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T Mertens

Publications and source records attributed to T Mertens.

At least 37 records · Page 2Linked to original sources
PubMed1996

DNA vector constructs that prime hepatitis B surface antigen-specific cytotoxic T lymphocyte and antibody responses in mice after intramuscular injection.

We tested the efficiency of induction of immune responses to the small hepatitis B surface antigen (HBsAg) in mice by intramuscular DNA immunization using different vector constructs that allow high levels of HBsAg expression in mouse cells. The HBsAg-specific responses of class I-restricted cytotoxic T lymphocytes (CTL) and of B cells (serum antibody titers) were measured. Following the intramuscular inoculation of 'naked' DNA, five different vector constructs of 4-8 kb, that contained or did not contain an intron and/or the neo gene, in which HBsAg expression was driven by promoter sequences derived from the immediate early region of HCMV, the SV40 enhancer/promoter region, or a retroviral 3' LTR efficiently primed responses of class I-restricted CD8+ CTL precursors. In contrast, the constructs in which HBsAg expression was driven by HCMV-derived promoter sequences stimulated significantly higher levels of HBsAg-specific serum antibody titers after intramuscular DNA injection than the SV40 or MPSV vector constructs. Large (15 kb) episomal vector constructs did not stimulate CTL or antibody responses. The data demonstrate that: (i) intramuscular DNA immunization represents an efficient technique for priming CTL and antibody responses to HBsAg; (ii) many vectors can be constructed that express an immunogenic product after intramuscular inoculation of 'naked' DNA; (iii) the efficiency of the tested vector constructs to prime after DNA immunization, either a CTL response, or an antibody response, differs.

Animals↗
PubMed1996

Reactivated fulminant hepatitis B virus replication after bone marrow transplantation: clinical course and possible treatment with ganciclovir.

A female chronic hepatitis B virus carrier (HBV-DNA negative) suffered from simultaneous hepatitis B virus and cytomegalovirus reactivation after in vivo T cell depletion preceding transplantation of an in vitro T cell depleted marrow graft for treatment of acute leukaemia. Interstitial pneumonia developing after bone marrow transplantation was successfully treated with ganciclovir (day 13 until day 46). The initially unnoticed extensive hepatitis B virus replication finally led to clinical hepatitis (day 85) and liver failure (day 96). Liver transplantation was performed, but the patient died from septicaemia. Retrospective analysis of hepatitis B virus DNA revealed that the HBV replication started immediately after T cell depletion and was completely suppressed during ganciclovir administration. Screening for HBV-DNA seems to be mandatory in comparable cases, and antiviral chemotherapy should be seriously considered.

Adult↗
PubMed1996

The UL97 gene product of human cytomegalovirus is an early-late protein with a nuclear localization but is not a nucleoside kinase.

The temporal expression of the UL97 gene product during human cytomegalovirus (HCMV) infection of human foreskin fibroblasts (HFF) and subcellular localization of this protein were analyzed by using a polyclonal antiserum raised against a truncated UL97 protein of 47 kDa. The UL97 protein was detectable 16 h after infection by Western blot (immunoblot) analysis. Since only reduced UL97 expression occurred in the presence of two inhibitors of DNA replication, phosphonoacetic acid and ganciclovir, we conclude that UL97 is an early-late gene, requiring DNA replication for maximum expression. By indirect immunofluorescence, the protein could be visualized in the nuclei of virus-infected HFF 22 h after infection. Nuclear localization of the UL97 protein was also detected in thymidine kinase-deficient 143B cells infected with a recombinant vaccinia virus containing the entire UL97 open reading frame (ORF), as well as in HFF transiently expressing the entire UL97 ORF under the control of HCMV major immediate-early promoter. However, transiently expressed 5'-terminal deletion mutants of the UL97 ORF in addition showed a cytoplasmic localization of the UL97 protein, confirming the presence of a nuclear localization site in the N-terminal region of the protein. Our high-pressure liquid chromatography analyses confirmed the ganciclovir phosphorylation by the UL97 protein, but no specific phosphorylation of natural nucleosides was observed, indicating that the UL97 protein is not a nucleoside kinase. During plaque purification of recombinant UL97-deficient HCMV, this virus was growth defective; hence, we presume that UL97 may be essential for the viral life cycle.

Amino Acid Sequence↗
PubMed1996

Myocarditis--cardiomyopathy. Consensus Report of the German Association for Internal Medicine, presented at the 100th annual meeting, Wiesbaden, 13 April 1994.

On the basis of several, partially divergent definitions, myocarditis-unlike the often aetiologically unexplained (idiopathic) cardiomyopathies (dilated, hypertrophic, restrictive)-can be classified as c specific disease of the myocardium. This disease often has a known cause and can be due to a large variety of aetiological agents (viral, autoreactive, toxic, infectious processes, etc.) (1). A question still to be answered is whether there is a connection between dilated cardiomyopathy and myocarditis, i.e. whether (virus-induced) myocarditis can progress via a subacute or chronic stage to dilated cardiomyopathy. This question is of considerable diagnostic and therapeutic relevance. The following consensus report thus deals with the clinically important problems related to the diagnosis of myocarditis and dilated cardiomyopathy, examines the aetiological role of immunological mechanisms and discusses the treatment of the two diseases and prognostic factors.

Cardiomyopathy, Dilated↗
PubMed1995

Male circumcision, sexually transmitted disease, and risk of HIV.

Our objective was to describe associations among male circumcision, behavioral and demographic variables, ulcerative and nonulcerative sexually transmitted disease (STD), and human immunodeficiency virus (HIV) infection via a cross-sectional study in Kigali, the capital of Rwanda. Our subjects were 837 married men who volunteered for HIV testing and counselling. Uncircumcised men had a relatively low-risk profile in that they reported fewer lifetime sexual partners and prostitute contacts than circumcised men and were more likely to live in rural areas with lower HIV prevalence rates. Uncircumcised men were also less likely to report a history of sexually transmitted disease (64% versus 73%, p = 0.01), although they were more likely to report genital ulceration (GUD) (24% versus 17%, p < 0.03) and to have inguinal adenopathy noted on physical exam (42% versus 29%, p = 0.009). Despite the low-risk profile, uncircumcised men had a higher prevalence of HIV infection than circumcised men (29% versus 21% HIV positive, p = 0.02), which was most marked in men reporting five or more lifetime sex partners (36% versus 23% HIV positive, p = 0.005) or contact with prostitutes (35% versus 23% HIV positive, p = 0.009). Circumcision remained a predictor of HIV infection in multivariate analyses (multivariate odds ratio 1.69, 95% confidence interval 1.16-2.47). Lack of circumcision is associated with a higher risk of HIV infection in Rwandan men. Further research is needed to determine whether this higher risk is due in part to poor hygiene or to complex mechanisms operating through the acquisition of other sexually transmitted diseases. Circumcision may be an appropriate risk reduction approach for men with known exposures to the virus when there are constraints to alternatives, such as condom use.

Adult↗
PubMed1995

Potties, pits and pipes: explaining hygiene behaviour in Burkina Faso.

Stool disposal practices have been shown to be associated with childhood diarrhoea. However, efforts to promote improved hygiene behaviour are hampered by a lack of understanding of what determines those behaviours. Data from 2793 household interviews with mothers of children from the town of Bobo-Dioulasso in Burkina Faso were analyzed to examine what differentiated mothers who reported using safer stool disposal practices from those who did not. Three 'outcomes' were considered: where the child was reported to defaecate; where the mother reported disposing of the child stools; and whether excreta were observed in the compound. Regression models were developed to identify those factors with the strongest independent associations with the outcomes. There was a consistent association between the source of water and the outcomes. Mothers with access to a tap in the yard reported using safe hygiene practices three times more often than mothers using wells outside the compound and twice as often as mothers who used public standpipes or wells within the yard. The source of water showed a similar pattern of association with observations of faecal matter in the environment. Improved sources of water may contribute to safer stool hygiene by reducing the time spent on water collection or by encouraging mothers to conform to higher standards of hygiene. Other factors which played a role in predicting the hygiene behaviour of mothers were the husbands' occupation, the number of health education sessions that she had attended, her zone of residence and family ownership of certain valuable objects. These factors are likely to be related and to be, to some extent, proxies for the real determinants of her behaviour. A model of the cultural, psycho-social and infrastructural proximate determinants of hygiene behaviour is proposed. Data from focus group discussions suggested that the main purpose of hygienic behaviour is to conform to existing norms of social etiquette. Trials of interventions based on changing such norms are needed to test whether this is an effective means of promoting of safer hygiene practices.

Burkina Faso↗
PubMed1995

Formation of differentiated tissues in vivo by periodontal cell populations cultured in vitro.

The periodontium contains heterogeneous mesenchymal cell populations with various differentiation potentials. The capacity of these cells for tissue formation as well as the origin of their precursors are still not entirely defined. In this study, cells originating from different periodontal tissues were cultured in vitro, and tissue formation in vivo following orthotopic re-implantation was investigated. Cells were recovered from the alveolar bone and periodontal ligament tissue of six minipigs, and cultured cells were then grown on extracted dental roots from the homologous animals by means of co-culture in vitro. Each minipig received 2 roots covered with alveolar bone cells, 2 roots covered with periodontal ligament cells, and 2 control roots (without cells) implanted into palatal bone defects. Intravital fluorochrome labeling was performed, and two minipigs were histologically examined after 2, 4, and 12 weeks in each case. Controls showed widespread resorption and ankylosis, whereas roots covered with cultured periodontal cells exhibited tissue formation in vivo. Alveolar bone cells synthesized a calcified cellular tissue resembling cellular cementum, suggesting that cells within this population might differentiate into cementoblasts when reimplanted with a dental substrate in vivo. Periodontal ligament cells exhibited no calcified tissue formation in vivo, but cells synthesized a connective tissue with orientated fiber bundles attached to both host bone and root, resembling periodontal ligament.

Alveolar Process↗
PubMed1995

In vivo/ex vivo T cell depletion for GVHD prophylaxis influences onset and course of active cytomegalovirus infection and disease after BMT.

Combined in vivo/ex vivo T cell depletion is effective in the prophylaxis of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT), but influences the occurrence of active cytomegalovirus (CMV) infection and disease. Twenty nine patients receiving a T cell-depleted marrow graft (Campath-1M) after intravenous application of the monoclonal antibody Campath-1G prior to conditioning were monitored for virus shedding and antigenaemia from day -7 to day +100. In seropositive patients in this group active CMV infection occurred more frequently (10 of 16) and much earlier (nine of 10 until day +21) than in 27 seropositive patients (10 of 27, P < 0.02) receiving cyclosporin A and methotrexate (CsA/MTX). Early active CMV infection after in vivo/ex vivo T cell depletion correlated strictly with an early increase in blood lymphocyte counts (P < 0.01), with predominance of NK cells and/or CD8+ T cells. Three cases of very early interstitial pneumonitis (IP) occurred after in vivo/ex vivo T cell depletion compared with none in the CsA/MTX group. IP was fatal in the only patient with early active CMV infection, who remained lymphocytopenic till death on day +31. This may indicate that an early immune response against CMV is possible and essential for favourable clinical outcome.

Adolescent↗
PubMed1995

[Risk factors in prematurity and intrauterine growth retardation in Burkina Faso].

A case-control study to investigate determinants of preterm delivery and intrauterine growth retardation (IUGR) in Bobo-Dioulasso, Burkina Faso, was conducted between December 1991 and November 1992. A total of 581 cases were recruited, 281 preterm infants with birthweight < 2500 g and 300 term infants with birthweight < 2500 g. 578 infants born at term with birthweights of 2500 g or more were recruited as controls. Logistic regression analyses identified three factors linked independently to both preterm delivery and IUGR: maternal illness during the pregnancy, nulliparity and failure to attend three antenatal consultations. In addition, primiparity and a maternal weight < 50 kg were associated with an increased risk of preterm delivery. Other factors associated with increased risk of IUGR were maternal height less than or equal to 155 cm, mid-upper arm circumference < 24 cm, and female sex of the infant. Improvements in the pre-pregnancy weight of women and in antenatal care focused on nulli- and primiparous women might in this population, reduce substantially the incidence of preterm delivery and IUGR.

Anthropometry↗
PubMed1995

Validating population surveys for the measurement of HIV/STD prevention indicators.

OBJECTIVE: To validate the World Health Organization/Global Programme on AIDS (GPA) protocol for measuring HIV/sexually transmitted disease prevention indicators pertaining to knowledge and sexual practices of the general population. METHODS: Data were collected in Uganda during 1993. Three different interview strategies were complemented with qualitative methods, including observations at visits and key-informant interviews. Two interview strategies consisted of structured questionnaires which were applied to 460 randomly selected people aged 15-49 years and 60 intentionally selected women who were known prostitutes. The third strategy involved in-depth interviewing and was applied to a random subset of all respondents (n = 75). RESULTS: The three interview strategies generated similar results for demographic characteristics. The strategies using structured questionnaires gave similar results with regards to the number of reported sex partners and the prevalence of condom use, but differed from in-depth interviews on these aspects. The high numbers of casual sex partners of female prostitutes was confirmed by in-depth interviews but not via the questionnaires. CONCLUSION: The GPA questionnaire may not be optimal to capture people at high risk and to assess sexual behaviour, especially of people at high risk. Nevertheless, the questionnaire provides the most realistic option, since in-depth interviews are expensive and not as objective in assessing trends over time. Evaluation studies of HIV interventions in the general population should therefore be complemented with small qualitative studies to detect and iron out biases in interpreting results.

Adolescent↗
PubMed1994

Sequence homology of the diabetes-associated autoantigen glutamate decarboxylase with coxsackie B4-2C protein and heat shock protein 60 mediates no molecular mimicry of autoantibodies.

Molecular mimicry between viral antigens and host proteins was often suggested to be involved in induction of autoimmune diseases. In type 1 diabetes where pancreatic beta cells are destroyed by autoimmune phenomena, a linear sequence homology between a major autoantigen, glutamate decarboxylase (GAD), and the 2C protein of coxsackie B4 was identified. In addition, a sequence homology between GAD and the mycobacterial heat shock protein 60 was described and the suggestions were made that molecular mimicry between GAD, coxsackievirus B4-2C protein, and/or heat shock protein 60 (hsp60) may be actively involved in an autoimmune reaction towards the pancreatic beta-cells. Our group was the first to isolate human monoclonal autoantibodies to GAD (MICA 1-6) from a patient with newly diagnosed type 1 diabetes. The MICA allowed a detailed characterization of the diabetes associated self-epitopes in GAD and represent a set of GAD autoantibodies present in sera from patients with type 1 diabetes. Using deletion mutants of GAD we demonstrated that the regions of GAD covering the homology sequences to coxsackievirus B4 and to the hsp60 were absolutely required for binding of the MICA to GAD. We now designed an antibody-based analysis to ask whether molecular mimicry between GAD and coxsackie B4-2C or hsp60 is relevant in type 1 diabetes. Since part of the MICA recognize conformational epitopes, they allow to test for conformational molecular mimicry in viruses that have been incriminated in the development of type 1 diabetes. Our data reveal no crossreactivity between the diabetes associated GAD epitopes defined by the MICA and hsp60, rubellavirus, cytomegalovirus, and coxsackie B1-B6 virus antigens. Neither coxsackie B4-specific antibodies in sera from normal individuals nor GAD-positive sera from patients with type 1 diabetes indicated a crossreactivity between coxsackie B4-2C and GAD. Although the regions in GAD homologous to coxsackie B4-2C and hsp60 represented parts of GAD indispensible for binding of diabetes associated autoantibodies they did not mediate a crossreactivity of autoantibodies between GAD and these two proteins. No evidence for molecular mimicry between GAD and a whole panel of foreign antigens was detected by autoantibodies in type 1 diabetes.

Amino Acid Sequence↗
PubMed1994

Identification of serotype-specific and nonserotype-specific B-cell epitopes of coxsackie B virus using synthetic peptides.

Coxsackie B viruses are thought to be involved in the induction of myocarditis. However, the diagnosis of acute infections by serology even today is practically impossible. The major problem is that no antigenic determinants of coxsackie B viruses have been identified or characterized which could be used as antigens in a rapid routine antibody screening test. Therefore, we synthesized overlapping peptides according to the sequence of the capsid protein VP1 of coxsackie B3 (CB3) virus in order to identify antigenic determinants located on VP1. Using sera raised against CB3 in mice, we were able to identify several antigenic determinants of CB3. Here we present a characterization of three epitopes found. We also tested the type-specificity of these antigenic determinants by using rabbit antisera against coxsackie viruses B1-B6. One antigenic determinant, peptide VP1-1, representing residues 1-15 of VP1, reacted highly type-specific for CB3. A second antigenic determinant (peptide VP1-3, residues 21-35 of VP1) reacted as well with the anti-CB3 sera as with the anti-CB4 sera. Therefore, the peptide VP1-3 seems to represent a non-type-specific antigenic determinant of coxsackie B viruses. Peptide VP1-24 (residues 229-243 of VP1) showed broad cross-reaction with anti-CB sera except with the anti-CB1 sera. This identification of type-specific and non-type-specific epitopes of coxsackie B viruses may provide the basis for the establishment of an effective and fast antibody screening test for coxsackie B viruses in patients with clinically suspected myocarditis.

Amino Acid Sequence↗