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Biomedical subjects

S Muller

Publications and source records attributed to S Muller.

At least 199 records · Page 11Linked to original sources
PubMed1996

Unconscious mood-congruent memory bias in depression.

The purpose of this study was to investigate an unconscious or implicit mood-congruent memory (MCM) bias in clinical depression. Many studies have shown an explicit memory bias, but no study has yet found an implicit MCM bias in clinical depression. The authors compared depressed and control group participants on a conceptually driven implicit memory test. After studying words of positive, neutral, and negative affective valences, participants produced free associations to various cues. Implicit memory or priming was demonstrated by the production of more studied than unstudied words to the association cues. Depressed participants showed more priming of negative words, whereas controls showed more priming of positive words, thus supporting the MCM pattern. Also, no implicit memory deficit was found in depressed participants. These findings are discussed in the context of several prominent theories of cognition and depression.

Adolescent↗
PubMed1996

Bacteremia due to Stenotrophomonas (Xanthomonas) maltophilia: a prospective, multicenter study of 91 episodes.

We identified 91 cases of bacteremia due to Stenotrophomonas (Xanthomonas) maltophilia in a prospective, multicenter observational study. The patients were highly compromised; the majority had an underlying malignancy, had received immunosuppressive therapy, and had indwelling venous catheters. Although 94% of patients received an antimicrobial agent to which the blood isolate was susceptible, the mortality among these patients 14 days after the onset of bacteremia was 21%. Mortality was significantly correlated with the presence of a hematologic malignancy or neutropenia or transplantation, immunosuppressive therapy, and a severity-of-illness score of > 4. S. maltophilia infection is associated with substantial morbidity and mortality among highly compromised patients. The organism is typically resistant to expanded spectrum beta-lactam agents and aminoglycoside antibiotics. Trimethoprim-sulfamethoxazole should be administered if the isolate is susceptible to this combination; addition of another agent to which the isolate is susceptible should be considered in treating patients who are neutropenic, immunocompromised, or critically ill.

Bacteremia↗
PubMed1996

Immunoelectron microscopical distribution of histones H2B and H3 and protamines during human spermiogenesis.

The fine structural distribution of histones H2B and H3, and protamines were localized by means of specific antibodies and ultrastructural immunocytochemistry in nuclei of human spermatids and spermatozoa. The antibodies were used to detect the nuclear basic proteins on section of testis and ejaculated spermatozoa by immunoelectron microscopy. A quantitative analysis of labelling density was performed on micrographs using an interactive image analysis system. The labelling density of somatic-type histones H2B and H3 and of their testis-specific variants was constant in the nuclei of young spermatids with round nuclei (stages 1-2), and then increased in intermediate spermatids (stages 3-4). Histone H3 labelling decreased at the end of the elongation phase (stage 5) while histone H2B labelling decreased in mature spermatids (stage 6) only. Spermatozoa were found to be weakly labelled by the anti-histone antibodies. The first signs of labelling of protamines and basic intermediate proteins appeared in spermatid nuclei at stage 4, increased further in stage 6 spermatids and persisted in all sperm nuclei. The present work shows that histone-to-protamine replacement occurs at the beginning of the spermatid maturation phase in human. However, histones are partially retained in mature spermatids and sperm nuclei.

Adult↗
PubMed1996

Effects of Plasmodium vinckei hemozoin on the production of oxygen radicals and nitrogen oxides in murine macrophages.

When murine peritoneal macrophages were loaded in vitro with Plasmodium vinckei hemozoin and stimulated with opsonized zymosan for 90 min or with lipopolysaccharide and/or murine interferon-gamma for 24 hr, significant decreases in the production of oxygen radicals and nitrogen oxides, respectively, could be detected by comparison with macrophages without hemozoin. Moreover, nonradioactive in situ hybridization and immunohistologic analysis in liver sections of P. vinckei-infected mice with more than 60% parasitemia showed that liver cells were still expressing considerable levels of inducible nitric oxide synthase in the late phase of murine malaria, but most of the liver macrophages presenting accumulation of malaria pigment were negative in this analysis. These results further indicate that malaria pigment accumulation may be responsible for toxicity and impairment of macrophage functions during murine malaria.

Animals↗
PubMed1996

Mimicry of viral epitopes with retro-inverso peptides of increased stability.

Two major limitations to the use of peptides as synthetic vaccines are their poor immunogenicity and low antigenic cross-reactivity with the epitopes of virus particles. Recently it has been shown that retro-inverso peptides corresponding to an immunodominant epitope of foot-and-mouth disease virus (FMDV) are able to mimic the structure and antigenic activity of natural L-peptides [1]. A series of L- and retro-inverso peptides of the loop 141-159 of the VP1 protein of FMDV has been synthesized. Antibodies to these peptides were produced by injecting rabbits with peptides covalently coupled to small unilamellar liposomes containing monophosphoryl lipid A as adjuvant. The retro-inverso peptides led to higher serum antibody titres which appeared earlier after the start of immunization and lasted longer than those found with L-peptides. Antibodies to retro-inverso peptides cross-reacted strongly with L-peptides and with virus particles, while guinea pig antisera to VP1 protein and virions cross-reacted strongly with the retro-inverso peptides. In view of their increased stability compared to natural L-peptides, retro-inverso peptidomimetics have considerable potential as synthetic viral vaccines.

Amino Acid Sequence↗
PubMed1996

Doppler-derived diastolic indices in dilated cardiomyopathy: a hemodynamic evaluation relating pre- and afterload parameters to flow velocity.

OBJECTIVE: To explain the well known finding of a normal early diastolic filling velocity in advanced grade heart failure due to dilated cardiomyopathy (DCM) exclusively by hemodynamics and to relate Doppler-flow velocity parameters to indices representing pre- and afterload. DESIGN: DCM was hypothesized to be a disorder in which pre- and afterload contribute in equal proportion to cardiac insufficiency independently from ischemic impairment of relaxation. PATIENTS: Twenty patients with DCM were enroled in the study after definitive exclusion of coronary and valvular heart disease. METHODS: Diastolic transmitral and transtricuspid Doppler readings and hemodynamic measurements were done simultaneously by two blinded observers. A Swan-Ganz catheter was employed. MAIN RESULTS: Simple and multiple regression analyses revealed early diastolic filling velocity to depend on hemodynamic parameters representing afterload. Pulmonary capillary wedge pressure (PCWP) was found to be directly related to early diastolic filling velocity. An inverse relation between early diastolic filling velocity and parameters representing afterload (systemic vascular resistance and mean arterial pressure) was demonstrated; however the most significant correlation using multiple regression analysis was shown between mitral early diastolic peak-flow velocity (dependent) and PCWP as well as systemic vascular resistance index (independents) (r = 0.75; P < 0.001). Correspondingly, the transtricuspid early diastolic peak-flow velocity was shown to be related to the equilibrium of right atrial pressure and pulmonary vascular resistance index. The atrial diastolic flow velocity parameters were found not to be related to hemodynamic indices. CONCLUSION: A definitive but not one-to-one relationship between early diastolic Doppler-flow indices and hemodynamic parameters was defined. A functional coupling of pre- and afterload can be considered the main determinant of early diastolic filling velocity in DCM.

Adult↗
PubMed1995

Efficient binding of reduced peptide bond pseudopeptides to major histocompatibility complex class I molecule.

Reduced peptide bond pseudopeptide analogues have been examined for their ability to bind murine class I molecules of the major histocompatibility complex (MHC). Eight pseudopeptide analogues of an antigenic peptide derived from Plasmodium berghei (H-Ser252-Tyr-Ile-Pro-Ser-Ala-Glu-Lys-Ile260-OH) were obtained by systematically replacing one peptide bond at a time by a reduced peptide bond psi (CH2-NH). The resulting analogues were then tested for their binding to a recombinant single chain SC-Kd class I molecule. The comparative results show that five analogues can efficiently mimic the parent peptide while the introduction of the reduced bond between P3-P4, P7-P8, and P8-P9 is deleterious for SC-Kd binding. The fact that more stable pseudopeptides containing reduced peptide bonds can bind major histocompatibility complex molecules is of great interest for the design of peptidomimetics with potential therapeutical properties. Such peptide analogues may prove useful for the development of peptide-based cytotoxic T lymphocyte vaccines.

Amino Acid Sequence↗
PubMed1995

Retro-inverso peptidomimetics as new immunological probes. Validation and application to the detection of antibodies in rheumatic diseases.

Retro-inverso peptides which contain NH-CO bonds instead of CO-NH peptide bonds are much more resistant to proteolysis than L-peptides. Moreover, they have been shown recently to be able to mimic natural L-peptides with respect to poly- and monoclonal antibodies (Guichard, G., Benkirane, N., Zeder-Lutz, G., Van Regenmortel, M. H. V., Briand, J. P., and Muller, S. (1994b) Proc. Natl. Acad. Sci. U.S.A. 91, 9765-9769). We have further tested the capacity of retro-inverso peptidomimetics to serve as possible targets for antibodies produced by lupus mice and by patients with rheumatic autoimmune diseases. Several retro-inverso peptides corresponding to sequences known to be recognized by autoantibodies were synthesized, namely peptides 28-45 and 130-135 of H3, 277-291 of the Ro/SSA 52-kDa protein, and 304-324 of the Ro/SSA 60-kDa protein, and tested with autoimmune sera by enzyme-linked immunosorbent assay. We have found that retro-inverso peptides are recognized as well as or even better than natural peptides by antibodies from autoimmune patients and lupus mice. This new approach may lead to important progress in the future development of immunodiagnostic assays, particularly in the case of diseases characterized by inflammatory reactions in the course of which the level of degradative enzymes is increased.

Amino Acid Sequence↗
PubMed1995

Cross-reactivity of antibodies to retro-inverso peptidomimetics with the parent protein histone H3 and chromatin core particle. Specificity and kinetic rate-constant measurements.

A series of monoclonal antibodies has been generated against an hexapeptide of sequence IRGERA corresponding to the C-terminal residues 130-135 of histone H3 and three analogues of this model peptide. The analogues correspond to the D-enatiomer, containing only D-residues, and two retro-peptides containing NH-CO bonds instead of natural amide peptide bonds. The chirality of each residue was maintained in the retro-peptide and inverted in the retro-inverso-peptide. Monoclonal antibodies were generated from mice immunized with the analogues coupled to neutral small unilamellar liposomes containing monophosphoryl lipid A as adjuvant. The reactivity of antibodies with the four analogues and with the parent protein H3 was studied in enzyme-linked immunosorbent assay and in a biosensor system. The equilibrium affinity constant (Ka) toward the retro-inverso-peptide of two out of three antibodies of IgG1 isotype induced against the L-hexapeptide was 7-75-fold higher than toward the homologous L-peptide. The range of Ka values of four antibodies of IgG1 and IgG2a isotypes generated against the retro-inverso-peptide was 0.6-1.9 x 10(9) M-1 for both the retro-inverso- and L-peptides. Furthermore, antibodies to the L- and retro-inverso-peptides cross-reacted strongly (in some cases better than with the homologous peptide) with the parent histone H3 and with chromatin subunits containing H3. The results are thus promising in respect to the potential use of retro-inverso-analogues, which are particularly stable, in the design of much more potent synthetic vaccines or to generate antibody probes.

Adjuvants, Immunologic↗
PubMed1995

Ubiquitin in homeostasis, development and disease.

Ubiquitin is the most phylogenetically conserved protein known. This 8,500 Da polypeptide can be covalently attached to cellular proteins as a posttranslational modification. In most cases, the addition of multiple ubiquitin adducts to a protein targets it for rapid degradation by a multisubunit protease known as the 26S proteasome. While the ubiquitin/26S proteasome pathway is responsible for the degradation of the bulk of cellular proteins during homeostasis, it may also be responsible for the rapid loss of protein during the programmed death of certain cells, such as skeletal muscle during insect metamorphosis. In addition, alterations in the expression and regulation of ubiquitin may play significant roles in pathological disorders. For example, dramatic increases in ubiquitin and ubiquitin-protein conjugates are observed in a wide variety of neurodegenerative disorders, including Alzheimer's disease. Patients suffering from the autoimmune disease systemic lupus erythematosus generate antibodies reacting with ubiquitin and ubiquitinated histones. At present, it is not known whether these changes in ubiquitin expression and regulation initiate pathological changes in these diseases or if they are altered as a consequence of these disorders.

Animals↗
PubMed1995

Mapping of B-cell epitopes recognized by antibodies to histones in subsets of juvenile chronic arthritis.

The sera of 138 patients with juvenile chronic arthritis (JCA) were tested in ELISA with the five individual histones, 34 histone peptides covering the full length of the four core histones, and two peptides corresponding to the N- and C-terminal domains of H1. The occurrence of IgG antibodies was examined regarding the different subsets of JCA (pauciarticular, polyarticular, and systemic onset) and regarding clinical features (chronic anterior uveitis, CAU) and other serological features (antinuclear antibodies, ANA). Seventy-two percent of the 138 sera reacted with at least 1 histone peptide. The peptides 204-218 of H1, 1-25 of H2B, and 111-130 of H3 were recognized by 22-28% of JCA sera, and 42% of JCA sera reacted with one or both peptides 1-25 of H2B and 111-130 of H3. The frequency of occurrence of anti-histone antibodies (AHA) regarding the type of histone fraction (H1, H2A, H2B, H3 and H4) or the regions of histones was not significantly different in the three subsets of JCA. No obvious association was found between IgG antibodies to histone peptides and uveitis. In the subset of pauciarticular JCA, 13/31 patients (41.9%) with CAU against 14/41 patients (34.1%) without CAU possessed IgG antibodies reacting with peptides of the C-terminal domain 83-135 of H3. This difference is not statistically significant. Finally, the presence of antibodies to histones and histone peptides cannot completely explain ANA reactivity found in patients' sera. Although antibodies to histone peptides occur frequently in the serum of children with JCA, the antibody profiles seem to be highly individual and do not correlate with disease subtype or activity. Identification of AHA present not only in the circulation but also in tissue deposits may provide better insight into the identification of pathogenic antibodies.

Amino Acid Sequence↗
PubMed1995

IgG autoantibody response in HTLV-I-infected patients.

Human T-cell leukemia virus type I (HTLV-I) is associated with a large spectrum of clinical manifestation including adult T-cell leukemia (ATL) and tropical spastic paraparesis or HTLV-I-associated myelopathy (TSP/HAM). In most cases, however, infected patients remain asymptomatic. The participation of the immune system in the pathogenesis of TSP/HAM has been suggested. In this study the IgG antibody response of HTLV-I-infected individuals has been investigated using both ELISA with a panel of nuclear and cytoplasmic proteins and peptides known to be recognized by antibodies from patients with various systemic autoimmune diseases, and immunoprecipitation of ribonucleoproteins from HeLa cell extracts. The results were compared with the reactivity of sera from individuals with non-HTLV-I-related neurological diseases and healthy blood donors. Raised levels of autoantibodies reacting with several nuclear and cytoplasmic antigens were found in TSP/HAM and ATL patients. In asymptomatic HTLV-I-seropositive individuals, both the prevalence and level of IgG antibodies were lower and directed only against a restricted set of antigens. The mechanism of induction of these antibodies still remains obscure. However, the results show that a significant autoimmune response exists in these patients and it may contribute to the pathogenesis of the disease.

Adult↗
PubMed1995

Ameloblastic fibrosarcoma of the jaws. A clinicopathologic and DNA analysis of five cases and review of the literature with discussion of its relationship to ameloblastic fibroma.

Ameloblastic fibrosarcoma, the malignant counterpart of the ameloblastic fibroma, is a rare odontogenic tumor characterized by benign epithelium and a malignant fibrous stroma. We have compared nuclear DNA content of five ameloblastic fibrosarcomas and three ameloblastic fibromas by image analysis. The three ameloblastic fibromas were diploid, whereas 1 of 5 ameloblastic fibrosarcomas was aneuploid. There was no correlation with histologic grade and aneuploidy. These five new cases were also added to a review of the literature, bringing the total cases of reported ameloblastic fibrosarcomas to 51. The ameloblastic fibrosarcoma occurs at a later age (mean, 27.5 years) compared with reported ameloblastic fibromas (mean, 14.6 to 22 years), which supports a step-wise malignant transformation. There was histologic documentation that 44% of ameloblastic fibrosarcomas developed in ameloblastic fibromas. In view of this data and of the reported cumulative recurrence rate of 18.3% for ameloblastic fibroma, it is recommended that ameloblastic fibromas be treated with complete surgical excision and long-term follow up rather than simple curettage or enucleation.

Adolescent↗
PubMed1995

Human T cell responses to autoantibody variable region peptides.

The origins and regulation of autoantibodies in SLE may involve idiotypic cell interactions. The purpose of this study was to determine if SLE patients have T cells reactive with the idiotopes of autoantibodies. Sequences of the variable regions of two DNA-binding autoantibodies (V lambda of antibody B3 and VH of 9G4) were selected according to the predicted location of their idiotypes defined previously by anti-idiotypic antibodies. The sequences were prepared as synthetic 16mer peptides (idiopeptides). Peripheral blood mononuclear cells were prepared from SLE patients (n = 28) and controls (n = 13) and put into multiple microcultures with idiopeptide for 6 days. The frequency of responding cultures was determined as those incorporating thymidine at levels above the mean plus three standard deviations of the control cultures lacking peptide. Of the 28 lupus patients, six responded to B3 idiopeptide and five to the 9G4 idiopeptide. Some patients responded to other idiopeptides, but only one normal individual responded to each reference peptide. The difference between the patient and control responses to all idiopeptides was significant by chi 2 analysis (P = 0.025). We conclude that patients with SLE show evidence of sensitisation of T cells to idiotopes of autoantibodies. Such anti-idiotypic T cells could either provide idiotype-specific help or suppression for autoantibody responses in SLE.

Adult↗
PubMed1995

Decreased erythrocyte membrane fluidity in poorly controlled IDDM. Influence of ketone bodies.

OBJECTIVE: To examine the factors that might alter the fluidity of erythrocyte membrane in insulin-dependent diabetes mellitus (IDDM) patients. RESEARCH DESIGN AND METHODS: The subjects were 10 health men and 30 IDDM mem: 10 with good blood glucose (BG) control (HbA1c 5.88 +/- 0.60% [mean +/- SD]), 10 with poor BG control (HbA1C 9.48 +/- 1.05%), and 10 with poor BG control and mild to moderate diabetic ketoacidosis (DKA) (HbA1C 9.12 +/-2.25%, strongly positive ketonuria 3+ and elevated plasma beta-hydroxybutyrate). Erythrocyte membrane fluidity was determined by fluorescence polarization using 6-(9-anthroyloxy stearic acid as fluorescent probe. RESULTS: Membrane fluidity was normal in the diabetic patients with good BG control but significantly lower in the two groups of patients with poor BG control than in the healthy subjects (P < 0.01). The membrane fluidity in the poor BG control groups was also lower in the patients with DKA than in those without DKA (P < 0.01). CONCLUSIONS: The factors that most influence membrane fluidity in IDDM patients appear to be hyperglycemia and ketone bodies.

Adult↗