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Biomedical subjects

L Gürtler

Publications and source records attributed to L Gürtler.

At least 19 recordsLinked to original sources

The monoclonal CD4 antibody M-T413 inhibits cellular infection with human immunodeficiency virus after viral attachment to the cell membrane: an approach to postexposure prophylaxis.

Infectious cellular uptake of human immunodeficiency virus (HIV) is initiated by a complex sequence of interactions between the viral envelope gp120/gp41 complex and the cellular CD4 receptor resulting in the exposure of a hydrophobic region of gp41 that mediates the irreversible fusion of the virus with the cell membrane. Here we show that viral penetration into a susceptible cell can be inhibited by the high-affinity monoclonal CD4 antibody (CD4 mAb) M-T413 even when it is added as late as 30-120 min after the initial contact of virus with the cell membrane. Inhibition of infection was assessed by monitoring cultures for 34 days after exposure to virus using four different methods simultaneously, including detection of viral DNA by PCR. The interval during which HIV remains sensitive to postbinding neutralization by CD4 mAb depends on strain of virus and type of target cell. Preparations of recombinant soluble CD4 (and the immunoadhesin CD4-IgG1) were much less efficient when compared with mAb M-T413, particularly in blocking infection by fresh HIV-1 isolates. Also cellular transmission of HIV, as determined by syncytia formation within 24 hr, was prevented by mAb M-T413 when added within 45 min of contact of infected H9 cells with uninfected C8166 cells. Together with the favorable clinical experience obtained with CD4 mAbs as immunomodulatory drugs, these data suggest that infusion of CD4 mAb M-T413 may be a therapeutic modus for immediate prophylactic intervention after occupational exposure to HIV and for prevention of intrapartum mother-to-infant HIV transmission.

Animals

Inter-alpha-trypsin inhibitor polymorphism in African blacks.

The inter-alpha-trypsin inhibitor (ITI) polymorphism was analyzed in an African Negroid population using polyacrylamide gel isoelectric focusing and subsequent immunoblotting. Gene frequencies of ITI*1, ITI*2, ITI*3 and ITI*4 were calculated to be 0.564, 0.083, 0.337 and 0.004, respectively. One unknown rare allele, ITI*6, determines further phenotypes in combination with the alleles ITI*1 and ITI*3. Gene frequency of ITI*6 was calculated to be 0.012. The common alleles are represented by ITI*1 and ITI*3. The allele distribution is therefore different from European and Asian populations.

Alpha-Globulins

[Differences in detectability of human immunodeficiency virus type 1 in tears and blood lymphocytes].

Reported data on the isolation of the human immunodeficiency virus type 1 (HIV-1) from tears are controversial. The purpose of the study was to try to isolate HIV-1 from tears in a large sample of HIV-1-positive patients at different stages of infection. 53 tear samples were obtained from 50 patients. Additionally isolation of HIV-1 from peripheral blood lymphocytes (PBL) was attempted. HIV-1 was isolated from none (= 0%) of the 53 tear samples. Isolation from PBL was successful depending on absolute CD4+ lymphocyte count and Walter Reed staging (Walter Reed stage 6: 83%; stage 2 to 5: 11%; p less than 0.0001). Treatment with zidovudine was not related to the frequency of HIV-1 isolation. These results suggest that tears of patients infected with HIV-1 contain low or no quantities of tissue-culture-infectious units of HIV-1. Nosocomial infection with HIV-1 from tears appears to be unlikely. The known precautions for the prevention of spread of viral disease in ophthalmological practice are sufficient and should be strictly followed.

Adolescent

[Azidothymidine and the nervous system].

By December 1988 reports on 525 ARC- (AIDS-Related Complex) and AIDS-patients with neurological or neuropsychological signs treated with Zidovudine (AZT = 3'-Azido-2,3'Dideoxythymidine) had been published in literature. In 204 (38.8%) cases of HIV infection a temporary improvement in the neurological deficits was reported. Peripheral and central neurological side-effects were observed in 124 (23.6%) patients.

AIDS Dementia Complex

[Possible long-term prognosis in epidemiologically significant virus infections].

The long-range prognosis of viral diseases must be assessed differently according to their geographical occurrence. The genetic disposition, environmental factors and additional infectious diseases play a decisive part here. Vaccinations are the most important measures in the prevention of these infections. The spectrum of possible chemotherapeutic intervention for viral infectious diseases is very small, which usually makes specific treatment impossible. The most important infective viruses epidemiologically, which lead to persistent complications, are discussed in detail as follows: influenza virus, measles virus, human T-cell leukaemia virus, human immuno-deficiency virus, hepatitis B and C virus. In a discussion conclusions are drawn from the virologist's point of view for a possible long-range prognosis, which depends on the one hand on the infective agent and on the other on individual reactivity. The last chapter talks about insurance medical aspects of the most important infective viruses, which have already been discussed virologically. Some scientific developments are shown which could be future solutions of problems in diagnosis and prognosis. Such new developments could help insurance medical officers to important decision parameters for long-range prognosis, which are still largely missing at present.

Cause of Death

[HIV and nervous system manifestations: a review].

Since 1986 the notation Human Immunodeficiency Virus (HIV) is used for the retroviral agent of the Acquired Immunodeficiency Syndrome (AIDS). At the beginning of the therapeutical interest in the immunodeficiency syndrome have been primarily focussed in the internal complications. 1982 one reported for the first time about nervous system manifestations (NS-M) in HIV-patients; according to the latest reports NS-M are diagnosed in 39-63% of these patients. In this review all important aspects of the pathogenesis, clinic and therapy for the HIV-associated peripheric- and central-neurological (like e.g. acute and chronic meningitis/meningoencephalitis, dementia, opportunistic infections, polyneuropathies and myopathies) and psychiatric diseases are described.

AIDS Dementia Complex

Prevalence of antibodies against hepatitis A virus, hepatitis B virus, and Treponema pallidum in Mauritius.

A seroepidemiological study on the prevalence of antibodies against hepatitis A virus (HAV), hepatitis B virus (HBV) and Treponema pallidum was conducted in various groups of the population of the state of Mauritus (Islands of Mauritus and Rodrigues). 618 sera were tested. The overall prevalence of anti-HAV was 86.1% and yielded and age-dependent increase. Serological evidence for acute or chronic HBV infection was found in 3.8%; 4.5% were positive for anti-HBc alone, and in 12.6% past HBV infection was detected. No age- or sex-dependent increase in the prevalence of anti-HBc was found. There were differences in the anti-HBc prevalence among the various groups of population ranging from 5.9 (flight personnel) to 58.3% (prison inmates). Treponemal antibodies were detected in 6.0% and showed a fairly marked age-dependent increase. Our study suggests that vaccination programmes against HAV and HBV would be beneficial for the Mauritian population.

Adolescent

(K15R M52E) aprotinin is a weak Kunitz-type inhibitor of HIV-1 replication in H9 cells.

The (K15R M52E) aprotinin is a recombinant molecule with a broader inhibition spectrum against serine proteinases and a higher affinity towards certain proteinases as compared to native aprotinin. This aprotinin variant was produced in E. coli, isolated and purified to homogeneity. The inhibitor was further tested for its effectiveness to reduce human immunodeficiency virus type 1 (HIV-1) replication. Virus growth was followed by an ELISA which detects the amount of virus core protein p24. At a concentration of 50 microM, the recombinant (K15R M52E) aprotinin clearly reduced HIV-1 replication in H9 cells.

Amino Acid Sequence

Comparative evaluation and practical importance of instrument-free HIV-1 antibody screening assays.

Four instrument-free, visually read assays for detection of HIV-1 antibody were evaluated using 1,133 serum specimens from blood donors and patients in a rural hospital in Northern Zaire. Sensitivity for the four assays ranged from 85.9% to 95.0% and specificity ranged from 88.5% to 98.6%. Problems were caused by uninterpretable results in the range of 2.8% to 7.8%, decreasing somewhat the value of those systems. Based on our results, practicability and costs of the assays, we propose a hierarchy for testing for blood donors and for diagnosis of AIDS, adapted for hospitals in tropical countries.

Acquired Immunodeficiency Syndrome

Multicenter evaluation of a new recombinant enzyme immunoassay for the combined detection of antibody to HIV-1 and HIV-2.

A newly developed recombinant antigen-based anti-HIV-1/HIV-2 enzyme immunoassay (Abbott Recombinant HIV-1/HIV-2 EIA) was evaluated against a second generation anti-HIV-1 EIA (Abbott Recombinant HIV-1 EIA). Five thousand and twenty-nine sera from European blood donors and 403 sera from central African blood donors were used in the evaluation, along with four panels and one cohort. The panels included 99 'problem' sera, 733 sera with antibodies to HIV-1 from asymptomatic people and from patients at different disease stages, 25 serial bleeds from five plasmapheresis donors seroconverting for antibodies to HIV-1, and 202 sera with antibodies to HIV-2 collected from healthy and diseased people of European or west African origin. In addition, 734 sera collected from a west African cohort were tested. Using Western blot as the reference standard, the specificity obtained by the recombinant anti-HIV-1 EIA (HIV-i EIA) was 99.90% [99.81-99.99%; 95% confidence limits (95% CL)] with European blood donor sera; 99.50% (98.78-100%) with Central Africa blood donor sera; 92.93% (87.78-98.08%) with 'problem' sera and 99.43% (98.87-100%) with sera from a west African cohort. Using the same samples, the recombinant anti-HIV-1/HIV-2 EIA (HIV-1/HIV-2 EIA) yielded a specificity of 99.84% (99.73-99.95%), 99.50% (98.78-100%), 95.96% (92.00-99.92%) and 98.58% (97.69-99.47%), respectively. All 776 Western blot-confirmed anti-HIV-1 sera were reactive in both EIAs, and the EIA-reactive samples from seroconverting plasma donors were always observed for both assays in the same serial bleed. For HIV-2, the HIV-1 EIA yielded an overall sensitivity of 75.83% (69.93-81.72%) compared with 99.53% (98.58-100%) for HIV-1/HIV-2 EIA. The addition of a recombinant env-protein of HIV-2 to the recombinant env and core proteins of HIV-1 on the solid phase of HIV-1 EIA improved the detection of anti-HIV-2 while preserving the assay's overall specificity and sensitivity for the detection of anti-HIV-1.

AIDS Serodiagnosis

[Initial results of the anti-HIV-1/2 combined ELISA].

Between March 30 and July 31, 1989, 117,874 blood donations were tested for anti-HIV-1 and in a combined ELISA for anti-HIV-1/HIV-2 (both Abbott). On each repeat reactive (14 = 0.01% for anti-HIV-1 and 400 = 0.34% for anti-HIV-1/HIV-2), a Western blot (WB) was performed. Two donors, who tested repeatedly reactive in both ELISAs, were confirmed anti-HIV-1 positive by WB. As the specificity of anti-HIV-1/HIV-2 ELISA is considerably lower (99.66%) than of anti-HIV-1 (99.99%), introduction of a different HIV-2 specific ELISA should be discussed to prevent loss of too many blood donations and donors through anti-HIV screening.

AIDS Serodiagnosis

Carbohydrate components of human immunodeficiency viruses type I and II.

The terminal carbohydrate residues of HIV I and II were detected by ferritin labeled lectins in electron microscopy. Different cell lines, which were infected with HIV I and II, expressed different terminal carbohydrate residues, which could also be detected on the viral envelope by electronmicroscopy. Especially N-Acetylgalactosamine residues were detected by Vicia villosa agglutinin only on Jurkat cells. This may have functional implications, since this lectin recognizes contrasuppressor T cells.

Carbohydrate Metabolism