GM1 antibodies that bound with lipopolysaccharide of C. jejuni from a control patient and from the other GBS patient without anti-GM1 antibodies. This binding was inhibited by cholera toxin but not by pretreatment with sialidase. The C. jejuni isolate from the GBS patient with serum anti-GM1 antibodies did not contain anti-GM1 antibody-binding epitopes. Our results strongly support the hypothesis that anti-GQ1b antibodies in MFS patients are induced during the antecedent C. jejuni infection. In GBS patients, mechanisms other than molecular mimicry may also be involved in the production of anti-GM1 antibodies.

Antibodies, Bacterial↗
PubMed1997

Cytomegalovirus infections and anti-GM2 antibodies in Guillain-Barré syndrome.

To investigate whether antecedent cytomegalovirus (CMV) infections in patients with Guillain-Barré syndrome are associated with the presence of specific antiganglioside antibodies, acute phase serum samples from 130 patients with Guillain-Barré syndrome and 200 controls were tested. Anti-GM2 IgM antibodies were found more often in patients with Guillain-Barré syndrome with CMV infection (22%) than in patients without the infection (2%) (P = 0.003). CMV infections may elicit anti-GM2 antibodies in susceptible patients, which may contribute to the pathogenesis of Guillain-Barré syndrome associated with CMV.

Chromatography, Thin Layer↗
PubMed1996

Campylobacter jejuni infections and anti-GM1 antibodies in Guillain-Barré syndrome.

The group of patients with Guillain-Barr'e syndrome (GBS) is very heterogenous with regard to antecedent infections, immunological parameters, clinical manifestations, and response to treatment. In this study, the presumed pathogenic factors anti-GM1 antibodies and Campylobacter jejuni infections were related to the clinical characteristics. Serum from 154 patients with GBS, 63 patients with other neurological diseases (OND), and 50 normal controls (NC) were tested for the presence of antibodies against GM1 and C. jejuni. Anti-GM1 antibodies were detected in 31 (20%) GBS patients, 5 (8%) OND patients, and in none of the NC. Evidence for a recent C. jejuni infection was found in 49 (32%) GBS patients and less often in OND patients (11%) or NC (8%). In GBS patients, the presence of anti-GM1 antibodies was significantly associated with C. jejuni infections. The subgroup of GBS patients with anti-GM1 antibodies suffered more often from a rapidly progressive and more severe neuropathy with predominantly distal distribution of weakness, without deficits of cranial nerves or sensory disturbances. The subgroup with C. jejuni infection also more often had a severe pure motor variant of GBS. Recovery of the patients with anti-GM1 antibodies and C. jejuni infections was not as good after plasma exchange compared with intravenous immunoglobulins.

Antibodies↗
PubMed1996

Cytomegalovirus infection and Guillain-Barré syndrome: the clinical, electrophysiologic, and prognostic features. Dutch Guillain-Barré Study Group.

Guillain-Barré syndrome (GBS) is usually preceded by infections, in particular cytomegalovirus (CMV) and Campylobacter jejuni infection. We studied the clinical and electrophysiologic features of 20 CMV-associated GBS patients and compared the findings with earlier established data of C. jejuni-related GBS patients (n = 43) and of GBS patients without these infections (n = 71). The patients all participated in the Dutch GBS trial in which we compared the effect of intravenous immune globulins and plasma exchange. We demonstrate that CMV-related GBS patients have a different clinical pattern in comparison with the other two GBS groups. They are significantly younger, initially have a severe course indicated by a high frequency of respiratory insufficiency, and often develop cranial nerve involvement and severe sensory loss. This is in contrast to C. jejuni infection, which is associated with motor GBS. Both infections are associated with delayed recovery compared with the GBS patients without these infections.

Cytomegalovirus Infections↗
PubMed1995

Serum anti-GQ1b IgG antibodies recognize surface epitopes on Campylobacter jejuni from patients with Miller Fisher syndrome.

Three patients who had diarrhea prior to the development of Miller Fisher syndrome are presented. Campylobacter jejuni was isolated from stool specimens from all patients. High titers of anti-GQ1b IgG antibodies were demonstrated in the serum of these patients by enzyme-linked immunosorbent assay and thin-layer chromatography overlay. In enzyme-linked immunosorbent assay inhibition studies the anti-GQ1b IgG antibodies bound specifically to whole bacteria of the Miller Fisher syndrome-associated C. jejuni strains. The presence of anti-GQ1b IgG binding epitopes on the surface of the C. jejuni from the patients was not exclusively associated with a specific Penner serotype. It is suggested that anti-GQ1b antibodies are formed during the initial infection that elicits Miller Fisher syndrome. The cross-reactivity of anti-GQ1b IgG antibodies with surface epitopes on Miller Fisher syndrome-associated C. jejuni strains supports the hypothesis of molecular mimicry between bacteria and neural tissue.

Adult↗
PubMed1995

Anti-GM1 IgG antibodies and Campylobacter bacteria in Guillain-Barré syndrome: evidence of molecular mimicry.

In Guillain-Barré syndrome antibodies to GM1 and the presence of an antecedent Campylobacter jejuni infection are correlated with a more severe course of the disease. From a group of 137 consecutive GBS patients, 11 sera had elevated titers of anti-GM1 IgG antibodies during the acute stage of disease. Each serum sample was preincubated with three different Penner serotypes of whole C. jejuni (PEN O:4/59, PEN O:41) and Campylobacter coli (PEN O:22) bacteria. The PEN O:4/59 serotype, isolated from the stools of a Guillain-Barré syndrome patient, inhibited 63 to 93% of the anti-GM1 activity in 6 of 11 patients. The PEN O:41 inhibited 63 to 100% of the anti-GM1 antibody activity in 9 of 11 patients. The PEN O:22 inhibited anti-GM1 antibody activity in only 2 of 11 patients (80 and 86%). Two Guillain-Barré syndrome patients did not show antibody absorption by any of the Campylobacter serotypes tested, although this does not exclude the involvement of other serotypes. An Escherichia coli control strain did not significantly absorb anti-GM1 antibodies. The results of this study indicate that anti-GM1 IgG antibodies in Guillain-Barré syndrome sera recognize surface epitopes on whole Campylobacter bacteria and that this recognition is strain-specific. This provides evidence for molecular mimicry in the pathogenesis of Guillain-Barré syndrome.

Adolescent↗
PubMed1995

Inflammatory neuropathies--pathogenesis and the role of intravenous immune globulin.

The inflammatory neuropathies may be subdivided into an acute form, Guillain-Barré syndrome, and a chronic form referred to as chronic inflammatory demyelinating polyneuropathy. More recently a chronic, asymmetrical pure motor neuropathy with multifocal conduction blocks has been described. All three neuropathies are considered to be immune-mediated. Their response to therapy is discussed, with special emphasis on high-dose intravenous immune globulin. For Guillain-Barré syndrome the efficacy of intravenous immune globulin has been proven in a randomized clinical trial. In chronic inflammatory demyelinating polyneuropathy a response rate of over 60% in newly diagnosed patients is suggested. Clinical prognostic criteria, however, seem to be very important to predict the effect of intravenous immune globulin. In multifocal motor neuropathy intravenous immune globulin is at present the only alternative to cyclophosphamide.

Campylobacter jejuni↗
PubMed1995

Guillain-Barré syndrome without sensory loss (acute motor neuropathy). A subgroup with specific clinical, electrodiagnostic and laboratory features. Dutch Guillain-Barré Study Group.

We analysed data obtained from 27 out of a group of 147 patients with Guillain-Barré syndrome, who did not have sensory loss during a follow-up period of 6 months (motor Guillain-Barré syndrome). These patients had a distinctive clinical pattern compared with the other 120 Guillain-Barré syndrome patients. The clinical course was marked by a more rapid onset of weakness (3.9 versus 6.1 days, P = 0.002), an earlier nadir (6.3 versus 9.1 days, P < 0.001), an initially predominant distal weakness (67% versus 27%, P < 0.001), sparing of the cranial nerves (26% versus 68%, P < 0.001) and the disease was more often preceded by a gastro-intestinal illness (41% versus 13%, P = 0.001) often caused by a Campylobacter jejuni infection (67% versus 28% in the other Guillain-Barré syndrome patients, P < 0.001). High titres of anti-GM1 antibodies were also significantly more common in motor Guillain-Barré syndrome patients (42% versus 5%, P < 0.001). Electromyographic data of the motor Guillain-Barré syndrome patients at nadir revealed little or no evidence for demyelination. Abundant denervation activity was present in half of the patients. The response to immune globulin treatment was good but with plasma exchange significantly fewer motor Guillain-Barré syndrome patients reached the stage of independent locomotion after a follow-up period of 6 months especially if the acute motor neuropathy occurred after a C.jejuni infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗