Mette Munch - Academia.edu (original) (raw)
Papers by Mette Munch
B-lymphoblastoid cell-lines may develop spontaneously in mononuclear cells from patients with mul... more B-lymphoblastoid cell-lines may develop spontaneously in mononuclear cells from patients with multiple sclerosis, an observation rarely seen in healthy individuals. Examination of such spontaneously established B-cell lines reveal the presence of Epstein-Barr virus and retrovirus particles. We have speculated that in predisposed individuals, a dual infection with retrovirus and late acquired Epstein-Barr virus plays an aetiological role in the development of multiple sclerosis. This hypothesis is supported by a number of observations, including the ®nding that infection with Epstein-Barr virus may be a prerequisite for developing multiple sclerosis. The association between multiple sclerosis and infection with Epstein-Barr virus and retrovirus is evaluated in this study.
B-lymphoblastoid cell-lines may develop spontaneously in mononuclear cells from patients with mul... more B-lymphoblastoid cell-lines may develop spontaneously in mononuclear cells from patients with multiple sclerosis, an observation rarely seen in healthy individuals. Examination of such spontaneously established B-cell lines reveal the presence of Epstein-Barr virus and retrovirus particles. We have speculated that in predisposed individuals, a dual infection with retrovirus and late acquired Epstein-Barr virus plays an aetiological role in the development of multiple sclerosis. This hypothesis is supported by a number of observations, including the ®nding that infection with Epstein-Barr virus may be a prerequisite for developing multiple sclerosis. The association between multiple sclerosis and infection with Epstein-Barr virus and retrovirus is evaluated in this study. Journal of NeuroVirology (2000) 6, S76 ± S79.
Type-l inhibitor oTplasminogcn activalors (PAI-I) occurs in purified preparations in a latenr for... more Type-l inhibitor oTplasminogcn activalors (PAI-I) occurs in purified preparations in a latenr form thal can be activated with dcnaturants; in vivo, Iiltency is prevented by binding to vitroncctin. WC have compared latent, dcnaturant-actiwcd and rcactivcccntrc-clcavcd human PAL1 with respect to thermal stability and affinity to monoclonal antibodies. By both criteria. latent and cleaved PAI-I are very similar or indistinguishable. and clearly diKerent rrom active PAI-I. Our tindings suggest that the conformations or latent and reactive ccntre-clcavcd PAI-I arc similar and rcsemblc the so-called relaxed (R) serpin conformation, while that oT active PAI-I is different and rcscmbles the stressed (S) scrpin conrormation.
Blood, 1997
Sequence variations in the Epstein-Barr virus (EBV) encoded latent membrane protein-1 (LMP-1) gen... more Sequence variations in the Epstein-Barr virus (EBV) encoded latent membrane protein-1 (LMP-1) gene have been described in a Chinese nasopharyngeal carcinoma-derived isolate (CAO), and in viral isolates from various EBV-associated tumors. It has been suggested that these genetic changes, which include loss of a Xho I restriction site (position 169425) and a C-terminal 30-base pair (bp) deletion (position 168287-168256), define EBV genotypes associated with increased tumorigenicity or with disease among particular geographic populations. To determine the frequency of LMP-1 variations in European wild-type virus isolates, we sequenced the LMP1 promoter and gene in EBV from lymphoblastoid cell lines from healthy carriers and patients without EBV-associated disease. Sequence changes were often present, and defined at least four main groups of viral isolates, which we designate Groups A through D. The widespread prevalence of LMP-1 sequence variations, particularly the Xho I polymorphism ...
Ugeskrift for laeger, Jan 9, 2002
Journal of Veterinary Diagnostic Investigation, 2004
Three 1-tube Reverse Transcriptase Polymerase Chain Reactions (RT-PCR) directed against the genes... more Three 1-tube Reverse Transcriptase Polymerase Chain Reactions (RT-PCR) directed against the genes encoding the nucleoprotein (NP) and the H5 and H7 hemagglutinin (HA) gene, respectively, were used for detection of avian influenza virus (AIV) in various specimens. A total of 1,040 samples originating from chickens experimentally infected with 2 different low pathogenic avian influenza viruses, from domestic ducks and from wild aquatic birds were examined. The outcome of 1) the universal AIV RT-PCR including a PCR-enzyme-linked immunosorbent assay (ELISA) procedure directed against NP (NP RT-PCR-ELISA) and 2) the subtype specific RT-PCR for H5 and H7 were compared to the results obtained by inoculation of the same specimens into the allantoic cavity of embryonated specific pathogen free (SPF) hen's eggs. Using inoculation in SPF fowl eggs as standard the sensitivity of the NP RT-PCR-ELISA and the RT-PCR for H5 or H7 was 91% and 94%, and the corresponding specificity 98% and 96%. I...
Journal of Neuroimmunology, 1998
Journal of Neuroimmunology, 1994
Introduction Demyelinetion is a major pathogenic feature of multiple sclerosis, resulting in the ... more Introduction Demyelinetion is a major pathogenic feature of multiple sclerosis, resulting in the formation of lipid laden microglia (MG) and macropheges (M~,). Opsonisation of myelin with anti-myelin Aim contributes to its uptake, which results in free radical end cytokine release which contribute to further phagenytosis. The receptors involved in this process have been investigated. Materials and Methods MG or MS were co-incubated with radioiodineted rat myelin + opsonisatinn end either native LDL (which binds to the LDL receptor), oxidiscd LDL (scavenger receptor), zymosen (CR3, mannose/fucose end B glycen receptor) or mennose for 18hrs; or the calls were pre-incubeted with OX42 (entiCR3) or PAP (FOR) or for 5hrs followed by 18hr with myelin. In all cases the cells were washed, solnhilised, end the 1251 counted. Results It was found that oxLDL, zymosan, OX42 and mannose cause dose dependent inhibition of myelin uptake. PAP also has this effect, however it did not distinguish between myelin and opsonised myelin. Conclusions Myelin phagocytosis in MG and MO occurs via the CR3, FoR, scavenger and mennose/fucose receptors, and therefore specific blockage of these receptors has the potential to modulate demyelination.
Journal of Neuroimmunology, 1995
Molecular Pathology, 1996
Aims-(1) To study the frequency of putative malignancy associated point mutations and a 30 base p... more Aims-(1) To study the frequency of putative malignancy associated point mutations and a 30 base pair (bp) deletion in exon 3 of the C-terminus of the Epstein-Barr virus (EBV) encoded latent membrane protein (LMP)-1 (BNLF-1) gene in wild type EBV strains. (2) To assess the influence of these mutations on the tumorigenicity of lymphoblastoid cell lines (LCL).
FEBS Letters, 1991
Type‐1 inhibitor of plasminogen activators (PAI‐I) occurs in purified preparations in a latent fo... more Type‐1 inhibitor of plasminogen activators (PAI‐I) occurs in purified preparations in a latent form that can be activated with denaturants; in vivo, latency is prevented by binding to vitronectin. We have compared latent, denaturant‐activated and reactive centre‐cleaved human PAI‐1 with respect to thermal stability and affinity to monoclonal antibodies. By both criteria, latent and cleaved PAI‐1 are very similar or indistinguishable, and clearly different from active PAI‐1. Our findings suggest that the conformations of latent and reactive centre‐cleaved PAI‐1 are similar and resemble the so‐called relaxed (R) serpin conformation, while that of active PAI‐1 is different and resembles the stressed S serpin conformation.
Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1993
The latent form of type-1 plasminogen activator inhibitor (PAI-1) acquires inhibitory activity by... more The latent form of type-1 plasminogen activator inhibitor (PAI-1) acquires inhibitory activity by denaturation followed by refolding. We show here that the reactions of denatured/refolded PAI-1 with plasminogen activators are affected by low concentrations of SDS, which may remain after using SDS for denaturation. Without SDS, the active fraction of denatured/refolded PAI-1 comprised around 60%. Increasing SDS concentrations led to conversions to an inert form without inhibitory activity; then to a substrate form, that is being cleaved proteolytically in the reactive centre by the activators without complex formation, and finally to a second inert form. The first two conversions were associated with changes of the reactivity with monoclonal antibodies and of the thermal stability, respectively. Our results define clearly different interconvertible forms of denatured/refolded PAI-1, distinguish these from the latent and the reactive-centre-cleaved forms, and provide conditions for reproducibly producing reactive-centre-cleaved PAI-1 and PAI-1/activator complexes.
Avian Diseases, 2003
A one-tube reverse transcriptase/polymerase chain reaction coupled with an enzyme-linked immunoso... more A one-tube reverse transcriptase/polymerase chain reaction coupled with an enzyme-linked immunosorbent assay (RT-PCR-ELISA) was developed for the rapid detection of avian influenza virus (AIV) in clinical specimens. A total of 419 swab pools were analyzed from chickens experimentally infected with low-pathogenicity AIV, from wild aquatic birds, and from domestic ducks. The AIV was detected in 32 swab pools by RT-PCR-ELISA compared to 23 by virus isolation (VI) in embryonated specific pathogen free (SPF) chicken eggs. Thus, 39% more specimens were positive by RT-PCR-ELISA than by VI. Two of the twenty-three VI-positive specimens were negative when tested by RT-PCR-ELISA. The diagnostic sensitivity and specificity of the RT-PCR-ELISA was 91% and 97%, respectively, using VI in SPF eggs as the gold reference standard.
Archives of Virology, 2001
Acta Neurologica Scandinavica, 2009
Acta Neurologica Scandinavica, 1997
Acta Neurologica Scandinavica, 1997
Acta Neurologica Scandinavica, 1997
The Lancet, 1997
CCR-5 heterozygosity confers a higher probability of nonprogression during the first 3 years afte... more CCR-5 heterozygosity confers a higher probability of nonprogression during the first 3 years after seroconversion. Slow progressors have only a small increase in the frequency of CCR-5 heterozygosity relative to the general white population. This result can be easily biased due to the time period for non-progression selected or to genetic differences inherent in our cohort. A previous study of individuals infected by sexual transmission showed a maximum difference in disease progression between heterozygous and homozygous wild-type subjects between 10-12 years after seroconversion. 4 These results are consistent with the proposed role of CCR-5 as the major co-receptor for HIV-1 monocytotropic strains which are known to be more prevalent in infected individuals early in disease. Relative to heterozygotes, individuals homozygous for the wild type allele could support increased levels of viral replication and therefore might progress more rapidly to AIDS. The presence of the mutant allele may prevent efficient HIV-1 replication by a reduction in the number of available receptors. This effect may be amplified by secondary increases in the level of antiviral chemokine secretion. A lack of significant protection late in disease might suggest the evolution of viruses toward the use of alternative co-receptors, such as fusin. We thank the medical staff in hospitals and private practitioners who kindly collaborate with the GRIV project in France. This work was funded by Sidaction and by ARS (Association de Recherche contre le Sida).
B-lymphoblastoid cell-lines may develop spontaneously in mononuclear cells from patients with mul... more B-lymphoblastoid cell-lines may develop spontaneously in mononuclear cells from patients with multiple sclerosis, an observation rarely seen in healthy individuals. Examination of such spontaneously established B-cell lines reveal the presence of Epstein-Barr virus and retrovirus particles. We have speculated that in predisposed individuals, a dual infection with retrovirus and late acquired Epstein-Barr virus plays an aetiological role in the development of multiple sclerosis. This hypothesis is supported by a number of observations, including the ®nding that infection with Epstein-Barr virus may be a prerequisite for developing multiple sclerosis. The association between multiple sclerosis and infection with Epstein-Barr virus and retrovirus is evaluated in this study.
B-lymphoblastoid cell-lines may develop spontaneously in mononuclear cells from patients with mul... more B-lymphoblastoid cell-lines may develop spontaneously in mononuclear cells from patients with multiple sclerosis, an observation rarely seen in healthy individuals. Examination of such spontaneously established B-cell lines reveal the presence of Epstein-Barr virus and retrovirus particles. We have speculated that in predisposed individuals, a dual infection with retrovirus and late acquired Epstein-Barr virus plays an aetiological role in the development of multiple sclerosis. This hypothesis is supported by a number of observations, including the ®nding that infection with Epstein-Barr virus may be a prerequisite for developing multiple sclerosis. The association between multiple sclerosis and infection with Epstein-Barr virus and retrovirus is evaluated in this study. Journal of NeuroVirology (2000) 6, S76 ± S79.
Type-l inhibitor oTplasminogcn activalors (PAI-I) occurs in purified preparations in a latenr for... more Type-l inhibitor oTplasminogcn activalors (PAI-I) occurs in purified preparations in a latenr form thal can be activated with dcnaturants; in vivo, Iiltency is prevented by binding to vitroncctin. WC have compared latent, dcnaturant-actiwcd and rcactivcccntrc-clcavcd human PAL1 with respect to thermal stability and affinity to monoclonal antibodies. By both criteria. latent and cleaved PAI-I are very similar or indistinguishable. and clearly diKerent rrom active PAI-I. Our tindings suggest that the conformations or latent and reactive ccntre-clcavcd PAI-I arc similar and rcsemblc the so-called relaxed (R) serpin conformation, while that oT active PAI-I is different and rcscmbles the stressed (S) scrpin conrormation.
Blood, 1997
Sequence variations in the Epstein-Barr virus (EBV) encoded latent membrane protein-1 (LMP-1) gen... more Sequence variations in the Epstein-Barr virus (EBV) encoded latent membrane protein-1 (LMP-1) gene have been described in a Chinese nasopharyngeal carcinoma-derived isolate (CAO), and in viral isolates from various EBV-associated tumors. It has been suggested that these genetic changes, which include loss of a Xho I restriction site (position 169425) and a C-terminal 30-base pair (bp) deletion (position 168287-168256), define EBV genotypes associated with increased tumorigenicity or with disease among particular geographic populations. To determine the frequency of LMP-1 variations in European wild-type virus isolates, we sequenced the LMP1 promoter and gene in EBV from lymphoblastoid cell lines from healthy carriers and patients without EBV-associated disease. Sequence changes were often present, and defined at least four main groups of viral isolates, which we designate Groups A through D. The widespread prevalence of LMP-1 sequence variations, particularly the Xho I polymorphism ...
Ugeskrift for laeger, Jan 9, 2002
Journal of Veterinary Diagnostic Investigation, 2004
Three 1-tube Reverse Transcriptase Polymerase Chain Reactions (RT-PCR) directed against the genes... more Three 1-tube Reverse Transcriptase Polymerase Chain Reactions (RT-PCR) directed against the genes encoding the nucleoprotein (NP) and the H5 and H7 hemagglutinin (HA) gene, respectively, were used for detection of avian influenza virus (AIV) in various specimens. A total of 1,040 samples originating from chickens experimentally infected with 2 different low pathogenic avian influenza viruses, from domestic ducks and from wild aquatic birds were examined. The outcome of 1) the universal AIV RT-PCR including a PCR-enzyme-linked immunosorbent assay (ELISA) procedure directed against NP (NP RT-PCR-ELISA) and 2) the subtype specific RT-PCR for H5 and H7 were compared to the results obtained by inoculation of the same specimens into the allantoic cavity of embryonated specific pathogen free (SPF) hen's eggs. Using inoculation in SPF fowl eggs as standard the sensitivity of the NP RT-PCR-ELISA and the RT-PCR for H5 or H7 was 91% and 94%, and the corresponding specificity 98% and 96%. I...
Journal of Neuroimmunology, 1998
Journal of Neuroimmunology, 1994
Introduction Demyelinetion is a major pathogenic feature of multiple sclerosis, resulting in the ... more Introduction Demyelinetion is a major pathogenic feature of multiple sclerosis, resulting in the formation of lipid laden microglia (MG) and macropheges (M~,). Opsonisation of myelin with anti-myelin Aim contributes to its uptake, which results in free radical end cytokine release which contribute to further phagenytosis. The receptors involved in this process have been investigated. Materials and Methods MG or MS were co-incubated with radioiodineted rat myelin + opsonisatinn end either native LDL (which binds to the LDL receptor), oxidiscd LDL (scavenger receptor), zymosen (CR3, mannose/fucose end B glycen receptor) or mennose for 18hrs; or the calls were pre-incubeted with OX42 (entiCR3) or PAP (FOR) or for 5hrs followed by 18hr with myelin. In all cases the cells were washed, solnhilised, end the 1251 counted. Results It was found that oxLDL, zymosan, OX42 and mannose cause dose dependent inhibition of myelin uptake. PAP also has this effect, however it did not distinguish between myelin and opsonised myelin. Conclusions Myelin phagocytosis in MG and MO occurs via the CR3, FoR, scavenger and mennose/fucose receptors, and therefore specific blockage of these receptors has the potential to modulate demyelination.
Journal of Neuroimmunology, 1995
Molecular Pathology, 1996
Aims-(1) To study the frequency of putative malignancy associated point mutations and a 30 base p... more Aims-(1) To study the frequency of putative malignancy associated point mutations and a 30 base pair (bp) deletion in exon 3 of the C-terminus of the Epstein-Barr virus (EBV) encoded latent membrane protein (LMP)-1 (BNLF-1) gene in wild type EBV strains. (2) To assess the influence of these mutations on the tumorigenicity of lymphoblastoid cell lines (LCL).
FEBS Letters, 1991
Type‐1 inhibitor of plasminogen activators (PAI‐I) occurs in purified preparations in a latent fo... more Type‐1 inhibitor of plasminogen activators (PAI‐I) occurs in purified preparations in a latent form that can be activated with denaturants; in vivo, latency is prevented by binding to vitronectin. We have compared latent, denaturant‐activated and reactive centre‐cleaved human PAI‐1 with respect to thermal stability and affinity to monoclonal antibodies. By both criteria, latent and cleaved PAI‐1 are very similar or indistinguishable, and clearly different from active PAI‐1. Our findings suggest that the conformations of latent and reactive centre‐cleaved PAI‐1 are similar and resemble the so‐called relaxed (R) serpin conformation, while that of active PAI‐1 is different and resembles the stressed S serpin conformation.
Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1993
The latent form of type-1 plasminogen activator inhibitor (PAI-1) acquires inhibitory activity by... more The latent form of type-1 plasminogen activator inhibitor (PAI-1) acquires inhibitory activity by denaturation followed by refolding. We show here that the reactions of denatured/refolded PAI-1 with plasminogen activators are affected by low concentrations of SDS, which may remain after using SDS for denaturation. Without SDS, the active fraction of denatured/refolded PAI-1 comprised around 60%. Increasing SDS concentrations led to conversions to an inert form without inhibitory activity; then to a substrate form, that is being cleaved proteolytically in the reactive centre by the activators without complex formation, and finally to a second inert form. The first two conversions were associated with changes of the reactivity with monoclonal antibodies and of the thermal stability, respectively. Our results define clearly different interconvertible forms of denatured/refolded PAI-1, distinguish these from the latent and the reactive-centre-cleaved forms, and provide conditions for reproducibly producing reactive-centre-cleaved PAI-1 and PAI-1/activator complexes.
Avian Diseases, 2003
A one-tube reverse transcriptase/polymerase chain reaction coupled with an enzyme-linked immunoso... more A one-tube reverse transcriptase/polymerase chain reaction coupled with an enzyme-linked immunosorbent assay (RT-PCR-ELISA) was developed for the rapid detection of avian influenza virus (AIV) in clinical specimens. A total of 419 swab pools were analyzed from chickens experimentally infected with low-pathogenicity AIV, from wild aquatic birds, and from domestic ducks. The AIV was detected in 32 swab pools by RT-PCR-ELISA compared to 23 by virus isolation (VI) in embryonated specific pathogen free (SPF) chicken eggs. Thus, 39% more specimens were positive by RT-PCR-ELISA than by VI. Two of the twenty-three VI-positive specimens were negative when tested by RT-PCR-ELISA. The diagnostic sensitivity and specificity of the RT-PCR-ELISA was 91% and 97%, respectively, using VI in SPF eggs as the gold reference standard.
Archives of Virology, 2001
Acta Neurologica Scandinavica, 2009
Acta Neurologica Scandinavica, 1997
Acta Neurologica Scandinavica, 1997
Acta Neurologica Scandinavica, 1997
The Lancet, 1997
CCR-5 heterozygosity confers a higher probability of nonprogression during the first 3 years afte... more CCR-5 heterozygosity confers a higher probability of nonprogression during the first 3 years after seroconversion. Slow progressors have only a small increase in the frequency of CCR-5 heterozygosity relative to the general white population. This result can be easily biased due to the time period for non-progression selected or to genetic differences inherent in our cohort. A previous study of individuals infected by sexual transmission showed a maximum difference in disease progression between heterozygous and homozygous wild-type subjects between 10-12 years after seroconversion. 4 These results are consistent with the proposed role of CCR-5 as the major co-receptor for HIV-1 monocytotropic strains which are known to be more prevalent in infected individuals early in disease. Relative to heterozygotes, individuals homozygous for the wild type allele could support increased levels of viral replication and therefore might progress more rapidly to AIDS. The presence of the mutant allele may prevent efficient HIV-1 replication by a reduction in the number of available receptors. This effect may be amplified by secondary increases in the level of antiviral chemokine secretion. A lack of significant protection late in disease might suggest the evolution of viruses toward the use of alternative co-receptors, such as fusin. We thank the medical staff in hospitals and private practitioners who kindly collaborate with the GRIV project in France. This work was funded by Sidaction and by ARS (Association de Recherche contre le Sida).