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Biomedical subjects

Peter Erb

Publications and source records attributed to Peter Erb.

16 recordsLinked to original sources
PubMed2006

Human herpesvirus 8 oral shedding in HIV-infected men with and without Kaposi sarcoma.

OBJECTIVES: Two main routes of human herpesvirus 8 (HHV-8) transmission are known: sexual, predominantly in men who have sex with men; and nonsexual, in endemic populations. Both routes implicate saliva, so identifying the factors that influence oral HHV-8 shedding is important. METHODS: Using polymerase chain reaction and immunohistochemistry, we prospectively analyzed HHV-8 infection of oral epithelial cells in 98 Swiss HIV Cohort Study patients, with mean follow-up of 9.4 years, and correlated data to immune status, HHV-8 serology, and Kaposi sarcoma (KS) history, as well as survival. RESULTS: Sixty-eight (43.9%) of the 98 men were HHV-8 seropositive, and 33 (33.67%) had a history of KS. In both groups, men who have sex with men were significantly more affected than heterosexuals (P < 0.05). Of 77 patients, 9 (11.6%) were oral HHV-8 polymerase chain reaction positive, and 2 of these were also positive by immunohistochemistry. Oral HHV-8 detection was not influenced by the immune status, but a trend toward higher detection was observed in patients with KS (P = 0.084). Oral HHV-8 shedding had no predictive value either for the development of KS lesions or for survival. CONCLUSIONS: Human herpesvirus 8 can be present in oral epithelial cells and is shed independent of the patient's immune status, indicating that oral HHV-8 shedding may occur at any time in HHV-8-seropositive individuals.

Adult↗
PubMed2005

Role of apoptosis in basal cell and squamous cell carcinoma formation.

Long-term ultraviolet-light (UV) exposure of human skin epidermis is associated with an increased risk for the development of skin cancers, such as melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). UV radiation not only induces DNA damage in epidermal cells, it also interferes with skin homeostasis, which is maintained by a unique distribution pattern of apoptosis-inducing and -preventing molecules. If the DNA damage is not repaired or the damaged cells are not eliminated by apoptosis, the consequence can be cell transformation, uncontrolled proliferation and eventually skin tumor formation. An important "repair" gene is the p53 suppressor gene. Excessive UV exposure can mutate the p53 gene leading to the loss of its repair function and thus apoptosis resistance of the DNA-damaged cell. For BCC formation an additional pathway has been identified. Mutation of genes of the Hedgehog signaling pathway evokes the downregulation of apoptotic genes and upregulation of anti-apoptotic genes preventing the elimination of damaged cells. In addition, BCC and SCC strongly express the apoptosis-inducing Fas-ligand (FasL) which may help the tumor to escape the attack of immune effector cells. Silencing the genes involved in tumor formation by RNA interference might become a promising new approach to treat skin tumors.

Animals↗
PubMed2004

Cough and fear of sleep: early clinical signs of Bordetella pertussis in an adult.

Pertussis is increasing in frequency among adults, but early diagnosis requires special attention to details in the medical history. We describe a 64 year-old male with classic signs and symptoms of pertussis and documented Bordetella pertussis infection that were overlooked because he presented with a chief complaint of cough and fear of falling asleep. Coughing paroxysms and a feeling of suffocation (30-60 seconds) only occurred at night after short periods of deep sleep (30-45 minutes). The physicians did not observe these episodes during daytime examinations, and the basis of the patient's fear of sleep was not explored. We recommend reassessment of how adults describe symptoms of pertussis, including fear of sleep, and we suggest the use of PCR technology to allow early diagnosis and prompt treatment.

Anti-Bacterial Agents↗
PubMed2004

Persistent apoptosis in HIV-1-infected individuals receiving potent antiretroviral therapy is associated with poor recovery of CD4 T lymphocytes.

CD4 T-cell depletion in HIV-1 infection is partly the result of T-cell apoptosis. Spontaneous apoptosis (SA) and apoptosis markers Fas-associated death-domain-like IL-1 beta converting enzyme (FLICE)-like inhibitory protein (FLIP), Bcl-2, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), TRAIL receptor 1, and Fas were determined in 55 HIV-1 infected persons treated with highly active antiretroviral therapy (HAART) for 48 months. Despite suppressive HAART, SA remained elevated. Increased SA of peripheral blood mononuclear cells (PBMCs) and CD8 T lymphocytes and increased TRAIL receptor 1 expression strongly predicted a poorer recovery of CD4 T-cell count. HAART did not significantly alter anti-or proapoptotic markers in cultured PBMCs and T lymphocytes. The significant relationship between residual T-lymphocyte apoptosis and CD4 T-cell recovery suggests that persistent apoptosis may impede immune restoration.

Adult↗
PubMed2004

Infection with human herpesvirus 8 and transplant-associated gammopathy.

BACKGROUND: The role of human herpesvirus (HHV)-8 in the pathogenesis of multiple myeloma and its pre-malignant state of monoclonal gammopathy is unclear. HHV-8 is transmitted by organ transplantation, representing a unique model with which to investigate primary HHV-8 infection. METHODS: The authors studied the incidence of clonal gammopathy in renal transplant recipients and correlated it with previous and recent HHV-8 infection. RESULTS: Clonal gammopathy was observed in 31 of 162 (19%) HHV-8-seronegative patients, in 5 of 17 (29%) HHV-8-seropositive patients, and in 9 of 24 (38%) HHV-8 seroconverters within 5 years after transplantation. Gammopathy was often transient, and no progression to myeloma was observed. Two patients with persistent gammopathy developed B-cell lymphoma. In a logistic regression model, HHV-8 serostatus of the graft recipient was significantly associated with subsequent development of gammopathy, with a relative risk (RR) of 1.9 and a 95% confidence interval (CI) of 0.5 to 6.4 for an HHV-8-seropositive recipient and an RR of 2.9 and a 95% CI of 1.01 to 8.0 for seroconverters as compared with baseline (HHV-8 seronegative). Other significant variables were cytomegalovirus (CMV) serostatus and the intensity of immunosuppression (RR of 10.4 and 95% CI of 2.6-41.7 for a CMV-negative recipient with a CMV-positive donor vs. a CMV-negative recipient with a CMV-negative donor and RR of 17.6 and 95% CI of 2.0-150.8 if OKT3 was used vs. no use of antilymphocytic substances). CONCLUSIONS: Transplant recipients with HHV-8 infection are more likely to develop clonal gammopathy. However, this risk is much lower than the risk conferred by CMV infection and antilymphocytic therapy, arguing against a major role of HHV-8 infection in the pathogenesis of clonal plasma cell proliferation.

Antilymphocyte Serum↗
PubMed2004

Prevalence of human T-cell leukemia virus types I and II in Switzerland.

The retroviruses human immunodeficiency virus (HIV)-1/2 and human T-cell leukemia virus (HTLV)-I/II share modes of transmission, suggesting that efforts to monitor the current HIV-1 epidemic in Switzerland should be complemented by assessment of HTLV-I/II prevalence. This study presents an updated evaluation of HTLV-I/II infection among groups within the Swiss population polarized towards either low or increased risk of infection. Archived serum and peripheral blood mononuclear cell (PBMC) samples were examined for evidence of HTLV-I/II infection by enzyme-linked immunosorbant assay (ELISA), type-specific Western blot, type-specific polymerase chain reaction (PCR), DNA sequence analysis, and virus culture. Among blood donations obtained from low-risk Swiss donors, we report a complete lack of HTLV-II infection and the occurrence of HTLV-I infection limited to a prevalence of 0.079 per 100,000 (1/1,266,466). Among high-risk HIV-positive persons and HIV-negative persons at increased risk of HIV-infection, we report a focus of HTLV-I and HTLV-II infection at prevalence rates of 62 per 100,000 (1/1,620) and 309 per 100,000 (5/1,620), respectively. The finding of low HTLV-I/II prevalence among Swiss blood donors and containment of HTLV-I/II infection within known risk-groups does not support initiation of HTLV-I/II screening for Swiss blood, tissue, and organ donations.

Blood Donors↗
PubMed2003

Enhanced gene silencing by the application of multiple specific small interfering RNAs.

Small interfering RNA duplexes (siRNA) induce gene silencing in various eukaryotic cells, although usually in an incomplete manner. Using chemically synthesized siRNAs targeting the HIV-1 co-receptor CXCR4 or the apoptosis-inducing Fas-ligand (FasL), co-transfection of cells with two or more siRNA duplexes targeting different sites on the same mRNA resulted in an enhanced gene silencing compared with each single siRNA. This was shown in the down-regulation of protein and mRNA expression, and functionally in the inhibition of CXCR4-mediated HIV infection and of FasL-mediated cell apoptosis. Transfection efficiency determined for the FasL-specific siRNAs was dose-dependent and varied among the siRNAs tested, but was not the main reason for the enhanced gene silencing.

Apoptosis↗
PubMed2003

Intravenous opiate maintenance in a cohort of injecting drug addicts.

BACKGROUND: Drug addiction is a major problem in many societies. The opiate maintenance program includes a prospective cohort of injecting drug addicts, treated with opiates such as heroin intravenously. An important aim of this program is to keep patients under medical supervision in order to reduce the health hazards associated with illicit drug consumption. In this paper we report the performance of this drug policy in terms of retention and analyse treatment withdrawals and hospitalisations. METHODS: Treatment retention was assessed using the Kaplan-Meier method (treatment withdrawals were defined as the event of interest). We analysed factors associated with treatment withdrawal using Cox regression analysis. In addition, we analysed hospitalisations occurring during the study period. RESULTS: Of 175 patients included in the study, 76 withdrew from the study. Of these, 29 were transferred to a substitution program. The 3-year probability of remaining in the study was 61.7% (95%CI: 54.8-69.4%). Risk of treatment withdrawal was independently associated with age (hazard ratio 0.88 [95%CI: 0.82-0.95]) and years of intravenous drug use (hazard ratio 1.11 [95%CI: 1.04-1.18]). No association was found between risk of treatment withdrawal and HIV-, Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) serostatus. The percentages of HIV, HBV and HCV seroconversions observed during the study period were 0.7, 16.2 and 23.3%, respectively. A total of 84 hospitalisations were recorded in 49 patients, mainly due to infectious diseases. Hospitalised patients were not more likely to withdraw from the program. CONCLUSIONS: Retention is high in the intravenous opiate maintenance program and favours the continuation of this drug policy. Individuals with a shorter history of injecting drug use and of older age are more likely to continue intravenous opiate maintenance treatment.

Adult↗
PubMed2003

Inhibition of T helper 2-type responses, IgE production and eosinophilia by synthetic lipopeptides.

In allergy and asthma, the fine balance between the T helper (Th) 1, Th2 and T regulatory cytokine responses appears to be shifted towards Th2. Here, we report that synthetic lipopeptides which contain the typical lipid part of the lipoprotein of gram-negative bacteria stimulate a distinct regulatory cytokine pattern and inhibit several Th2 cell-related phenomena. The most potent analogue of synthetic lipopeptides, lipopeptide CGP 40774 (LP40) was not active in MyD88-deficient mice and stimulated Toll-like receptor (TLR)-2, but not TLR-4. LP40 potentiated the production of IFN-gamma and IL-10, but not IL-4 and IL-5 by human T cells. In addition, triggering of TLR-2 by lipopeptides promoted the in vitro differentiation of naive T cells towards IL-10- and IFN-gamma-producing T cells and suppressed IL-4 production by Th2 cells. Accordingly, LP40 inhibited IgE production induced by allergen, anti-IgD antibody, Nippostrongylus brasiliensis or murine acquired immunodeficiency virus. Furthermore, ovalbumin-induced lung eosinophilic inflammation was abolished and Schistosoma mansoni egg-induced granuloma size and eosinophil counts were suppressed in mice by LP40. These results demonstrate that stimulation of TLR-2 by lipopeptides represents a novel way for possible treatment of allergy and asthma by regulating the disrupted cytokine balance.

Allergens↗
PubMed2003

Fas ligand downregulation with antisense oligonucleotides in cells and in cultured tissues of normal skin epidermis and basal cell carcinoma.

Fas ligand (FasL), a member of the tumor necrosis factor family, induces apoptosis upon interaction with Fas-receptor-expressing cells. FasL normally plays an important immune regulatory role, but it can also cause severe skin diseases if overexpressed and it may serve some tumors for immune evasion. Thus, in situ inhibition of FasL expression with antisense oligonucleotides in patients may be a novel approach to overcome its pathogenic role. We designed and evaluated 15 phosphorothioate antisense oligonucleotides directed against different regions of the human FasL mRNA. They exhibited different inhibitory activities on FasL expression in HEK293 cells. The most potent antisense oligonucleotide, ASO8, specifically downregulated 90% FasL expression at the protein level and 80% at the mRNA level. FasL downregulation reduced the effector function of HEK293 cells toward Fas receptor positive target cells. Further studies demonstrated that ASO8 efficiently inhibited FasL synthesis in split skin and basal cell carcinoma tissue. Our results show that the modulation of FasL expression by antisense oligonucleotides is possible in cells as well as tissue and indicate that antisense oligonucleotides may provide a promising strategy for the therapy of FasL-mediated disorders.

Apoptosis↗
PubMed2002

Tumor necrosis factor-related, apoptosis-inducing ligand supports growth of mouse mastocytoma tumors by killing tumor-infiltrating macrophages.

TRAIL antisense transfected mastocytoma cells (R56VTas) injected into syngeneic DBA/2 mice demonstrate significantly delayed tumor growth compared to mock transfected cells (R56VTMo). TRAIL expression in R56VTas cells was successfully, albeit not completely, downregulated, as shown by Western blots, flow-cytometric analysis and functionally by loss of cytolytic activity against TRAIL-R-bearing target cells. Immunohistochemic and immunoblotting analyses of ex vivo tumors confirmed the lower expression of TRAIL by the antisense transfection compared to the mock transfection. Investigating the mechanism of the delayed tumor growth, it was found that neither T nor NK cells but activated macrophages infiltrated the tumors. The number of infiltrating macrophages was significantly lower in the mock transfected compared to the TRAIL antisense transfected tumor sections, indicating that TRAIL-expressing tumor cells may lyse macrophages. Indeed, activated macrophages proved to be sensitive to TRAIL-mediated apoptosis. This indicates that, although macrophages can infiltrate the mastocytoma R56VT, they are in part eliminated by TRAIL-expressing tumor cells, allowing the tumor to rapidly grow. Hence, downregulation of TRAIL allows more macrophages to survive and to better attack the tumor cells, slowing down tumor growth. In conclusion, TRAIL expressed on R56VT tumor cells can impair an important innate immune defense mechanism against tumors by eliminating effector macrophages.

Animals↗
PubMed2002

Antiretroviral therapy reduces markers of endothelial and coagulation activation in patients infected with human immunodeficiency virus type 1.

We investigated the effect of antiretroviral therapy on vascular activation in 41 human immunodeficiency (HIV)--infected patients receiving a regimen that included either at least 1 protease inhibitor (PI; n = 21) or a nonnucleoside reverse-transcriptase inhibitor (NNRTI; n = 20). A control group of 21 healthy subjects was included for comparison. Levels of endothelial markers (soluble vascular cell adhesion molecule [sVCAM]--1, soluble intercellular adhesion molecule--1, and von Willebrand factor) were higher in HIV-infected persons before treatment than in control subjects and decreased significantly after 5--13 months of treatment. Levels of sVCAM-1 and von Willebrand factor correlated significantly with initial virus load. d-dimer concentrations also decreased significantly after initiation of treatment. PI- and NNRTI-containing regimens had similar effects. Therapy did not reduce levels of the soluble platelet (sP) activation markers sP-selectin and CD40 ligand. The inhibition of markers of vascular activation may counterbalance sequelae of therapy-induced dyslipidemia and potentially prevent development of atherosclerosis in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Intralesional interferon in basal cell carcinoma: how does it work?

Basal cell carcinoma (BCC) is the most common skin cancer among Caucasians, and its incidence is increasing. Intralesional injection of interferon alpha (IFN alpha) has been shown to provide a safe and effective treatment for BCCs. The predominant mechanism for the effect of IFN alpha on BCC has been partially identified. We have shown that in untreated patients, BCC cells constitutively express CD95 ligand (CD95L), but not the receptor. BCC cells make use of the CD95 ligand to escape from a local immune response by averting the attack from activated CD95 receptor-positive CD4+ T cells. The CD95L of BCC cells is functional as CD95+ target cells incubated on BCC cryosections become apoptotic and are lysed. In IFN alpha-treated patients BCC cells express not only CD95L but also CD95 receptor, and regress by committing suicide or fratricide through apoptosis induction via CD95 receptor-CD95L interaction. Peritumoral infiltrating cells, predominantly CD4+ T cells, may support regression of BCC by the secretion of cytokines such as IFN gamma or interleukin-2 which may also be responsible for the up-regulation of CD95 on BCC cells.

Basal Cell Carcinoma↗
PubMed2002

Differential expression of viral Bcl-2 encoded by Kaposi's sarcoma-associated herpesvirus and human Bcl-2 in primary effusion lymphoma cells and Kaposi's sarcoma lesions.

Expression of human herpesvirus 8 viral Bcl-2 protein was demonstrated in spindle cells of late-stage Kaposi's sarcoma lesions but not in primary effusion lymphoma cell lines. In contrast, strong expression of human Bcl-2 was found in stimulated primary effusion lymphoma cells, whereas in Kaposi's sarcoma lesions preferential mononuclear cells, and to a lesser extent spindle cells, stained positive.

Herpesvirus 8, Human↗
PubMed1998

HIV-1-infected patients with focal neurologic signs: diagnostic role of PCR for Toxoplasma gondii, Epstein-Barr virus, and JC virus.

OBJECTIVE: To evaluate nested PCR for Toxoplasma gondii (TOX), JC virus (JCV) and Epstein-Barr virus (EBV) for diagnosis of toxoplasmic encephalitis (TE), progressive multifocal leukencephalopathy (PML) and primary central nervous system lymphoma (PCL). METHODS: A prospective study encompassed 26 HIV-1-infected individuals presenting with focal neurologic signs and symptoms. Nested PCR was performed on both supernatants and pellets of centrifuged cerebrospinal fluid (CSF), on plasma and on white blood cells (WBCs). For a retrospective study, stored CSF supernatants were available from an additional 27 HIV-1-infected patients with TE, PML, and PCL. RESULTS: TE, PML or PCL was diagnosed in 13 of 26 patients in the prospective group. Plasma and WBC analysis by PCR was not informative except in one case of TE. TOX and JCV were detected by PCR in the CSF pellets of four of five patients with TE, and of four of five patients with PML, respectively, but in no other cases. EBV was detected not only in three of three cases of PCL, but also in six patients suffering from other conditions. PCR on the CSF supernatants was less sensitive for all three etiologies. These results correlated with those of the retrospective PCR analysis, for which only stored CSF supernatants were available, revealing sensitivities of 33%, 50% and 66% for TE, PML and PCL, respectively, but specificities of 100%. CONCLUSIONS: In the clinical routine, TOX and JCV PCR on centrifuged CSF pellets can be recommended to obtain an early diagnosis of TE and PML. Under these conditions, EBV PCR helps to exclude PCL as a cause of FBLs, as it is highly sensitive, but not specific, for PCL in HIV-1-infected individuals.

Journal Article↗