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Biomedical subjects

T Herrmann

Publications and source records attributed to T Herrmann.

At least 109 records · Page 6Linked to original sources
PubMed1993

[Gynecologic brachytherapy--from low-dose-rate to high-tech].

The transition from low-dose-rate (LDR) brachytherapy to high-dose-rate (HDR) afterloading treatment is in progress in most centres of radiation therapy. First reports of studies comparing HDR and LDR treatment in cervix cancer demonstrate nearly equal local control. In our own investigations on 319 patients with primary irradiated carcinoma of the cervix (125 HDR/194 LDR) we found the following control rates: Stage FIGO I 95.4%/82.9% (HDR versus LDR), stage FIGO II 71.4%/73.7%, stage FIGO III 57.9%/38.5%. The results are not significant. The side effects--scored after EORT/RTOG criteria--showed no significant differences between both therapies for serious radiogenic late effects on intestine, bladder and vagina. The study and findings from the literature confirm the advantage of the HDR-procedure for patient and radiooncologist and for radiation protection showing at least the same results as in the LDR-area. As for radiobiological point of view it is important to consider that the use of fractionation in the HDR-treatment is essential for the sparing of normal tissues and therefore a greater number of small fractionation doses in the brachytherapy should be desirable too. On the other hand the rules, which are true for fractionated percutaneous irradiation therapy (overall treatment time as short as possible to avoid repopulation of tumor cells) should be taken into consideration in combined brachy-teletherapy regime in gynecologic tumors. The first step in this direction may be accelerated regime with a daily application of both treatment procedures. The central blocking of the brachytherapy region from the whole percutaneous treatment target volume should be critically reflected, especially in the case of advanced tumors.

Aged↗
PubMed1992

In vivo responses of CD4+ and CD8+ cells to bacterial superantigens.

Staphylococcal enterotoxin B (SEB) is a bacterial superantigen that binds to major histocompatibility complex (MHC) class II molecules and specifically activates T cells bearing V beta 8 T cell receptor domains. We have compared several aspects of the response of CD4+ and CD8+ T cell subsets to SEB in vivo. V beta 8+ cells in both subsets proliferated to a similar extent upon SEB injection. Furthermore, mRNA for interferon-gamma was induced in both subsets with similar kinetics and SEB dose-response. Finally CD8+ (but not CD4+) T cells from SEB-injected mice exhibited SEB-specific lysis of MHC class II-bearing target cells. Collectively, these data indicate that the CD4: MHC class II interaction confers no detectable selective advantage to CD4+ cells in the in vivo response to SEB. The observed effector functions of both subsets may contribute to SEB-induced immunopathology.

Animals↗
PubMed1992

The viral superantigen Mls-1a induces interferon-gamma secretion by specifically primed CD8+ cells but fails to trigger cytotoxicity.

Superantigens can be operationally defined by their ability to stimulate CD4+ and CD8+ T cells via the T cell receptor beta chain variable domain (TcR V beta). We show here that effector functions of CD8+ T cells specific for superantigens differ depending upon the nature of the superantigen involved. Hence, activated CD8+ T cells bearing TcR V beta specific for the superantigen Mls-1a [encoded in the open reading frame of the 3' long terminal repeat of endogenous mouse mammary tumor virus (MMTV)] are unable to lyse Mls-1a-bearing target cells despite the fact that they release interferon-gamma (IFN-gamma) upon Mls-1a stimulation. In contrast CD8+ T cells specific for the exogenous superantigen staphylococcal enterotoxin B (SEB) readily mediate both lysis and IFN-gamma secretion when exposed to SEB-bearing target cells. This dissociation between lysis and IFN-gamma production by Mls-1a-specific CD8+ T cells is independent of the initial stimulus used for activation and appears not to be simply explained by a low Mls-1a determinant density. We suggest that this phenomenon reflects differing TcR affinity thresholds for lymphokine secretion and cytolysis. Such differences may be exploited by retroviruses such as MMTV in order to escape immunosurveillance.

Animals↗
PubMed1991

A recombinant C-terminal fragment of staphylococcal enterotoxin A binds to human MHC class II products but does not activate T cells.

Binding of staphylococcal enterotoxin A (SEA) to MHC class II encoded proteins is a prerequisite for its subsequent activation of a large fraction of T lymphocytes through interaction with variable segments of the TCR-beta chain. We cloned SEA in Escherichia coli and produced four recombinant fragments covering both the N- and C-terminal regions. These fragments were used to analyze the interaction between SEA and the human MHC class II products. A C-terminal fragment of SEA, representing amino acids 107-233 bound to HLA-DR and HLA-DP but did not activate T cells. The three other fragments (amino acids 1-125, 1-179 and 126-233) neither bound to MHC class II Ag nor activated T cells. SEA apparently bind to HLA-DR and HLA-DP through its C-terminal part, whereas T cell activation is dependent on additional parts of the protein.

Base Sequence↗
PubMed1991

Effects of short-lasting inactivations of the ventral hippocampus and medial septum on long-term and short-term acquisition of spatial information in rats.

This study was aimed at testing the effects of a reversible inactivation of the hippocampal formation on long-term and short-term acquisition of spatial information. Rats chronically equipped with either bilateral cannulae into the ventral hippocampus or a single cannula into the medial septum had to locate, in a circular platform with 18 holes on the periphery, the unique hole leading to a hidden shelter in order to avoid bright light. In Expt. 1, following 16 days of training (1 trial/day, 24 h ITI) without physical intervention, the location of the correct hole was changed on both Days 17 and 23, and the rats were either sham-injected or injected with lidocaine. Both hippocampally and septally lidocaine-injected rats relearned the new location at a rate similar to corresponding sham-injected animals. In Expt. 2, a massed-trial version of the task was used, in which the rats had to learn a new hole location on each daily session (3 trials, ITI = 1 min). Animals were sham-injected or lidocaine-injected on alternate sessions. While sham-injected rats improved in orientational accuracy over successive trials, both hippocampally and septally lidocaine-injected rats failed to display any between-trial improvement. The impairment displayed by lidocaine-injected rats when their hippocampus was inactivated confirms the role of the hippocampus in short-term spatial memory (Expt. 2). In contrast, short-lasting inactivation of the hippocampus did not prevent long-term spatial learning (Expt. 1). These results suggest that the hippocampus could process information 'off-line' in the delay between temporally discontiguous learning trials, and show that short-term and long-term spatial learning rely on distinct neurobiological mechanisms.

Animals↗
PubMed1991

Spatial problem-solving in a wheel-shaped maze: quantitative and qualitative analyses of the behavioural changes following damage to the hippocampus in the rat.

The behaviour of sham-operated rats and rats with damage to the dorsal hippocampus was compared in a complex spatial problem-solving task using a 'hub-spoke-rim' wheel type maze. Compared to the classical Olton 8-arm radial maze and Morris water maze, this apparatus presents the animal with a series of possible alternative routes both direct and indirect to the goal (food). The task included 3 main stages: exploration, feeding and testing, as do the classic problem-solving tasks. During exploration, hippocampal rats were found to be more active than sham rats. Nevertheless, they displayed habituation and a relatively efficient circumnavigation, though, in both cases, different from those of sham rats. During test trials, hippocampal rats were characterized as being less accurate, making more errors than sham rats. Nevertheless, both groups increased their accuracy of first choices over trials. The qualitative analyses of test trial performance indicated that hippocampal rats were less accurate in terms of the initial error's deviation from the goal, and less efficient in terms of corrective behaviour than sham rats which used either the periphery or the spokes to attain economically the goal. Surprisingly, hippocampal rats were not limited to a taxon type orientation but learned to use the periphery, a tendency which developed over time. Seemingly, for sham rats, the problem-solving process took the form of updating information during transit. For hippocampal rats, the use of periphery reflected both an ability to discriminate its usefulness in reaching the goal via a taxis type behaviour, and some sparing of ability to generalize the closeness and the location of the goal. These results, especially the strategic correction patterns, are discussed in the light of Sutherland and Rudy's 'configurational association theory'.

Animals↗
PubMed1991

Staphylococcal enterotoxin-dependent lysis of MHC class II negative target cells by cytolytic T lymphocytes.

The enterotoxins of Staphylococcus aureus (SE) are extremely potent activators of human and mouse T lymphocytes. In general, T cell responses to SE are MHC class II dependent (presumably reflecting the ability of SE to bind directly to MHC class II molecules) and restricted to responding cells expressing certain T cell receptor beta-chain variable (TCR V beta) domains. Recently we demonstrated that CD8+ CTL expressing appropriate TCR V beta could recognize SE presented on MHC class II-bearing target cells. We now show that MHC class II expression is not strictly required for T cell recognition of SE. Both human and mouse MHC class II negative target cells could be recognized (i.e., lysed) in a SE-dependent fashion by CD8+ mouse CTL clones and polyclonal populations, provided that the CTL expressed appropriate TCR V beta elements. SE-dependent lysis of MHC class II negative targets by CTL was inhibited by mAb directed against CD3 or LFA-1, suggesting that SE recognition was TCR and cell contact dependent. Furthermore, different SE were recognized preferentially by CTL on MHC class II+ vs MHC class II- targets. Taken together, our data raise the possibility that SE binding structures distinct from MHC class II molecules may exist.

Animals↗
PubMed1991

Human major histocompatibility complex class II-negative colon carcinoma cells present staphylococcal superantigens to cytotoxic T lymphocytes: evidence for a novel enterotoxin receptor.

The staphylococcal enterotoxins (SE) bind to major histocompatibility complex (MHC) class II molecules on target cells and activate T cells expressing particular T cell receptor V beta sequences. In this report we demonstrate that SE bind to the MHC class II- SW620, Colo320DM and WiDr human colon carcinoma cell lines and direct cytotoxic T lymphocytes (CTL) to mediate strong target cell killing. Flow cytometry analysis, immunoprecipitation and Northern blotting experiments failed to demonstrate any surface expression of HLA-DR, HLA-DP and HLA-DQ isotypes on the SW620 colon carcinoma cell line, whereas abundant expression of these isotypes was seen on Raji cells, SEB and SEC1 were efficiently presented at picomolar concentration by the MHC class II- colon carcinoma cells and MHC class II+ Raji cells, whereas SEA and SED were preferentially presented on the MHC class II+ Raji cells. An anti-HLA-DR monoclonal antibody inhibited SEB-induced CTL targeting to Raji, but did not influence the killing of SW620 cells. Our data suggests the existence of functionally active SE-binding structures on human colon carcinoma cells which are distinct from the conventional MHC class II molecules. The possibility that these putative new SE receptors play a role in the enterotoxin action of SE must be considered.

Antigens, Bacterial↗
PubMed1991

Role of the medial and lateral septum in a variable goal spatial problem solving task.

Rats with lesions to the medial (MS) or lateral septal (LS) nuclei were compared to normal controls (CNT) in the acquisition of a spatial working memory task. In this task, animals were first allowed to explore the unbaited three-table apparatus before being fed on one of the two possible goal tables. Animals were then tested on their ability to return to the table where they just had been fed. Only rats with medial septal damage were clearly impaired on this problem, an impairment that dissipated over days. In contrast, the performance of LS rats was not significantly different from controls. During the second phase of the experiment, the same animals received either atropine sulphate (50 mg/kg, IP), atropine methylnitrate (50 mg/kg, IP), or an equivalent volume of saline. Atropine sulphate produced a sharp decrease in performance by all subjects. Meanwhile, atropine methylnitrate produced a mild temporary deficit only in LS rats. Overall, these results confirm that the medial septum plays a crucial role in the acquisition of problem solving. In addition, these results also suggest that the lateral septum may play a possible role in some form of spatial behavior easily disrupted by atropine methylnitrate.

Animals↗
PubMed1991

Mismatch between radionuclide and contrast angiography in the assessment of the perfusion of a transplanted kidney.

When early complications occur after a kidney transplant, radionuclide angiography may be useful in determining a possible vascular origin. The authors describe the case of a patient with anuria continuing 24 hours after transplantation. Radionuclide angiography showed a defect at the site of the renal graft, suggestive of arterial or venous thrombosis. Contrast angiography was performed immediately but showed no vascular abnormality; neither did radionuclide angiography performed the next day. The authors concluded that a spasm at the site of the renal artery anastomosis, overcome by contrast angiography, could explain this phenomenon.

Adult↗
PubMed1991

[Radiogenic pneumopathy--synopsis of roentgen image and electron microscopy findings].

Radiation-induced pneumapathia is one of the most frequent complications after radiotherapy to the chest and occurs especially after radiation of bronchial carcinoma (frequency 40-70%, using 50 Gy). The broad ranges of reported frequency indicate differences in defining the degree of radiation-induced damage (clinical picture, plain film, and lung function parameters). This study is to compare plain film findings with electromicroscopy in order to correlate radiological signs with the underlying histo-morphological process.

Animals↗
PubMed1991

The hydroxyproline content in the lung tissue of young pigs after fractionated irradiation with photons or neutrons.

The radiation response of normal lung tissue was studied in 99 young pigs. Five fractions of Co-60-photons and of neutrons with an average energy of 6.2 MeV were applied during overall treatment times of five and 35 days respectively. The irradiation field comprised the whole of the right lung. At eight to ten weeks and at eight to 13 months animals were sacrificed and the removed lungs were investigated histopathologically and biochemically. Radiation induced fibrosis was evaluated by determining the ratio of hydroxyproline concentration of irradiated and non-irradiated lung in the same animal. Above a threshold there was a significant increase of the hydroxyproline ratio with increasing doses. Histopathological findings and hydroxyproline ratio were in close agreement. RBE values between 3.8 and 4.5 were calculated in accordance with the results using the other criteria of lung damage in our studies on pigs.

Animals↗
PubMed1990

Septum and medial frontal cortex contribution to spatial problem-solving.

An attempt was made to contrast the effects of lesions to the medial frontal cortex and septum in two spatial tasks. In the fixed-goal (FG) task, the food was located on the same table throughout testing, and the start table was randomly varied from day to day. In the variable-goal (VG) task, the start table remained constant but the food was randomly distributed on one or the other of the two remaining tables. In both tasks, normal animals performed better than frontal and septal rats whose performance, however, improved over days in the FG, but not in the VG, task. In both tasks, significant improvement within days was found in medial frontal animals, but not in septal animals. Additional analyses revealed that septal animals had a general pattern of disrupted exploration and a tendency to use a response strategy (i.e. to repeat the same response both within and between days) which decreased over days in the FG task. In contrast, medial frontal animals did not demonstrate disrupted exploration nor any response tendency. It is concluded that both septal and medial frontal cortical damage produce a common spatial working memory impairment. However, there is some evidence to suggest that this common memory impairment could result from disruption of distinct mechanisms in septal and frontal animals. It is proposed that medial frontal lesions could affect some specific mechanism related either to attentional processes or to the ability to anticipate future events, whereas septal damage would interfere with the building of comprehensive and flexible spatial memories.

Animals↗
PubMed1990

Activation of MHC class I-restricted CD8+ CTL by microbial T cell mitogens. Dependence upon MHC class II expression of the target cells and V beta usage of the responder T cells.

The T cell response to microbial T cell mitogens (MTM) such as enterotoxins from Staphylococcus aureus (SE) and the soluble mitogen from Mycoplasma arthritidis, resemble the minor lymphocyte stimulatory locus (Mls) response in several aspects. An important feature of the Mls response is it restriction to CD4+ cells. This study demonstrates that in contrast to Mls, the MTM response includes both CD4+ and CD8+ subsets. Both CD4+ and CD8+ cells expanded in IL-2 after stimulation with SEB showed preferential expression of T cell receptors bearing V beta 8 domains. Mouse and human target cells could be lysed in the presence of MTM both by MTM-stimulated CD8+ lymphocytes and by MHC class I-restricted CTL clones of defined Ag specificity. MTM-induced lysis required the expression of MHC class II, but not class I Ag, on the target cells. Inhibition studies of SEB and Ag-dependent cytolysis by CTL clones underlined the crucial role of CD3 and LFA-1 in both instances, but showed CD8 dependence only for AG-dependent cytolysis. Together these findings suggest important differences between the putative MTM-mediated interaction of TCR with MHC molecules and the classical TCR/MHC interaction involved in MHC-restricted Ag recognition.

Animals↗
PubMed1990

High affinity IL-2 receptors on a Hodgkin's derived cell line.

Hodgkin and Sternberg Reed (H and SR) cells, the putative malignant cells of Hodgkin's disease carry regularly T-cell activation antigens, like CD30 and CD25 (low affinity IL-2 receptor). We have investigated the Hodgkin cell line L540, bearing characteristic markers of H and SR cells for its expression of the low affinity IL-2 receptor (IL-2R) and for IL-2. Expression of the low affinity IL-2R was found on mRNA level, by detection of specific 3.5 kb and 1.4 kb mRNA and on the protein level by immunoprecipitation of a 55,000 mol. wt molecule from detergent extracts of surface iodinated cells, however IL-2 specific mRNA was not detected. Scatchard plot analysis revealed the presence of 2 x 10(3) high affinity IL-2Rs. Crosslinking experiments directly demonstrated the high affinity IL-2R to consist of the 55,000 mol.wt light chain (L), and the 70/75,000 (H1/H2) heavy chains. IL-2 was rapidly internalized by these receptors, suggesting that they can be functional. The expression of functional IL-2Rs might be involved in induction or differentiation of Hodgkin's disease.

Fluorescent Antibody Technique↗