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Biomedical subjects

B Müller

Publications and source records attributed to B Müller.

At least 217 records · Page 12Linked to original sources
PubMed1996

Synthetic peptides coupled to the lipotripeptide P3CSS induce in vivo B and Thelper cell responses to HIV-1 reverse transcriptase.

To evaluate the ability of the lipotripeptide P3CSS to increase peptide-specific immune responses in vivo, we immunized mice from different inbred strains (BALB/c, C3H/HeJ, C57BL/6) with the 22-mer lipopeptide conjugates P3CSS-[RT-(522-543)] and P3CSS-[RT-(528-549)] of HIV-1 reverse transcriptase (RT) which included an immunodominant Th epitope [i.e. RT-(528-543)] characterized previously. Analysis of T and B cell responses to these lipopeptide conjugates indicated that specific Th responses could be readily induced in vivo. The peptide segments could also efficiently prime mice for secondary recognition of native RT. The use of shorter peptides permitted a delineation of the minimal T cell recognition site of this RT C-terminal region [i.e. RT-(528-540)]. Close to this T cell epitope we identified a B cell determinant containing the motif EQVD [RT-(546-549)] which was recognized in three different strains of mice (H-2b, H-2d and H-2k). A comparison with X-ray analysis of the C-terminal region of HIV-1 reverse transcriptase indicated exposed positions of these Th and B cell epitopes. Both the presence of T and B cell sites and its limited polymorphism make the region RT-(528-549) a promising candidate for vaccine design. The use of the P3CSS adjuvant/carrier principle as a nontoxic adjuvant may be of major importance in the development of vaccines applicable to humans.

Adjuvants, Immunologic↗
PubMed1996

Unrepresentative behavior of T cell receptor-transgenic CD4+ T cells upon adoptive transfer: lack of need for priming and an extended booster dose-response.

The response of CD4+ T cells taken from DO11.10 alpha beta TCR-transgenic mice to their specific antigen, ovalbumin, was examined in an adoptive transfer system. Read out was the % frequency of KJI-26.1+ (clonotype positive) cells within the Thy-1.2+ (T cell) population in lymph nodes. Control experiments indicated that these cells were uniformly CD4+. Immunizing the transgenic mice had no detectable effect on this frequency. Furthermore, the frequency in recipients of adoptively transferred lymph node cells was not affected by priming of the donors with ovalbumin by various procedures. Transfers were into syngeneic SCID recipients, except in one experiment, where irradiated recipients were shown to behave in the same way. Examining the effect of varying the amount of booster antigen, the response increased slowly with dose, up to a plateau in the range of 10-100 mg ovalbumin. The lack of need for priming is unusual, in comparison with an adoptive transfer of non-transgenic cells, as is the extended dose response range with such a high optimum dose. This enhanced responsiveness is interpreted in terms of a lack of down-immunoregulation in these transgenic mice.

Adoptive Transfer↗
PubMed1996

Increase in the expression of alpha E beta 7, characteristic of intestinal intraepithelial lymphocytes, on T cells in the lung epithelium of patients with interstitial lung diseases and in synovial fluid of patients with rheumatic diseases.

The intestinal epithelium contains a distinct group of lymphocytes (iIEL). The majority of iIEL are T cells characterized by a phenotype different from PBL. This phenotypic peculiarity has led to the hypothesis that iIEL, develop in a thymus-independent fashion, that they may develop locally in the gut epithelium itself and that they have the distinct function of providing a first line of defense in the gut. We looked at the expression of the gut-associated surface molecule alpha E beta 7 on T cells in inflamed tissues outside the gut epithelium. The already high frequency of 41.8% alpha E beta 7+ T cells in bronchoalveolar lavage from healthy lungs rises to a median of 61% in a fibrotic lung. In synovial fluid the percentage of T cells expressing alpha E beta 7 was diverse; it was not as high as in the lung but was elevated compared to PBL levels. In both tissues, the increase in alpha E beta 7 expression correlated with an increase in CD8+ cells. We discuss our data in the context of a model in which iIEL can leave the gut epithelium and become involved in inflammatory processes, possibly related to autoimmune disease.

Arthritis, Rheumatoid↗
PubMed1996

MIB-1 immunoreactivity correlates with metastatic dissemination in primary thick cutaneous melanoma.

BACKGROUND: The proliferation rate of transformed cells is a putative prognostic indicator. MIB-1 is a murine monoclonal antibody to a Ki-67 epitope that detects a nuclear antigen found only in proliferating cells. OBJECTIVE: The aim of this study was to test for a correlation between MIB-1 immunoreactivity and the metastatic potential of malignant melanoma. METHODS: MIB-1 reactivity (% total tumor nuclei) was assessed in 34 formalin-fixed, paraffin-embedded primary cutaneous melanomas and correlated with metastatic potential and overall survival (follow-up, 10.5 +/- 1.8 years). RESULTS: Whereas no correlation was found between MIB-1 reactivity and metastases in primary thin cutaneous melanoma (Breslow thickness, < 0.75 mm; mean thickness, 0.39 +/- 0.16 mm), good correlation was found (p = 0.0001) in primary thick cutaneous melanoma (Breslow thickness, > 1.5 mm; mean thickness, 3.0 +/- 1.3 mm). MIB-1 reactivity was 12.3% +/- 7.7% and 0.7% +/- 1.3% with and without metastases, respectively, and was highest in the primary melanomas that later metastasized. However, overall survival in patients with thick cutaneous melanoma and metastases did not correlate with MIB-1 reactivity. CONCLUSION: MIB-1 proliferative activity is a useful prognostic indicator in primary cutaneous melanomas thicker than 1.5 mm and may predict the development of metastases.

Antibodies, Monoclonal↗
PubMed1996

[Magnetic resonance tomography of the kidney: the testing of new pulse sequences and comparison with CT in the differential diagnosis of space-occupying lesions].

PURPOSE: To evaluate new pulse sequences (turbo-spin-echo [TSE] and turbo-field-echo [TFE] sequences) for study protocol optimisation and to assess the role of MRI in the differential diagnosis of renal tumours. METHODS: In six volunteers MRI of the kidney was performed at 0.5 T using a conventional T2 weighted spin-echo (SE) sequence (TR/TE 1800/90 ms) and three different TSE sequences (TR 1800-5000 ms, TE 90-150 ms). Additionally CT and MRI was performed in 34 patients with 41 renal masses. Two readers evaluated both images regarding the differentiation between malignant and benign masses. RESULTS: The pilot study showed that the heavily T2-weighted TSE sequence (TR/TE 5500/150 ms) was superior to other sequences with regard to image quality and differentiation of the corticomedullary junction. In the clinical study malignant tumours were correctly classified with CT and MRI in 86.4% and 95.5% of the cases, whereas the accuracy in the diagnosis of benign lesions of CT and MRI was 73.7% and 89.5%, respectively. CONCLUSION: Using new puls sequences MRI is superior to CT in the differential diagnosis of renal tumours. MRI is superior to CT in the differentiation between complicated cysts and cystic or hypovascular renal cell carcinomas.

Diagnosis, Differential↗
PubMed1996

Mutations disrupting the ordering and topographic mapping of axons in the retinotectal projection of the zebrafish, Danio rerio.

Retinal ganglion cells connect to their target organ, the rectum, in a highly ordered fashion. We performed a large-scale screen for mutations affecting the retinotectal projection of the zebrafish, which resulted in the identification of 114 mutations. 44 of these mutations disturb either the order of RGC axons in the optic nerve and tract, the establishment of a topographic map on the tectum, or the formation of proper termination fields. Mutations in three genes, boxer, dackel and pinscher, disrupt the sorting of axons in the optic tract but do not affect mapping on the tectum. In these mutants, axons from the dorsal retina grow along both the ventral and the dorsal branch of the optic tract. Mutations in two genes, nevermind and who-cares, affect the dorsoventral patterning of the projection. In embryos homozygous for either of these mutations, axons from dorsal retinal ganglion cells terminate ventrally and dorsally in the tectum. In nevermind, the retinotopic order of axons along the optic nerve and tract is changed in a characteristic way as well, while it appears to be unaffected in who-cares. Two mutations in two complementation groups, gnarled and macho, affect the anteroposterior patterning of the projection. In these mutants, nasodorsal axons branch and terminate too soon in the anterior tectum. In 27 mutants belonging to six complementation groups, retinal axons do not form normal termination fields. Some implications for models concerning the formation of topographic projections are discussed.

Animals↗
PubMed1995

Impaired action of thyroid hormone associated with smoking in women with hypothyroidism.

BACKGROUND: The effect of smoking on thyroid function is controversial, and its effect on thyroid hormone action is unknown. We investigated the effects of cigarette smoking in women with various grades of hypothyroidism and in normal women. METHODS: We studied 138 normal women and 135 women with primary hypothyroidism, of whom 84 had subclinical hypothyroidism and 51 overt hypothyroidism. Sixty of the women with hypothyroidism were reevaluated during thyroxine therapy. The women were categorized as smokers or nonsmokers according to their responses to a questionnaire. Thyroid function was evaluated by measurements of serum thyrotropin, free thyroxine, and triiodothyronine. Peripheral thyroid hormone action was assessed by a clinical score and measurements of ankle-reflex time and serum lipids and creatine kinase. RESULTS: Among the women with subclinical hypothyroidism, the smokers had a higher mean (+/- SD) serum thyrotropin concentration (21.3 +/- 16.6 vs. 12.7 +/- 7.2 mU per liter, P = 0.004) and a higher ratio of serum triiodothyronine to serum free thyroxine (by 30 percent, P = 0.003) than the nonsmokers. Their serum concentrations of total cholesterol and low-density lipoprotein (LDL) cholesterol were higher (by 16 percent, P = 0.013; and 28 percent, P = 0.003, respectively). Among the women with overt hypothyroidism, the serum concentrations of thyrotropin, free thyroxine, and triiodothyronine were similar in the smokers and nonsmokers. As compared with the nonsmokers, the smokers had a clinical score indicating a greater degree of hypothyroidism (P < 0.001), higher serum concentrations of total and LDL cholesterol (by 25 percent, P < 0.001; and 24 percent, P = 0.002, respectively), longer ankle-reflex time (by 25 percent, P < 0.001), and higher serum concentrations of creatine kinase (by 236 percent, P < 0.001). There were dose-response relations between smoking and serum concentrations of total and LDL cholesterol, serum creatine kinase concentrations, and ankle-reflex time in the women with overt hypothyroidism, and between smoking and serum concentrations of total and LDL cholesterol in the women with subclinical hypothyroidism. CONCLUSIONS: Smoking increases the metabolic effects of hypothyroidism in a dose-dependent way. This may be explained by alteration of both thyroid function and hormone action.

Adult↗
PubMed1995

Identification of polymorphic sites of the human bradykinin B2 receptor gene.

The characterization of the genomic organization of the B2 bradykinin receptor gene enabled us to systematically search for polymorphic markers in this gene in a South German cohort (N = 179). We identified at least three polymorphic sites in each of the three exons existing: (i) in exon 1 next to the promoter region, a tandem repeat polymorphism consists of three common alleles, (ii) in exon 2 at nucleotide position 181 of the cDNA a C to T transition leads to an aminoacid substitution from arginine to cysteine in the receptor protein at position 14 (R14C), and (iii) a more complex repeat polymorphism, located in the 3' not-translated region of exon 3, comprises at least two common alleles and two rare variants. These new genetic markers provide valuable tools to elucidate a potential role of a hereditary dysfunction of the B2 bradykinin receptor gene in disorders such as hypertension or ischemic heart disease.

Alleles↗
PubMed1995

Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XXVII. Inhibition of leucocyte adherence to endothelium by the oligoamine RE 1492C and the NO-donor RE 2047.

The oligoamine RE 1492C (N,N',N"-4-phenylbutyl-1,3,5-benzene-trimethanamine-N,N',N"- triethylcarbamate ) inhibited the electrically provoked leucocyte adhesion to the endothelium of rat mesenteric venoles. An oral dose of 60 mg/kg gave a significant inhibition of 65-78%. This is comparable to effects seen after i.v. administration of iloprost or PGE1, respectively. In the same dosage the NO-donor RE 2047 (3-methyl-N-nitroso-sydnone-5-imine) produced an inhibition of 21-27%.

Animals↗
PubMed1995

Evolution of seed storage protein genes: legumin genes of Ginkgo biloba.

Legumin-like seed storage proteins have been intensively studied in crop plants. However, little is known about the molecular evolution of these proteins and their genes and it was assumed that they originated from an ancestral gene that already existed at the beginning of angiosperm evolution. We have evidence for the ubiquitous occurrence of homologous proteins in gymnosperms as well. We have characterized the major seed storage globulin from Ginkgo biloba by amino acid sequencing, which reveals clear homology to legumin-like proteins from angiosperms. The Ginkgo legumin is encoded by a gene family; we describe two of its members. The promoter regions contain sequence motifs which are known to function as regulatory elements involved in seed-specific expression of angiosperm legumins, although the tissues concerned are different in gymnosperms and angiosperms. The Ginkgo legumin gene structure is divergent from that of angiosperms and suggests that the evolution of legumin genes implicated loss of introns. From our data and from functional approaches recently described it becomes obvious that the posttranslational processing site of legumin precursors is less conserved than hitherto assumed. Finally, we present a phylogenetic analysis of legumin encoding sequences and discuss their utility as molecular markers for the reconstruction of seed plant evolution.

Amino Acid Sequence↗
PubMed1995

Interplay between the human TCR/CD3 epsilon and the B-cell antigen receptor associated Ig-beta (B29).

T and B lymphocytes are characterized by the surface expression of highly variable antigen receptors called the T-cell (TCR) and B-cell (BCR) receptor. In both B and T cells, binding of antigen to their respective surface receptors results in transmembrane signaling which leads either to programmed cell death or to proliferation and differentiation. The human and murine TCR consist of the highly variable TCR alpha and beta or gamma and delta chains recognizing antigen and the non-covalently associated invariable CD3 complex (gamma, delta, epsilon) and zeta. The antigen-recognizing surface membrane-bound immunoglobulin (Ig) molecules on the surface of human and murine B cells are non-covalently associated with a heterodimeric protein complex of Ig-alpha (MB-1) and Ig-beta (B29). Like the CD3 complex associated with TCR the Ig-associated proteins are predicted to regulate the assembly and transport of the Ig complex to the cell surface and to couple membrane-bound Ig to intracellular signal transduction pathways. To gain more insight into structure/function relationships between CD3 proteins and Ig-alpha and Ig-beta, we transiently co-transfected pairs of expression vectors encoding either TCR/CD3 chains on the one hand and Ig-alpha or Ig-beta on the other into Cos cells. Thus we found a very strong interaction between CD3 epsilon and Ig-beta mediated by the extracellular domains. Experiments in which we could stain Jurkat T cells with soluble Ig-beta but not Ig-alpha protein indicated the recognition of CD3 epsilon by Ig-beta even in the context of the whole TCR/CD3 complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Moclobemide versus clomipramine in depressed patients in general practice. A randomized, double-blind, parallel, multicenter study.

In a double-blind, randomized, controlled, multicenter clinical trial in general practice, lasting 7 weeks, a fixed dose of moclobemide (400 mg daily) was compared with a fixed dose of clomipramine (150 mg daily). A total of 147 patients with DSM-III-R major depression were included in the study. After a 1-week drug-free washout period, patients were stratified, according to total scores on the Hamilton Rating Scale for Depression (HAM-D), into two groups--HAM-D total scores, 11 to 15 points, and HAM-D total scores, 16 points or more. A comparison of the therapeutic effect of the two treatments was based on HAM-D total scores and the classification of patients into therapeutic response categories defined on the basis of total rating score, complete response, HAM-D < or = 7 points; partial response, HAM-D, 8 to 15 points; or no response, HAM-D > or = 16 points. The Newcastle Diagnostic Rating Scale (1965) was used to classify the patients into two groups, endogenous and nonendogenous. Adverse events were registered by use of the UKU side effect scale. Clinical global assessments of severity, efficacy, and tolerance were completed during the active treatment period. Compliance to treatment was based on levels of the drugs in plasma and the number of returned capsules. One hundred forty-two patients were evaluated for clinical effects. The results of the efficacy analyses showed therapeutic equivalence between moclobemide and clomipramine. There were no differences in the outcome of the two treatment groups or the two diagnostic groups (endogenous and nonendogenous).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Characterization of the cell-wall polysaccharides of Arabidopsis thaliana leaves.

The cell-wall polysaccharides of Arabidopsis thaliana leaves have been isolated, purified, and characterized. The primary cell walls of all higher plants that have been studied contain cellulose, the three pectic polysaccharides homogalacturonan, rhamnogalacturonan I and rhamnogalacturonan II, the two hemicelluloses xyloglucan and glucuronoarabinoxylan, and structural glycoproteins. The cell walls of Arabidopsis leaves contain each of these components and no others that we could detect, and these cell walls are remarkable in that they are particularly rich in phosphate buffer-soluble polysaccharides (34% of the wall). The pectic polysaccharides of the purified cell walls consist of rhamnogalacturonan I (11%), rhamnogalacturonon II (8%), and homogalacturonan (23%). Xyloglucan (XG) accounts for 20% of the wall, and the oligosaccharide fragments generated from XG by endoglucanase consist of the typical subunits of other higher plant XGs. Glucuronoarabinoxylan (4%), cellulose (14%) and protein (14%) account for the remainder of the wall. Except for the phosphate buffer-soluble pectic polysaccharides, the polysaccharides of Arabidopsis leaf cell walls occur in proportions similar to those of other plants. The structure of the Arabidopsis cell-wall polysaccharides are typical of those of many other plants.

Amino Acids↗