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Biomedical subjects

M Munch

Publications and source records attributed to M Munch.

At least 19 recordsLinked to original sources

Serum levels of mannan-binding lectin in chickens prior to and during experimental infection with avian infectious bronchitis virus.

Mannan-binding lectin (MBL) is a glycoprotein and a member of the C-type lectin super family, the collectin family, and the acute phase protein family. The MBL exerts its function by directly binding to microbial surfaces through its carbohydrate recognition domains, followed by direct opsonization or complement activation via MBL-associated serine proteases (MASP)-1 and -2. Thus, MBL plays a major role in the first-line innate defense against pathogens. We investigated the MBL concentrations in serum during experimental infectious bronchitis virus (IBV) infections in chickens. The results showed that the acute phase MBL response to infection with IBV was, to a degree (P < 0.0068), dependent on whether the chickens were inoculated after 12 h of rest (dark) or after 12 h of activity (light). The acute phase response in chickens challenged after 12 h of activity peaked after 4.6 d with an increase of 24%, whereas the acute phase response in chickens challenged after 12 h of rest peaked after 3.1 d with an increase of 51%. The specific antibody titer against IBV was also tested, and a difference (P < 0.0091) between the two experimental groups was found with peak titer values of 6,816 and 4,349. However, the highest value was found in chickens inoculated after 12 h of activity. Thus, an inverse relation exists between the MBL response and the IBV specific antibody response. The ability of MBL to activate the complement cascade was tested in a heterologous system by deposition of human C4 on the chicken MBL/MASP complex. The complement activation was directly associated with the concentration of MBL in serum, indicating neutralization of the virus before the humoral antibody response took over.

Acute-Phase Reaction↗

Detection and subtyping (H5 and H7) of avian type A influenza virus by reverse transcription-PCR and PCR-ELISA.

Avian influenza virus infections are a major cause of morbidity and rapid identification of the virus has important clinical, economical and epidemiological implications. We have developed a one-tube Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) for the rapid diagnosis of avian influenza A. A panel of reference influenza strains from various hosts including avian species, human, swine and horse were evaluated in a one tube RT-PCR using primers designed for the amplification of a 218 bp fragment of the NP gene. The PCR products were detected by PCR-ELISA by use of an internal catching probe confirming the NP influenza A origin. The PCR-ELISA was about 100 times more sensitive than detection of PCR products by agarose gel electrophoresis. RT-PCR and detection by PCR-ELISA is comparable in sensitivity to virus propagation in eggs. We also designed primers for the detection of the influenza. A subtypes H5 and H7 shown to have pathogenic potential in poultry. The H5 primers cover the cleavage site of the HA gene and specifically amplify influenza A subtype H5. The H7 primers also cover the HA cleavage site and detected all H7 reference strains investigated. In addition, the H7 primers also amplified very weak and/or additional bands on an agarose gel from other subtypes. However, the H7 origin and the pathogenic potential defined by the presence or absence of basic amino acids at the cleavage site can be determined by sequencing of the PCR product. As far as we know this is the first demonstration of RT-PCR detection on a panel of H7 strains using only one primer set.

Animals↗

Molecular characterization of HERV-H variants associated with multiple sclerosis.

Our objective was to characterize retroviral sequences by RT-PCR with gag and env primers on RNA from RT-positive retroviral particles produced by multiple sclerosis (MS) derived B-lymphoblastoid cell lines. Sequence variants with high homology to the potentially functional subgroup RGH of the human endogenous retrovirus RTVL-H/HERV-H family were found. The same sequences were also specifically found in the particulate fraction of a series of MS patient plasma samples and were absent in controls. South-Western blots demonstrate the presence of a nucleic acid binding protein, corresponding in size and function to the nucleocapsid protein, Gag NC, of other retroviruses. We also present indications for transmission of the retrovirus to PHA-stimulated lymphocytes from healthy individuals.

B-Lymphocytes↗

Treatment of perforating collagenosis of diabetes and renal failure with allopurinol.

We present a case of widespread reactive perforating collagenosis in a 63-year-old woman undergoing haemodialysis after diabetic nephropathy, who was treated successfully with allopurinol. The patient responded well and rapidly to a dose of 100 mg allopurinol daily. It is suggested that more patients with reactive perforating collagenosis may benefit from allopurinol therapy.

Allopurinol↗

Epstein-Barr virus and multiple sclerosis.

It has been suggested that the Epstein-Barr virus (EBV) plays a role in the etiology of multiple sclerosis (MS), but individual epidemiologic studies have been inconclusive, in part because of the high prevalence of previous infection among individuals without MS. We conducted a systematic review of case-control studies comparing EBV serology in MS patients and controls. Eight published investigations were identified, including a total of 1,005 cases and 1,060 controls. The summary odds ratio of MS comparing EBV seropositive individuals with EBV seronegative individuals was 13.5 (95% CI = 6.3-31.4). The strength and consistency of this association and the high sensitivity and specificity of EBV serology suggest that these results are not readily explained by an aspecific immune activation among MS patients. These findings support a role of EBV in the etiology of MS.

Antibodies, Viral↗

The association between multiple sclerosis and infection with Epstein-Barr virus and retrovirus.

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 finding 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.

Antigens, Viral↗

The significance of Epstein-Barr virus seropositivity in multiple sclerosis patients?

The objective of this study was to evaluate and investigate the significance of the previously found 100% seropositivity toward Epstein-Barr virus (EBV) found in multiple sclerosis (MS) patients in contrast to healthy controls. Using a commercially available ELISA-test (Biotest), which differentiates infections with EBV into previous infections, primary infections, reactivated infections and no previous infection, we found 137 of 138 MS patients and 124 of 138 healthy controls seropositive. A primary infection in 4 of the 124 EBV seropositive healthy controls in contrast to no primary infections in the MS EBV seropositive group was significant (P=0.049652, Fishers exact test). This may be suggestive of a lack of primary infections in MS patients, and thus strengthens the idea that MS patients are infected with EBV before development of MS. Further studies are in progress to analyse whether EBV infection is a prerequisite for the development of this disease.

Adult↗

A single subtype of Epstein-Barr virus in members of multiple sclerosis clusters.

OBJECTIVES: Epidemiological studies strongly indicate an infectious involvement in multiple sclerosis (MS). Epstein-Barr virus (EBV), to which all multiple sclerosis patients are seropositive, is also interesting from an epidemiological point of view. We have reported a cluster of MS patients with 8 members from a small Danish community called Fjelsø. To further evaluate the role of EBV in MS we have investigated the distribution of EBV subtypes in cluster members and in control cohorts. MATERIALS AND METHODS: Blood mononuclear cells were isolated from cluster members, unrelated MS patients, healthy controls, including healthy schoolmates to the Fjelsø cluster patients and finally from persons with autoimmune diseases in order to investigate the number of 39 bp repeats in the EBNA 6-coding region in the EBV seropositive individuals. RESULTS: We observed a preponderance of the subtype with 3 39 bp repeats in the EBNA 6-coding region both in the MS patients and the healthy controls. In the Fjels cluster all 8 cluster members were harbouring this subtype, which is significantly different from the finding in healthy controls (n = 16), which include 8 schoolmates to the cluster members and 8 randomly selected healthy persons (Fischer's exact test P = 0.0047), and also compared to all non-clustered individuals studied (P = 0.017). CONCLUSION: Infection with the same subtype of EBV links together the 8 persons from the Fjelsø cluster who later developed MS. This finding adds to the possibility that development of MS is linked to infection with EBV.

Adult↗

Epstein-Barr virus strain characterization.

The Epstein-Barr virus (EBV), a ubiquitous human herpesvirus originally described in cultured lymphoblasts from African Burkitt's lymphoma, is the causative agent of infectious mononucleosis, but appears to be involved in the pathogenesis of a variety of diseases. EBV has the ability to establish lifelong persistent infection, where only a restricted pattern of the viral proteins is expressed. Periodic reactivation of EBV occurs, where mature EBV particles are produced. Strain variation is potentially important in the biology and epidemiology of EBV, and in attempts to relate EBV to associated diseases. Analysis of the EBV genomes isolated from patients with EBV-associated diseases and from various parts of the world has so far failed to identify conclusive disease-specific viral subtypes. This review focuses on the different strategies which have been used for strain characterization or subtyping of EBV.

Adaptation, Physiological↗

Serial changes in atrial natriuretic peptide and endothelin-1 concentrations. Their relationships to the cardiac performance of patients hospitalized for acute myocardial infarction.

AIM: The study was designed to assess temporal changes in atrial natriuretic peptide (ANP) and endothelin-1 (ET) concentrations in patients hospitalized for acute myocardial infarction (AMI) and their relationships to cardiac performance determined by radionuclide ventriculography. PATIENTS AND METHODS: 20 patients with first AMI were studied. Blood samples were drawn within the first 4-18 h, after 18-24 h, and on days 2, 3 and 6. Plasma concentrations of ANP and ET were measured in blood samples taken simultaneously. Radionuclide ventriculography was performed on the day of discharge to determine left-ventricular ejection fraction (LVEF), left-ventricular end-diastolic volume index, end-systolic volume index and left-ventricular stroke volume index. RESULTS: Median concentrations of ET decreased from 2.15 pmol/l on admission to 1.45 pmol/l at discharge (32%, p < 0.001). Median ANP rose from 29 to 79 pg/ml (172%, p < 0.001). The increment in ANP and the decrease in ET concentrations from admission to discharge was inversely correlated (r = -0.81, p < 0.005). ANP was inversely correlated to LVEF (r = -0.82, p < 0.001) and to the end-systolic volume index at discharge (r = -0.73, p < 0.003). CONCLUSION: Dynamic and inverse fluctuations in ET and ANP occur within the 1st week of AMI. The magnitude of endocrine activation in the ANP-ET system seems to reflect an impairment in the left-ventricular systolic performance.

Atrial Natriuretic Factor↗

[Changes among residents in homes for the aged in Bergen between 1985-96].

Homes for the aged are intended for elderly people who, by and large, are able to perform basic activities of daily living (ADL) on their own, but who, in spite of this, need or wish to live in an institutional setting, where only minor nursing facilities are available. The present study focuses on the changes in mental capacity and in the altered need for nursing assistance with ADL functions which developed among residents at 13 homes for the aged in the city of Bergen, between 1985 and 1996. In 1985, the average age for residents was 84 years; and in 1996 it was 87 years. The average duration of stay was 30 and 38 months, respectively. There was a significant increase in the proportion of mentally impaired residents (28% and 35%). There was also an increase in the percentage in need of intensive nursing care (34% and 41%). The changes in residents living in the homes were not caused by dementia. It is concluded that homes for the aged are used increasingly for elderly in need of nursing care. There is an obvious mismatch between tasks and resources.

Activities of Daily Living↗

[Prevalence of left ventricular hypertrophy in Danish patients with hypertension].

The aim of this investigation was to study the prevalence of left ventricular hypertrophy (LVH) in a hypertensive population with reference to a normotensive control group. From the general population, 3498 men and women aged 35, 45, 55 and 65 years old were invited to a health examination. Participants with blood pressure above 160 mmHg systolic and/or 95 mmHg diastolic or participants currently taking antihypertensive medication or having done so during the previous six months were asked to undergo an echocardiographic examination. Controls were randomly selected from the same population. Of 552 participants in the final study population, 194 were normotensive controls and 358 were in the hypertensive group. Echocardiographic measurements were made according to the "Penn" conventions and indexed for body surface. Cutoff values for LVH were 134 grams per m2 for males and 102 grams per m2 for women. Overall, we found that the prevalence of 1 VH was 14%/20% (men/women) in normotensives and 25%/26% in hypertensives (p < 0.01). By subdivision in age and sex groups we found that the relation between normotensives and hypertensives was significant in the age group of 65 years (p < 0.02 for males and p < 0.05 for females). The association between blood pressure and 1 VH in the general population is weak. 1 VH is only significantly more frequent among hypertensives as compared to normotensives in older people.

Aged↗

Sequence analysis of the Epstein-Barr virus (EBV) latent membrane protein-1 gene and promoter region: identification of four variants among wild-type EBV isolates.

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 LMP-1 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 and the 30-bp deletion, indicate that they cannot be used as simple markers for oncogenic viruses related to particular forms of EBV-associated tumor. Several of the structural changes detected occur, however, at sites where they may affect transcription, translation, or function of LMP-1. Future in vitro studies should aim to establish the functional importance of variations at these sites.

Amino Acid Sequence↗

Characterization of retroviruses from patients with multiple sclerosis.

These studies were performed to characterize retroviruses found in cell lines spontaneously developed from peripheral blood mononuclear cells (PBMNC) from 6 multiple sclerosis patients, a patient with progressive myelopathy and a healthy control. The cell lines are B-lymphoblastoid and produce Epstein-Barr virus (EBV) particles or express EBV proteins. The B-lymphoblastoid cell lines are also characterized by production of low, fluctuating amounts of retrovirus. The low productivity complicates purification and characterization, but implementation of product-enhanced reverse transcriptase (PERT) assays has provided a highly useful tool for monitoring retrovirus production. By electron microscopy, the retroviral particles appear type-C-like. Functional assays indicate the presence of Pol, Gag and Env. Indirect ELISA demonstrates a significant relation between disease activity and reactivity towards retroviral peptides. Molecular characterization is primarily based on RT-PCR, cloning, sequencing and Northern- or Southern analyses. Molecular characterization is continuing.

Autoantigens↗

The implications of Epstein-Barr virus in multiple sclerosis--a review.

The objective of this article is to bring together knowledge about Epstein-Barr virus (EBV) in relation to multiple sclerosis (MS) in order to evaluate its implications in this disease. All MS patients are EBV seropositive, but EBV is not normally detected in the brain. EBV can explain many of the epidemiological dogmas known in MS. In addition, other studies point towards the involvement of EBV in MS. Despite this, other co-actors seem also to be involved. We still need to know whether EBV may be an initiating factor in MS or whether it is a factor in the pathogenesis. Possible ways of EBV involvement are discussed: direct involvement, an autoimmune inducing factor or a transactivating factor. A current treatment study of MS patients with a specific herpes antiviral drug may add further information to the etiology and pathogenesis of MS.

Autoimmune Diseases↗

Prevalence of left ventricular hypertrophy in a hypertensive population.

AIMS: This investigation was set up to study the prevalence of left ventricular hypertrophy in a hypertensive population with reference to a normotensive control group. From the general population 3498 men and women aged 35, 45, 55 and 65 years old were invited to a health examination. Participants with blood pressure above 160 mmHg systolic or 95 mmHg diastolic or those taking antihypertensive medication or having done so during the previous 6 months were asked to undergo an echocardiographic examination. Normotensive controls were randomly selected from the same population. Of 552 participants in the final study population, 194 were normotensive controls and 358 were in the hypertensive group. Echocardiographic measurements were made according to the Penn conventions and indexed for body surface. Cut-off values for left ventricular hypertrophy were 134 g.m-2 for males and 102 g.m-2 for women. RESULTS: Overall, the prevalence of left ventricular hypertrophy was 14%/20% (men/women) in normotensives and 25%/26% in hypertensives (P < 0.01). After subdivision by age and sex, there was a significant difference in the prevalence of left ventricular hypertrophy between normotensives and hypertensives only in the 65-year-old group (P < 0.02 for males and P < 0.05 for females). CONCLUSIONS: The association between blood pressure and left ventricular hypertrophy in the general population is weak. Left ventricular hypertrophy is only significantly more frequent among hypertensives as compared to normotensives in older people.

Adult↗

[Paraquat poisoning. Treatment and prognosis].

Treatment of paraquat intoxication is most often in vain if initial treatment is delayed. We report a case where the patient was admitted 25 hours after oral intake of paraquat. The patient died due to respiratory insufficiency secondary to peroxidative pulmonary fibrosis in spite of combined continuous haemodialysis and haemofiltration. Principles of treatment are reviewed.

Adult↗