Biomedical subjects

C A Vedeler

Publications and source records attributed to C A Vedeler.

At least 37 records · Page 2Linked to original sources

PubMed2001

Fc receptors for immunoglobulin G--a role in the pathogenesis of Guillain-Barré syndrome and multiple sclerosis.

Receptors for the Fc part of IgG (FcgammaR) constitute a family of cell-surface molecules expressed on almost every cell of the immune system. They are also present on non-lymphoid cells such as Schwann cells and endothelial cells. By linking humoral and cell-mediated responses, FcgammaR are key in defending against pathogens. Polymorphisms in some FcgammaR genes are associated with infectious and autoimmune diseases. It was found recently that certain FcgammaRIIA and FcgammaRIIIB allotypes are correlated with the disease course of Guillain-Barré syndrome (GBS) and multiple sclerosis (MS). This may imply that clearance of circulating autoantibodies and immune complexes is important in the pathogenesis of these diseases.

Animals↗

PubMed2001

Molecular genetic analysis of Charcot-Marie-Tooth 1A duplication in Norwegian patients by quantitative photostimulated luminescence imaging.

Around 70% of Charcot-Marie-Tooth 1 (CMT1) cases are caused by a dominantly inherited 1.5-Mb duplication at 17p11.2-12 (CMT1A). Using photostimulated luminescence (PSL) imaging of MspI Southern blots, hybridization signals of the probe pVAW409R3a in relation to cohybridized probe SF85a, were densitometrically quantified and an RFLP allele-band ratio determined. A total of 55 Norwegian CMT patients and 16 asymptomatic family members from 26 separate families, clinically and neurophysiologically classified as CMT1 (n=46) and CMT2 (n=9), were studied. Thirty-two of 46 CMT1 cases (69.6%), all heterozygous but one homozygous for the pVAW409R3a MspI polymorphism, from 12 of 21 families (57.1%) were positive for the CMT1A duplication. In autosomal dominant familial cases (n=30), 26 of 30 cases (86.7%), all heterozygous, from six of seven families (85.7%) were positive for duplication. None of the CMT2 patients, asymptomatic family members or healthy controls were positive for duplication. The CMT1A frequency of duplication in Norwegian CMT1 patients is in general agreement with those reported in other European countries and the present results show that quantitative densitometric PSL imaging is a highly reliable test in diagnosing CMT1A duplication.

Charcot-Marie-Tooth Disease↗

PubMed2001

[Neuromuscular complications of sepsis].

BACKGROUND: Neuromuscular complications are common in patients treated for sepsis and multiple organ dysfunction in critical care units. Failure to wean from the ventilator, due to involvement of the respiratory system, and severe muscular weakness are typical symptoms. Electrophysiological examination demonstrates fibrillation potentials and reduction of compound muscular action potential amplitudes. MATERIAL AND METHODS: We report three patients with severe muscular weakness during treatment of critical illness. RESULTS: Critical illness polyneuropathy was the main cause of weakness in two patients, with a presumed superimposed myopathy in one. A third patient had critical illness myopathy. INTERPRETATION: Critical illness polyneuropathy and myopathy--either as separate or combined entities--are common causes of muscular weakness during treatment of critical illness. These disorders are often difficult to distinguish from each other, as the clinical and electrophysiological findings may overlap. Sepsis and multiple organ dysfunction are the main aetiological factors, but certain drugs may contribute in the pathogenesis. No specific treatment exists. In the most severe cases long-lasting physiotherapy and rehabilitation is needed.

Aged↗

PubMed2001

[Neuromuscular complications of myxoma].

BACKGROUND: Myxomas are the most common type of primary cardiac tumours. As they are most often located in the left atrium, primary neurological manifestations are often multiple embolic infarcts in the central nervous system. MATERIAL AND METHODS: We describe a patient with acute aphasia due to left temporal haemorrhage. Later he developed acute ataxia due to right cerebellar infarct. RESULTS: Magnetic resonance also showed multiple supra- and infratentorial infarcts. Echocardiography revealed a myxoma in the left atrium which was treated by surgical excision. There were no signs of myxoma recurrence or embolic infarcts at follow-up. INTERPRETATION: Echocardiography should be included in the diagnostic work-up of patients with cerebrovascular events, especially in young patients with multiple infarcts.

Cerebral Infarction↗

PubMed2001

Recombination breakpoints in the Charcot-Marie-Tooth 1A repeat sequence in Norwegian families.

OBJECTIVE: To investigate the recombination breakpoint in a 3.2 kb junction fragment of the 24 kb CMT1A repeat sequences (CMT1A-REPs) on chromosome 17p11.2-12. MATERIALS AND METHODS: Thirty-eight Norwegian CMT1 patients and 15 asymptomatic family members of 15 separate families including 10 normal controls were investigated using repeat (REP)-PCR. RESULTS: Twenty-six (68.4%) of the CMT1 patients from 9 (60%) families were positive for the CMT1A duplication which was not found in any of the controls. In 89.9% of the REP-PCR positive families the recombination breakpoint was mapped to a 1.7 kb "hot-spot" region, and in 11.1% of the families to a 1.5 kb region telomeric to the 1.7 kb region. CONCLUSION: The frequency and regions for CMT1A-REPs crossover events in Norwegian CMT1A cases are similar to what is found in other populations. REP-PCR is not, however, as sensitive as other diagnostic methods to detect the CMT1A duplication.

Charcot-Marie-Tooth Disease↗

PubMed2001

Fcgamma receptor polymorphisms in populations in Ethiopia and Norway.

Seventy-seven healthy Ethiopians were genotyped for polymorphisms in the immunoglobulin G Fc receptors (FcgammaR) FcgammaRIIa, FcgammaRIIIa and FcgammaRIIIb, including the SH allele. The genotype and allele frequencies were compared with those of 96 healthy Norwegians. Ethiopians had higher frequencies of the SH-FcgammaRIIIb (P = 0.001), FcgammaRIIIa-158 V (P = 0.026) and FcgammaRIIIb-Na2 (P = 0.046) alleles. The genotype distributions of FcgammaRIIa, FcgammaRIIIa and FcgammaRIIIb, however, did not differ significantly from those of the Norwegians. The data were also compared with those reported from studies on other ethnic groups. The variation of different polymorphisms both within and between ethnic groups may influence differences in the incidence rates of infectious and autoimmune diseases.

Adult↗

PubMed2000

Neutralizing antibodies to interferon (IFN) alpha-2a and IFN beta-1a or IFN beta-1b in MS are not cross-reactive.

Sera from patients with MS treated with recombinant interferon (rIFN) alpha-2a, rIFNbeta-1a, or rIFNbeta-1b were analyzed for cross-reacting neutralizing antibodies (NAB). Because cross-reactivity was not found, switching treatment from rIFNbeta-1a or rIFNbeta-1b to rIFNalpha-2a might provide a secondary treatment response in patients with NAB to rIFNbeta-1a or rIFNbeta-1b. A positive treatment response also might be achieved by switching NAB rIFNalpha-2a-positive patients to rIFNbeta-1a or rIFNbeta-1b.

Adult↗

PubMed2000

IgG Fc-receptor polymorphisms in Guillain-Barré syndrome.

The authors studied immunoglobulin G (IgG) Fc receptor (FcgammaR) IIA, IIIA, and IIIB polymorphisms in 62 patients with Guillain-Barré syndrome (GBS) and in 89 healthy controls. The FcgammaR genotypes and allele frequencies did not differ significantly between the patients with GBS and the controls. Patients homozygous for the FcgammaRIIIB neutrophil antigen (NA) 1 allele had a significantly less severe disease than patients heterozygous or homozygous for the NA2 allele. The FcgammaRIIIB NA1/NA1 genotype has high affinity for IgG1 and IgG3, and clearance of circulating autoantibodies and immune complexes may therefore be of importance in the pathogenesis of GBS.

Female↗

PubMed2000

IgG allotypes and subclasses in Norwegian patients with multiple sclerosis.

Multiple sclerosis (MS) is a multifactorial disease in which genetic and environmental factors apparently have a major influence on the susceptibility and course of the disease. In the present study we have investigated the genetic basis and subclass levels of IgG in MS. Hundred and thirty-six Norwegian patients with MS and 92 controls were genotyped for IgG allotypes of the GM and KM systems. IgG and IgG subclasses were quantified in sera from 115 MS patients and 20 controls. Neither GM nor KM allo-, haplo- or genotypes were significantly correlated with susceptibility, severity or course of the disease. The G1M (3) (3), G2M (23) (23) and G3M (5) (5) allotypes were significantly correlated with high serum levels of IgG3, whereas high IgG2 levels were correlated with G1M (3) (3) and G2M (23) (23) in both patients and controls. Serum levels of IgG subclasses were not significantly correlated with course or severity of the disease. The results indicate no major role for IgG allotypes or IgG subclass levels in the pathogenesis of MS.

Female↗

PubMed2000

Real-time quantitative polymerase chain reaction. A new method that detects both the peripheral myelin protein 22 duplication in Charcot-Marie-Tooth type 1A disease and the peripheral myelin protein 22 deletion in hereditary neuropathy with liability to pressure palsies.

In Charcot-Marie-Tooth type 1A disease (CMTIA), heterozygosity for the peripheral myelin protein 22 (PMP22) duplication increases the gene dose from two to three, whereas, in hereditary neuropathy with liability to pressure palsies (HNPP), heterozygosity for the PMP22 deletion reduces the gene dose from two to one. Thirty-eight Norwegian patients with CMT1, 4 patients with HNPP, 15 asymptomatic family members, and 45 normal controls were studied using the ABI 7700 sequence detection system and the TaqMan method of real-time quantitative polymerase chain reaction (PCR). Using a comparative threshold cycle (Ct) method and albumin as reference gene, the gene copy number by PMP22 gene duplication or deletion on chromosome 17p11.2-12 was quantified. The PMP22 duplication ratio ranged from 1.50 to 2.21, the PMP22 deletion ratio ranged from 0.44 to 0.55, and the PMP22 ratio in normals ranged from 0.82 to 1.27. All samples were run in triplicate, with a mean standard deviation of 0.07 (range 0.01-0.17). Thirty-four of thirty-eight CMT1 patients (89.6%) had the PMP22 duplication and the four HNPP patients had the PMP22 deletion. This was not found in any of the asymptomatic family members or the controls. Real-time quantitative PCR is a sensitive, specific, and reproducible method for diagnosing PMP22 duplication and deletion. The method is fast, allowing 13 patients to be diagnosed in 2 h. It involves no radioisotopes and requires no post-PCR handling. In our opinion, real-time quantitative PCR is the first method of choice in diagnosing PMP22 duplication and deletion.

Charcot-Marie-Tooth Disease↗

PubMed2000

Oligoclonal bands in cerebrospinal fluid: a comparative study of isoelectric focusing, agarose gel electrophoresis and IgG index.

OBJECTIVE: To compare the sensitivity and specificity of isoelectric focusing (IEF) with immunofixation, agarose gel electrophoresis (AGE) and the IgG index in detecting intrathecally synthesized IgG in multiple sclerosis (MS) and in other nervous system disorders. MATERIALS AND METHODS: Cerebrospinal fluid (CSF) and serum from 147 patients with various nervous system diseases, 20 of whom had MS, were compared with IEF, AGE and the IgG index. RESULTS: CSF-restricted oligoclonal bands (OCB) were found in 20 of 20 patients with MS using IEF and in 9 of 20 using AGE. OCB were found in 12 patients with other nervous system disorders (OND) using IEF and 4 using AGE. The mean IgG index was 0.50 in OND and 0.96 in MS (P< 0.0001). Of 20 MS patients, 9 had an IgG index above the defined cut-off value of 0.72. CONCLUSIONS: IEF is about twice as sensitive as AGE in detecting OCB in MS. IEF is also far superior to the IgG index in determining intrathecal IgG synthesis.

Adolescent↗

PubMed2000

Inflammatory neuropathies: update.

This review focuses on recent neuroimmunological findings in autoimmune inflammatory neuropathies. In Guillain-Barré syndrome and paraneoplastic neuropathy most current investigations are centred on the hypothesis of molecular mimicry. In chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy the data on immunopathology are more fragmentary. Why and how patients with autoimmune inflammatory neuropathies raise an increased anti-self-reactivity and how this leads to disease remains a major challenge for future research.

Humans↗

PubMed2000

Interferon-alpha2a effects on complement activation and regulation in MS patients.

OBJECTIVES: To evaluate the treatment effect of recombinant interferon-alpha2a (rIFN-alpha2a) on complement activation and regulation in MS patients. MATERIAL AND METHODS: Plasma levels of the complement activation products C3bc and terminal complement complex (TCC) and serum levels of the complement regulatory proteins, complement receptor 1, CR1 (CD35) and the membrane inhibitor of reactive lysis, protectin (CD59), were determined by enzyme-linked immunosorbent assay (ELISA) in MS patients treated with IFN-alpha2a (14 patients) or placebo (7 patients). RESULTS: The level of soluble CD35 decreased while the level of TCC and to a lesser degree C3bc increased in the IFN-alpha2a treated patients during the initial part of the treatment. There was also a concomitant reduction of leukocytes in the same patients. CONCLUSIONS: The results indicate that complement is activated during the initial phase of rIFN-alpha2a treatment. This could partly be due to a concomitant reduction in soluble CD35.

Adult↗

PubMed1999

The expression of CD59 in experimental allergic neuritis.

Complement is implicated as an effector in inflammatory demyelination occurring in Guillain-Barré syndrome (GBS) and in experimental allergic neuritis (EAN). CD59, a potent complement regulatory protein that inhibits the formation of the terminal cytolytic membrane attack complex (MAC), is expressed on human and rat Schwann cells. In EAN the expression of CD59 was increased on Schwann cells during demyelination and axonal degeneration, evaluated by immunostaining of nerve sections and teased fibres. Mac-1 (CD11b) positive leukocytes were localized close to the Schwann cells showing enhanced CD59 staining. The increased CD59 expression in EAN could therefore be due to the release of cytokines or other immunoregulatory molecules from the inflammatory cells. However, interferon gamma (IFN-gamma) or tumor necrosis factor alfa (TNF-alpha) did not upregulate the expression of CD59 on rat Schwann cells in culture. The increased expression of CD59 in EAN is likely to be important in the protection of Schwann cells from MAC.

Animals↗

PubMed1997

The long-term prognosis of Guillain-Barré syndrome. Evaluation of prognostic factors including plasma exchange.

Fifty-two patients with Guillain-Barré syndrome (GBS) were re-examined 1-14 years (median 7 years) after the initial onset of symptoms. At the follow-up 38 patients (73%) reported being completely symptom-free. Neurological examination revealed that 11 patients (21%) had motor and 16 patients (31%) had sensory signs, mainly distal in the lower limbs. One patient (2%) had cranial nerve signs. Fifteen patients (29%) had areflexia, generally of the ankle jerks. Severe pareses (high maximal disability grade), long duration of maximal symptoms and recovery were significantly associated with persistent disability. Age, sex, preceding infection, latency between infection and the onset of disease, weakness as an initial symptom, autonomic dysfunction, speed of progression, electro-physiological signs of axonal degeneration, cerebrospinal-fluid protein concentration and treatment with plasma exchange did not significantly influence the disability grade at follow-up.

Disability Evaluation↗

PubMed1996

Soluble complement receptor type 1 in serum and cerebrospinal fluid of patients with Guillain-Barré syndrome and multiple sclerosis.

Activation of complement is critically involved in inflammatory reactions in both Guillain-Barré syndrome (GBS) and multiple sclerosis (MS). Soluble human complement receptor 1 (sCR1) blocks complement activation by both classical and alternative pathways. We studied serum and cerebrospinal fluid (CSF) concentrations of sCR1 in 23 patients with GBS, 27 patients with MS and 30 controls. No significant differences were found between patients and controls. Transient liver affection probably caused high serum sCR1 levels in two patients with GBS. The serum and CSF sCR1 levels were not correlated to the disease activity of GBS and MS, nor to the relapsing-remitting or chronic-progressive forms of MS. In GBS the CSF sCR1 levels correlated with the CSF total protein concentrations (r = 0.9, P < 0.01), suggesting that sCR1 leaks from serum into CSF via a damaged blood-nerve barrier. The serum sCR1 levels in GBS were slightly higher than in MS (P < 0.05). Whether this reflects changes in the release or consumption of sCR1 in these patients is at present unknown.

Adult↗

PubMed1996

Guillain-Barré syndrome in northern Tanzania: a comparison of epidemiological and clinical findings with western Norway.

To study Guillain-Barré syndrome (GBS), the clinical files of GBS patients, 59 in northern Tanzania (1984-1992) and 56 in western Norway (1980-1992), were retrospectively reviewed and compared. The average annual incidence rate for GBS in the Kilimanjaro region was 0.83/100,000 population as compared to 1.2/100,000 reported in western Norway (25). GBS patients in the Tanzanian series were younger, had less antecedent infection and were a longer time interval from onset to admission and in hospital. On examination arm and sensory involvement were less common and urinary sphincteric involvement more common in the Tanzanian series. The overall mortality rate was higher in the Tanzanian series, 15.3% (9/59) versus 1.8% (1/56). HIV infection was found in 30.5% (11/36) of GBS patients in the Tanzanian series as compared to 3.4% (161/4687) in corresponding blood donors. There was no evidence of HIV infection in the Norwegian series. The HIV-seropositive GBS patients in comparison with HIV seronegatives had a shorter duration of onset, greater neurological involvement and a higher mortality rate, 45.5% (5/11) versus 16% (4/21). This study shows that apart from minor clinical differences and an increased mortality rate in the Tanzanian series GBS was similar in both series. GBS in the Tanzanian series was strongly associated with HIV infection, and seropositives by comparison with seronegatives appeared to have more severe disease.

AIDS-Related Opportunistic Infections↗

PubMed1995

The influence of tumour necrosis factor-alpha, interleukin-1 beta and interferon-gamma on the expression and function of the complement regulatory protein CD59 on the human colonic adenocarcinoma cell line HT29.

CD59 is a 18-25 kDa glycoprotein which, by inhibiting the formation of the membrane attack complex, protects homologous cells from complement mediated damage. We have described recently the expression and complement regulatory function of CD59 on colonic adenocarcinoma cells both in vivo and in vitro. In this study we have examined the influence of cytokines on the expression and complement regulatory function of CD59 on the colonic adenocarcinoma cell line HT29. CD59 expression on the HT29 cells was up-regulated after stimulation by mononuclear cells activated by mixed lymphocyte reaction and by culture supernatants from activated mononuclear cells. Similarly, a dose-dependent increase in CD59 expression was observed after stimulation with both tumour necrosis factor-alpha and interleukin-1 beta. A dose-dependent increase in the level of CD59 expression was also seen using low concentrations of interferon-gamma (IFN-gamma), while CD59 expression on cells cultured with high IFN-gamma concentrations was comparable to non-stimulated cells. Cytokine treated cells were more resistant to lysis by homologous complement than non-stimulated cells, and the increase in CD59 expression was shown to be partially responsible for this. The present data strengthen the role of CD59 as a possible participant in tumour escape.

Adenocarcinoma↗