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T Herrmann

Publications and source records attributed to T Herrmann.

At least 145 records · Page 8Linked to original sources
PubMed1988

The human intermediate-affinity interleukin 2 receptor consists of two distinct, partially homologous glycoproteins.

In this report we demonstrate that the human intermediate-affinity-type interleukin (IL) 2 receptor (IL 2R) consists of two distinct glycoproteins designated H1 and H2, whereas the high-affinity IL 2R consists of three chains, H1, H2 and the light chain (L), the Tac antigen. They are neither linked by disulfide bridges to each other nor to the L chain. Similar to the L chain, H1 and H2 apparently carry intramolecular disulfide bonds. From affinity-labeled IL 2 intermediate-affinity receptor complexes, we deduced an apparent mol. mass of 70 kDa for H1 and of 75 kDa for H2 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and of 55 kDa for H1 and of 85 kDa for H2 in SDS-PAGE/urea. As demonstrated by limiting proteolysis, both glycoproteins display high homologies or even identity proximal to the IL 2-binding sites. The areas which are responsible for the striking differences between H1 and H2 in SDS-PAGE/urea are located distally to the IL2-binding site and, in contrast to the L chain, are protected from the action of exogenous proteases by the plasma membrane.

Cross-Linking Reagents↗
PubMed1988

Demonstration of two distinct forms of released low-affinity type interleukin 2 receptors.

The release of interleukin 2 (IL2)-binding proteins, derived from the 55-kDa low-affinity IL2 receptor (IL2R; L chain), has been observed for virtually all L chain-bearing cells in either humans, the mouse or the rat. Based on the characterization of the released human L chain as a molecule 10 kDa smaller than the cell surface receptor, either proteolytic cleavage or differential splicing of the L chain-encoding mRNA have been suggested as mechanisms underlying the receptor release. Combining affinity labeling of the L chain with 125I-labeled IL2 and immunoprecipitation with L chain-specific monoclonal antibodies applied for the detection of soluble mouse IL2R revealed the existence of two classes of soluble receptors, one being of the same size as cell surface expressed L chain, the other of 45-kDa apparent molecular mass. These findings raise the possibility of mechanisms of receptor release other than those discussed for human L chain.

Animals↗
PubMed1988

The high affinity interleukin 2 receptor: evidence for three distinct polypeptide chains comprising the high affinity interleukin 2 receptor.

Low and high affinity receptors for interleukin 2 were investigated on interleukin 2 (IL-2) receptor bearing cells by chemical cross-linking of 125I-labelled IL-2 to its receptor, or membrane proteins associated with the IL-2 binding sites. SDS-PAGE analysis of the cross-linked complexes of the murine CTLL 16 cells and human T-blasts, which bear high and low affinity IL-2 receptors, showed three distinct bands. The fastest of those three bands ran in parallel to the single band of 65-70 kDa found on the only low affinity receptor bearing mouse T-lymphoma Eb, which is thought to be one beta-chain (55 kDa IL-2 binding protein) and one IL-2. Both upper bands ran in parallel with those produced by the 2C8 clone of the NK-like cell line YT which lacks the 55 kDa binding protein and bears only a single class of receptors with an intermediate affinity. Internalisation studies using CTLL 16 cells revealed that all three bands disappeared under conditions allowing receptor internalisation. Low and high affinity binding sites of CTLL 16 cells were destroyed by trypsinisation and the IL-2 binding properties of the cells were regenerated in parallel with the reappearance of all bands. These results show in addition to the beta-chain (55 kDa binding protein) and the alpha-chain 75 kDa binding protein, an IL-2 membrane protein complex with an apparent mol. wt of 115 kDa in CTLL 16 cells. They are the first direct indication of a putative gamma-chain of the high affinity IL-2 receptor.

Animals↗
PubMed1988

[Children of parents irradiated prior to conception--a longitudinal study (results, 1986)].

The results of a longterm study on 55 children are presented whose parents were treated by radiotherapy. Five or ten years after a first examination, these children were submitted to a check-up investigation of their physical and intellectual development. The group of twenty irradiated fathers received an average dose to the gonads of 0.55 Gy (0.01 to 6.4 Gy), the group of twenty irradiated mothers 0.72 Gy (0.01 to 8.0 Gy). In all parents the most frequent finding was Hodgkin's disease, which was diagnosed as a neoplasm in 23 cases. Chemotherapy was applied in two out of 40 patients. The proof of paternity was made with a 86% accuracy for ten out of twenty fathers by determination of HLA types. A conception was demonstrated beyond all doubt after a dose to the testicles of 1.2 Gy in the irradiated fathers and after a dose to the ovaries of 3.0 Gy in the irradiated mothers. The offspring of the F1 generation showed no modification in the sex ratio. In the primary examination, a rate of 5.5% of severe malformations was found (trisomy E, bradyacousia of the inner ear, cleft hands and feet). 24% of the children had malformations which needed a treatment (hernias, torticollis, hip dysplasia). 18 out of 55 children (33%) presented abnormalities in the widest sense of the word. Three children (5.5%) were premature infants, and there is a general tendency towards shortened pregnancy (-3.6 days). Hernias (7/55) are a frequent finding. In children of both sexes, carporadiography shows a delayed development which is not compensated in the check-up examinations at five or ten years, but does not cause an underdevelopment in body height as compared to great normal collectives. The results suggest a slightly increased malformation rate among children whose parents were treated by radiotherapy. Above all the connective and supporting tissue seems involved. Some proposals are made how to give a radiogenetic advice to tumor patients who want to have children.

Abnormalities, Radiation-Induced↗
PubMed1987

The mouse high affinity IL 2 receptor complex. I. Evidence for a third molecule, the putative gamma-chain, associated with the alpha- and/or beta-chain of the receptor.

Low and high affinity receptors for interleukin 2 were investigated on mitogen-activated mouse T lymphocytes and on interleukin 2 (IL2) receptor-bearing T cell lines by chemical crosslinking of 125I-labelled interleukin 2 (125I IL2) to its binding proteins or membrane proteins associated with the IL2 binding sites. In all cells investigated, the crosslinking produced a 65-70 kD complex thought to be one beta-chain molecule (55 kD IL2 receptor) and one IL2. Occasionally, a 120-130 kD band could be seen which is thought to be IL2 bound to beta-chain homodimer. Using low IL2 concentrations (200 pM), high affinity receptor-bearing cells showed specific additional complexes. Either bands of 85 kD, 105 kD and greater than 160 kD or of 90 kD and 115 kD and greater than 160 kD could be found when mouse T blasts or CTLL 16 cells were used, respectively. In the exclusively low affinity receptor-bearing T cell line Eb, only a single band of 70 kD (beta-chain + IL2) was detectable. These results show that in addition to a 85-90 kD complex, as shown already in humans, a third complex of 105-115 kD exists in mice that is specifically associated with high affinity receptors. This is the first indication of a putative gamma-chain of the high affinity IL2 receptor. All IL2-containing complexes of the mouse cells could be precipitated by the newly developed MAb AMT 45-20 raised against the beta-chain of the mouse IL2R and recognizing an epitope distinct from those recognized by the MAb AMT 13 or IL2. This suggests that either 1) all complexes contain the beta-chain, 2) share an antigenic determinant with the beta-chain, or 3) that the higher mw complexes become coprecipitated with the beta-chain.

Animals↗
PubMed1987

[Prognosis of non-Hodgkin's lymphomas in the Dresden district with special reference to combined radio-/chemotherapy].

The total population affected with non-Hodgkin's lymphoma and treated by means of radiotherapy or combined radio-chemotherapy between 1960 and 1985 at the Medical Academy Dresden was analysed as to prognosis. 247 patients were classified according to the previous German scheme, 79 were subdivided on the basis of the recommendations laid down in the Kiel classification. The remission rates and survival curves achieved will stand out the comparison with international literature (remission rates of the low malignancy group amounted to 85.3 p.c. and those of the high malignancy group to 80.0 p.c.; the 5-years survival rates of the low malignancy group amounted to 61.9 p.c. and those of the high malignancy group to 41.7 p.c.). The influence of histology, clinical stage and involvement of organs is discussed on the basis of our results and informations obtained in literature. Our analysis confirms the high importance which must be attached to a common radiologic-internal outpatient-department for co-ordinating the diagnostic and therapeutical programme.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

[Repair mechanisms of the lung--experimental and clinical results].

The effect of dose and time and of the RBE on the pulmonary reaction to radiation has been studied by means of trials with young pigs. 70 animals received a fractionated (five and 15 fractions) telecobalt irradiation of the right lung over total treatment periods T of five, 23, and 35 days. The influence of dose and time on the pulmonary reaction to radiation is defined at the ED50 level (effective dose, after which 50% of animals will suffer from radiopathy) by a proportionality of D approximately N0.32 X T0.05. An alpha/beta value of 3.7 Gy is calculated according to the LQ model. An RBE value of 4.0 to 4.1 was determined in 38 animals treated over five and 35 days with the 6.2 MeV neutrons of the cyclotron Rossendorf. The experimentations on animals allow to classify the lung reaction as late effect. The clinical results found in literature show that this classification is also valid for human lung reaction to fractionated radiotherapy. So it is not possible to achieve a considerable increase of the pulmonary tolerance dose by increasing the total treatment period. The best sparing of the respiratory organ is obtained by an application of small single doses which allows to profit from the large repair capacity of pulmonary tissue. These results, as well as our considerations regarding the latent time between therapy and lung reaction, and some trials on laboratory rodents allow to speak of a radiogenic pneumopathy with the proprieties of a late reaction characterized by a pneumonitis appearing previously and changing into pulmonary fibrosis.

Animals↗
PubMed1986

Fractionated lung irradiation in young pigs with 6.2 MeV neutrons and cobalt-60.

Irradiations of the right lung with 6.2 MeV neutrons (38 test animals) and 60Co photons (34 test animals) were made using young pigs. Twenty animals were used as controls. Five fractions were administered in an overall treatment time of 5 or 35 days. The radiogenic pneumopathy was monitored with clinical, radiological and histological investigations, and by determining the hydroxyproline content in the lung tissue. The pneumopathy in pigs given neutrons developed after a shorter latency period and followed a more rapid and serious course than that in animals given gamma rays. While after photons the extension of the overall treatment time from 5 to 35 days led to a measurable but low increase of the ED50 this was not true for neutrons. The relative biological effectiveness (RBE) for the 6.2 MeV neutrons compared with 60Co photons was 4.0 for an overall treatment time of 5 days and 4.1 for 35 days.

Animals↗
PubMed1986

The time-dose relationship for radiation-induced lung damage in pigs.

The dose-time relationship of radiogenic pneumopathy was studied in 68 young pigs. The right lungs of the animals were irradiated by means of a telecobalt unit. Dose distribution calculations and the preparation and execution of irradiation were chosen to largely parallel the treatment of patients. The radiation response of the lungs was quantified by chest-X-rays, functional studies and histological and biochemical investigations of the autopsy specimens. The dose which produced unambiguous signs of radiation pneumopathy in at least 50% of the individuals (ED50), was used to draw an iso-effect plot. A steep slope of the iso-effect line was found when the number of fractions was increased from 5 to 15. In contrast, the iso-effect line showed only a small slope when the influence of overall time was investigated. Significant differences between doses for early and late reactions of the lungs could not be detected. The radiogenic lung reaction in pigs is adequately described by the relation D approximately N0.32 X T0.05 and an alpha/beta value of 3.7 Gy. These results are in a good agreement with those derived for mice by other investigators. The good comparability of the biological findings obtained with pigs to man points to the application of this dose-time relation in radiotherapeutical practice.

Animals↗