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Biomedical subjects

H Wagner

Publications and source records attributed to H Wagner.

At least 613 records · Page 34Linked to original sources

[Biocybernetic tests on the identification and mathematical modelling of the motor regulation system and its disorders].

By means of the biocybernetically conceived step and impulse loads on the forearm the motor postural regulation of healthy test persons and neurological patients with rigor, spasticity and flaccid pareses of slight degree, respectively, were examined. The analysis of the forms of the transient processes rendered possible a significant differentiation of the groups of test persons and patients. With the help of the mathematical mode the response curves of healthy test persons as well as of patients could be simulated with sufficient exactness. Apart from the step and impulse loads psendorandom binary series of test signals are particularly suitable for the analysis of the motor postural regulation.

Adult↗

Reactivity of human lymphocytes to teratoma preparations as revealed by the macrophage electrophoretic mobility (MEM) technique.

By means of the MEM technique, the lymphokine release by human lymphocytes has been measured after exposure to 3M KCl extracts from malignant teratoma tissue. Clear-cut responses were found in 149 out of 171 cancer patients (87%) regardless of the primary cancer site. In contrast, only 15 out of 93 (16%) individuals from a control group without detectable malignant disease gave such a response. Subdivision of that control group showed, however, that only 1 of 46 healthy blood donors, but 14 of 47 (30%) hospital patients with benign tumours (7 of 19), inflammatory diseases or degenerative and metabolic disorders (7 of 28) reacted to the teratoma-derived material. It appears to be possible that malignant teratoma tissues contain a mixture of oncofetal or phase-specific antigens which correspond to the multifarious differentiation structures of the three germ layers developing in such tumours. If the lymphocyte response of tumour patients is due to the sensitization to analogous tumour-associated antigens in vivo, it remains to be clarified whether or not the less frequent lymphocyte response of hospital patients without neoplastic diseases may be directed to another quality of antigens.

Adolescent↗

Increased ammonia production during forearm ischemic work test in McArdle's disease.

A patient with typical features of late onset McArdle's disease is described. During forearm ischemic work test the patient exhibited an exaggerated increase in ammonia release, largely exceeding normal values. It is suggested, that this is due to an activation of the myokinase/myoadenylate deaminase pathway. Besides lack of lactate release increased ammonia release during ischemia may be a typical feature of McArdle's disease.

Ammonia↗

Lyt-23+ cyclophosphamide-sensitive T cells regulate the activity of an interleukin 2 inhibitor in vivo.

Sera of thymus-bearing normal mice contain high levels of Interleukin 2 (II-2) inhibitor, whereas sera of athymic nu/nu mice do not. Evidence is presented that cyclophosphamide-sensitive Lyt-23+ T cells induce high II-2 inhibitor activity in the recipient nu/nu mice in the course of a graft-vs.-host reaction. The II-2 inhibitor has an approximately 50,000 mol wt. Its function is neither antigen specific nor H-2 restricted. During ontogeny, its activity parallels the development of T cell reactivity, i.e., it is absent both in the amniotic fluid and in sera of unborn mice, but increases to high levels during the early postnatal phase. The II-2 inhibitor described is viewed as an example of a T cell-dependent, in vivo regulatory mechanism able to effectively counteract the nonspecific activity of the Lyt-1+ helper T cell-derived II-2. Because the II-2 inhibitor activity is rather high in vivo, II-2 activity will exist only in close proximity to its producer cell, thereby maintaining specificity during the in vivo induction of cytotoxic T lymphocytes

Animals↗

Frequency analysis of cytotoxic T lymphocyte precursors in chimeric mice. Evidence for intrathymic maturation of clonally distinct self-major histocompatibility complex- and allo-major histocompatiblilty complex-restricted virus-specific T cells.

To study whether the thymic major histocompatibility complex (MHC) imposes a constraint on the receptor repertoire of maturating cytotoxic T lymphocyte (CTL) precursors, the restriction phenotypes of virus-specific CTL of MHC-compatible and of MHC-incompatible thymus- and bone marrow-grafted (A X B)F1 chimeric mice were compared. Dependent on the mode of in vitro sensitization, thymocytes or splenocytes of both types of chimeric mice generated Sendai virus-specific, self-MHC-or allo-MHC-restricted CTL. By applying the limiting-dilution technique, the CTL-precursor (CTL-P) frequencies of self-MHC-restricted and allo-MHC-restricted virus-specific T cells as well as of alloreactive T cells were determined. The data obtained revealed that independent of MHC differences between thymus and bone marrow, the frequencies of self-MHC-restricted and allo-MHC-restricted CTL-P were comparable, and in the same older of magnitude as those previously determined in conventionally reared mice. Self-MHC-restricted, virus-specific CTL-P were in a three- to fivefold excess over allo-MHC-restricted CTL-P. A segregation analysis revealed that clonally distinct CTL-P give rise to either self-restricted or allo-MHC-restricted, virus-specific CTL. Both sets were found not only in the spleen, but also in the thymus of chimeric mice, formally demonstrating the intrathymic differentiation pathway of self-MHC as well of allo-MHC-restricted CTL-P. These data reveal no major constraint of the thymic MHC on the capacity of T cells to recognize viral antigens either in the context of self-MHC or of allogeneic MHC products.

Animals↗

H-2 restriction as a consequence of intentional priming. Frequency analysis of alloantigen-restricted, trinitrophenyl-specific cytotoxic T lymphocyte precursors within thymocytes of normal mice.

An in vitro acute-depletion protocol was used to detect trinitrophenyl (TNP)-specific, allo-major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) within thymocytes of inbred mice. After removal of alloreactivity, the negatively selected cells could be sensitized to become TNP-specific, allo-MHC-restricted cytotoxic T cells. A precursors frequency analysis revealed a three- to ninefold lower frequency of allo-MHC-restricted CTL precursors (CTL-P) as compared to self-MHC-restricted CTL-P. The specificity analysis of clonally distributed allo-MHC-restricted CTL-P excluded cross-reactivity as an explanation of allo-MHC restriction. These results provide direct evidence that thymic T cells are composed of a mixture of self-MHC- and allo-MHC-restricted immunocompetent T cells and that antigen-driven selection of precommitted T cells dictates the H-2-restriction phenotype, i.e., H-2 restriction is a consequence of priming.

Animals↗

[Familial incidence of Crohn disease].

This study reports about the frequent incidence of Crohn's disease in four families. This evidence in confirmed by literature. Relatives of patients with Crohn's disease are ten times more likely to suffer from that disease than those of healthy families. Familial accumulation of Crohn's disease can possibly be explained by genetic factors. Other factors like autoimmunological processes, infections, overnutrition and deficient composition of alimentation with refined carbohydrates might start Crohn's diseases in these families.

Adolescent↗

Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin 1 and interleukin 2.

The site of action of the immunosuppressive drug cyclosporin A in in vitro cytotoxic allograft responses has been localized. General cytotoxic effects of the drug on proliferating T cells became apparent at concentrations of 500-1000 ng/ml, while selective effects were observed at concentrations of 10-100 ng/ml. The selective effects included a blockade of interleukin 2 release from activated T helper cells on the one hand and inhibition of interleukin 1 release from splenic adherent cells on the other. While cyclosporin A did not interfere with the intracellular events required for the activation and subsequent clonal expansion of alloreactive T cells, the lack of interleukin 1 and interleukin 2 induced by cyclosporin A results in an inability of T responder cells to mount cytotoxic allograft responses in vitro.

Animals↗

(+/-)[125Iodo] cyanopindolol, a new ligand for beta-adrenoceptors: identification and quantitation of subclasses of beta-adrenoceptors in guinea pig.

(+/-)[125Iodo] cyanopindolol (ICYP) is a radioligand which binds with an extraordinarily high affinity and specificity to beta-adrenoceptors. In contrast to (+/-) [125Ido]-hydroxybenzylpindolol (IHYP), the new ligand has neither affinity to alpha-nor to 5-HT-receptors. The dissociation constants of ICYP for beta- adrenoceptors in various tissues range from 27 to 40 pM, thereby exceeding the affinity of IHYP by a factor of approximately 3. ICYP does not discriminate between beta 1- and beta 2-adrenoceptors. Therefore, the densities of the two receptor subtypes can be determined from competition curves of ICYP by drugs previously found to show in vitro selectivity for beta 1-adrenoceptors. The guinea pig left ventricle contains only beta 1-adrenoceptors, whereas in a lung tissue, the ratio of beta 1-to beta 2-adrenoceptors is 1 to 4. The calculated affinities of five beta 1-selective antagonists for beta 1-adrenoceptors were nearly identical in the ventricle and the lung. Kinetic studies of ICYP binding to guinea pig lung membranes indicated that the dissociation reaction consists of two components, a fast process (t 1/2 = 9 min) and a slower process (t 1/2 = 8.8 h). A mathematical treatment revealed two possibilities of interpretation: 1. Two forms of the receptor exist which are interconvertible. 2. The (+)- and (-)- enantiomers of ICYP dissociate with different rate constants. The low dissociation constant of ICYP in combination with its high specific radioactivity (2175 Ci mmole -1) allows binding studies to be carried out with small protein and ligand concentrations, e.g. 3 microgram protein per assay in guinea pig lung membranes.

Adrenergic beta-Antagonists↗

On the overload effect of sound impulses to the inner ear.

Test series with both continuous and intermittent sound exposure to guinea pig ears yielded an area within the coordinates load frequency and load level in which a dose principle is valid more or less exactly. Exceeding the upper (level) borderline of this area provokes a damage of the organ of Corti nearly independent of the load dose. Sound levels of such order of magnitude mainly occur at sound impulses. However, to estimate the hair-cell damaging effect of a given sound impulse one needs its time or frequency function in addition to the peak level. A first order approximation seems to be possible by means of a 1/3-octave band level analysis.

Acoustic Stimulation↗

Influence of body temperature on the set-up and recovery of noise-induced cochlea damage.

Hypothermia during exposure to noise reduced hair-cell damage which, on the contrary, was prevented from recovering by narcosis and hypothermia. Hyperthermia is apparently able to eliminate the narcosis dependent limitation of metabolism. A noise damage happens to develop by decompensating the excessively overburdened metabolism, whereas recovery seems to depend on the availability of a highly intracellular level of biological energy.

Acoustic Stimulation↗

[Radiation injuries of the locomotor system (author's transl)].

Radiation injuries of the locomotive apparatus manifest themselves in three ways, each one of which may appear alone or in combination with the other two: 1. Radiation osteonecrosis 2. Growth disturbance due to epiphyseal injury. 3. Scar formation in the skin, fascia, and muscles The results of corrective operative procedures depend almost totally on the condition of the soft tissue. In those patients with a reasonable life expectancy, extensive operation procedures are indicated if they will restore or preserve function in the extremity.

Adult↗

A visually-driven postural after-effect.

Viewing a large-scale moving scene typically causes a free standing observer to lean in the direction of the seen motion. It was also noted that when the visual motion ceases, the observer drifts back toward the upright position, but instead of this body movement stopping at the vertical, it tends to continue so that the observer remains leaning in the opposite direction for several seconds before finally returning to the upright. The two experiments reported here were designed to investigate the determinants of this postural after-effect in relation to a pitch vection stimulus. Our findings clearly showed that the after-effect was dependent upon (1) the establishment of a prior visually-induced body lean, and (2) sight of the static display on the cessation of motion. The notion of an internalised representation of body position was invoked to account for these results.

Adult↗