Biomedical subjects

Jörg Trojan

Publications and source records attributed to Jörg Trojan.

8 recordsLinked to original sources

PubMed2006

Psychophysical 'perceptual maps' of heat and pain sensations by direct localization of CO2 laser stimuli on the skin.

Brain activation patterns derived from neurofunctional methods are often implicitly regarded as being directly related to subjective perceptual experience in an iso- or at least homomorph manner, neglecting the operational differences between these two dimensions. This paper (a) introduces a method for assessing 'perceptual maps' of stimulation patterns presented to the body surface, providing a means to parametrically relate neural representation and subjective percept, and (b) applies this method to demonstrate the existence of 'somatotopic maps' of hot and painful stimulus patterns independent from mechanoceptive co-activation. Brief (90 ms) CO2 laser pulses were presented in an array of multiple stimulation sites on the dorsal forearms (N. radialis area, C7 dermatome) of healthy subjects. Perceived locations were indicated with a 3D tracker without touching the skin, and (mis-)localizations in distal-proximal direction were analyzed. Stimuli were localized with overall mean errors of 22 mm (SD: 16 mm) toward the wrist and 24 mm (SD: 18 mm) toward the elbow. Somatotopic representation of thermal-nociceptive stimuli could be demonstrated in all subjects, independent from mechanoceptive co-activation. The perceptual maps revealed striking individual (mis-)localization patterns, many subjects exhibiting 'stretched', some 'condensed' somatotopic representations. In estimating the mapping parameters from physical to perceptual space linear regressions generally provided a good fit (adj. R2>0.80 in 10 out of 12 subjects). Nonlinear models were advantageous in some subjects only. Our method can be useful in assessing inter-individual differences or experimentally induced shifts in somatotopic processing.

Adult↗

PubMed2006

Treatment of HCV infection with interferon alpha-2b and ribavirin in a patient with X-linked lymphoproliferative syndrome.

Chronic hepatitis C (HCV) infection in patients with primary immunodeficiency increases the risk of an accelerated progression of HCV-related liver disease. Here, we report a patient with X-linked lymphoproliferative syndrome infected with HCV and Epstein-Barr virus (EBV). After combination treatment with interferon alpha-2b and ribavirin, clearance of HCV-RNA was achieved, and noteworthily, EBV DNA also became undetectable.

Antiviral Agents↗

PubMed2005

The saltation illusion demonstrates integrative processing of spatiotemporal information in thermoceptive and nociceptive networks.

In sensory saltation, first reported by Geldard and Sherrick (Science 178:178-179, 1972), a stimulus is displaced towards a second one following closely in time and space as a function of the delay between the stimuli. The distance between stimulus locations is restricted by the extension of sensory fields in the primary somatosensory cortex. Saltation is assumed to reflect dynamic changes in these cortical representations. The present study demonstrates for the first time saltation in thermoceptive and nociceptive pathways with CO(2) laser stimulation. Stimuli were presented to the dorsal forearms of 18 healthy subjects at two intensities. Saltation patterns consisted of a reference stimulus S0 near the wrist, the first test stimulus S1 at the reference location after a fixed onset delay of 1,000 ms, and a second test stimulus S2 at a location 105 mm distant from reference after a variable onset delay of 60-516 ms. Perceived positions were indicated by the subjects without skin contact with a 3D tracker. As expected, subjects mislocalized S1 towards S2. Mean S1 displacement was 51+/-36 mm. Decreasing delays between S1 and S2 resulted in increasing displacements, independent of intensity. However, since no clear-cut discrimination of thermal versus nociceptive activation could be achieved definite conclusions about differences between the two modalities cannot be drawn. In addition, effects of body site on the saltation characteristics were observed. The saltation paradigm constitutes a promising approach to the functional analysis of spatiotemporal dynamics in thermoceptive and nociceptive networks to supplement brain-mapping approaches to cortical sensory fields.

Adult↗

PubMed2005

Sensitization and habituation of AMH and C-fiber related percepts of repetitive radiant heat stimulation.

OBJECTIVE: Pain perception involves neuronal plasticity at peripheral and central stages, resulting in sensitization or habituation, depending on intensity and temporal features of stimulation. Concurrent assessment of perceptual change over different time spans is therefore important for understanding the dynamics of pain processing. METHODS: A new psychophysical procedure was established to assess sensitization and habituation during repetitive radiant heat stimulation. Short-term perceptual change (<1 min) during trials with 10 stimuli applied at 3 frequencies (0.2-0.6-1.8 Hz) and 3 intensities was assessed for AMH-II or C-fiber related percepts. Perceptual changes were monitored for medium-term (1-15 min) and for long-term (15-90 min) time spans. RESULTS: Short-term sensitization occurred only at frequencies above 0.3 Hz and was affected by both stimulus frequency and intensity, but the AMH-fiber related sensitization depended on intensity only above 0.6 Hz. Multiple stimulation of the same skin area during medium-term time spans resulted in habituation. No long-term perceptual changes occurred. CONCLUSIONS: The procedure permits concurrent assessment of short-term sensitization and medium-term habituation, assumed to be related to spinal windup and cutaneous nociceptive fiber fatigue, respectively. SIGNIFICANCE: The method is suitable for quantitative sensory testing of dynamic pain processing over different time spans, relevant in clinical testing of pain and in drug assessment.

Adult↗

PubMed2005

In vitro chemosensitivity to gemcitabine, oxaliplatin and zoledronic acid predicts treatment response in metastatic gastric cancer.

Individual response of disseminated cancer to chemotherapy is unpredictable. In vitro chemotherapy-induced apoptosis can be measured and might be a method to evaluate in vivo activity of tested drugs. In this report, tumor cells of a patient with signet cell carcinoma of the stomach and diffuse bone marrow infiltration were cultured and tested for in vitro chemosensitivity. The drugs gemcitabine, oxaliplatin and zoledronic acid were found to induce in vitro tumor cell apoptosis synergistically, and subsequently were used as combination chemotherapy regimen. An initially existing disseminated intravascular coagulopathy quickly resolved and after 6 months of treatment on ongoing complete response was induced, thus confirming the results of in vitro chemosensitivity testing.

Aged↗

PubMed2003

N-terminus of hMLH1 confers interaction of hMutLalpha and hMutLbeta with hMutSalpha.

Mismatch repair is a highly conserved system that ensures replication fidelity by repairing mispairs after DNA synthesis. In humans, the two protein heterodimers hMutSalpha (hMSH2-hMSH6) and hMutLalpha (hMLH1-hPMS2) constitute the centre of the repair reaction. After recognising a DNA replication error, hMutSalpha recruits hMutLalpha, which then is thought to transduce the repair signal to the excision machinery. We have expressed an ATPase mutant of hMutLalpha as well as its individual subunits hMLH1 and hPMS2 and fragments of hMLH1, followed by examination of their interaction properties with hMutSalpha using a novel interaction assay. We show that, although the interaction requires ATP, hMutLalpha does not need to hydrolyse this nucleotide to join hMutSalpha on DNA, suggesting that ATP hydrolysis by hMutLalpha happens downstream of complex formation. The analysis of the individual subunits of hMutLalpha demonstrated that the hMutSalpha-hMutLalpha interaction is predominantly conferred by hMLH1. Further experiments revealed that only the N-terminus of hMLH1 confers this interaction. In contrast, only the C-terminus stabilised and co-immunoprecipitated hPMS2 when both proteins were co-expressed in 293T cells, indicating that dimerisation and stabilisation are mediated by the C-terminal part of hMLH1. We also examined another human homologue of bacterial MutL, hMutLbeta (hMLH1-hPMS1). We show that hMutLbeta interacts as efficiently with hMutSalpha as hMutLalpha, and that it predominantly binds to hMutSalpha via hMLH1 as well.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Immunological monitoring during therapeutic vaccination as a prerequisite for the design of new effective therapies: induction of a vaccine-specific CD4+ T-cell proliferative response in chronic hepatitis B carriers.

We characterized the anti-viral T-cell response in 22 chronically infected patients, who participated in a European multi-center randomized placebo-controlled, double-blind study therapeutic vaccination trial with pre-S1, pre-S2 and S antigenic components of the hepatitis B virus (HBV). It induced a significant HBsAg-specific T-cell proliferation and the production of Th2-cytokines (i.e. IL-5). A specific induction of Th1-lymphokines was not detectable although this has been demonstrated in this study in response to the nucleocapsid protein (HBcAg). Further analysis indicated that this approach does not activate HBV-specific CD8+ T-lymphocytes as detected by ELISPOT-assay. Our results might explain why a specific therapeutic vaccine, although safe and well-tolerated is not always able to break tolerance leading to the clearance of the hepatitis B virus.

Adult↗

PubMed2002

hMutSalpha forms an ATP-dependent complex with hMutLalpha and hMutLbeta on DNA.

The DNA binding properties of hMutSalpha and hMutLalpha and complex formation of hMutSalpha with hMutLalpha and hMutLbeta were investigated using binding experiments on magnetic bead-coupled DNA substrates with nuclear extracts as well as purified proteins. hMutSalpha binding to homoduplex DNA was disrupted by lower NaCl concentrations than hMutSalpha binding to a mismatch. ATP markedly reduced the salt resistance of hMutSalpha binding but hMutSalpha still retained affinity for heteroduplexes. hMutSalpha formed a complex with hMutLalpha and hMutLbeta on DNA in the presence of ATP. This complex only formed on 81mer and not 32mer DNA substrates. Complex formation was enhanced by a mismatch in the DNA substrate, and hMutLalpha and hMutLbeta were shown to enter the complex at different ATP concentrations. Purified hMutLalpha showed an intrinsic affinity for DNA, with a preference for single-stranded over double-stranded DNA.

Adaptor Proteins, Signal Transducing↗