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Biomedical subjects

J Ahlers

Publications and source records attributed to J Ahlers.

At least 19 recordsLinked to original sources
PubMed1999

HIV-specific immunity following immunization with HIV synthetic envelope peptides in asymptomatic HIV-infected patients.

OBJECTIVE: A phase I trial was conducted to evaluate the safety and immunogenicity of an HIV synthetic peptide vaccine in HIV-seropositive individuals. The immunogens used in this study were PCLUS 3-18MN and PCLUS 6.1-18MN envelope peptides. METHODS: Eight HIV-infected patients received six subcutaneous injections of 160 microg PCLUS 3-18MN in Montanide ISA 51 and were followed longitudinally for a year after the first immunization. Peripheral blood mononuclear cells (PBMC) were tested for peptide-specific T helper and cytotoxic T cell (CTL) responses, HIV-1MN neutralizing antibodies and antibodies against HIV PCLUS 3 and P18 MN peptides. RESULTS: PCLUS 3-1 8MN-specific T helper responses were significantly increased at 36 weeks (P < 0.05, after adjustment for multiple comparisons) following initial immunization with PCLUS 3-18MN. A P18MN-specific CTL response, not present prior to vaccination, was observed after immunization in one patient. Serum HIV-1 MN-neutralizing antibody titers increased in each of the three patients who had low titers prior to immunization. Plasma HIV RNA levels and CD4 cell counts did not change appreciably during the study period. CONCLUSIONS: This trial demonstrates that both peptides can be safely administered to HIV-infected individuals and that PCLUS 3-18MN induces increases in HIV peptide-specific immune responses.

AIDS Vaccines↗
PubMed1998

Definition of T cell epitopes within the 19 kDa carboxylterminal fragment of Plasmodium yoelii merozoite surface protein 1 (MSP1(19)) and their role in immunity to malaria.

MSP1(19) is one of the leading malaria vaccine candidates. However, the mechanism of protection is not clear. To determine whether MSP1(19)-specific effector T cells can control parasitaemia, we analysed the specificity of T cells induced following immunization with recombinant forms of P. yoelii MSP1(19) and asked whether they could protect mice. There was no evidence that effector T cells were capable of protecting since: (1) immunization of mice with yMSP1(19), but not defined epitopes, was able to induce protection; and (2) long term MSP1(19)-specific CD4+ T cell lines were incapable of adoptively transferring protection. In contrast, priming mice with the T cell epitopes resulted in a rapid anamnestic antibody response to MSP1(19) after either challenge with MSP1(19) or parasite. Thus, MSP1(19) contains multiple T cell epitopes but such epitopes are the targets of helper T cells for antibody response but not of identified effector T cells capable of controlling parasitaemia.

Adoptive Transfer↗
PubMed1996

Genetic regulation of protective immune response in congenic strains of mice vaccinated with a subunit malaria vaccine.

The C-terminal 19-kDa, epidermal growth factor-like region of the merozoite surface protein 1 (MSP1) has been used as a vaccine to induce protective immunity to Plasmodium yoelii in mice and to Plasmodium falciparum in monkeys. To analyze the mechanisms and genetic regulation of this MSP1 vaccine-induced protection, we studied the immunologic correlates of protection in H-2 recombinant and congenic mouse strains on the B10 background. Multiple H-2-linked loci were found to contribute, each with a different mechanism. One locus mapped to the I-A region based on the strong protection in C57BL/10 mice compared with intermediate protection in B10.A(4R) mice and the lack of a difference between B10.AKM and B10.MBR mice. Differences in efficacy of passively transferred antisera from vaccinated C57BL/10 vs B10.A(4R) mice indicated that the protection regulated by the I-A locus was at least in part Ab dependent. Two loci mapped to the right of I-A (FE, H-2S, or H-2D) based on a correlation with the number of H-2k loci to the right of I-A in mice that were I-Ak. One effect was Ab independent and may correspond to a possible negative effect of the I-Ek locus. T cells from protected and nonprotected strains differed in their production of IFN-gamma and TNF-alpha following immunization with MSP1(19), but it was unclear how the differential patterns of cytokine expression related to the level of protection. Thus, MSP1(19) vaccine-induced protection is regulated by H-2-linked loci corresponding to two different immune mechanisms. These findings may indicate the need for more than one Ag in a vaccine to protect an HLA-diverse population.

Animals↗
PubMed1995

Assessment of structurally related chemicals: toxicity and ecotoxicity of acrylic acid and acrylic acid alkyl esters (acrylates), methacrylic acid and methacrylic acid alkyl esters (methacrylates).

BUA compiled the available data on toxicity and ecotoxicity for several acrylic and methacrylic acid esters and their corresponding acids. A comparison of these data revealed a qualitative similarity in the toxicological and ecotoxicological properties of the compounds considered. The data indicate that methacrylates are less reactive than the corresponding acrylates.

Acrylates↗
PubMed1994

Helper-cytotoxic T lymphocyte (CTL) determinant linkage required for priming of anti-HIV CD8+ CTL in vivo with peptide vaccine constructs.

CTL are a critical component of protective immunity against viral infections, but requirements for in vivo priming of CTL are not completely understood. Covalent linkage of a helper determinant to a CTL determinant, analogous to that required for cognate help for antibody production, does not appear to be necessary in vitro, but its necessity has not been extensively explored in vivo, especially at a molecular level. We previously defined peptides encompassing multideterminant regions of HIV-1 gp160 (cluster peptides) recognized by Th from mice and humans of multiple MHC types. To investigate the requirement for Th in the development of CTL in vivo, in the context of developing a synthetic peptide vaccine for HIV active in multiple strains of mice, we immunized with compound peptides representing an immunodominant CTL epitope, P18, of gp160, co-linearly synthesized at the C-terminus of three cluster peptides. Spleen cells from compound-peptide-immunized mice of three MHC haplotypes sharing the Dd class I MHC molecule but with different class II molecules exhibited enhanced gp160-specific CD8+ CTL activity and CD4+ Th. In contrast, immunization with P18 alone or a mixture of cluster peptide and P18 elicited only marginal CTL activity. These results imply a requirement for determinant linkage in CTL induction in vivo similar to that already well recognized for cognate help for antibody induction. The results also define promising peptide HIV vaccine candidates for induction of CTL, as well as neutralizing antibodies, in diverse MHC types.

AIDS Vaccines↗
PubMed1993

[Treatment and results of ruptures of the patellar tendon].

Ruptures of the patellar ligament are rather uncommon. In younger individuals they are due to adequate trauma, in older individuals spontaneous ruptures occur after inadequate trauma. We observed eight traumatic (mean = 26.5 years) and eleven spontaneous ruptures (mean = 57.5 years) between 1980 and 1990. There is no alternative to surgical repair of the ruptured or torn-out patellar ligament. Tendon-repair with supportive wire-looping and early functional physiotherapy produces a good functional result. The outcome of patients treated in this manner shows persisting slightly muscular atrophy of minor degree and limited knee mobility with only a little all-day handicap.

Adult↗
PubMed1993

Osseous fixation of a penile prosthesis after transsexual phalloplasty: a case report.

We report on a patient who had undergone female-to-male transsexual surgery and subsequent phalloplasty by means of a free latissimus dorsi muscle graft with pudendal nerve coaptation elsewhere 10 years ago. The surgical strategy for implantation and osseous fixation of a penile prosthesis is described. We discuss whether the primary implantation of a penile prosthesis during 1-stage surgical phalloplasty is more advantageous in comparison with the currently favored secondary implantation. Phalloplasty should be represented by a 1-stage surgical procedure encompassing the creation of a neourethra, restoration of tactile and possibly erogenous sensibility, and implantation of a penile prosthesis. The result should have aesthetic value and be pleasing to the patient.

Adult↗
PubMed1993

An approach to development of specific T-lymphocyte lines by use of preprocessed antigens in Plasmodium vinckei vinckei murine malaria.

The development of parasite-specific T-cell lines represents one approach to the potential identification of relevant immunogens in erythrocytic malarial infection. However, the use of parasitized-erythrocyte lysates as antigens inhibits the proliferation of T cells. To circumvent this problem, we preincubated antigen-presenting cells (APCs) from spleens of malaria-naive, BALB/c mice with a Plasmodium vinckei vinckei (hereafter referred to as P. vinckei)-parasitized erythrocyte lysate. APCs were subsequently irradiated and washed prior to being incubated with T lymphocytes from P. vinckei-immune, histocompatible mice. After 8 to 10 cycles of antigenic stimulation and rest, two T-cell lines were analyzed. Both lines were predominantly CD4+. Proliferation assays demonstrated marked lymphocyte blastogenesis to syngeneic but not allogeneic APCs that had preprocessed malarial antigen. Antigen incubated directly with T cells and nonpulsed APCs in vitro did not result in T-cell proliferation. Assays of interleukin-2 (IL-2), IL-4, IL-5, and gamma interferon were compatible with one cell line being predominantly TH1 and the other being TH2. Thus, APCs that have preprocessed malarial antigen and are free of extraneous parasite material induce highly reactive, antigen-specific, major histocompatibility complex-restricted T-cell lines that functionally appear capable of inducing humoral and/or cell-mediated immunity.

Animals↗
PubMed1993

[The value of the radiologic Lachman test in anterior cruciate ligament ruptures].

A radiologic Lachman test of both knees was performed in 35 patients with surgically verified tears of the anterior cruciate ligament (ACL). We found a mean anterior drawer of 3.2 mm for uninjured joints, 4.5 mm for isolated ACL-tears and 10.8 mm for complex ACL-injuries. Sensitivity of the radiological Lachman test was 95% for complex ACL-injuries as only 23% in case of isolated ACL-ruptures. Failure of diagnosis due to clinical investigation in case of ACL-ruptures could not be proved by means of radiological Lachman-test. Technical requirements and radiation exposure are further disadvantages. Clinically doubtful cases of acute knee injuries should therefore be investigated with other diagnostic procedures.

Adolescent↗
PubMed1992

[Incidence and causes of malalignment following tibial intramedullary nailing].

After intramedullary nailing of the tibia a malpositioning is frequently seen. Incidence and cause are discussed controversially. We evaluated 386 postoperative radiographs after intramedullary nailing of the tibia. Type and location of the fracture, site of nail-insertion and postoperative axis-deviation were evaluated. Correlation-tests performed for these parameters proved significant correlation only between malpositioning in recurvation and height of nail-insertion at the tibial tuberosity. Especially proximal fractures of the tibia tended to this misplacement. Other assumed correlations could not be statistically confirmed in this retrospective analysis.

Female↗
PubMed1992

[MR tomography of injuries of the medial collateral ligaments of the knee joint].

Frequency and characteristics of lesions of the medial collateral ligaments (MCL) were studied by MRI in 155 patients with trauma to the knee. There were abnormalities of the MCL in 38% of cases with ligamentous injuries and in 27% these were combined with meniscal tears. 11% of these patients showed isolated rupture of MCL and as a result of the MRI findings were treated conservatively. By means of T2*-weighted images the individual lesions could be accurately localised. Characteristic findings have been defined.

Humans↗
PubMed1992

[Experimental trial of intraoperative spinal ultrasound].

Dorsal operative stabilization of spinal fractures by internal fixation is an established means of treatment directed at releasing the extrinsic compression of the intraspinal contents caused by the fractured posterior surface of the vertebral body. There are few ways of assessing how successful the repositioning is intraoperatively. Intraoperative ultrasound with a special small transducer is possible, but it is difficult to reach the intraspinal area by this means, because it is surrounded by bones. A laminectomy would destabilize the injured vertebral column even further. By experiments performed on six human vertebral columns we show that it is possible to view the entire length of the fractured posterior surface by ultrasound. The beam has to be projected between the laminae vertebrae following a small laminotomy. Preliminary intraoperative experiences with eight patients confirm our experimental results. The intraoperative ultrasound results have been confirmed by preoperative and postoperative CT. We expect the necessity for laminectomy for examination of the posterior surface of the vertebral body to decline in frequency in the near future.

Child↗
PubMed1991

[Simultaneous rupture of the patellar tendon and the contralateral quadriceps tendon in chronic kidney insufficiency].

Simultaneous ruptures of the patellar tendon and the contralateral quadriceps tendon, happening either spontaneously or with a preceding minor trauma, is a rare event especially in young patients. Major degenerative changes in the tendons' structure are most often a prerequisite for a trauma such as this. The reasons for these excessive pathological findings in tendon tissue structure can be chronic renal failure and resulting secondary hyperparathyroidism. The causal relationship will be discussed in front of a patients case history followed by a review of the relevant literature.

Adult↗
PubMed1991

Interaction with functional membrane proteins--a common mechanism of toxicity for lipophilic environmental chemicals?

1. The effects of several phenols, anilines and aliphatic alcohols on yeast plasma membrane H(+)-ATPase and purine transport system as well as on Na+, K(+)-ATPase and adenosine uptake by Chinese hamster ovary cells (CHO) were investigated. 2. In all cases an inhibition was observed, which could be correlated with the octanol/water partition coefficients of the substances tested, thus making quantitative structure-activity predictions possible. 3. The observed effects correlated well with the influence of the chemicals on cell growth. 4. The results suggest a common mechanism of toxicity by the action of hydrophobic xenobiotics on biomembranes.

Adenosine Triphosphatases↗
PubMed1991

Construction of peptides encompassing multideterminant clusters of human immunodeficiency virus envelope to induce in vitro T cell responses in mice and humans of multiple MHC types.

To make synthetic peptide vaccines effective in a broad population of outbred humans, one would have to incorporate enough antigenic determinants to elicit recognition by T cells of most HLA types. We have previously defined multideterminant regions of the human immunodeficiency virus (HIV) envelope that include overlapping determinants seen by proliferating T cells of three or four haplotypes of mice. We have now tested the hypothesis that synthetic peptides encompassing such multideterminant regions will be recognized by T cells of multiple murine MHC types as well as by human T cells representing multiple HLA types. Six such peptides of 20-33 residues in length were prepared, and tested for their ability to stimulate T cells from mice of four distinct MHC types immunized with recombinant envelope protein rgp 160, as well as from 42 HIV-infected humans of different HLA types. Results identify several such peptides that are broadly recognized by mice of four H-2 types and by 52-73% of infected humans who still retain IL-2 productive responses to control recall antigens such as influenza A virus or tetanus toxoid. 86% of such infected donors tested against at least three peptides respond to at least one of the six peptides, and 77% of an additional group of seropositives respond to a mixture of the peptides. Moreover, the peptides can be used to immunize mice to elicit T cells reactive with the intact HIV envelope protein. These peptides therefore may be useful for both vaccine development in the broad human population, and diagnostic or prognostic use.

Animals↗