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Biomedical subjects

H Hof

Publications and source records attributed to H Hof.

At least 19 recordsLinked to original sources
PubMed2006

Inverse planned stereotactic intensity modulated radiotherapy (IMRT) in the treatment of incompletely and completely resected adenoid cystic carcinomas of the head and neck: initial clinical results and toxicity of treatment.

BACKGROUND: Presenting the initial clinical results in the treatment of complex shaped adenoid cystic carcinomas (ACC) of the head and neck region by inverse planned stereotactic IMRT. MATERIALS: 25 patients with huge ACC in different areas of the head and neck were treated. At the time of radiotherapy two patients already suffered from distant metastases. A complete resection of the tumor was possible in only 4 patients. The remaining patients were incompletely resected (R2: 20; R1: 1). 21 patients received an integrated boost IMRT (IBRT), which allow the use of different single doses for different target volumes in one fraction. All patients were treated after inverse treatment planning and stereotactic target point localization. RESULTS: The mean follow-up was 22.8 months (91-1490 days). According to Kaplan Meier the three year overall survival rate was 72%. 4 patients died caused by a systemic progression of the disease. The three-year recurrence free survival was according to Kaplan Meier in this group of patients 38%. 3 patients developed an in-field recurrence and 3 patient showed a metastasis in an adjacent lymph node of the head and neck region. One patient with an in-field recurrence and a patient with the lymph node recurrence could be re-treated by radiotherapy. Both patients are now controlled. Acute side effects >Grade II did only appear so far in a small number of patients. CONCLUSION: The inverse planned stereotactic IMRT is feasible in the treatment of ACC. By using IMRT, high control rates and low side effects could by achieved. Further evaluation concerning the long term follow-up is needed. Due to the technical advantage of IMRT this treatment modality should be used if a particle therapy is not available.

Adult↗
PubMed2006

Gliotoxin-mediated suppression of innate and adaptive immune functions directed against Listeria monocytogenes.

Gliotoxin is an immunosuppressive apoptogenic mycotoxin produced by a number of fungi including important human pathogens as Aspergillus fumigatus. In order to elucidate the potential role of gliotoxin as immunoevasive fungal virulence factor we studied the effects of gliotoxin on the innate and adaptive T cell-mediated immune response against the facultatively intracellular bacterium Listeria monocytogenes. Gliotoxin induced apoptosis of bone marrow-derived macrophages, dendritic cells and CD8 T cells in a dose- and cell type-dependent manner. In vitro the apoptogenic effect of gliotoxin correlated with a strong reduction of TNF-alpha and interleukin (IL)-12 production by dendritic cells and bone marrow-derived macrophages infected with L. monocytogenes and in the case of infected macrophages also in reduced NO-production and recognition by L. monocytogenes-specific CD8 T cells. Further gliotoxin pre-treatment of CD8 T cells reduced target cell lysis. In vivo, treatment of mice with gliotoxin increased the bacterial burden during the innate and the adaptive phase of primary L. monocytogenes infection. Taken together, these results demonstrate the suppressive effects of gliotoxin on the innate and also on the adaptive T cell-mediated antilisterial immunity.

Animals↗
PubMed2006

A new, broad-spectrum azole antifungal: posaconazole--mechanisms of action and resistance, spectrum of activity.

Posaconazole, a new triazole antifungal, exerts principally the same mechanism of action as the other azole derivatives, i.e. it inhibits the ergosterol production by binding and inhibiting the lanosterol-14alpha-demethylase which is present in almost all fungi except Pneumocystis and Pythium. Posaconazole has an exquisitely high affinity to this target. Since posaconazole has a chemical structure different from fluconazole and voriconazole, it can interact with an additional domain of the target so that it may inhibit even mutated strains resistant to fluconazole and voriconazole. In addition posaconazole is a bad substrate for efflux pumps in fungi, so it can stay active when other azoles are already inactive. Furthermore, the spectrum of posaconazole is rather large including also some zygomycetes resistant to other azoles. In conclusion, posaconazole is actually the most potent azole derivative used in medicine. A combination of posaconazole with other groups of antifungals may have a favourable effect. There are several methods to test the in vitro activities of posaconazole including the E-test, though interpretive breakpoints are still lacking.

Antifungal Agents↗
PubMed2005

Lentinan has a stimulatory effect on innate and adaptive immunity against murine Listeria monocytogenes infection.

Lentinan, a (1-3)-beta glucan from Lentinus edodes, is licensed as an immunostimulatory drug. We tested the effect of lentinan in the well-established model system of the murine Listeria monocytogenes infection. Pre-treatment of bone marrow macrophages and dendritic cells with lentinan resulted in increased production of TNF-alpha and IL-12 after L. monocytogenes infection in vitro. After lentinan treatment bone marrow macrophages showed increased NO-production and enhanced cytotoxic activity against L. monocytogenes. Pre-treatment of mice with lentinan resulted in increased concentrations of TNF-alpha, IL-12 and IFN-gamma and also an increased number of L. monocytogenes specific CD8 T cells in the spleen. The bacterial burden in spleen and liver of mice was significantly reduced during primary and secondary Listeria infection after lentinan pre-treatment of mice. In summary these results show that lentinan enhances the protective CD8 T-cell response against L. monocytogenes probably by a mechanism that involves the IL-12-mediated augmentation of the specific antilisterial CD8 T-cell response.

Adjuvants, Immunologic↗
PubMed2005

[Treatment of metastases--the place of radiotherapy].

Radiotherapy has a permanent place in the treatment of metastases. Irradiation--both in palliative and curative intent--is applied mainly to treat brainand bone metastases. In the case of the latter, an appreciable reduction in pain, but also recalcification of osteolytic lesions posing a threat to bone stability can be induced. The neurological symptoms of cerebral metastases, as well as overall survival, are also improved. Here, local tumor control is largely equal to that achieved with surgical treatment of metastases. Through the use of very precise stereotactic irradiation techniques sparing normal tissue, side effects can also be kept low. Similar techniques of precision irradiation are now also being applied to visceral metastases. Impressive remission rates have been achieved in the lungs and liver.

Aged↗
PubMed2005

Quantitative analysis of lung and tumour mobility: comparison of two time-resolved MRI sequences.

The purpose of this study was to describe the use of parallel imaging technique (PAT) using dynamic MRI in lung and tumour mobility during the breathing cycle. 20 patients with stage I non-small cell lung carcinoma were investigated using two dynamic gradient echo sequences with PAT (TrueFISP (fast imaging with steady precession), and fast low angle shot (FLASH). Craniocaudal distance from the apex to the diaphragm of the thorax and tumour mobility during the breathing cycle were measured. Signal-to-noise ratio (SNR) of the tumour was determined. In spite of the different temporal resolutions both trueFISP and FLASH sequence proved to be adequate to continuously measure lung motion and tumour mobility. SNR of the tumour was significantly higher using the trueFISP sequence than FLASH sequence (20.7+/-3.6 vs 5.8+/-2.3, p<0.01). Mobility of the tumour bearing hemithorax was significantly lower compared with the non-tumour bearing hemithorax (p<0.05). Dynamic MRI using PAT allows for continuous quantitative documentation of tumour mobility and lung motion. Because of the higher SNR, trueFISP sequence provides a better delineation of intrapulmonary lesions with a sufficient temporal resolution.

Aged↗
PubMed2004

[Stereotactic irradiation of lung tumors].

Stereotactic irradiation of lung tumors is a relatively new technique aiming at increased applicable radiation doses by a reduction of normal tissue involvement. As a result of adequate patient immobilization, three dimensional treatment planning and highly precise target point definition, the safety margins generally used in conventional radiotherapy can be reduced significantly. Increased fraction doses, which have an amplified biological effect, can be used and lead to a shortening of the overall treatment time. Especially for localized early-stage non-small-cell lung cancer the achieved dose escalation is proven to correlate with an increased local tumor control. But also the utilization for the therapy of lung metastases of solid tumors is possible. In spite of small patient cohorts and limited long-term data compared to conventional radiotherapy the results are promising.

Dose Fractionation, Radiation↗
PubMed2004

Trichosporon asahii infection of a dialysis PTFE arteriovenous graft.

Trichosporon species are the causative agents of superficial skin infections, such as white piedra. Immunocompromised hosts, particularly those with underlying hematological malignancy, are at risk of developing invasive infection, which usually progresses to disseminated life-threatening disease. Peritonitis caused by Trichosporon has been described in end-stage renal disease patients treated with continuous ambulatory peritoneal dialysis. Here, we report on a Trichosporon infection of an arteriovenous graft in a patient on chronic hemodialysis. The infection was successfully treated with fluconazole and total surgical resection of the graft.

Antifungal Agents↗
PubMed2003

History and epidemiology of listeriosis.

Listeriae are used as a tool by different specialities in biomedical research. There are now at least four major fields of interest in Listeria: (1). the role in medical microbiology: Listeria monocytogenes causes severe diseases of men and animals and is difficult to treat; (2). the role in food microbiology: Listeria is a food-borne pathogen and is found in various food items; (3). the role in cell biology: L. monocytogenes is a facultative intracellular parasite having an intense cross-talk and interactions with the host cell; (4). the role in immunology: basic knowledge on cell-mediated immunity has been acquired through the model of listeriosis. This paper presents information on the past and the actual situation in research on Listeria and listeriosis.

Animals↗
PubMed2001

Dynamic antigen presentation patterns of Listeria monocytogenes-derived CD8 T cell epitopes in vivo.

Little information exists regarding the presentation of antigenic peptides in infected tissues. In this study the in vivo presentation of four different CD8 T cell epitopes of Listeria monocytogenes was monitored. Peptide presentation was measured by a new, highly sensitive, ex vivo Ag presentation assay that was based on the testing of freshly isolated cells from infected spleens with peptide-specific CD8 T cell lines in an IFN-gamma-specific ELISPOT assay. Remarkably, the peptide presentation pattern of splenocytes and that of macrophages purified from spleens of L. monocytogenes-infected mice were different from those of in vitro infected macrophage-like cell lines. The in vivo Ag presentation pattern of splenocytes also exhibited dynamic changes during the first 48 h of infection. In vivo peptide presentation at later time points postinfection was biased toward immunodominant CD8 T cell epitopes, while at an early time point, 6 h postinfection, subdominant and dominant CD8 T cell epitopes were presented with similar strength. In summary, our studies show that Ag presentation during an infection is a highly dynamic process that only can be fully appreciated by the study of cells infected in their physiological environment.

Animals↗
PubMed2001

A novel approach of direct ex vivo epitope mapping identifies dominant and subdominant CD4 and CD8 T cell epitopes from Listeria monocytogenes.

We used a novel approach for the direct ex vivo identification and characterization of T cell epitopes based on the screening of peptide spot libraries with freshly isolated splenocytes in a sensitive enzyme-linked immunospot (ELISPOT) assay. This technique was applied for the analysis of splenocytes from Listeria monocytogenes-infected BALB/c and C57BL/6 mice. The screening of peptide spot libraries covering the whole listeriolysin O and p60 of L. monocytogenes confirmed all known CD4 and CD8 T cell epitopes of these proteins and additionally revealed six new H-2(d) and six new H-2(b)-restricted T cell epitopes. New epitopes were categorized into CD4 and CD8 T cell epitopes by ex vivo ELISPOT analysis with separated T cell populations. The quantitative analysis of cells reactive with these CD4 and CD8 T cell epitopes revealed the existence of dominant and subdominant CD4 and CD8 T cell populations during L. monocytogenes infection. As a consequence of these data we suggest that ELISPOT-based screening of peptide spot libraries could be a general approach for the rapid identification and characterization of pathogen-specific T cell populations during various infectious diseases.

Animals↗
PubMed2001

Listeria monocytogenes: a causative agent of gastroenteritis?

The intestinal tract is the major portal of entry for Listeria monocytogenes, which becomes ingested via contaminated food. The pathogenic strains penetrate the mucosal tissue either directly, via engulfment by enterocytes, or indirectly, via active penetration of the Peyer's patches. There are now several reports clearly demonstrating that, in some cases, acute enteritis may be the only symptom of Listeria infection or may precede the typical symptoms of listeriosis such as sepsis and meningitis or encephalitis. Therefore, Listeria monocytogenes should be included in the list of foodborne gastrointestinal pathogens. Furthermore, a history of enteritis should prompt the physician to include listeriosis, which is often difficult to diagnose, in the differential diagnosis. Although Listeria monocytogenes is undoubtedly a potential enteric pathogen, it is still debatable whether its detection in a routine bacteriological examination of a stool specimen is of clinical significance.

Diagnosis, Differential↗
PubMed2001

Galactomannan enzyme immunoassay for monitoring systemic infection with Aspergillus fumigatus in mice.

Intravenous (i.v.) infection of immunocompetent mice with Aspergillus fumigatus was used to investigate the ability of a commercial galactomannan enzyme-linked immunosorbent assay (ELISA) to monitor the course of organ infection after dissemination. The test detected 100% of the fungemias which occurred for up to 5 days after infection. When blood-cultures became negative but there was a high load of fungi in the parenchymal organs and a positive culture from the brain, the ELISA was again positive in all animals. However, when blood cultures as well as brain cultures were negative and lower amounts of fungi demarcated by immune cells were present in the liver and kidneys which was the case between day 5 and 30 of infection, the test was negative in most of the animals. Therefore, the test was excellent for detection of early i.v. infection with Aspergillus fumigatus but not suited for detection of limited organ infection in immunocompetent mice.

Animals↗
PubMed2001

Regulation of microglia by CD4+ and CD8+ T cells: selective analysis in CD45-congenic normal and Toxoplasma gondii-infected bone marrow chimeras.

Microglia, the resident macrophage population of the central nervous system, is rapidly activated in murine Toxoplasma encephalitis (TE). However, the precise contribution of microglia to intracerebral immune reactions and the in vivo regulation of microglial activity are still poorly understood. To selectively analyse microglial reactions in TE, we have established a model of radiation-induced CD45-congenic bone marrow chimeras between CD45.2+ C57BL/6 (recipient) and CD45.1+ B6.SJL (donor) mice. These chimeras allow a differentiation of radioresistant CD45.2+ microglia from all other leukocytes, which exhibit the CD45.1+ haplotype. In the normal brain, microglia produced tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-10, and IL-15 mRNA. In TE, marked microglial activation was observed with a de novo expression of IL-12p40 and inducible nitric oxide synthase mRNA, upregulation of IL-1beta and TNF-alpha mRNA, a continuous production of IL-10, and IL-15 mRNA, an induction of major histocompatibility class I and II antigens, intercellular adhesion molecule-1, and leukocyte function-associated antigen-1. Furthermore, selective depletion of CD4+ and/or CD8+ T cells in the chimeras revealed that microglial cytokine production was critically regulated by CD8+T cells, whereas expression of cell surface molecules was less dependent on T cells. These findings demonstrate a specific regulation of microglia by T lymphocytes during the course of TE.

Animals↗
PubMed2001

Influence of liposomal amphotericin B on CD8 T-cell function.

Liposomal amphotericin B was immunosuppressive on target cell lysis in vitro and on protection mediated by cytotoxic CD8 T cells in murine listeriosis. When dosages usually used for therapy in humans were compared, the immunosuppressive effect of 5 mg of liposomal amphotericin B/kg of body weight/day was similar to that of standard amphotericin B at 1 mg/kg/day, but a dosage of liposomal amphotericin B of 1 mg/kg/day was not suppressive in vivo.

Amphotericin B↗
PubMed2001

Toxoplasma gondii infection of neurons induces neuronal cytokine and chemokine production, but gamma interferon- and tumor necrosis factor-stimulated neurons fail to inhibit the invasion and growth of T. gondii.

The intracellular parasite Toxoplasma gondii has the capacity to persist in the brain within neurons. In this study we demonstrated that T. gondii infected murine cerebellar neurons in vitro and replicated within these cells. Stimulation with gamma interferon (IFN-gamma) and/or tumor necrosis factor (TNF) did not enable neurons to inhibit parasite invasion and replication. Cultured neurons constitutively produced interleukin 1 (IL-1), IL-6, macrophage inflammatory protein 1alpha (MIP-1alpha), and MIP-1beta but not transforming growth factor beta1 (TGF-beta1), IL-10, and granulocyte-macrophage colony-stimulating factor. Neuronal expression of some cytokines (IL-6, TGF-beta1) and chemokines (MIP-1beta) was regulated by infection and/or by IFN-gamma and TNF.

Animals↗