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Biomedical subjects

M Bruns

Publications and source records attributed to M Bruns.

At least 19 recordsLinked to original sources
PubMed1998

Induction of protective cytotoxic T cell responses in the presence of high titers of virus-neutralizing antibodies: implications for passive and active immunization.

The effect of preexistent virus-neutralizing antibodies on the active induction of antiviral T cell responses was studied in two model infections in mice. Against the noncytopathic lymphocytic choriomeningitis virus (LCMV), pretreatment with neutralizing antibodies conferred immediate protection against systemic virus spread and controlled the virus below detectable levels. However, presence of protective antibody serum titers did not impair induction of antiviral cytotoxic T lymphocyte (CTL) responses after infection with 10(2) PFU of LCMV. These CTLs efficiently protected mice independent of antibodies against challenge with LCMV-glycoprotein recombinant vaccinia virus; they also protected against otherwise lethal lymphocytic choriomeningitis caused by intracerebral challenge with LCMV-WE, whereas transfused antibodies alone did not protect, and in some cases even enhanced, lethal lymphocytic choriomeningitis. Against the cytopathic vesicular stomatitis virus (VSV), specific CTLs and Th cells were induced in the presence of high titers of VSV-neutralizing antibodies after infection with 10(6) PFU of VSV, but not at lower virus doses. Taken together, preexistent protective antibody titers controlled infection but did not impair induction of protective T cell immunity. This is particularly relevant for noncytopathic virus infections since both virus-neutralizing antibodies and CTLs are essential for continuous virus control. Therefore, to vaccinate against such viruses parallel or sequential passive and active immunization may be a suitable vaccination strategy to combine advantages of both virus-neutralizing antibodies and CTLs.

Animals↗
PubMed1998

Enhancement of hepatitis B virus infection by noninfectious subviral particles.

The biological function of the huge excess of subviral particles over virions in hepatitis B virus infections is unknown. Using the duck hepatitis B virus as a model, we unexpectedly found that subviral particles strongly enhance intracellular viral replication and gene expression. This effect is dependent on the multiplicity of infection, the ratio of virions over subviral particles, and the time point of addition of subviral particles. Most importantly, we show that the pre-S protein of the subviral particles triggers enhancement and requires the presence of the binding regions for putative cell-encoded virus receptor proteins. These data suggest that enhancement is due either to the recently described transactivation function of the pre-S protein or to signalling pathways which become activated upon binding of subviral particles to cellular receptors. The findings are of clinical importance, since they imply that infectivity of sera containing hepadnaviruses depends not only on the amount of infectious virions but also decisively on the number of particles devoid of nucleic acids. A similarly dramatic enhancing effect of noninfectious particles in other virus infections is well conceivable.

Animals↗
PubMed1997

Protection of mice by an attenuated variant against the wild-type lymphocytic choriomeningitis virus.

L cells persistently infected with strain Armstrong lymphocytic choriomeningitis virus generated a variant which failed to develop the lethal neurologic disease after application to the brain. This virus was able to protect mice from the fatal consequences when inoculated intracerebrally prior to challenge with wild-type (wt) virus. After infection of mice with the attenuated variant and thereafter with the wt virus, production of the latter was extraordinarily reduced. As expected, virus elimination was finally achieved by cytotoxic T lymphocytes, whose activation was accelerated. Furthermore, two events seem to play an important part in this enhanced virus reduction. First, from the beginning of the infection with wt virus, neutralizing antibodies could be noticed. The second observation was an excessive production of interferon-alpha 1 day after the challenge infection.

Animals↗
PubMed1996

Novel fibroblast-specific monoclonal antibodies: properties and specificities.

Specific detection of fibroblasts has been one of the unsolved problems in cell biology. Because monoclonal antibodies (MoAbs) might provide an easy and reproducible method of fibroblast detection, we have produced a panel of MoAbs raised against cell surface proteins of human dermal fibroblasts. Using flow cytometry and immunohistochemistry, we have shown that two of these MoAbs, FibAS01 and FibAS02, react exclusively with human fibroblasts. They do not react in vitro with human keratinocytes, endothelial cells, or blood cells. Immunohistologic experiments investigating the binding pattern of the MoAbs FibAS01 and FibAS02 in cryostat sections of different tissues confirmed the flow cytometric results. In human skin, the antibodies exclusively labeled fibroblasts. In other human tissues such as lymph nodes, placenta, kidney, muscle, thyroid gland, gall bladder, cartilage, and tendon, the specificity for fibroblasts was borne out. Neither antibody reacts with fibroblasts from mouse, rat, or pig. The isotype was defined as an IgG1 for both. By western blot analysis, both antibodies detected a molecule of 60-65 kDa under reducing and nonreducing conditions. By immunoelectron microscopy, we observed the antigens on the cell surface without any clustering at specific sites. These data demonstrate that the two MoAbs, FibAS01 and FibAS02, exclusively recognize human fibroblasts.

Animals↗
PubMed1995

Skin fibroblasts are the only source of nidogen during early basal lamina formation in vitro.

The purpose of this study was to determine whether nidogen, the linkage protein of the basal lamina, is of epidermal or dermal origin. The development of the basal lamina was studied in an in vitro skin model. Preputial fibroblasts seeded onto a nylon mesh attached, proliferated, and developed a rich extracellular matrix (dermal model). Preputial keratinocytes were added to the dermal model to form a keratinocyte dermal model that ultrastructurally resembled in many respects human skin. Ultrastructural analysis revealed early stages of dermal development, including an incomplete basal lamina, aggregates of dermal filamentous material connecting to the lamina densa, bundles of 10-nm microfibrils, formation of premature hemidesmosomes, anchoring filaments, and anchoring fibrils. The cell origin of nidogen was determined in the dermal model and in the epidermal and dermal components of the keratinocyte dermal model. Specific antibodies and a cDNA probe for nidogen were used for immunofluorescence microscopy, Western and Northern blots, and for in situ hybridization studies. Our data show that fibroblasts are the only source of nidogen during early basal lamina formation. Although fibroblasts can synthesize nidogen and deposit it in the dermal matrix, no basal lamina will form unless they are recombined with keratinocytes. This suggests that the epidermis plays a major regulatory role in the production and assembly of nidogen into the basal lamina.

Basement Membrane↗
PubMed1994

Characterization of a virus variant produced by L cells persistently infected with lymphocytic choriomeningitis virus.

Continuous cultivation of murine L cells infected with lymphocytic choriomeningitis virus strain Armstrong leads to production of L(Arm) cells, which produce a predominantly cell-associated attenuated variant, the L(Arm) virus. The relatively few infectious particles that are released have lost the ability to form plaques on L cells and to cause illness in mice even if inoculated intracerebrally. Based on equal protein M(r)s, antigenicity and protein kinase activity, essentially identical results were obtained for the purified Armstrong and L(Arm) viruses. There was also no difference in production and release of particles with the potential to cause homologous interference. Such particles consisted of two types, one of which was highly susceptible to u.v.-irradiation, the other was highly resistant. In the case of the L(Arm) virus interfering particles, it appears that the u.v.-irradiation-susceptible forms represented infectious virus. Purified L(Arm) virus particles contained considerable quantities of subgenomic forms of (small) S- and (large) L-RNA and their complementary counterparts, which all appeared to be replicated autonomously in an unenriched manner.

Animals↗
PubMed1994

Immunologic parameters in systemic sclerosis.

BACKGROUND: Immunologic abnormalities seem to play an important role in important role in systemic sclerosis (SSc). METHODS: We studied the following immune parameters to get more insight into SSc: autoantibodies (antinuclear antibodies (ANA), anti-Scl-70, anticentromere antibodies (ACA) subsets of lymphocyte subpopulations and markers of their activation, as well as serum levels of IL-2, the soluble IL-2 receptor (SIL-2R), IL-6 and its correlation to N-terminal procollagen-III propeptide (P III P), and finally, the IL-6 production by SSc and normal dermal fibroblasts. RESULTS: In patients with active SSc, we found a reduced number of CD2+ T-lymphocytes and an increase in the expression of T-lymphocyte activation markers such as CD25+ and CD71+, HLA-DR Ia, as well as elevated serum levels of SIL-2LR and IL-6. SSc fibroblasts did not produce more IL-6 than normal fibroblasts in monolayer cultures. CONCLUSIONS: Our data show that a wide range of immunologic parameters are altered in SSc. In general, T-helper (TH) lymphocytes are activated possibly because of reduced T-suppressor (TS) and natural killer (NK)-cell levels. TH may polyclonally stimulate B cells, which in turn produce higher amounts of autoantibodies. Our findings support the concept that TH cell-derived cytokines/growth factors stimulate matrix protein synthesis by fibroblasts, resulting in generalized fibrosis.

Adolescent↗
PubMed1994

Intranasal sphenoethmoidectomy: an evolution of technique.

Intranasal sphenoethmoidectomy was originally used primarily for the provision of adequate drainage of acute and subacute bacterial sinusitis. However, the spectrum of inflammatory sinus disease has changed dramatically since the popularization of broad-spectrum antibiotics, and chronic hyperplastic rhinosinusitis has replaced acute sinusitis as the primary indication for ethmoidectomy. In such cases total or almost total disease removal is crucial to providing long-term drainage and ventilation. We describe several modifications of the Yankauer sphenoethmoidectomy technique that enable the sinus surgeon to provide clearance of disease and excellent drainage for all sinuses by complete marsupialization of the sphenoid, ethmoid, and maxillary sinuses. These modifications include (1) complete rather than partial removal of the middle turbinate, (2) extended middle meatal antrostomy with palatine bone resection to the pterygoid process with delineation of the inferior and medial orbital wall, and (3) introduction of operative endoscopes as adjunctive tools in areas inaccessible to conventional visualization. The current technique and results in nearly 2000 procedures are described.

Chronic Disease↗
PubMed1993

Decrease in peritonitis rate by integrated disconnect system in patients on continuous ambulatory peritoneal dialysis.

The prevention of peritonitis is of major concern for successful long-term continuous ambulatory peritoneal dialysis (CAPD) treatment. The effect of a Y-system on peritonitis incidence and patient morbidity was observed in a comparative, retrospective single-center analysis over a period of 5 years. The integrated disconnect system prolonged the peritonitis-free period from 1:11 patient-months, observed with the conventional system, to greater than 1:50 patient-months. The rate of hospitalization was reduced by 45%.

Humans↗
PubMed1990

Virus-specific delayed-type hypersensitivity (DTH). Cells mediating lymphocytic choriomeningitis virus-specific DTH reaction in mice.

We had previously shown that the local lymphocytic choriomeningitis virus-induced delayed-type hypersensitivity (DTH) reaction in mice consists of two well delineated phases that are mediated by CD8+ and CD4+ T lymphocytes, respectively. These findings have been confirmed and extended by showing that the first CD8+ cell-dependent part of the response was enhanced by either the presence of CD4+ cells or systemic treatment with IL-2 and that it developed in the absence of detectable numbers of mononuclear phagocytes, whereas the later CD4+ cell part required monocytes or related elements. Furthermore, in the DTH reaction that was elicited with noninfectious viral Ag in mice previously immunized by infection, only the CD4+ cells participated. Thus, the two phases of the lymphocytic choriomeningitis-viral DTH reaction are principally different, which has to be taken into account when trying to assess the relevance of DTH during this virus infection.

Animals↗
PubMed1990

Mode of replication of lymphocytic choriomeningitis virus in persistently infected cultivated mouse L cells.

During persistent infection of mouse L cells with strain Armstrong lymphocytic choriomeningitis virus, the latter undergoes characteristic changes, including loss of mouse pathogenicity and failure to form plaques on cultivated cells. We call this virus L(Arm) and have analyzed transcription and translation of its S-RNA, which codes for the viral nucleoprotein (NP) and the glycoprotein precursor (GP-C). In L(Arm) virus-infected L cells, S-RNA and genomic-sized viral complementary S-RNA (VC-S-RNA) were detected and, in addition, considerable quantities of shortened molecules of either species. The cells' content of NP was high, but they contained little GP-C; instead, a viral glycoprotein with MW 65,000 was present. We propose a hypothesis in which it is assumed that along the VC-S-RNA there is more than one recognition site for the viral RNA-dependent RNA polymerase, which leads to the generation of truncated forms of S-RNA, VC-S-RNA, and mRNA for GP-C; this, in turn, results in relative overproduction of NP and relative underproduction of GP-C as well as the emergence of a new form of viral glycoprotein.

Animals↗
PubMed1990

Effect of rimantadine on cytotoxic T lymphocyte responses and immunity to reinfection in mice infected with influenza A virus.

Administration of rimantadine to mice via drinking water, following a prophylactic dose, reduced lung virus titers by greater than 3 log10 plague-forming units (pfu)/ml but caused only marginal reductions in lung virus titers when therapy was started 8 h after exposure to virus. Mice given rimantadine prophylactically plus therapeutically were resistant to rechallenge with virus at a dose equivalent to that used for the primary infection (50 pfu/mouse) but not to a high dose (1 x 10(5) pfu/mouse). Virus-neutralizing-antibody titers were reduced only by rimantadine treatment, which included prophylaxis, whereas the cytotoxic T lymphocyte (CTL) response was depressed by treatment given with or without prophylaxis. Mice infected with rimantadine-resistant virus had no decrease in CTL or antibody responses when treated with rimantadine. Therefore, the depression in CTL and antibody responses associated with rimantadine treatment appears to be due to a decrease in the amount of viral antigen available or interference with viral antigen processing and not to nonspecific immunosuppressive effects.

Adamantane↗
PubMed1989

Efficacy of rimantadine hydrochloride in the treatment of influenza infection of mice.

Rimantadine HCl was assessed for its effect on influenza A virus titer in lungs of infected BALB/c mice. Rimantadine administered orally via drinking water, with and without an intraperitoneal prophylactic loading dose, was compared to intraperitoneal administration. Mice were infected with a non-lethal dose of influenza A/Port Chalmers/H3N2 virus and the pulmonary virus titers were determined at intervals over a 21 day period. Prophylactic treatment with rimantadine followed by oral administration resulted in up to a 4 log10 reduction in pulmonary virus titer. The oral doses given to the mice were comparable on a mg/kg/day basis to those recommended for treatment of human infections. Reductions in pulmonary virus titers also occurred after intraperitoneal rimantadine treatment which included a prophylactic dose, but the reductions in pulmonary virus titers were less striking and not consistent over the course of infection. There were no significant reductions in pulmonary virus titers by either route if treatment was started 8 h after exposure to virus.

Adamantane↗
PubMed1988

Host cell-dependent homologous interference in lymphocytic choriomeningitis virus infection.

The generation of virus progeny as well as transcription, translation, and replication of the viral small RNA (S-RNA), which codes for the nucleoprotein (NP) and the glycoprotein precursor (GPC), was followed in L and MDCK cells after infection with multiplicities (m.o.i.) ranging from 0.01 to 100. In L cells, the yields of both plaque-forming units and interfering particles varied inversely with the m.o.i. Northern blot analysis revealed that early after infection with high multiplicity NP-mRNA was present, but later few or no signals of any specificity were registered. After low m.o.i. the results were negative at 8 hr, but large quantities of mRNAs for NP and GPC as well as viral genomic S-RNA and genomic-sized complementary S-RNA had been synthesized at 48 hr. In MDCK cells, throughout the range of m.o.i. both entities attained lower levels and most were generated at m.o.i. one. The degree of hybridization correlated roughly with the quantity of infectious virus to which the cells had been exposed. In the cells of both lines the NP-mRNA corresponded to the synthesis of its translation product, but once produced, most of it appeared to be retained in the phosphorylated form. We assume that the homologous interference seen in L cells after infection with high m.o.i. results from a host-dependent inhibition of viral transcription and replication mediated by NP.

Animals↗
PubMed1988

Lymphocytic choriomeningitis virus. X. Demonstration of nucleoprotein on the surface of infected cells.

Of a total of 17 monoclonal antibodies (MAb) directed against structural proteins of the lymphocytic choriomeningitis (LCM) virus, 3 were specific for the viral nucleoprotein (p63) and attached to the plasma membrane of infected cells, as disclosed by the indirect immunofluorescence procedure and complement-mediated cytolysis. We had previously demonstrated that a portion of the nucleoprotein (p63E) was part of the envelope of the intact virion (M. Bruns, W. Zeller, H. Rohdewohld, and F. Lehmann-Grube (1986) Virology 151, 77-85), and we now show that after external iodination of virions followed by limited proteolysis the label was attached to the smallest peptide thus obtained. If purified nucleocapsids were labeled with 125I, digested as before, and incubated with an anti-p63 MAb that has the ability to bind the surface of the infected cell, a similarly small peptide was precipitated; an antibody specific for p63 but not recognizing it on the cell surface precipitated the largest peptide and failed to bring down the small one. We conclude that the epitopes complementary to a few of our anti-p63 MAb are represented on both the virion and the surface of virus-infected cells.

Antibodies, Monoclonal↗