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Biomedical subjects

I Müller

Publications and source records attributed to I Müller.

At least 19 recordsLinked to original sources
PubMed1992

Central role for TCR/CD3 ligation in the differentiation of CD4+ T cells toward A Th1 or Th2 functional phenotype.

Activated CD4+ T cells can be classified into distinct subsets; the most divergent among them may be considered to be the IL-2 and IFN-gamma-producing Th1 clones and the IL-4 and IL-5-producing Th2 clones. Because Th1 and Th2 clones can usually be detected only after several months of culture, we used conditions that modulate the IL-2 and IL-4 production in short term culture. Here we show that freshly isolated and subsequently in vitro-activated CD4+ T cells that were cultured for 11 days with rIL-2 and restimulated showed a IFN-gamma+ IL-2+ IL-3+ IL-4- IL-5- pattern. Because these cells were not capable of providing B cell help for IgG1, IgG2a, or IgE in an APC- and TCR-dependent T-B cell assay, they expressed a phenotype typical for most Th1 clones. In contrast, activated T cells that were cultured for 11 days with IL-2 plus a mAb to CD3 and then restimulated produced a IFN-gamma- IL-2- IL-3+ IL-4+ IL-5+ pattern. These cells were capable of providing B cell help for IgG1, IgG2a, and IgE synthesis and thus presented a phenotype typical for Th2 clones. Similar results were observed when mitogenic mAb to Thy-1.2 or to framework determinants of the alpha beta TCR were used. The induction of Th1- and Th2-like cells did not depend on the relative expression of CD44 or CD45 by the T cells before activation in vitro. Because the incubation of activated T cells with anti-CD3/TCR mAb induced high unrestricted lymphokine production, the latter might be responsible for the Th2-like lymphokine pattern observed after restimulation. To address this point, TCR V beta 8+ and V beta 8- T cell blasts were co-cultured in the presence of mAb to V beta 8. After restimulation, V beta 8+ cells had a IL-4high IL-2low phenotype and V beta 8- cells had a IL-4low IL-2high phenotype. This demonstrates that TCR ligation but not lymphokines alone are capable of inducing Th2-like cells, and this points out a central role for the TCR in the generation of T cell subsets.

Animals↗
PubMed1992

Role of T cell subsets during the recall of immunologic memory to Leishmania major.

The contributions of different T cell subpopulations to the maintenance of immunity during secondary Leishmania major infections were analyzed in healed, resistant animals by depletion of T cell subsets in vivo. The strong delayed-type hypersensitivity mounted in immune genetically resistant mice upon challenge with viable promastigotes was mediated by both CD4+ and CD8+ T cells. Each T cell subpopulation alone contributes, although to a different extent, to the resolution of secondary lesions; both subsets, however, are required for an efficient and rapid healing of the secondary lesions and the decrease in the parasite burden in infected tissues. The results indicate that in immune, genetically resistant CBA mice, the activity of both T cell subsets is required for successful resistance to reinfection and an efficient maintenance of immunity.

Animals↗
PubMed1992

Immunobiology of experimental leishmaniasis.

Self-cure versus uncontrolled disease progression in experimental murine cutaneous leishmaniasis depends upon a delicate interplay among various activated cells of the host's immune system. Susceptibility or resistance to infection with Leishmania major is correlated with the ability of different inbred strains of mice to produce the characteristic spectra of lymphokines upon infection. Appropriate experimental interventions now allow the modulation of these responses, providing the possibility to render genetically susceptible mice resistant to infection and, vice versa, to cause genotypically "healer" strains to express a "non-healer" phenotype. These experimental manipulations have proven to be powerful tools in the dissection of the underlying immune mechanisms and cellular parameters responsible for susceptibility and resistance, and will perhaps allow the identification of molecules of parasite origin that induce deleterious immune responses to infection with Leishmania, and thus to exclude them from future vaccines. More importantly, rational immune intervention could permit the diversion of established host-damaging immune responses to host-protective immunization.

Animals↗
PubMed1992

Rapid diagnosis of Chlamydia trachomatis in male patients by antigen detection in urine samples.

To investigate the diagnostic value of testing urine samples as a rapid method for the detection of chlamydial antigen in males, first-catch urine (FCU) and urethral swab samples were obtained from 668 male patients and examined by an enzyme immunosorbent assay (EIA). Positive results were further analyzed by direct fluorescence antibody tests of the EIA sediment. Antigen detection was possible in 12.7% out of the urethra, in 10.8% out of FCU and in a total of 14.5% of the tested persons. Testing only FCU would have missed chlamydia detection in 25 (25.8%) out of a total of 97 chlamydia-positive males. Testing only genital samples would have missed 12 positive cases (12.4%). The sensitivity and specificity of the EIA test of FCU as compared with urethral swabs were 70.6 and 97.9%, respectively, and differed between urine collected before (sensitivity: 84%; specificity: 98.6%) and after (sensitivity: 65%; specificity: 97.7%; p = 0.1254) urethral sampling. The quantitative evaluation of the EIA results demonstrates that the mean value of the extinction rates was highest in specimens corresponding to a positive result from both sampling sites. This study indicates that the chlamydial detection rate was lower in FCU than in urethral samples. FCU testing may be suitable when urethral sampling is not possible; due to its high rate of unconfirmed borderline extinction, positive results should be confirmed with another chlamydial antigen detection test such as direct immunofluorescence.

Adolescent↗
PubMed1992

[Differentiation of fattening and slaughtering performance and carcass quality of broiler genotypes with and without the dwarf factor and fast or slow feathering under heat stress].

In a comparative study the influences were tested of the origins NWR (normal-growth White Rocks) and ZWR (dwarf-growth White Rocks) with a speed for slow (K) and fast (k) feathering as well as the effect of a high environmental temperature (UT, 32 +/- 2.5 degrees C) on the fattening and slaughtering performance of male broilers and their meat quality. Also investigated were effects of these factors on the fatty acid pattern of the two valuable parts--breast and leg. Dwarf broilers kept under high UT had a lower liveweight (LM8) in their 8th week as compared with NWR and animals kept under the usual UT. No influence was found of the feathering on the fattening and slaughtering performance. The effect of heat stress (high UT) and of the dwarfing gene on the breast and leg parts was statistically highly significant (P < 0.001). Dwarfed broilers and animals under normal UT exhibited a smaller slaughtering proportion as compared with normal animals and animals under a higher UT. The abdominal fat content was significantly higher under heat stress. Meat quality showed no dependence on the origin or the climatic conditions. In the fatty acid analysis no dependence could be detected of the FS pattern on the origins (genotypes), whereas an effect was found of the UT on some unsaturated and saturated fatty acids. Palmitic acid and stearic acid formed the largest part of all saturated FS investigated. Among the unsaturated FS the oil, linoleic, and palmitic acids reached the highest share. The effect of higher UT was not uniform in the FS pattern. The sum of saturated FT was increased under heat stress, thus suggesting a more favourable fat quality of the meat.

Adipose Tissue↗
PubMed1991

Conformational and epitope mapping of herpes-simplex-virus type-1 thymidine kinase using synthetic peptide segments.

Adjacent peptide segments covering the complete sequence of herpes-simplex-virus type-1 thymidine kinase (HSV1-TK) of 376 amino acids were synthesized in order to experimentally verify the three-dimensional structure of the HSV1-TK active site, which was previously determined by molecular modeling. 26 peptides have been prepared by multiple solid-phase synthesis using the 9-fluorenylmethoxycarbonyl strategy. The purified peptides were linked covalently to bovine serum albumin. The peptide/ELISA of the synthesized bovine-serum-albumin conjugates using polyclonal rabbit anti(HSV1-TK)serum resulted in ten epitopes, which correlate excellently with the computer-proposed active site of HSV1-TK. CD spectra of the HSV1-TK peptides were recorded in trifluoroethanol/water (9:1 by vol.) An eigenvalue method based on CD spectra of 15 well known protein structures was used to calculate the relative percentage of secondary structures from the CD data. The computer model of the HSV1-TK showed full conformity with the folding pattern determined by CD of the synthetic peptide segments. Therefore, conformational peptide mapping with CD-based secondary structures combined with epitope mapping from the peptide/ELISA is an efficient and reliable method to support computer-aided protein design.

Amino Acid Sequence↗
PubMed1991

Exacerbation of experimental murine cutaneous leishmaniasis with CD4+ Leishmania major-specific T cell lines or clones which secrete interferon-gamma and mediate parasite-specific delayed-type hypersensitivity.

Leishmania major-specific T cell lines were derived from mice sensitized to the parasite. The cells were of the CD4+ T cell lineage and, upon adoptive transfer, were found to be capable of inducing parasite-specific delayed-type hypersensitivity. Adoptive transfer of these L. major-specific T cells to syngeneic recipients which were either normal, T cell deficient or B cell and antibody deficient led to exacerbation of infection upon subsequent challenge with L. major. This suggested that host T cells, B cells and antibody were not required for the L. major-specific T cells to exert their exacerbative effect on the course of cutaneous leishmaniasis. Additional studies revealed that the adoptive transfer of graded doses of these L. major-specific T cells always resulted in exacerbation of infection. Study of the localization pattern of the cells following transfer showed that they migrate preferentially to the site of the lesions. Furthermore, although the induction phase of this phenomenon was immunologically specific, its effector phase was not. Finally, T cell clones were derived from the L. major-specific T cell lines. The T cell clones were phenotypically and functionally identical to the T cell lines from which they were derived. Adoptive transfer of these parasite-specific T cell clones to normal syngeneic recipients induced an exacerbated course of infection with L. major. Interestingly, when these cloned T cells were specifically activated in vitro, the cells produced interleukin 2 and interferon-gamma, but no interleukin 4, indicating that they belong to the murine Th1 subset of CD4+ T cells.

Animals↗
PubMed1991

Experimental infections in chickens with Chilomastix gallinarum, Tetratrichomonas gallinarum, and Tritrichomonas eberthi.

Flagellates from the caeca of a diseased hen and a diseased goose were transmitted to 35 specific pathogen-free (SPF) chickens. The flagellates of chicken origin were identified as Chilomastix gallinarum, Tritrichomonas eberthi, and Tetratrichomonas gallinarum. T. eberthi was not detected in the material of goose origin. Morphologic studies did not reveal any differences between Chilomastix and Tetratrichomonas specimens from chicken or goose origin. The species from the goose were identified as C. gallinarum and T. gallinarum (Syn. T. anseris Hegner, 1929). Both trichomonad species produced pseudocysts that developed in the faeces of chickens within 3 h after excretion. Only 17% of the trichomonads excreted had reached the pseudocyst stage. All three flagellate species are infective to chickens when inoculated per rectum or per os or when consumed with chlorinated tap water. The prepatency period was always less than 24 h. SPF chickens between 2 and 30 days of age were equally susceptible. The infections persisted at a high level of intensity throughout the observation periods, i.e. up to 7 months. Of 35 inoculated SPF chickens, 2 developed disease (emaciation, ruffled feathers, diarrhoea, dilatation of the caeca). The three flagellate species were cultivated in Diamond's medium for 110 days. Cryopreserved and cultivated flagellates retained their infectivity to chickens.

Animals↗
PubMed1991

[The content of DNA, RNA and total protein in different skeletal muscles, in the diaphragm, in the right and left heart ventricles and in the musculature of the esophagus, the stomach and the urinary bladder of normally developed piglets and splayleg piglets of different body weights].

Studies were conducted into concentrations of RNA, DNA, and total protein in various skeletal muscles, diaphragm, right and left ventricles as well as in musculature of the oesophagus, stomach, and urinary bladder of 25 normally developed piglets and 24 sprayleg piglets of differentiated body weight (B.W.). DNA concentration was found to be at its highest in piglets of lowest B.W. The Protein: DNA-quotient increased along with growing B.W. The average value of this quotient in the anterior tibial muscle and brachial triceps muscle of sprayleg piglets was lower than that in normally developed piglets. Average values of the RNA:DNA quotients in the brachial triceps muscle, anterior section of the long dorsal muscle, left ventricle, and stomach muscles were also lower in sprayleg piglets. In newborn piglets, DNA concentrations in ventricles as well as in the muscles of the stomach and oesophagus were higher than those recordable from skeletal muscles. Causes of incapability of newborn piglets to stand on their own feet are discussed in some detail.

Animals↗
PubMed1991

[Bioclimatic assessment of a tropical site--a criterion for decisions concerning breeding and technology for successful animal production in the tropics].

The values of the body temperature and breathing frequency were taken from young pigs and sows at a tropical location in order to study the relations between measured climatic values and their complex derivations (the amount of cooling down, enthalpy, sultriness factor, and water vapour pressure). The relevance was weighted of the natural and calculated climatic values for the thermoregulation of the animals. A practical example is given of the discrepancies between a genuine tropical climate and the demands made by pigs and hens on their climatic environment. From this, conclusions are drawn for successfully keeping and breeding these species at tropical locations.

Animals↗
PubMed1990

Immune responses to defined epitopes of the circumsporozoite protein of the murine malaria parasite, Plasmodium yoelii.

We have investigated the immunogenicity of defined sequences of the circumsporozoite (CS) protein of the murine malaria parasite, Plasmodium yoelii. A 21-ner synthetic peptide from the nonrepetitive region of the CS protein (position 59-79, referred to as Py1) induced T cell proliferative responses in H-2d and, to a lesser extent, in H-2b mice. Conversely, a synthetic peptide (referred to as Py4) consisting of four (QGPGAP) repeats of the P. yoelii CS protein, induced an antibody response only in H-2b mice. No antibody response was observed when the Py3 peptide, consisting of three (QGPGAP) repeats, was used as an immunogen. When cross-linked to the Py4 repetitive peptide, the Py1 sequence behaved as a T helper epitope allowing the production of anti-Py4 antibodies in H-2d mice. Several long-term T cell lines and clones specific for the nonrepetitive Py1 peptide were originated in vitro from both H-2d and H-2b mice. These lines and clones were CD4+ and proliferated in a major histocompatibility complex-restricted fashion. Furthermore, Py1-specific T cell lines and clones did not proliferate in the presence of synthetic peptides from an analogous region of another rodent malaria parasite, P. berghei, despite the high degree of homology existing in this sequence of the two CS proteins. Finally, supernatants from 7 out of 13 clones (from BALB/c mice) produced detectable amounts of interleukin 2 and interferon-gamma; whereas supernatants from the 4 clones from C57BL/6 and 2 from BALB/c mice contained detectable amounts of interleukin 5. These results show that functionally heterogenous CD4+ T cell populations, belonging to either TH1 or TH2 subset, are activated upon immunization of mice with the P. yoelii Py1 synthetic peptide. It is not yet known what differential role these CD4+ subsets play during the malaria infection or after immunization with different malaria T cell epitopes. This knowledge may have a particular impact in the design of effective subunit vaccines against malaria.

Amino Acid Sequence↗
PubMed1990

Peptide-primed CD4+ cells and malaria sporozoites.

We have mapped a T cell epitope in the circumsporozoite (CS) protein of the murine malaria parasite, Plasmodium yoelii. A 21-mer synthetic peptide corresponding to the amino acid positions 59-79 (referred to as Py1), induced specific proliferation in BALB/c and C57BL/6 mice, and provided help for the production of antibodies to peptides from the repetitive region, (QGPGAP)n, of the same CS protein, when mice were immunized with the Py1 peptide conjugated to the repetitive peptide. Long-term CD3+CD4+CD8-TCR alpha beta+ T cell lines and clones were derived from both strains of mice. These lines and clones, that proliferated in an MHC-restricted fashion, did not recognize peptides from the homologous region of another murine malaria parasite, P. berghei. About 50% of these clones produced detectable amounts of IFN-gamma and IL-2, whereas the remaining produced IL-4, IL-5, and IL-6. In preliminary experiments, some of these clones specifically inhibited P. yoelii sporozoite development in vitro and conferred protection in vivo in passive transfer experiments. These findings show that heterogenous T cell populations are activated in mice upon immunization with a short peptide from the P. yoelii CS protein and that some of these cells could be active in the effector arm of the immune response against malaria sporozoites.

Amino Acid Sequence↗
PubMed1990

Effects of centrally administered substance P on cyclic AMP levels in particular brain areas of rats.

Effects of centrally (intracerebro-ventricularly) administered synthetic substance P on the metabolism of cAMP in 19 brain areas were investigated. Substance P administration increased cAMP levels considerably in the frontal cortex, the central gray matter and in the nucleus of the solitary tract, and to a lesser extent in the bed nucleus of the stria terminalis and in the anterior hypothalamic nucleus. Cyclic AMP levels were decreased in the globus pallidus, the habenula, the posterior hypothalamic nucleus and in the locus coeruleus while other brain areas showed no changes in cAMP levels.

Animals↗
PubMed1979

Aggregation of sponge cells. Function of a lectin in its homologous biological system.

For the first time, the biological role of a lectin in the process of reaggregation of single cells from the same species (marine sponge: Geodia cydonium Jam.) is described. The galactose-specific lectin does not promote aggregation, but prevents the antiaggregation receptor from disaggregating cell clumps. Competition experiments showed that the lectin inactivates the antiaggregation receptor by binding to it, most likely via its terminal galactose residues. The lectin converts reversibly aggregation-deficient cells (carrying functional cell membrane-bound antiaggregation receptor molecules) to aggregation-susceptible cells.

Animals↗
PubMed1979

Aggregation of sponge cells. XX. Self-aggregation of the circular proteid particle.

In the extracellular space of the tissue of the sponge Geodia cydonium, circular proteid particles are found which carry as subunits the aggregation factor and a series of glycosyltransferases. Using the technique of velocity sucrose gradient centrifugation, the sedimentation coefficient (S020,w) of the particle-monosomes was determined to be 90. By means of the Svedberg equation a molecular weight of 1.3 . 10(8) daltons could be estimated. The monosomes aggregate in the presence of Ca2+ to higher complexes via disomes, trisomes, and pentasomes. The complexes can be redissociated by dodecyl sulfate but not by EDTA. During the Ca2+-mediated self-aggregation, the particles lose their biological activity with respect to their aggregation promoting function.

Animals↗