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T Herrmann

Publications and source records attributed to T Herrmann.

At least 91 records · Page 5Linked to original sources

[The radiobiological aspects in the blocking of sensitive structures from the irradiation field].

BACKGROUND: In some cases the total dose has to be reduced in a section of an irradiation field by means of a transmission block. This can be performed in 2 different ways: 1. A part of the planned fractions is blocked. 2. The dose of each fraction is reduced using a transmission block (transmission < 100%). METHOD: For both methods the biological tumor and normal tissue doses were calculated using the linear-quadratic model. A clinical case is discussed. RESULT AND CONCLUSION: With transmission blocks a therapeutic gain can be obtained.

Carcinoma, Bronchogenic↗

Identification and characterization of rat gamma/delta T lymphocytes in peripheral lymphoid organs, small intestine, and skin with a monoclonal antibody to a constant determinant of the gamma/delta T cell receptor.

A mAb called V65 was raised to a CD3+, TCR-alpha/beta- rat/mouse T cell hybrid that selectively reacts with all CD3+, TCR-alpha/beta- rat lymphocytes. Both anti-CD3 and V65 precipitate a 48- to 50-kDa heterodimeric protein from digitonin-lysed surface-iodinated cells. V65+ but not V65- T cells and T cell hybridoma cells express TCR-gamma mRNA. Together, these results show that V65 detects a constant determinant of the rat TCR-gamma/delta. In the presence of either IL-2 or IL-4, V65 stimulates proliferation in peripheral rat gamma/delta T cells. Approximately 90% of gamma/delta T cells from peripheral lymphoid organs have the same cell surface phenotype as thymus-derived MHC class I-restricted alpha/beta T cells, i.e., they are CD4- but express the CD8 alpha/beta heterodimer together with CD2 and CD5. In contrast, gamma/delta T cells from the epithelium of the small intestine lack CD2, CD4, and CD5 and express CD8 alpha only. Finally, V65 directly identifies a dense network of dendritic cells in the epidermis as gamma/delta T cells. These dendritic epidermal T cells are absent from athymic rats, indicating that like their mouse counterparts, they are thymus dependent.

Animals↗

Control of the rat T cell response to retroviral and bacterial superantigens by class II MHC products and Tcrb-V8.2 alleles.

The in vitro response of unprimed rat T cells to retroviral and bacterial superantigens (SAg) was analyzed with TCR V beta 8.2-, 8.5-, 10-, and 16-specific mAbs. Specific stimulation of V beta 8.2 and 8.5 CD4 cells was observed in the response to Mls1a, the retroviral SAg encoded by integrated provirus Mtv-7 (Mtv-7 SAg), which was presented by mouse B cells or mouse fibroblasts transfected with DR1 genes and the Mtv-7 SAg. Additionally, a strong response of V beta 16 CD4 cells to an as yet unidentified mouse SAg was found. Only some of the bacterial SAg known to stimulate mouse and human T cells also activated rat lymph node cells. SEA, SEE, and TSST-1 stimulated rat T cells well; SEB, SEC1, and SED did not. This defect was apparently a result of weak binding to rat MHC class II molecules because presentation by human MHC class II molecules restored T cell activation. Under these conditions, SEB stimulated V beta 8.2+ and 8.5+ CD4 and CD8 cells from Lewis rats. A comparison of several rat strains revealed an unresponsiveness to SEB or Mtv-7 SAg for V beta 8.2 cells from F344 and DA rats. Determination of the nucleotide sequences of the Tcrb-V8.2 of these strains revealed differences between SAg-responsive and SAg-unresponsive Tcrb-V8.2 in seven amino acids, four of them located in the putative SAg contact site. The significance of these findings for the evolution of TCR-SAg interactions is discussed.

Alleles↗

Preferential TCR V usage in rat repertoire selection: V alpha 8 imparts both positive thymic selection by and alloreactivity to RT1f.

Using a panel of newly developed mAb to two rat TCR V alpha and four TCR V beta segments, TCR V usage in CD4 and CD8 T cells of eight RT1 congenic strains sharing the LEW background was analyzed by flow cytometry. While no striking effects on V beta 8.2 and 8.5 usage were observed, a 3- to 4-fold over-representation of V beta 10 in the CD4 as compared with the CD8 subset in all strains suggested a preference of V beta 10 for MHC class II products. The degree of 'overselection' was mapped to the RT1.B/D region. In addition, an allele-specific overselection of V alpha 4+ CD4 T cells was mapped to RT1.B/Du and of V beta 16+ CD8 T cells to RT1.Au. Finally, a dramatic overselection of V alpha 8+ CD8 T cells by RT1f (14% in RT1f versus 1-2% in other haplotypes) provides the most striking case yet for an intrinsic affinity of a TCR V segment for an MHC product. V alpha 8+ CD8 T cells are not only overselected by RT1f in the thymus, but also during the alloreactive response of peripheral CD8 T cells to RT1f. The implications of these findings for the contribution of TCR V segments to TCR-MHC interactions in repertoire selection and alloreactivity are discussed.

Animals↗

[Problems of radiotherapy in Germany after the recent events in Hamburg].

BACKGROUND: During the 3rd Symposium on "Experimental Radiotherapy and Clinical Radiobiology" (Hamburg, March 1994) the consequences of the recent events in the Department of Radiotherapy of the University-Hospital in Hamburg for daily radiotherapy practice in Germany were discussed. The following topics were covered: information of the patient, choice of therapy, development of new treatment modalities, ethics committee, follow-up and role of radiobiology. DISCUSSION AND RESULTS: Information of the patient: Due to the insecure juridical situation in Germany there is a tendency to inform patients excessively, which is rather confusing for them. Adequate information of patients is a difficult task for physicians considering their daily workload. Choice of therapy: Unfortunately in Germany radiotherapists are often not initially involved in planning of the overall treatment strategy for individual cancer patients. The recent events in Hamburg led to a decreased referral of cancer patients for radiotherapy. This might even hold for tumor entities where radiotherapy is an essential part of therapy. Another problem is that dose might be reduced inadequately. This would reduce complications but also significantly increase local failure. Development of new treatment modalities: There are no special juridical problems with the conduction of clinical studies for optimization of radiation treatments. Ethics committee: Ethics committees are not only meant to safeguard patients but also protect physicians and institutions from the consequences of questionable research. FOLLOW-UP: Only radio-oncologists are adequately trained for follow-up after radiation treatment. Nevertheless, because of administrative, financial, legal and political problems many patients in Germany are not regularly seen by the radiation oncologist after end of radiation treatment. Always when new treatment strategies are established, careful follow-up is of special concern. Role of radiobiology: The main obligation of clinical radiobiology is to introduce radiobiological knowledge into clinical practice. This may be best promoted by a period of radiobiological research during residency. However, close collaboration between radiotherapists and radiobiologists is only possible at very few centres in Germany, because the institutes of radiobiology are dismantled systemically.

Aftercare↗

The importance of the timing of a gap in radiotherapy of squamous cell carcinomas of the head and neck.

AIM: This paper analyses whether the timing of interruptions during radiotherapy of squamous cell carcinomas of the head and neck influences treatment results. PATIENTS AND METHODS: Hundred and ninety-two patients irradiated with curative intent between 1975 and 1985 (63% after surgery and 37 as primary treatment) were analysed with regard to the occurrence, timing, duration and causes of treatment interruptions. In a multivariate analysis, these factors as well as stage, site, extent of surgery etc. were related to 5-year survival rates. RESULTS: Interruptions of the prescribed course of radiotherapy decreased the survival rate from 61% to 28%. No adverse effect of a break was seen if it occurred during the first 3 weeks whereas survival dropped to 18 to 25% with a break later in the course of radiotherapy. CONCLUSION: Timing of treatment interruption in squamous cell carcinomas is a crucial factor determining the chances of tumor cure. The detrimental effect of treatment interruptions increases as treatment progresses. This finding supports the hypothesis that tumor clonogen repopulation accelerates towards the end of radiotherapy of squamous cell carcinomas.

Carcinoma, Squamous Cell↗

The CD8 T cell response to staphylococcal enterotoxins.

Staphylococcal enterotoxins (SE) are superantigens that bind to MHC class II molecules and activate T lymphocytes via the T cell receptor (TCR) V beta domain. By analogy with T cell responses to conventional peptide antigens, it might be predicted that CD4 (MHC class II restricted) cells would respond better to SE than CD8 (MHC class I restricted) cells. Here we summarize evidence that in fact CD8 cells respond as well as CD4 cells to SE both in vitro and in vivo. These findings emphasize the unique character of TCR-superantigen interactions.

Animals↗

[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↗

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↗

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↗

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↗

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↗