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Biomedical subjects

J Ennen

Publications and source records attributed to J Ennen.

At least 19 recordsLinked to original sources
PubMed2001

Attention deficits in minimal hepatic encephalopathy.

Minimal hepatic encephalopathy (HE) is characterized by a decrease of psychomotor speed, and deficits in visual perception, visuo-spatial orientation, and visuo-constructive abilities. Attention deficits have also been proposed to be part of the syndrome. Several attempts were made in the past to elaborate suitable psychometric means for the assessment of minimal HE. However, there is still no "gold standard" for the diagnosis of minimal HE. We recently evaluated the so called "PSE-Test" for the assessment of minimal HE, a test battery which does not include a test predominantly aimed at the assessment of attention. We therefore presented a battery of attention tests in addition to the PSE-Test to a group of cirrhotics without clinical signs of HE compared to a healthy control group matched for age and education to determine whether the addition of special attention tests would increase the diagnostic sensitivity of the PSE-Test. It was shown that the patients with a pathological PSE-Test result differed significantly from controls in all attention tests applied, while the patients with normal PSE-Test results achieved attention test results similar to that of the controls. Thus, the PSE-Test results represent attention deficits as well as deficits in motor skills, visuo-spatial orientation, and visual construction.

Adult↗
PubMed1999

Coenzyme Q10, a cutaneous antioxidant and energizer.

The processes of aging and photoaging are associated with an increase in cellular oxidation. This may be in part due to a decline in the levels of the endogenous cellular antioxidant coenzyme Q10 (ubiquinone, CoQ10). Therefore, we have investigated whether topical application of CoQ10 has the beneficial effect of preventing photoaging. We were able to demonstrate that CoQ10 penetrated into the viable layers of the epidermis and reduce the level of oxidation measured by weak photon emission. Furthermore, a reduction in wrinkle depth following CoQ10 application was also shown. CoQ10 was determined to be effective against UVA mediated oxidative stress in human keratinocytes in terms of thiol depletion, activation of specific phosphotyrosine kinases and prevention of oxidative DNA damage. CoQ10 was also able to significantly suppress the expression of collagenase in human dermal fibroblasts following UVA irradiation. These results indicate that CoQ10 has the efficacy to prevent many of the detrimental effects of photoaging.

Antioxidants↗
PubMed1994

CD8+ T lymphocytes of African green monkeys secrete an immunodeficiency virus-suppressing lymphokine.

Following natural and experimental infection by simian immunodeficiency virus SIVagm of African green monkeys (AGMs), the natural host, there is no evidence for the development of an immunodeficiency. Within the framework of our studies on human immunodeficiency virus (HIV)/SIV pathogenesis, we investigated the influence of CD8 T lymphocytes on SIVagm replication in AGM CD4 T lymphocytes in vitro. The following observations were made: (i) Peripheral blood mononuclear cells from both seronegative and seropositive AGMs contained only a low proportion (i.e., 10%) of CD4+ lymphocytes, whereas a high proportion (80%) of CD8+ cells was detected. Even after persistent SIVagm infection, CD4 T lymphocytes do not decrease in number. (ii) The target of in vitro infection of peripheral blood cells is the CD4+ mononuclear cell (T lymphocytes, monocytes) and SIVagm infects by binding to the CD4 molecule. (iii) In both naturally and experimentally SIVagm-infected AGMs the CD4+ T cells and monocytes, but not the CD8+ T cells, harbor DNA provirus. (iv) Virus reisolation and virus replication of SIVagm in CD4 T lymphocytes from seropositive AGMs is suppressed in the presence of autologous CD8 T lymphocytes or a soluble factor produced by these cells. Taken together, one possible reason for the apathogenicity of the SIVagm infection in AGMs may be the suppression of virus replication by a soluble, yet unidentified factor secreted by CD8 lymphocytes quantitatively dominating among peripheral blood cell populations. We have tentatively termed this factor "immunodeficiency virus-suppressing lymphokine." In addition, we show that immunodeficiency virus-suppressing lymphokine from AGMs is able to suppress HIV-1 replication in human CD4+ T cells.

Animals↗
PubMed1994

[Sensitivity studies on the demonstration of HIV-1 particles using RT HIV-1 PCR in pooled plasma before virus inactivation].

The goal of this study was the establishment of a reverse-transcription polymerase chain reaction (PCR) test and the evaluation of its sensitivity to detect an HIV-1 contamination in pooled plasma samples prior to the solvent-detergent (SD) inactivation procedure. Pooled plasma samples were spiked with known concentrations (1,000-0.1 TCID50/ml) of HIV-1, originated from tissue culture supernatants. Unspiked plasma samples were used as negative controls. After reverse transcription, a PCR in 4 different HIV-gene regions (gag, pol, env, ltr) followed by a hybridisation with specific probes was done. The achieved sensitivity in 3 tests (pol. gag, ltr) was 0.1 TCID50/ml and 1.0 TCID50/ml in the env-PCR system. It was shown in previous studies that by inactivation of pooled plasma with the SD technique a reduction of HIV-1 infectivity greater than 10(6) is achieved. The combination of PCR testing and the SD inactivation procedure makes it possible for the first time to define the maximum amount of contaminating HIV-1 in case of a negative PCR result. According to this procedure, the residual HIV-1 load of virus-inactivated plasma would not exceed 1 TCID50 per 1,000 litres at worst.

Blood↗
PubMed1993

Inactivation of HIV infectivity by the chlorite-oxygen reaction product tetrachlorodecaoxygen.

OBJECTIVE: Since the chlorite-oxygen reaction product tetrachlorodecaoxygen (TCDO) anion complex promotes efficaciously tissue repair and has antibacterial activity, our aim was to determine the effects of TCDO on the replication of HIV and on the infectivity of free HIV particles. DESIGN: The effects of TCDO on cellular HIV replication machinery and the consequences of TCDO for infectivity of HIV virions were evaluated. METHODS: Virus yields in supernatants of TCDO-supplemented cultures of HIV-infected cells or virus infectivity in TCDO-treated virus stocks were quantified by titration assays and then calculating the 50% tissue culture infectious dose. RESULTS: First, TCDO did not affect the replication of HIV in persistently infected lymphocytic and monocytic cell lines or in peripheral blood mononuclear cells. Second, supplementation of HIV stocks with TCDO markedly decreased the infectivity of HIV particles in a concentration dependent manner. Third, the binding of gp120 envelope glycoprotein of HIV-1 to cells is blocked by pre-incubation with TCDO. Fourth, the inhibition of HIV replication by the reverse transcriptase inhibitor 3'-azido-3'-deoxythymidine (zidovudine) in de novo infected cell cultures was not affected by the simultaneous addition of TCDO. However, the delayed virus spread of HIV in cultures in the presence of suboptimal concentrations of zidovudine could significantly be blocked by the simultaneous addition of TCDO. Fifth, TCDO failed to induce the chromosomally integrated HIV-1 provirus in the T-lymphoma cell line ACH2. CONCLUSIONS: TCDO appears to inactivate HIV particles directly, but has no influence on the intracellular replicative machinery of HIV. Our results suggest that a clinical evaluation of the TCDO complex as chemotherapy for HIV infection and full-blown AIDS should be considered, particularly in patients concomitantly receiving zidovudine.

Antiviral Agents↗
PubMed1993

Interferon-gamma-activated monocytes impair infectivity of HIV particles by an oxygen metabolite-dependent reaction.

Mononuclear phagocytes generate microbicidal oxygen metabolites spontaneously and after phagocytic stimulation by a NADPH-dependent enzymatic reaction called the oxidative burst. The spontaneous release of reactive oxygen radicals and intermediates (ROI) increases five- to eightfold after treatment of monocytes with the lymphokine interferon-gamma (IFN-gamma). The effect of the IFN-gamma-activated release of ROI by human monocytes on the infectivity of free human immunodeficiency virus (HIV) in the supernatant was investigated with the following results. First, IFN-gamma-activated, but neither control monocytes nor lipopolysaccharide-stimulated monocytes effectively decreased the infectivity of cell-free HIV-1 in culture medium supernatant. Second, the mechanism of inactivation was dependent on the enhanced spontaneous release of ROI by IFN-gamma-activated mononuclear phagocytes, since either the enzyme catalase or the free radical scavenger butylated hydroxyanisole (BHA) could block this activity. Third, soluble and solid-phase HIV-1 outer envelope glycoprotein (gp120) failed to trigger the oxidative burst activity after specific gp120-monocytic CD4 receptor interaction. These results indicate an anti-viral effect of IFN-gamma-activated monocytes/macrophages on HIV-1 which may have important implications for our understanding of spread of the virus in the body and the development of full-blown AIDS after a long period of latency.

Butylated Hydroxyanisole↗
PubMed1992

AIDS vaccine: present problems and future perspectives.

Vaccination has proved to be an effective means for the prevention of infectious diseases. Advances in our understanding of the human immunodeficiency virus (HIV) and the immune system of the host may lay the foundation for the development of an AIDS vaccine. Current attempts to develop vaccines focus on the development of substances that will produce a different type of immune response from that which occurs naturally. Progress has been made in understanding the mechanisms by which the AIDS virus stimulates an neutralizing antibody response and triggers specific cytotoxic T lymphocytes in the host. The pressing need for a vaccine has prompted the testing of several candidate vaccines based on the simian immunodeficiency virus (closely related to HIV) in the macaque animal model for AIDS. The lessons learned from these trials will be valuable for developing future vaccines.

AIDS Vaccines↗
PubMed1992

Influence of prostatic disease and prostatic manipulations on the concentration of prostate-specific antigen.

We examined the influence of different factors [benign prostatic hyperplasia (BPH), prostatic carcinoma (PCA), organ volume, weight of resected tissue, transurethral catheter] on the serum prostate-specific antigen (PSA) levels in 253 patients with BPH (n = 138; 54%) and PCA (n = 115; 46%). Only in 57.2% of the BPH patients, PSA values were < 4 ng/ml, in 74.6% < 7 ng/ml. In 108 patients with BPH, a transurethral prostatectomy was performed. PSA values correlated significantly with the sonographically determined prostatic volumes and less precisely with the weight of the resected tissue. The PSA concentration per milliliter of prostatic volume was 0.12 ng/ml, per gram of resected tissue it was 0.21 ng/ml. An incidental PCA was found in 12/108 patients (11%). The PSA values were identical with those of the total collective in regard to volume and tissue weight. In 11 patients, we examined possible alterations of the PSA values before and until 24 h after prostatic massage. Only insignificant alterations were seen, a massive increase was not found in any patient. Searching for an absolutely valid 'normal value' appears hardly appropriate. However, the usefulness of PSA is increased when the sonographically determined prostatic volume is included. A rectal examination of the prostate has no influence on the PSA value.

Aged↗
PubMed1992

Vaccine protection against SIVmac infection by high- but not low-dose whole inactivated virus immunogen.

Eight rhesus macaques were immunized intramuscularly four times (0, 1, 2, and 4 months) over a period of 4 months with a formalin-inactivated whole Simian immunodeficiency virus (SIV) vaccine in the presence of muramyl dipeptide (MDP) as adjuvant. Four animals received 0.5 mg and the other four received 0.1 mg immunogen per injection. Three weeks after the final immunization, the vaccinated monkeys along with two control monkeys were challenged intravenously with 50 MID50 of SIVmac251-32H. At the time of challenge, one monkey from the high dose group had a high titer (1:761) of antibody able to neutralize in vitro the homologous 32H strain of SIV mac. All other animals had lower but measurable titers (1:57-1:453), although there was no correlation between the levels of neutralizing antibody and subsequent protection. Upon challenge, three of four animals from the low dose group (plus the nonvaccinated control animals) became infected as demonstrated by reisolation of virus from peripheral blood mononuclear cells, by SIVmac-specific polymerase chain reaction, and by the development of a strong anamnestic response. In the sera from these animals the titer of neutralizing antibody rose to over 1:5,100. All other animals (one from low dose group and all four of the high dose group) remained negative by all parameters at 4 months post challenge. These data indicate that when used in conjunction with MDP, the amount of immunogen required per immunization for protection against challenge is between 0.1 and 0.5 mg.

Animals↗
PubMed1991

Augmentation of interleukin 2-activated cytotoxicity after treatment of cells with inhibitors of interferon production.

Low-density human lymphocytes cultured with recombinant interleukin 2 (rIL-2) generated a high level of interferon(s) (IFN). Consistently more IFN including IFN-tau was produced during the first 3 days of culture with rIL-2 than during the subsequent 4 days. That ability was mainly associated with mepacrine+ cells and was decreased by low concentrations of leucine methyl ester (Leu-O-Me) or ammonium chloride. Leu-O-Me was employed either for the pretreatment of cells before the culture or as the additive to culture medium. The decrease in IFN production after pretreatment was associated with enhanced rIL-2-activated cytotoxicity. Similarly, 1 mM of ammonium chloride or 1 mM of Leu-O-Me added to rIL-2 supplemented cultures for 3 days showed an association between inhibition of IFN-tau generation and increased activation of cytotoxic activity. Thus NK cells appear to regulate their own response to rIL-2 activation and the control mechanism seems to be associated with the ability of the cells to produce IFN(s) and possibly other cytokines.

Cells, Cultured↗
PubMed1991

The quest for an AIDS vaccine: the state of the art and current challenges.

Despite intense efforts worldwide, using state-of-the-art methods and techniques and despite ever-increasing knowledge about the molecular and structural make-up of HIV, a practical vaccine against acquired immunodeficiency syndrome (AIDS) has yet to be developed. The increasing use of recombinant DNA techniques and synthetic peptide technology has allowed many groups to identify at the epitope level the regions of HIV proteins which act as targets for (and stimulate) the immune response. Epitopes which stimulate and bind neutralizing antibodies have been examined in detail and an ever-increasing number of antibody-dependent cellular cytotoxicity (ADCC) and cytotoxic T lymphocytes (CTL) epitopes are being defined, as are potentially harmful (immunosuppressive or enhancing) domains. It still is not clear which of the different immune responses (or combinations thereof) it will be necessary to stimulate in order to protect from infection. Infected humans develop neutralizing antibodies, ADCC-inducing antibodies and CTL responses against a variety of viral proteins but it is not known which of these can control or prevent infection in vivo. The extensive knowledge of HIV and the immune response it elicits is being used to design and produce a wide variety of putative vaccines, ranging from whole inactivated virus, through recombinant organisms/proteins, to synthetic peptides although each has its inherent advantages and disadvantages. The very nature of HIV makes vaccine development difficult at best. However, recent successes using whole inactivated virus or virus-infected cells in the macaque simian immunodeficiency virus (SIVmac) model system at least show that protection against lethal lentivirus infection can be achieved.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1991

Inhibition of HIV-1 replication and NF-kappa B activity by cysteine and cysteine derivatives.

HIV-1 proviral DNA contains two binding sites for the transcription factor NF-kappa B. HIV-1-infected individuals have, on average, abnormally high levels of tumour necrosis factor alpha (TNF alpha) and abnormally low plasma cysteine levels. We therefore investigated the effects of cysteine and related thiols on HIV-1 replication and NF-kappa B expression. The experiments in this report show that cysteine or N-acetylcysteine (NAC) raise the intracellular glutathione (GSH) level and inhibit HIV-1 replication in persistently infected Molt-4 and U937 cells. However, inhibition of HIV-1 replication appears not to be directly correlated with GSH levels. Cysteine and NAC also inhibit NF-kappa B activity as determined by electrophoretic mobility shift assays and chloramphenicol acetyl-transferase (CAT) gene expression under control of NF-kappa B binding sites in uninfected cells. This suggests that the cysteine deficiency in HIV-1-infected individuals may cause an over-expression of NF-kappa B-dependent genes and enhance HIV-1 replication. NAC may be considered for the treatment of HIV-1-infected individuals.

Acetylcysteine↗
PubMed1991

Mutational analysis of the simian immunodeficiency virus SIVmac nef gene.

We are using site-directed mutagenesis of single viral genes to identify and analyze the genetic determinants of human and simian immunodeficiency virus pathogenicity. In a first approach, we have constructed a series of simian immunodeficiency virus SIVmac nef mutants by partial deletion and insertions in the nef gene, as this gene is a candidate gene for the establishment and maintenance of latency. nef insertion mutants replicated faster than wild-type SIVmac, suggesting that the nef gene product acts as a negative factor for replication. Surface phenotyping revealed that cultures permanently infected with nef mutants exhibit an enhanced expression of viral proteins on the outer cell surface. We have analyzed the properties of the mutant viruses in cell culture and intend to use rapidly replicating mutants (putatively unable to undergo latency) as model vaccine viruses in the rhesus monkey.

Base Sequence↗
PubMed1990

Decreased accessory cell function of macrophages after infection with human immunodeficiency virus type 1 in vitro.

Peripheral blood monocytes from human immunodeficiency virus (HIV)-infected individuals or AIDS-related complex/AIDS patients ex vivo exhibit distinct alterations in some but not all immune functions. In studies presented here, monocytes from healthy donors were infected with HIV 1 in vitro and co-cultures with autologous uninfected T lymphocytes were set up. The monocyte/macrophage (M phi)-dependent T cell function was determined by measurement of proliferative and secretory [interleukin (IL)2, interferon-gamma] responses to lectin (phytohemagglutinin), mitogen (anti-CD3 monoclonal antibody), or recall antigen (tetanus toxoid, tuberculin). Accessory function of M phi was normal after HIV infection when optimal amounts (10%-20%) were added to the T lymphocytes. However, HIV infection of M phi significantly decreased T cell proliferative responses and secretion of IL2 when supplemented at limited dilution (0.5%-5%), although interferon-gamma production was not affected. Whereas the lipopolysaccharide-triggered M phi production of IL1 was not impaired by HIV 1 infection, there was a significant decrease in this response when anti-CD3 monoclonal antibody or tetanus toxoid were used to trigger the peripheral blood mononuclear cells. The impairment of proliferation of T lymphocytes in the presence of HIV 1-infected M phi could be overcome by addition of exogenous IL 1. Taken together, these data clearly show that the mononuclear phagocyte-dependent enhancement of stimulated T cell proliferation and lymphokine secretion is decreased when the restricted numbers of monocytes/M phi are HIV 1 infected. There are, therefore, two possible roles of M phi in HIV infection and progression to disease. First, as a reservoir and vehicle for dissemination of the virus, and second, as an immune cell whose essential functions are impaired by infection.

Antigen-Presenting Cells↗
PubMed1990

Immunological studies of the basis for the apathogenicity of simian immunodeficiency virus from African green monkeys.

Potential reasons for the lack of pathogenicity of the simian immunodeficiency virus SIVagm in its natural host, the African green monkey (AGM, Cercopithecus aethiops), were investigated with respect to immunological mechanisms. The functional immune response of monkeys to infection was similar (though not identical) to that of humans to infection with human immunodeficiency virus type 1 (HIV-1). In the sera of infected animals, neutralizing antibodies were found to be low or absent, and in particular there was no neutralization of the various isolates by homologous sera. There was no detectable antibody/complement cytotoxicity, though AGM sera were able to initiate antibody-dependent cellular cytolysis of infected cells in the presence of healthy effector peripheral blood lymphocytes. As in the human/HIV system, macrophages from AGMs are readily infected by SIVagm. Two possibly important differences between the AGM/SIVagm system and the human/HIV system are (i) the low immune response of the AGMs to the core protein of SIVagm and (ii) the significantly lower inhibitory effect of SIVagm proteins on the proliferation of AGM lymphocytes.

Animals↗
PubMed1989

Effect of dexamethasone on mechanisms responsible for regulation of polyclonal B-cell response.

The effect of dexamethasone (Dex) on the differentiation of pokeweed mitogen (PWM), or Staphylococcus aureus Cowan I (SAC)-stimulated human peripheral blood mononuclear cells (PBMC), into immunoglobulin secreting cells (ISC) was studied with special emphasis on the regulatory role of IL-2 in these systems. Dex, known to reduce endogenous IL-2 production and expression of IL-2 receptors, reduced the proliferation of pokeweed mitogen-activated T-cells, and the proliferation was restored by exogenous recombinant interleukin 2 (rIL-2). Furthermore, Dex enhanced in PWM and in SAC-stimulated cultures, the number of ISC. Addition of rIL-2 resulted in a further increase of ISC in SAC-stimulated cultures, whereas in PWM-stimulated cultures the enhancing effect of Dex was reversed. When IL-2 receptors were blocked by a monoclonal anti-IL-2 receptor antibody rIL-2 was no longer suppressive. Addition of monocytes to PWM-stimulated cultures resulted in suppression or the number of ISC, which was even more pronounced when monocytes were pretreated with rIL-2. In contrast to ISC, neither a suppressive effect of rIL-2 nor an enhancing effect of Dex was observed when PWM-stimulated cultures were evaluated for cells with intracytoplasmic immunoglobulin (plasma cells). From these results we conclude that Dex, by blocking IL-2 production and receptor expression, interferes with IL-2 mediated induction and/or activation of suppressor mechanisms.

B-Lymphocytes↗
PubMed1989

The effect of interleukin 2 on Fc-gamma receptor function of human monocytes requires specific intercellular interaction.

We examined the effect of interleukin 2 (IL 2) on the capacity of human monocytes to secrete reactive oxygen species triggered via Fc-gamma receptor (Fc gamma R) function as measured by chemiluminescence (CL). IL 2 did not activate highly purified (hp) monocytes to respond to Fc gamma R-mediated phagocytic stimulation with an enhanced respiratory burst activity, unless low numbers of T lymphocytes had been cocultured with hp monocytes. The degree of monocyte activation in peripheral blood mononuclear cells (PBMC) by IL2 was dependent on T lymphocytes to monocytes ratios as well as on IL 2 concentrations. Optimal Fc gamma R function was detected with IL 2 concentrations of 60 to 600 U/ml and one to two T lymphocytes per monocyte, whereas higher cellular ratios were suppressive. Supernatants from IL 2-treated PBMC contained interferon-gamma (IFN-gamma) and monocyte activating factor (MAF) activity (= enhanced monocytic Fc gamma R mediated CL). The secretion of both cytokine activities was strongly enhanced by a cooperative function of monocytes. The correlation of IL 2-induced secretion of IFN-gamma and MAF activity was striking; however, monoclonal anti-IFN-gamma antibodies failed to abrogate IL 2-stimulated and lymphocyte-dependent monocyte activation. Although IL 2 had no direct monocyte activating effect, pretreatment of hp monocytes with IL 2 led to a monocyte priming: subsequent coculture with autologous control T lymphocytes enhanced the monocyte Fc gamma R-mediated CL response. The priming of monocytes by IL 2 was dependent on the interaction of IL 2 with the monocytic IL 2 receptor, as shown by inhibition experiments with anti-IL 2 receptor monoclonal antibodies. Thus, we observed an IL 2-driven monocyte/T lymphocyte interaction leading to an increased Fc gamma R-mediated monocytic respiratory burst activity and to the secretion of a soluble MAF activity, but there were no detectable amounts of IFN-gamma.

Antigens, Differentiation↗