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L Gürtler

Publications and source records attributed to L Gürtler.

At least 37 records · Page 2Linked to original sources
PubMed2000

Hodgkin's disease related Kaposi's sarcoma in a non HIV infected male patient: a case report and review of the literature on a rare condition.

A higher incidence of coexisting lymphoproliferative disease and Kaposi's sarcoma (KS) has been reported. However, the association of Hodgkin's disease (HD) and KS is a rare condition, and only 41 cases have been found upon a literature review of the last 33 years. In this study the case of a 70 year-old male patient with consecutive appearance of Hodgkin's disease (HD) and Kaposi's sarcoma (KS) without evidence of HIV infection or other immunodeficiency is presented. The data suggest, that the association of KS with HD may be due to common pathogenic mechanisms, rather than a direct causal relationship, except the requirement of an impaired immune system for the development of KS. Recently development of HD and KS has been associated with EBV and HHV-8, respectively. Neither immunosuppression, nor EBV or HHV-8 infection alone result in development of HD or KS. There is no clear time relationship between the development of KS and HD when the two occurred together in the same patient. That finding, coupled with the rarity of the association, suggest, that the association is more likely coincidental.

Aged↗
PubMed2000

Inhibition of adenovirus DNA polymerase by modified nucleoside triphosphate analogs correlate with their antiviral effects on cellular level.

Adenovirus (Ad) infection results in significant morbidity and mortality in both immunocompetent and immunosuppressed hosts. There is currently no licensed chemotherapy effective in dealing with this virus infection. In this study the anti-adenoviral activity of a group of modified nucleoside analogs was investigated. The most efficient 3-fluorosubstituted nucleoside triphosphate inhibitors of Ad DNA polymerase were 3'-fluorothymidine triphosphate (IC50 0.63 microM), 2',3'-dideoxy-3'-fluoroguanosine triphosphate (IC50 0.71 microM) and 2',3'-dideoxy-3'-fluorouridine triphosphate (IC50 2.96 microM). The most efficient 2',3'-dideoxynucleoside triphosphates were 2',3'-dideoxycytidine triphosphate (ddCTP; IC50 1.0 microM), 2',3'-dideoxyadenosine triphosphate (IC50 1.6 microM) and 2',3'-dideoxythymidine triphosphate (IC50 1.82 microM). Kinetic studies indicate competitive inhibition of adenovirus DNA polymerase by ddCTP. These data confirm results previously obtained at the cellular level using a focus reduction assay involving Ad2-infected FL cells. Whereas the D-enantiomers 3'-fluorothymidine and 2',3'-dideoxycytidine are potent inhibitors of adenoviral replication, the corresponding L-enantiomers exhibited no inhibitory activity.

Adenoviruses, Human↗
PubMed2000

Shortening of the diagnostic window with a new combined HIV p24 antigen and anti-HIV-1/2/O screening test.

Because antibodies to the human immunodeficiency virus (HIV) are absent in the very early phase of HIV infection, there remains a slight residual risk for HIV transmission by blood donations by viremic but antibody negative donations. To shorten the diagnostic window between infection and the detection of antibodies, Enzygnost HIV Integral (Dade Behring, Germany) was developed. With this new test, HIV p24 antigen and HIV antibodies can be detected simultaneously in a single test. In a multicenter study the new screening assay has been compared with various tests that detect only HIV antibodies or HIV p24 antigen and with assays which permit a simultaneous detection of HIV antigen and HIV antibodies. The new assay showed 100% sensitivity for the detection of antibodies to HIV-1, groups M (n=1102) and O (n=55), and HIV-2 (n=289). In 23 out of 52 seroconversion panels, seroconversion was detected 2-18 days earlier with the new combined antigen/antibody test compared to single antibody tests. All samples from a viral load panel (n=451), all samples containing p24 antigen (n=302), and all but one of the cell culture supernatants (n=38) infected with various HIV-1 subtypes or HIV-2 were identified reliably by the new test. The specificity of the assay for 4002 unselected blood donors was 99.78% initially and 99.80% after retesting. Potentially interfering factors had no systematic influence on specificity. By testing for p24 antigen, which is present prior to the onset of antibody production in some cases of recent HIV infection, the new assay reduces the diagnostic window as compared to third generation screening assays, thus permitting an earlier diagnosis of HIV infection.

AIDS Serodiagnosis↗
PubMed2000

Comparison of ritonavir plus saquinavir- and nelfinavir plus saquinavir-containing regimens as salvage therapy in children with human immunodeficiency type 1 infection.

BACKGROUND: In this retrospective study we compared the antiretroviral effect of regimens consisting of simultaneous administration of two protease inhibitors (PI) with at least one nucleoside reverse transcriptase inhibitor on plasma viral load (VL) and CD4 cell count in HIV-infected children intensively pretreated with nucleoside reverse transcriptase inhibitors and PIs. METHODS: Eleven HIV-infected children were changed to antiretroviral combination regimens including two PIs and followed for a median time of 24 weeks. Group A comprised six patients who were given ritonavir + saquinavir (SQV) and Group B consists of five patients who were changed to nelfinavir + SQV. Patients were treated with these combinations with 2 PIs because of treatment failure (increasing viral load) of prior PI therapy or clinical signs of disease progression. OUTCOME MEASURES: Serial determinations of plasma viral load (Amplicor, Roche) and CD4 cells were performed every 4 to 8 weeks. The detection limit of the Amplicor-reverse transcriptase-PCR assay was 50 copies/ml (1.7 log10). RESULTS: In Group A the median VL reduction was 1.1 log10 after 3 months and 1.4 log10 after 6 months. In Group B median VL decreased 0.1 and 0.2 log10 after 3 and 6 months. In both groups during the study period none of the patients reached undetectable VL. The relative changes of CD4 cells above baseline in Group A showed a median increase of 7% after 3 months and 23% after 6 months. In Group B after 3 months CD4 cells did not increase, and after 6 months the median relative increase was only 7%. Both combination therapies were well tolerated, not necessitating any drug interruption during study period. CONCLUSIONS: In children with intensive prior antiretroviral treatment, a salvage therapy including two PIs demonstrated antiretroviral efficacy in some patients. In this study the reduction of the VL as well as the increase of CD4 cells was more pronounced with ritonavir + SQV than with nelfinavir + SQV. With both combinations complete suppression of HIV replication was not achieved. Therefore the long term effect of these combinations may be limited by the emergence of resistant HIV strains.

Adolescent↗
PubMed1999

Coreceptor requirements of primary HIV type 1 group O isolates from Cameroon.

HIV-1 group O has its epicenter in Cameroon and neighboring countries and is responsible for 3 to 5% of all HIV infections in this region. It is believed that HIV-1 group O was introduced into the human population by a separate cross-species transmission, occurring independently of the HIV-1 (group M and group N) and HIV-2 transmissions. We have studied the coreceptor requirements of 12 primary HIV-1 O-type isolates from individuals with different clinical symptoms. Only 2 of these 12 viruses showed a syncytium-inducing phenotype after infection of primary peripheral blood mononuclear cells (PBMCs) and were infectious for the T cell line C8166. These isolates used CXCR4 as a coreceptor for entry, whereas the remaining isolates used only CCR5 efficiently. One isolate was able to use BOB and CCR8 as coreceptors in addition to CXCR4. All group O isolates tested were efficiently inhibited by SDF-1 or RANTES, the natural ligands of CXCR4 and CCR5, respectively. These results indicate that CXCR4 and CCR5 are the principal coreceptors for HIV-1 O-type viruses. Most of the HIV-1 group O isolates studied were derived from patients at later stages of the disease. Although HIV-1 group O and group M infections do not differ in their pathogenesis, the studied isolates did not evolve to use a broad range of coreceptors as described for HIV-1 group M and HIV-2.

Adult↗
PubMed1999

A new antioxidative vitamin B6 analogue modulates pathophysiological cell proliferation and damage.

The new large scale synthesis of the yellow colored vitamin B6 analogue 5'-O-phosphono-pyridoxylidenerhodanine (2) (B6PR) leads to oligohydrates of its monosodium salt (4). The light-red hemiheptadecahydrate (8 1/2 hydrate) (4a) was crystallized and its three-dimensional structure determined by X-ray crystallography. Special nucleotide and protein interaction properties together with scavenging antioxidative function are combined in this simple water-soluble vitamin B6 analogues B6PR. High (mM) concentrations were untoxic to 'healthy' not affected cells and primary tissues. Complexation of ions (e.g. Ca2+, Fe2+, and Zn2+), modulation of nitric oxide synthases (NOS I-III), nitric oxide (NO) metabolism, and reactive oxygen species (ROS) was found. Special cytoprotecting, immunomodulating, stimulating and inhibiting activities were observed in vitro, not in comparison with some natural and synthetic pyridoxines. Low B6PR suppressed proliferation, high induced selective cell death of some cancer cell lines. Low B6PR protected HIV-1-infected CD4+ HUT 78 cells against HIV-1-mediated destruction (complete inhibition of HIV-1-induced syncytia formation and cell death) and reduced p24 level. Autoreactive S100beta-specific T cells of Lewis rat, a model of multiple sclerosis, could be influenced. Oxidative damage and age, acquired and inherited disease related pathophysiological disorders can be treated by this new cytopathology-selective versatile acting B6PR.

Animals↗
PubMed1998

Evaluation of different V3 peptides in an enzyme immunoassay for specific HIV type 1 group O antibody detection.

Strategies to discriminate group O from group M infections need to be improved. We have developed and evaluated an HIV-1 group O V3 peptide-based enzyme immunoassay (PEIA) for specific HIV-1 group O antibody detection among HIV-1-infected patients. Synthetic peptides, derived from the amino acid sequences of the V3 loop of 15 different group O strains and 7 group O consensus sequences, were evaluated in a PEIA against a panel of genetically confirmed group O (n = 33), group M (n = 90), and HIV-1 antibody-negative sera (n = 17). The best-performing PEIA(s) were then used to screen 134 sera of European and 336 sera of Cameroonian origin for the presence of anti-HIV-1 group O antibodies. The reactivity of reference ("gold standard") sera to individual peptides in the PEIA resulted in the selection of five different peptides with sensitivities (sens), specificities (spec), and test efficiencies (TEs) in the range of 90 to 100%. Improvement of the PEIA was obtained with simultaneous reactivity of at least two different peptides in separate wells of an ELISA plate, together with stringent criteria for positivity. We were able to select seven peptide combinations each with a sens, spec, and TE of 96.9, 100, and 99.2%, respectively. None of the 134 European and 4 (1.2%) of the 336 Cameroonian samples sera were group O positive in the optimized HIV-1 group O PEIA; this was confirmed by the repeated presence of reactives, in agreement with the present knowledge of group O infection distribution. Finally, we were able to develop a strategy with a higher TE (99.2%) than the previously used ANT-70 (98.5%) and ANT-70/MVP5180 (95.7%). Our results show that optimal specificity rather than optimal sensitivity makes the V3 PEIA a sufficiently accurate epidemiological tool to be useful in estimating specifically group O infection among HIV-1-infected patients.

Cameroon↗
PubMed1998

Differential diagnosis of HIV type 1 group O and M infection by polymerase chain reaction and PstI restriction analysis of the pol gene fragment.

HIV-1 group O serological screening or confirmation strategies so far have not proved 100% sensitive and specific, indicating a lack of antibody reactivity or cross-reactivity with group O antigens. Therefore, genetic analysis currently represents the only method by which confirm presumed HIV-1 group O or group O/M infections. We have optimized the sensitivity (100%) and specificity (100%) of an HIV-1 group O/M-specific PCR of a pol gene fragment. In addition, we report on a highly sensitive (97.2%) and specific (100%) method for differentiation between HIV-1 group O and group M viruses, using PCR and PstI enzyme restriction fragment analysis of a pol fragment. Compared with sequencing, these methods are fast, inexpensive, and simple.

DNA, Viral↗
PubMed1998

HIV type 1 V3 serotyping of Tanzanian samples: probable reasons for mismatching with genetic subtyping.

HIV-1 V3 serotyping is used to classify immunodeficiency viruses on the basis of antibody binding to V3 peptides derived from env genetic subtypes. Although it shows a reasonable overlap, it has been reported to be distinct from viral genetic subtypes. The aim of this study is to determine the feasibility of HIV-1 serotyping to predict genetic subtypes in an East African setting, where multiple HIV-1 subtypes have coexisted for many years. HIV-1 genetic subtypes of 86 AIDS patients in Mbeya Town, southwest Tanzania, were determined, using env nucleic acid sequencing as the basis for comparison. Those data were compared with V3 serotyping results obtained by four different methodologies. Four HIV-1 genetic subtypes were identified, including A (25, 29%), C (47, 55%), D (13, 15%), and G (1, 1%). The sensitivity and specificity of those serotyping assays varied considerably: sensitivity for genetic subtype A (40-48%), C (52-96%), and D (9-31%); and specificity for genetic subtype A (77-95%), C (46-63%), and D (97-100%). We further tried to identify reasons for the discrepancies between serotyping results and genetic subtypes. By means of logistic regression analysis three amino acid residues within the V3 loop (positions 12, 13, and 19; V, H, and A for serotype A, I, R, and T for serotype C) were found to be most important for antibody binding; a deviation from the subtype-specific amino acids was highly related to mismatched results. In addition, we have shown that phenetic analysis of V3 amino acid sequence data could be used to predict the majority of V3 serotypes (93-94%). Our data demonstrated that for the majority of specimens HIV-1 V3 serotyping results closely match the subtype of the analyzed sample as revealed by the V3 loop amino acid sequence. However, our data demonstrate that HIV-1 serotyping is not sufficiently accurate to predict genetic subtypes in Tanzania, where subtypes A, C, D, and G are circulating. This was due to highly similar amino acid sequences throughout the prevalent genetic subtypes, which caused the inability of HIV-1 V3 serotyping to differentiate subtype A from C as well as D from C. Instead, the serotyping results reflect the frequency distribution of V3 serotypes. To investigate HIV-1 genetic subtypes in population-based studies in this African setting additional or modified algorithms are needed.

Acquired Immunodeficiency Syndrome↗