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H Voigt

Publications and source records attributed to H Voigt.

At least 19 recordsLinked to original sources
PubMed2006

CD28-mediated costimulation impacts on the differentiation of DC vaccination-induced T cell responses.

Costimulatory signals such as the ones elicited by CD28/B7 receptor ligation are essential for efficient T cell activation but their role in anti-tumour immune responses remains controversial. In the present study we compared the efficacy of DC vaccination-induced melanoma specific T cell responses to control the development of subcutaneous tumours and pulmonary metastases in CD28-deficient mice. Lack of CD28-mediated costimulatory signals accelerated tumour development in both model systems and also the load of pulmonary metastases was strongly increased by the end of the observation period. To scrutinize whether lack of CD28 signalling influences priming, homing or effector function of Trp-2(180-188)/K(b)-reactive T cells we investigated the characteristics of circulating and tumour infiltrating T cells. No difference in the frequency of Trp-2(180-188)/K(b)-reactive CD8+ T cells could be demonstrated among the cellular infiltrate of subcutaneous tumours after DC vaccination between both genotypes. However, the number of IFN-gamma-producing Trp-2-reactive cells was substantially lower in CD28-deficient mice and also their cytotoxicity was reduced. This suggests that CD28-mediated costimulatory signals are essential for differentiation of functional tumour-specific CD8+ T-effector cells despite having no impact on the homing of primed CD8+ T cells.

Adoptive Transfer↗
PubMed2005

Some physico-chemical parameters that influence proteinase K resistance and the infectivity of PrPSc after high pressure treatment.

Crude brain homogenates of terminally diseased hamsters infected with the 263 K strain of scrapie (PrP Sc) were heated and/or pressurized at 800 MPa at 60 degrees C for different times (a few seconds or 5, 30, 120 min) in phosphate-buffered saline (PBS) of different pH and concentration. Prion proteins were analyzed on immunoblots for their proteinase K (PK) resistance, and in hamster bioassays for their infectivity. Samples pressurized under initially neutral conditions and containing native PrP Sc were negative on immunoblots after PK treatment, and a 6-7 log reduction of infectious units per gram was found when the samples were pressurized in PBS of pH 7.4 for 2 h. A pressure-induced change in the protein conformation of native PrP Sc may lead to less PK resistant and less infectious prions. However, opposite results were obtained after pressurizing native infectious prions at slightly acidic pH and in PBS of higher concentration. In this case an extensive fraction of native PrP Sc remained PK resistant after pressure treatment, indicating a protective effect possibly due to induced aggregation of prion proteins in such buffers.

Animals↗
PubMed2005

[Arterial hypertension and dementia].

Arterial hypertension (AH) is considered to be an important risk factor for vascular cognitive impairment and probably for Alzheimer's disease, too. In the current review we provide an overview of the major prospective clinical trials on this issue. With respect to the inconsistent findings of these studies one must state that the interrelations between AH and dementia are still incompletely understood. Regarding therapy there thus is a simple rule: AH should be treated until normal blood pressure values are reached. As long as the hypothesis of a J-curve between blood pressure and cognitive dysfunction has not been disproved, overaggressive blood pressure lowering cannot be recommended. Regarding the aim of preventing dementia, there is no evidence for the superiority of a specific antihypertensive treatment regimen.

Antihypertensive Agents↗
PubMed2003

The use of the murine model of infection with Leishmania major to reveal the antagonistic effects that IL-4 can exert on T helper cell development and demonstrate that these opposite effects depend upon the nature of the cells targeted for IL-4 signaling.

In contrast to mice from the majority of inbred strains, BALB mice develop aberrant Th2 responses and suffer progressive disease after infection with Leishmania major. These outcomes depend on the production of Interleukin 4, during the first 2 d of infection, by CD4+ T cells that express the Vbeta4-Valpha8 T cell receptors specific for a dominant I-A(d) restricted epitope of the LACK antigen from L. major. In contrast to this well established role of IL-4 in Th2 cell maturation, we have recently shown that, when limited to the initial period of activation of dendritic cells by L. major preceding T cell priming, IL-4 directs DCs to produce IL-12, promotes Th1 cell maturation and resistance to L. major in otherwise susceptible BALB/c mice. Thus, the antagonistic effects that IL-4 can have on Th cell development depend upon the nature of the cells (DCs or primed T cells) targeted for IL-4 signaling.

Animals↗
PubMed2001

Repeated low-dose treatment of rats with pilocarpine: low mortality but high proportion of rats developing epilepsy.

Systemic administration of pilocarpine in rats can result in a chronic behavioral state that is similar to human temporal lobe epilepsy. The pilocarpine model of epilepsy is widely used for studying the factors that contribute to the development of epilepsy as a consequence of status epilepticus (SE). For this purpose, pilocarpine is either administered alone at a high systemic dose or in combination with lithium, which markedly potentiates the convulsant effect of pilocarpine. Both experimental protocols, however, are associated with high mortality rates. In the present study, we evaluated whether mortality rate in rats can be decreased by repeated administration of low doses of pilocarpine. The time the rats spent in SE was limited by diazepam. Preliminary experiments in lithium-free rats indicated that repeated low-dose administration of pilocarpine is too time-consuming to produce SE compared to single high-dose administration. All subsequent experiments were performed in lithium-pretreated rats. Single-dose injection of 30 mg/kg pilocarpine produced SE in approximately 70% of the animals, but 45% of the rats died although SE was interrupted by diazepam after 90 min. Repeated i.p. administration of 10 mg/kg pilocarpine at 30-min intervals resulted in SE after 2-4 injections; the mean dose of pilocarpine needed to induce SE was 26 mg/kg. When SE was interrupted after 90 min, mortality rate was below 10%, which was significantly lower compared to the protocol with one single administration of 30 mg/kg pilocarpine. In contrast to mortality rate, the development of spontaneous recurrent seizures did not differ between experimental protocols. Almost all rats which had experienced a SE of at least 60 min developed chronic epilepsy. Average latency to the first spontaneous seizure was approximately 40 days. The frequency and severity of spontaneous seizures was not significantly different between protocols, although animal groups with repeated low-dose treatment tended to have higher frequencies of spontaneous seizures compared to single-dose administration. The present study demonstrates that systemic treatment of lithium-pretreated rats with several low doses of pilocarpine efficiently produces SE and chronic epilepsy with much lower mortality rates than single-dose pilocarpine.

Animals↗
PubMed2001

IL-4 instructs TH1 responses and resistance to Leishmania major in susceptible BALB/c mice.

Immunity to infection with intracellular pathogens is regulated by interleukin 12 (IL-12), which mediates protective T helper type 1 (TH1) responses, or IL-4, which induces TH2 cells and susceptibility. Paradoxically, we show here that when present during the initial activation of dendritic cells (DCs) by infectious agents, IL-4 instructed DCs to produce IL-12 and promote TH1 development. This TH1 response established resistance to Leishmania major in susceptible BALB/c mice. When present later, during the period of T cell priming, IL-4 induced TH2 differentiation and progressive leishmaniasis in resistant mice. Because immune responses developed via the consecutive activation of DCs and then T cells, the contrasting effects of IL-4 on DC development and T cell differentiation led to immune responses that had opposing functional phenotypes.

Animals↗
PubMed1999

New insights into the role of the cytoskeleton in phagocytosis of Entamoeba histolytica.

Entamoeba histolytica, a human parasite, crosses the natural barriers of the intestine and, in turn, spreads into the deeper organs, resulting in amoebiasis. The motility of the parasite and its ability to lyse or phagocytose human cells facilitates passage of the amoeba through the intestinal epithelium. Little is known about the uptake of material by this parasite; nevertheless, the cytoskeleton is believed to play a role in phagocytosis. Myosin IB, an actin-binding protein, localizes to the phagocytic cup and, with time, surrounds the internalized phagosome itself. The role of unconventional myosins in phagocytosis has also been demonstrated in other cell types, suggesting that this molecular mechanism is a common denominator in phagocytic events. Here, we summarize the emerging view of the role of unconventional myosins as well as other cytoskeleton-associated proteins in pseudopod formation at early stages of phagocytosis and during the late step of this process in E. histolytica.

Animals↗
PubMed1999

Myosin IB from Entamoeba histolytica is involved in phagocytosis of human erythrocytes.

Entamoeba histolytica is a protozoan parasite that causes amoebic dysentery in humans. The disease is prevalent worldwide. Infection with E. histolytica results in invasion of the intestine by the parasite, followed by tissue damage and inflammation. During this invasive process, parasites kill and phagocytose human epithelial cells, immune cells and erythrocytes. Expression of amoebic pathogenicity requires a dynamic cytoskeleton that allows movement, tissue penetration and changes in parasite morphology. Myosin IB is a member of the myosin I family of motor proteins. Studies conducted both with Dictyostelium discoideum, a non-pathogenic amoeba, and with the yeast Saccharomyces cerevisiae indicate the involvement of myosin IB in cellular processes including movement, phagocytosis and endocytosis. Recently, we isolated the gene encoding myosin IB from E. histolytica. Thus, we decided to analyze the role of myosin IB in pathogenesis of amoeba. Using a specific anti-myosin IB antibody, this protein was localized in cell regions including the pseudopod, vesicles and underneath the plasma membrane. When E. histolytica was activated for erythrophagocytosis, myosin IB was markedly recruited to both the phagocytic cup and around internalized phagosomes. To analyze the role of myosin IB in phagocytosis, a strain overexpressing the myosin IB gene was constructed. This strain synthesizes threefold more myosin IB than the wild-type strain. Challenge of the transfected cell line with erythrocytes showed that these amoebae were deficient in erythrophagocytosis mainly in the uptake step, suggesting a role for myosin IB in the pathogenic activity of a human parasite.

3,3'-Diaminobenzidine↗
PubMed1997

Molecular characterization of myosin IB from the lower eukaryote Entamoeba histolytica, a human parasite.

The complete amino acid sequence of the Entamoeba histolytica unconventional myosin IB (Eh-myosin IB) is reported. Sequencing of overlapping cDNA fragments reveals a single open reading frame which predicts a 130 kDa protein of 1049 aa. Eh-myosin IB presents the three characteristics domains of myosins I subclass 1. This protein presents homology with myosins IB from other amoebae, but striking homologies with vertebrate unconventional myosins were also observed. The predicted actin and ATP-binding sites are located in the head domain. The heavy chain phosphorylation region is homologous to metazoan myosins I with an acidic residue present at the phosphorylation site. In the neck domain, an IQ motif indicates potential binding of calmodulin to the myosin I heavy chain. In the tail of Eh-myosin IB the three characteristic regions of myosin I are found. A putative membrane binding domain a very short domain rich in alanine and proline we demonstrate to be functional for actin binding, and the src-homology 3 domain. The Entamoeba histolytica myosin IB is the first unconventional myosin so far described in a lower eukaryote.

Actins↗
PubMed1996

Increased matrix proteins, collagen and transforming growth factor are early markers of hepatotoxicity in patients on long-term methotrexate therapy.

BACKGROUND: Hepatotoxicity, which may lead to fibrosis and cirrhosis, often limits the use of long-term low dose methotrexate for psoriasis and autoimmune diseases. Standard light microscopy lacks sensitivity for early fibrosis. DESIGN: This is a retrospective study of immunohistochemical markers of early fibrosis including laminin and fibronectin, collagen deposition and lipocyte activation in hepatic biopsies of 36 psoriatic patients treated with methotrexate for one to five years, at an average dose of 20 mg/week. Biopsies before initiation of methotrexate (n = 36) showed minimal immunohistochemical expression of desmin, transforming growth factor alpha, matrix proteins, and collagen. Expression of laminin, fibronectin, collagens III and IV increased significantly and progressively over baseline values after cumulative doses of 1.5 +/- 0.25 g (n = 20) and 3 +/- 0.5 g methotrexate, respectively. Increases in desmin, smooth muscle actin and collagen type I also occurred but the changes were less consistent. Light microscopic abnormalities of hepatotoxicity were not detectable in any of these biopsies. CONCLUSIONS: Immunohistochemical quantification of matrix proteins and collagens type III and IV may be early, sensitive and dose responsive markers of methotrexate hepatotoxicity which progress with increasing cumulative doses of methotrexate.

Adult↗
PubMed1995

Topodermatographic image analysis for melanoma screening and the quantitative assessment of tumor dimension parameters of the skin.

BACKGROUND: The clinical need to identify and evaluate changes of cutaneous lesions in melanoma screening or follow-up of patients with cancer is of paramount importance. Because skin-lesion changes may be small and numerous, clinical assessment alone does not meet the requirements of quantitative assessment. Using the computer as a diagnostic tool for the image analysis of sequentially captured skin surface images has resulted in the technical problem of insufficient registration reproducibility. This paper describes the technical logistics, setup procedure, and clinical evaluation of the novel technique termed "topodermatography," which performs the quantitative videographic image analysis of skin-lesion changes over time. METHODS: Digitized measurements of skin-surface image parameters were performed using a high-speed processor with an onboard coprocessor, a high-resolution video camera, specifically designed image processing software, and a position framework for the adjustment of the patient's standing position. The topodermatographic image analysis was performed on 109 consecutive patients who were at risk for melanoma (N = 98), had lesions from Kaposi's sarcoma (N = 4), had metastatic skin deposits from melanoma (N = 3), and had breast cancer (N = 4). RESULTS: Skin lesion changes over time could be identified reliably within a few millimeters of diametric enlargement. In this series, a 0.51% early melanoma detection rate was assessed in 19 of 98 patients followed for 12 months. By monitoring manifest neoplastic skin lesions, tumor growth kinetics were analyzed quantitatively to determine the total area of skin involvement, thus facilitating precise response assessment. CONCLUSIONS: Topodermatographic image analysis helps to optimize screening and follow-up procedures for patients with melanoma and populations at risk for melanoma. In addition, metastatic tumor lesions on the skin can be monitored dynamically, facilitating the accurate evaluation of the impact of systemic therapy on multiple skin deposits from melanoma and nonmelanoma cancers.

Adolescent↗
PubMed1992

Cytoreductive combination chemotherapy for regionally advanced unresectable extramammary Paget carcinoma.

Extramammary Paget carcinoma (EPC) is considered to originate from the eccrine and apocrine glands of the adnexal skin of the axilla, vulva or penis, scrotum, or perineum. If immunohistochemical techniques with the use of cytoskeletal markers are applied in addition to histologic examination, EPC lesions are found to be multifocal adenocarcinoma of the adnexal sweat glands. So far, therapeutic approaches have included primary surgery, followed optionally by radiation therapy. It is possible to achieve a cure only when manifestations are detected early and confined regionally. The role of palliative chemotherapy has not yet been assessed in this disease, particularly because of the lack of compliance and follow-up in patients with EPC.

Aged↗
PubMed1992

[Calcium antagonists--determination of current status and therapeutic significance].

The important group of drugs known as calcium antagonists is surveyed from a clinico-pharmacological viewpoint. The recently introduced substances are presented in a detailed manner. Common features and differences in pharmacodynamics and pharmacokinetics of the individual calcium antagonists are explained and their differential therapeutic use in the treatment of chronic cardiovascular diseases is discussed. The article also reports on drug interferences, contraindications and possible extensions of indications. An assessment is made of results achieved so far when applying calcium antagonists in the treatment of chronic cardiovascular diseases and in the prevention of arteriosclerosis.

Calcium↗
PubMed1991

Enriching the sexual experience of couples: the Asian traditions and sexual counseling.

Drawing from Hindu and Buddhist Tantric traditions, central themes reflecting Asian approaches to sexuality are described and contrasted with contemporary values, assumptions, and objectives implicit in both sexual experience and in the clinical practice of sexual counseling. The Tantric ceremonial sex ritual provides a fertile source for several innovative behavioral assignments useful in sexual counseling. Five exercises in intimacy derived from the ancient Tantric sex ritual are presented and suggested as home assignments for couples: the creation of a ritual, synchronized breathing, sustained eye contact, motionless intercourse, and sexual exchange without orgasm. Applications to intimacy development, sexual enhancement, and sexual counseling for couples are described, creating a broad and meaningful context for responding to clients' sexual concerns.

Behavior Therapy↗