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Biomedical subjects

I Müller

Publications and source records attributed to I Müller.

At least 91 records · Page 5Linked to original sources

The effect of a dentifrice containing chlorhexidine and zinc on plaque, gingivitis, calculus and tooth staining.

In this 6 months randomized, stratified double-blind parallel study, plaque, gingivitis, calculus formation and tooth staining were assessed in 208 participants. The participants either used a 0.12% chlorhexidine rinse and a gum care dentifrice (positive control) or a placebo rinse and the gum care dentifrice (control) or the placebo rinse and an experimental dentifrice containing 0.4% chlorhexidine and 0.34% Zn2+ (experimental group). After 6 months product use, all groups had less plaque, less gingivitis and all developed calculus and tooth staining. For the positive control group and for the experimental group, significant reductions in plaque and gingivitis (gingival index and number of bleeding sites) were seen compared with the control group. Significantly more calculus developed in the positive control group, while the experimental group was not different from the control group. Finally, tooth staining was significantly higher for the groups using chlorhexidine containing products compared with the control group. The experimental dentifrice users however did develop significantly less staining compared with the positive control. It is concluded that the experimental dentifrice will contribute to a significant improvement in oral hygiene with less staining compared with using a 0.12% chlorhexidine rinse.

Adolescent↗

Tumor necrosis factor alpha (TNF-alpha) and TNF-beta and their receptors in experimental cutaneous leishmaniasis.

Experimental infection of BALB/c mice with Leishmania major leads to lesions which progress without healing and visceralization, reproducing the most severe forms of human leishmaniasis, while resistant mice like CBA spontaneously resolve lesions and develop protective immunity. Given the conflicting data pertaining to the role of tumor necrosis factor alpha (TNF) in Leishmania infection, we analyzed the expression of TNF, tumor necrosis factor beta (lymphotoxin), and TNF receptor type I (TNF-RI) and type II (TNF-RII) genes in vivo and correlated TNF gene expression in vivo with the production of biologically active TNF by lymphoid cells in vitro. No significant difference in the expression of TNF mRNA was found between susceptible and resistant strains of mice during the course of infection. The depletion of CD4+ T cells in vitro did not change the level of TNF mRNA in BALB/c lymph node cells but led to the total disappearance of TNF mRNA in CBA mice. Unprimed spleen cells did not produce detectable amounts of TNF, whereas 1 week after infection, TNF bioactivity was detected and increased in both strains of mice until 5 weeks of infection. While neutralization of TNF activity in vivo did not alter the course of infection in BALB/c mice, in CBA mice it led to an increase in lesion size and a delay in the healing process but did not interfere significantly with the outcome of infection. Finally, no significant difference in the levels of lymphotoxin, TNF-RI, or TNF RII mRNA expression was found between both strains. The information resulting from these investigations supports the notion that, in vivo, TNF is not the decisive factor responsible for the resistant versus susceptible phenotype in leishmania infection.

Animals↗

Expansion of gamma interferon-producing CD8+ T cells following secondary infection of mice immune to Leishmania major.

Reinfection of immune mice with Leishmania major elicits a secondary gamma interferon (IFN-gamma) response to which specific CD8+ T cells are essential. We have shown previously that specific CD8+ T cells from reinfected immune mice release substantially higher levels of IFN-gamma, a cytokine essential for the efficient activation of parasitized macrophages to kill intracellular L. major. By using an ELISPOT assay, which allows the detection of IFN-gamma production by individual cells, it is shown here that this elevated IFN-gamma response is the result of an increase of up to 50-fold in the frequency of parasite-specific CD8+ T lymphocytes in the spleens and draining lymph nodes of both immune reinfected CBA and BALB/c mice. This observation is additional evidence of the role that CD8+ T cells play in immunity to reinfection with L. major.

Animals↗

Rapid diagnosis of Chlamydia trachomatis with a nucleic acid probe in male and female patients.

To evaluate a commercially available DNA hybridization test, the Gen-Probe Pace 2 assay (GP) was compared with the Chlamydiazyme (CZ) for the detection of Chlamydia trachomatis in urethral and endocervical specimens. Samples were collected from 300 persons, including 199 registered and 43 nonregistered female prostitutes, examined for screening purposes, as well as 22 male and 36 female symptomatic sexually transmitted disease (STD) patients. The overall prevalence of C. trachomatis was 7.3% in all persons examined with an infection rate of 20.9% in the nonregistered prostitutes, 2.5% in the registered prostitutes and 13.8% in the STD patients. The overall concordance of both diagnostic methods was 98.7% in all samples examined, 100% in male and 98.6% in female samples. Specimens with discordant results were further analyzed by a direct immunofluorescence test (MicroTrak) and by the probe competition assay (PCA). All samples only positive in the GP assay could be confirmed by the PCA while one result which was positive in the CZ could not be confirmed by any other test. The GP assay was superior to the CZ, when compared with true-positive and -negative results. The data demonstrate that the GP assay can be recommended as an alternative diagnostic technique to the CZ for Chlamydia diagnosis.

Chlamydia Infections↗

Cadmium concentration in the renal cortex of kidney tumor patients and controls.

In this pilot study the concentration of cadmium was determined quantitatively in samples of renal cortex of 22 kidney cancer patients and 19 controls. Data on the three main sources of exposure to cadmium-diet, cigarette smoking and occupation-were obtained through interviews. No significant difference in Cd concentration between the tumor samples and the controls could be found. The mean Cd concentration was 50.9 +/- 25 mg/kg dry weight for cancer patients and 55.2 +/- 50 mg/kg for controls. Further, it was established that the age-dependent relationship for cadmium in the cortex was not valid for smokers.

Adult↗

Site-directed mutagenesis in the active site of the herpes simplex virus type 1 thymidine kinase gene.

The thymidine kinase (TK) of herpes simplex virus type 1 (HSV-1) contains three regions of homology to other ATP utilizing enzymes. We have altered one region of the protein, which seems to play an important role in phosphorylation substrates by site-directed mutagenesis. When the aspartate 162 was changed to asparagine, the enzyme lost its activity. To identify the inactive protein, expressed by a vaccinia vector in eukaryotic cells, a monospecific antiserum against a bacterial tryptophan E-HSV-1 TK fusion protein was made. These results support the suggestion that aspartate 162 is essential for the enzymatic activity.

Amino Acid Sequence↗

Leishmania major infection in BALB/c mice: protection or exacerbation by treatment with different doses of BCG.

The effect of live bacillus Calmette-Guérin (BCG), administered intraperitoneally to BALB/c mice, upon the development of lesions induced by subcutaneous infection with Leishmania major was examined. Lesions in mice given 10(7) BCG colony-forming units (CFU) 9 days before challenge with L. major were less severe and contained significantly fewer parasites than those of similarly infected control mice not given BCG. This effect of treatment with high doses of BCG upon the development of leishmanial lesions was observed using L. major promastigotes and amastigotes, whether or not 10(6) live BCG was included in the parasite inoculum. Lesions in mice given 5 x 10(4) BCG CFU 14 days before infection with L. major contained significantly fewer parasites than those of control mice not given BCG. Mice treated with low doses of BCG and infected with an L. major inoculum also comprising BCG exhibited larger lesions that contained more parasites. Interestingly, compared to naive mice infected with L. major, infection of naive mice with L. major mixed with live BCG consistently led to the development of more severe lesions that contained higher numbers of parasites. No correlation was found between the effect of BCG on the development of lesions induced by L. major and the amounts of IFN gamma, IL5 and TNF produced after in vitro antigenic challenge of either draining lymph node or spleen cells, the antigenic challenge being either live BCG or live L. major.

Animals↗

TH1 and TH2 T-cell subsets are differentially activated by macrophages and B cells in murine leishmaniasis.

The role of antigen-presenting cells in the differential expansion of TH1 and TH2 T cells in murine leishmaniasis was investigated. In general, macrophages preferentially induced gamma interferon and interleukin-2 secretion by syngeneic Leishmania-specific T cells, whereas B cells were more efficient in activating interleukin 4 production. B cells from susceptible BALB/c mice were better in inducing TH2 responses than B cells from resistant C57BL/6 mice, whereas macrophages from C57BL/6 mice were superior to BALB/c macrophages in inducing TH1 responses.

Animals↗

Gamma interferon response in secondary Leishmania major infection: role of CD8+ T cells.

CD8+ T cells have been shown to contribute to the rapid resolution of secondary lesions developing in immune mice challenged with Leishmania major. In the present study, we assessed directly the participation of specific CD8+ T cells in the memory response induced in immune mice by reinfection. Lymphocyte populations from reinfected immune mice exhibit marked secondary gamma interferon (IFN-gamma) responses. The participation of IFN-gamma-producing CD8+ T cells in the memory response elicited by secondary infectious challenge was demonstrated in both genetically resistant immune CBA mice and genetically susceptible immune BALB/c mice that were rendered resistant by administration of anti-CD4 monoclonal antibody in the early phase of the primary infection. The protective function of CD8+ T cells in experimental murine cutaneous leishmaniasis might thus be explained in part by their ability to secrete IFN-gamma. In this context, the neutralization of IFN-gamma at the time of reinfection reduced the Leishmania-specific delayed-type hypersensitivity response, showing that this cytokine is involved in the recall of immunological memory to L. major in vivo.

Animals↗

[New conservative therapy of phimosis].

A new conservative method for the treatment of phimosis is presented: similar to the labio-synechia of girls a local treatment with an oestrogen containing cream is performed successfully. After approximately three weeks about 90% of the boys could easily retract their prepuce. We hope that in future an operation will be less often necessary because of this successful conservative method.

Administration, Topical↗

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↗

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↗

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↗

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↗

[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↗

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↗