PubMed Health⌕ Search

Biomedical subjects

P Hasler

Publications and source records attributed to P Hasler.

At least 19 recordsLinked to original sources
PubMed2003

Subversion of B lymphocyte signaling by infectious agents.

Infectious agents and their hosts interact in a complex manner, involving not only superficially apparent mechanisms, but also the signaling machinery that governs host cells responses. Thus, signaling events, surface molecule expression, and transcriptional control may be affected in various cell types, with profound consequences for the function of individual cells and organ systems. Studies of the biochemistry of cell signaling and cell invasion by infectious agents have begun to detail the interplay between elements of infectious organisms and the host at the molecular level. Consequently, the resulting interferences with lymphocyte signaling may disturb the function of the immune system. In B cells, alterations of immune receptor signaling has implications for human diseases. By affecting the mechanisms of the host's immune defense, this may not only lead to inadequate elimination of an infectious agent, but also to autoimmunity or neoplasia.

B-Lymphocytes↗
PubMed2003

Serious bacterial infections in patients with rheumatoid arthritis under anti-TNF-alpha therapy.

OBJECTIVE: With rising numbers of anti-tumour necrosis factor alpha (TNF-alpha) treatments for rheumatoid arthritis (RA), Crohn's disease and other conditions, physicians unaware of potential pitfalls are increasingly likely to encounter associated severe infections. Our purpose was to assess the incidence and nature of severe infections in our RA patients under anti-TNF-alpha therapy. METHODS: We reviewed patient charts and records of the Infectious Disease Unit for serious infections in patients with RA in the 2 yr preceding anti-TNF-alpha therapy and during therapy. RESULTS: Serious infections affected 18.3% of patients treated with infliximab or etanercept. The incidence was 0.181 per anti-TNF-alpha treatment year vs 0.008 in the 2 yr preceding anti-TNF-alpha therapy. In several cases, only a few signs or symptoms indicated the severity of developing infections, including sepsis. CONCLUSIONS: A high level of suspicion of infection is necessary in patients under anti-TNF-alpha therapy. We suggest additional strategies for the prevention, rapid identification and pre-emptive therapy of such infections.

Adult↗
PubMed2002

[Comparison between line immunoassay (LIA) and enzyme-linked immunosorbent assay (ELISA) for the determination of antibodies to extractable nuclear antigenes (ENA) with reference to other laboratory results and clinical features].

INTRODUCTION: The line immunoassay (LIA) for the determination of antibodies to individual extractable antinuclear antigens (ENA) is a development of the enzyme-linked immunosorbent assay (ELISA) in which the antigens to be tested are adsorbed onto a nylon test strip. In addition, the antigen subspecificities B/B' and D in the case of Sm, the 70 kD, A and C components in the case of U1-snRNP and the Ro52 and Ro60 components in the case of SSA/Ro are present separately on the strips. The aim of the study was to determine whether the line immunoassay is suitable for routine laboratory use by means of a comparison with the ELISA. METHODS: Sera from 92 patients stored in our serum bank with known ENA profile as determined by ELISA and with at least one antibody to ENA were tested again with LIA. The clinical features and other available laboratory data taken from the patient records were used to classify the disease according to the relevant diagnostic criteria. In discrepant cases, antibodies to ENA were also determined by Western blot. These data were used to determine which of the two methods gave the more plausible results and to calculate the sensitivity and specificity for each autoantibody. RESULTS: There was good correlation between the two methods, especially for anti-CENP-B (centromere protein B) and anti-Jo1 (histidyl-tRNA transferase) antibodies. For anti-Sm, there was a trend toward higher specificity with the LIA in patients with systemic lupus erythematosus (SLE) if antibodies to Sm D were detected. The LIA was significantly more specific for the detection of antibodies to ribonucleoprotein (RNP) in mixed connective tissue disease and, if antibodies to the 70 kD component were present, also in SLE, although the sensitivity was significantly lower in this case. For anti-SSA/Ro, the specificity of the LIA was significantly higher than ELISA if anti-Ro60 was detected. In the case of anti-SS-B/La, anti-Scl70 (topoisomerase I), anti-CENP-B (centromere protein B) und anti-Jo-1 (histidyl-tRNA transferase), the sensitivity and specificity of the two methods were not significantly different. The LIA was significantly more specific but less sensitive for the detection of anti histone antibodies. CONCLUSION: The suitability of the LIA for routine laboratory determinations was confirmed.

Antibodies, Antinuclear↗
PubMed2001

B cell receptor signaling and autoimmunity.

The immune receptors of lymphocytes are able to sense the nature of bound ligands. Through coupled signaling pathways the generated signals are appropriately delivered to the intracellular machinery, allowing specific functional responses. A central issue in contemporary immunology is how the fate of B lymphocytes is determined at the successive developmental stages and how the B cell receptor distinguishes between signals that induce immune response or tolerance. Experiments with mice expressing transgenes or lacking signal transduction molecules that lead to abnormal lymphocyte development and/or response are providing important clues to the mechanisms that regulate signaling thresholds at different developmental stages. The studies are also revealing novel potential mechanisms of induction of autoimmunity, which may have a bearing on the understanding of human diseases.

Animals↗
PubMed2000

Determination of polychlorinated dibenzo-p-dioxins and dibenzo-furans in solid residues from wood combustion by HRGC/HRMS.

PCDD/PCDF were determined in solid samples from wood combustion. The samples included grate ashes, bottom ashes, furnace ashes as well as fly and cyclone ashes. The solid waste samples were classified into bottom and fly ash from native wood and bottom and fly ash from waste wood. For each of the four classes concentration distribution patterns from individual congeners, the sums of PCDD/PCDF and the international toxicity equivalents (I-TEQ) values are given. The I-TEQ levels of fly ash from waste wood burning can be approximately up to two thousand times higher than the values from fly ashes of natural wood. The I-TEQ levels in bottom ashes from waste wood combustion systems are as low as the corresponding ashes from the combustion of native wood. Grate ash samples from waste wood combustion systems with low carbon burnout show high levels of PCDD/PCDF.

Benzofurans↗
PubMed1998

Gynecologic laparoscopic surgery is not associated with an increase of serotonin metabolites excretion.

UNLABELLED: Gynecologic laparoscopic surgery is associated with a high incidence of postoperative nausea and vomiting (PONV). The specific antagonists of the 5-hydroxytryptamine-3 (5-HT3) receptor have been progressively introduced in anesthesiology to prevent or treat PONV. Although a large increase of serotonin has been documented after cisplatin treatment, the link between serotonin and PONV in surgery/anesthesiology is unknown. In a prospective study, we compared the excretion of the serotonin metabolite 5-hydroxyindoacetic acid (5-HIAA) in 40 women undergoing either gynecologic laparoscopic surgery (laparoscopy group) or traditional open laparotomy surgery (laparotomy group). Premedication, anesthetic technique, and postoperative pain treatment were standardized. The excretion of 5-H IAA corrected to creatinine was measured in all patients immediately after the induction of anesthesia and was repeated regularly until 9 h after induction. The excretion of 5-HIAA/creatinine was similar in the two groups; no increase was observed in either group. The incidence of nausea and vomiting was 40% and 35%, respectively, in the laparoscopy group versus 60% and 15%, respectively, in the laparotomy group (not significantly different). The excretion of 5-HIAA/creatinine was comparable in patients of both groups among those who vomited and those who did not. We conclude that the creation of a pneumoperitoneum during gynecologic laparoscopic surgery is not associated with an increase of 5-HIAA excretion. PONV after gynecologic laparoscopic surgery is not explained by an increase of serotonin secretion. IMPLICATIONS: The mechanism leading to the high incidence of postoperative nausea and vomiting after gynecologic laparoscopic surgery is unknown. The excretion of the serotonin metabolite 5-hydroxyindoacetic acid did not increase during the creation of the pneumoperitoneum and the first 9 h postoperatively. Increase of serotonin secretion from the gut may not explain postoperative nausea and vomiting associated with this surgery.

Adult↗
PubMed1997

[Treatment of chronic polyarthritis].

Rheumatoid arthritis (RA) is a chronic autoimmune disease involving progressive destruction of multiple joints and, in the later stages, significant mortality. Worldwide, 1% of the population is afflicted. Despite new insights into the autoimmune mechanisms during the last decade a cure has not been found, although pain, disability and general suffering can be alleviated via several therapeutic approaches when carefully coordinated. Early use of immunosuppressive therapy with DMARDs (disease modifying antirheumatic drugs), while avoiding their side effects, is critical for disease control. Counselling within a good doctor-patient relationship, with the additional help of physiotherapy and ergotherapy, increases the patient's capacity to cope with the disease. Hand and joint surgery, skillfully performed, decreases pain and disability. Newer strategies of immunosuppression, while encouragingly effective, are only short term. These experimental agents are more expensive, they are associated with side effects and their future place in RA therapy has yet to be defined.

Antirheumatic Agents↗
PubMed1995

Experience with the iodine-123 and technetium-99m labelled anti-granulocyte antibody MAb47: a comparison of labelling methods.

Four different methods of radiolabelling the anti-granulocyte monoclonal antibody MAb47 were compared and their influence on diagnostic value studied. The best clinical images were obtained following labelling with iodine-123 by the Iodogen method and direct labelling with technetium-99m after tris-(carboxyethyl)-phosphine treatment of MAb47 to achieve disulphide bridge reduction. 99mTc labelling using a specific ligand (MAb47-mtp), or a second method involving direct reduction with mercaptoethanol, led to an increased background activity in clinical studies, thus impeding the diagnosis of chronic disease. Fresh infections were clearly localized by all four preparations. The elimination of the activity from the blood was slower in the case of the iodinated MAb47, while the collected urine samples showed an excretion of about 10% of the injected activity per day independent of the labelling method. The results in terms of sensitivity and specificity were rather similar for all labelling methods and ranged from 90% to 99%.

Abscess↗
PubMed1995

Vasculitides in hairy cell leukemia.

Forty-two cases of vasculitis coincident with hairy cell leukemia (HCL) have been reported, of which 17 had panarteritis nodosa (PAN), 21 had cutaneous leukocytoclastic vasculitis (LCV), and 4 had vessel wall infiltration by hairy cells. PAN generally occurred after the diagnosis of HCL, splenectomy, and infection. HBs antigen was detected in 3 of 12 patients tested, whereas immune complexes were positive in 3 of 4 patients tested. LCV was often preceded by infection and was frequently detected before HCL. Serum immunoglobulin levels were generally elevated when measured. Cryoglobulins, complement, rheumatoid factor, and antinuclear antibodies showed no clear association with vasculitis in HCL. These reports suggest a role for infection and splenectomy as contributing factors to vasculitis.

Adult↗
PubMed1994

The effect of phosphorylation and site-specific mutations in the immunodominant epitope of the human ribosomal P proteins.

The immunodominant epitope recognized by lupus antiribosomal P protein antibodies (anti-P antibodies) is located within the 11 C-terminal residues common to the three P proteins. This epitope contains a potential phosphorylation site for casein kinase II and clusters of acidic and hydrophobic amino acids. To determine the role of each of these features in antigen recognition, lupus anti-P sera were tested for binding to phospho- and dephospho- forms of the P proteins and to synthetic peptide antigens in which site-specific modifications had been introduced. Immunoblot analysis revealed that anti-P antibodies specific for the phospho- form of the P proteins represented only a minor population of anti-P antibodies and, in many cases, were absent altogether. In contrast, when charged substitutions were introduced into either the acidic or hydrophobic clusters and tested by ELISA, striking reductions of 64-86% were observed. Conservative Gly-->Pro substitutions also produced a 73% average reduction in anti-P binding whereas substitution of either Ser-105 or the C-terminal Asp-115 resulted in a < 35% reduction in binding. These findings suggest that phosphorylation of the P proteins does not play a role in antibody recognition but that anti-P antibodies require both the acidic and hydrophobic clusters for optimal binding to synthetic peptide antigens. The remarkable degree of specificity demonstrated by these antibodies supports the view that anti-P autoantibodies result from a highly specific (at the B cell level) immune response to self antigen.

Amino Acid Sequence↗
PubMed1993

The effect of circulating serum factors from patients with systemic lupus erythematosus on protein kinase A (PKA) activity and PKA-dependent protein phosphorylation in T lymphocytes.

T lymphocytes from subjects with active systemic lupus erythematosus (SLE) exhibit reduced cAMP-inducible, protein kinase A (PKA)-dependent phosphorylation of several intracellular substrates compared with healthy and disease controls. To ascertain whether the persistent T cell activation observed during active SLE can result in impaired PKA-dependent protein phosphorylation, normal T cells were activated in vitro by monoclonal anti-CD3-epsilon antibody and recombinant IL1-alpha (rIL1-alpha) for 24 hr. T cell activation, verified by IL2 mRNA, IL2 receptor-alpha (IL2R-alpha) mRNA, and IL2R-beta mRNA expression, did not diminish cAMP-inducible, PKA-dependent protein phosphorylation. We also tested the hypothesis that circulating factors present in active SLE serum can decrease cAMP-inducible total PKA phosphotransferase activity and PKA-dependent protein phosphorylation in normal T lymphocytes. T cells cultured for 24 hr in medium supplemented with 10% active SLE sera (from subjects who exhibited the defect of PKA-dependent protein phosphorylation) exhibited similar total PKA phosphotransferase activity and substrate phosphorylation as cells cultured in normal AB serum. Moreover, the addition of interferon-alpha (IFN-alpha) and/or immune complexes (IC) did not diminish either total PKA activity or PKA-dependent substrate phosphorylation. Lastly, we found that the defect of PKA-dependent protein phosphorylation in active SLE T cells could not be reversed by culturing the cells in culture medium supplemented with 10% AB serum for 24 hr. In conclusion, (a) deficient cAMP-inducible, PKA-dependent phosphorylation in SLE T cells is not reversible by culturing cells in vitro; (b) there is no evidence to support the concept that serum factors, including IC and IFN-alpha, can induce a defect of PKA-dependent protein phosphorylation in normal T cells.

Adult↗
PubMed1993

Quality assurance and quality control methods for animal and human applications of no-carrier-added 6-[18F]fluorodopa for PET investigations of dopaminergic systems.

No-Carrier-Added (NCA) 6-[18F]fluoro-L-dopa (6-FDOPA) is being produced routinely for PET investigations of dopaminergic systems at our Institute. We describe here in detail the quality assurance methods involved in its multi-step developmental stage as a radiopharmaceutical. A method to remove toxic copper ions to prepare an injectable solution is described. The stability and shelf-life of NCA 6-FDOPA was also examined and results are discussed. Quality control involved three major aspects: (a) chemical purity, (b) radiochemical purity and (c) enantiomeric excess. A method for quick quality control of individual batch preparations is described.

Animals↗
PubMed1993

In vitro and in vivo testing of the dopamine D1 ligand [123I]SCH 23982 with respect to its potential application in SPET investigations.

[123I]SCH 23982, a dopamine D1 ligand, was labelled in a large scale process and then tested in vitro for binding to rat brain sections and membranes. Because of the promising values of KD = 1.5 x 10(-10) M and Bmax = 0.7 x 10(-11) mol/g, in vivo evaluation was performed on rats and normal volunteers to test its possible usefulness for SPET imaging. In competition experiments, a higher binding in the presence of sulpiride was found while ketanserin displaced [123I]SCH 23982 only at a 10,000-fold excess. Differences between rats and men were seen with respect to their metabolism. SPET investigations failed because the washout of [123I]SCH 23982 was too rapid.

Aged↗
PubMed1993

Insufficiency fractures of the sacrum. Twenty cases and review of the literature.

Over the past 10 years, 231 insufficiency fractures of the sacrum have been reported in the literature. These fractures, which are due to osteopenia, form a distinct subgroup of pathologic fractures. In 1.8% (n = 20) of the older-than-55-years female patients (total = 1,015) admitted to the authors' Rheumatology department between 1989 and 1991, a fracture of the sacrum was diagnosed. In all cases the diagnosis was confirmed with computed tomography. Frequency, age, sex, diagnosis, underlying diseases, and associated fractures of the 20 cases of insufficiency fractures of the sacrum are described and compared with those previously reported. Insufficiency sacral fracture as a cause of low-back pain in women older than 55 years of age is concluded to be a clinical entity.

Aged↗