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Biomedical subjects

L Gürtler

Publications and source records attributed to L Gürtler.

At least 73 records · Page 4Linked to original sources

Evidence for an antigen-specific cellular immune response in skin lesions of patients with psoriasis vulgaris.

Psoriasis vulgaris is an inflammatory skin disease characterized by excessively increased keratinocyte proliferation. Several lines of evidence support the idea that T cells infiltrating psoriatic skin lesions play a vital role in the pathogenesis of the disease. To establish whether lesional accumulation and activation of T lymphocytes reflect a specific local immune response, the TCR beta-chain variable (V beta) region gene usage was studied in chronic psoriatic plaques, normal skin, and paired blood lymphocytes. By semiquantitative PCR, we found that overexpression of either or both V beta 2 and V beta 6 gene families characterized the TCR repertoires of normal skin and psoriatic skin lesions. However, sequence analysis of the complementarity-determining region 3 (CDR3) of these V beta gene families demonstrated a marked TCR oligoclonality only in psoriatic lesions, not in normal skin or in blood lymphocytes. The amino acid sequences of the lesional TCR clones revealed that certain conserved junctional motifs were shared by different patients. A second biopsy taken from one of the psoriasis patients 18 mo later from a different anatomical site disclosed that the same TCR clones were again dominating. These data suggest that lesional psoriatic T lymphocytes expressing the prevailing TCR V beta genes represent an oligoclonal T cell subset that expanded from a few progenitor T cells in response to Ag in the skin of psoriasis patients. They are derived from a polyclonal T cell population that, by the expression of V beta 2 or V beta 6 TCR, appears to be predisposed for homing to the skin.

Adolescent↗

Detection of specific human immunodeficiency virus IgM antibodies.

This study was done to demonstrate whether the use of the antigen-sandwich human immunodeficiency virus (HIV) antibody-screening assays (3rd generation assays), which detect all classes of anti-HIV immunoglobulins, leads to an earlier detection of HIV IgM compared to the 2nd generation HIV antibody-screening assays. We tested sequential bleeds of three donors obtained from commercially available seroconversion panels. Anti-HIV testing was done before and after high-performance liquid chromatography separation of IgG and IgM fractions. The positive result of the first bleedings from all three panels was linked to the IgM fraction, while at that time the IgG fraction was still negative. For subsequent samples drawn 5-9 days later, a positive signal was obtained with the IgG fraction in addition to a stronger positive signal obtained with the IgM fraction. We conclude that an assay capable of simultaneously detecting different immunoglobulin classes, including IgM, will help to narrow the "window period" for serological detection of seroconversion to HIV by detecting anti-HIV IgM-containing samples earlier than conventional assays using only anti-human IgG enzyme conjugates (indirect anti-HIV-screening assay, 2nd generation assays).

HIV Antibodies↗

Reduced CD21 (CR2) and CD54 (ICAM-1) expression in MT2 cells with HIV-1 or HIV-2 strains.

Alterations in the expression of cell-surface receptors have been reported in HIV-infected cells for CD4, CD25 (IL-2 receptor), CD2, CD3 and CD8 and CD26. In the present study we provide evidence that CD21 is down-regulated in the human T-lymphoblastoid cell line MT2 after infection with HIV-1 and -2 isolates. The same effect was observed with ICAM-1 (CD54). CD21 expression was monitored by means of fluorescence intensity, its functional ability to bind to C3d and by quantitative measurement of CD21-antigen in supernatants and cell lysates using an immunoassay. In addition, the decrease of CD21 and ICAM-1-specific mRNA suggests a mechanism at a transcriptional level. Our data suggest that HIV might have a direct influence on the receptor expression.

Cell Line, Transformed↗

[Allogeneic transplantation and HIV infection: studies of HIV-infected tissue].

BACKGROUND: Because of the limited availability of autologous tissue, stored allograft is commonly used. Before grafting, bank tissue is subjected to chemical preservation procedures. This procedure is important to diminish antigenicity and to inactivate possible inherent viruses. The aim of this study was to determine the influence of different chemical preservation procedures like Cialit, Merthiolate, and formaldehyde on the presence of HIV DNA. METHODS: HIV-infected tissues were obtained from eight HIV-positive patients and examined using the polymerase chain reaction (PCR). RESULTS: After chemical treatment, we could observe the presence of HIV DNA in all examined tissues. CONCLUSIONS: The findings indicate the importance of the mandatory serological screening and selection in donor patients.

Adult↗

Resistance of HIV type 1 to proteinase inhibitor Ro 31-8959.

During replication of human immunodeficiency virus type 1 (HIV-1), proteolytic cleavage of Gag and Gag-Pol precursor proteins into different functional protein subunits is catalyzed by the viral proteinase, and this enzyme is the target of the antiviral proteinase inhibitor, Ro 31-8959. We investigated in vitro which HIV mutants with reduced sensitivity to Ro 31-8959 emerged during proteinase inhibition treatment; from three different HIV-1 strains, comparable progeny virus resistant to proteinase inhibitor were found, whereas the same experimental protocol detected no resistant HIV-2 mutants. Molecular analysis of the mutations underlying resistance revealed a multistep mechanism in which an amino acid exchange was common to all resistant isolates, and in all experiments preceded further exchanges at position 90 (leucine to methionine) and/or at position 54 (isoleucine to valine). For wild-type strains the 90% inhibitory concentrations of Ro 31-8959 were close to 20 nM, whereas HIV-1 mutants with all 3 amino acid exchanges had more than 50-fold increased 90% inhibitory concentrations (above 1000 nM). The primary event (Gly-48 to valine) occurs at the hinge of the flaps of the proteinase, thus hampering entry of the inhibitor to the active center and suggesting steric hindrance. Detailed knowledge of this stereotypic process could open inhibitor design, thus preventing conceivable escape of resistant virus on proteinase inhibitor action.

Amino Acid Sequence↗

Absence of HIV-1 DNA in cartilage from HIV-positive patients.

Human immunodeficiency virus (HIV) infections are mainly transferred by blood, semen or organ transplantations. Since allogenic transplants have an established place in reconstructive surgery, the possibility of transferring HIV with such transplants has been a subject of much concern. Postmortem cartilage samples were obtained from eight HIV-infected patients and examined using the polymerase chain reaction in order to detect proviral HIV-1 DNA (gag, pol, env). Blood, brain and spleen samples were also obtained and used as positive controls. Results showed that no cartilage sample contained any HIV-DNA, whereas proviral sequences were clearly demonstrated in perichondrium from six patients. These findings indicate that HIV is not present in cartilage of HIV-infected patients, making HIV transmission through cartilage grafting improbable when transplants from HIV-negative donors are used.

Adult↗

Epidemiology and clinical manifestation of HIV infection in northern Zaire.

1275 patients were evaluated for HIV-1 + 2 seroprevalence and its association with clinical symptoms of HIV infection. Of 667 apparently healthy subjects, 8.2% had anti-HIV-1 antibodies. In 465 patients with clinical signs of AIDS, 39.4% were seropositive. 143 patients with miscellaneous symptoms had positive predictive values for HIV infection between 67% (vaginal ulcerations) and 20% (profound pyogenic abscesses). The WHO definition for AIDS had a specificity of 78.3%, a sensitivity of 72.2% and a predictive value of 61.6%.

Adult↗

Blood-borne viral infections.

The selection of blood donors and the introduction of tests identifying virus-infected donors has led to a permanent increase in the safety of blood transfusion. In most European countries, there is a low risk of infection from viruses such as hepatitis B virus, hepatitis C virus and human immunodeficiency virus. Examples of viruses that pose a risk to children but not adults following transfusion-transmitted infection are parvovirus B19 and cytomegalovirus. Other viruses may be transmitted in the blood but, because of their low pathogenicity and high prevalence, they are not relevant for transfusion. Further work is required to determine the relevance of hepatitis A virus as a blood-borne viral infection. Human T-cell leukaemia virus is seldom transmitted during transfusion but may be an important risk factor in the future in some countries.

Animals↗

[HIV-1 and tears. Results of virus isolation and polymerase chain reaction (PCR)].

Beside the threat of infection via HIV-containing blood, the ophthalmologist is especially interested in the possibility of HIV infection via the tears of HIV-positive persons. In a first step, we tried to isolate HIV-1 from the peripheral blood lymphocytes (PBL) of 50 HIV-1-antibody-positive persons in different stages of disease and to detect reverse transcriptase (RT) and p24 antigen (p24-Ag) in the supernatant. Simultaneously we carried out the same tests on tears of these patients. In 10 persons tears were collected using Schirmer strips, in 40 persons by means of microcapillaries. In a second step 10 sample pairs (PBL and tears) were tested with the polymerase chain reaction to detect proviral sequences of HIV-1 (gag, pol, env). In the first step it was not possible to isolate HIV-1 from tears, nor was it possible to detect RT or p24-Ag from the supernatant. In contrast, this was successful in 32 of the 50 examined cases for the PBL. In the second step, it was possible to detect gag, pol and env in all 10 PBL samples, while gag and pol could be detected only in one tear sample and env not at all. Our results show that the tears of HIV-positive persons contain extremely low quantities of tissue-infectious units of HIV. In addition, proviral sequences seem to occur in much lower frequency in tears than in PBL. Infection with HIV via tears therefore appears very unlikely. These findings make it possible to assign tears a place in a semiquantitative ranking of different body fluids by HIV-1 concentration.

Adolescent↗

Human immunodeficiency virus type 1 and type 2 seroprevalence in cornea donors.

Routine screening of cornea donors for human immunodeficiency virus type 1 (HIV-1) has been established and has reduced the risk of HIV-1 transmission to a minimum. Screening for HIV-2 is less common. We evaluated 100 cornea donors for HIV-2 and 166 cornea donors for HIV-1 according to our routine screening procedure. Enzyme-linked immunosorbent assays (ELISAs) with high sensitivity were used to detect antibodies in donor blood. HIV-2 seroconversion was not found in any of the 100 cases tested, whereas HIV-1 seroconversion was detected in 4 of 166 cases; consecutive Western-blot analysis showed only 1 positive result. Thus, 1 of 166 cases (0.6%) had to be considered infected with HIV-1. Our findings of HIV-1 seroprevalence are comparable with those obtained in studies carried out in Europe and the United States. Data are lacking for comparison with our results concerning HIV-2 seroprevalence. Because of the epidemiologic situation of HIV-2 in Europe, different seroprevalence rates would be expected. Routine screening of potential cornea donors for HIV-2 in Germany may be necessary only if the seroprevalence rises in the population.

Adolescent↗