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Biomedical subjects

B Lang

Publications and source records attributed to B Lang.

At least 127 records · Page 7Linked to original sources

Antibodies to parvovirus B19 NS-1 protein in infected individuals.

Human parvovirus B19 is the aetiological agent of the common childhood disease erythema infectiosum (fifth disease). The infection is usually benign and self-limiting, but in adults cases of severe arthritis which may persist for years have been reported. Neutralizing antibodies directed against the structural proteins are usually produced shortly after the infection. The immune response against the third major protein, the non-structural protein NS-1, of parvovirus B19 has not been characterized so far. We cloned and expressed the full-length NS-1 protein and fragments thereof in Escherichia coli. The purified recombinant proteins were used to investigate the presence of antibodies to the NS-1 protein in sera from patients with parvovirus B19 infection. Specific antibodies could be detected in sera from patients suffering from severe parvovirus B19-associated arthritis using Western blot analysis and an ELISA. Sera from patients with acute or past infection without complications did not contain detectable levels of immunoglobulin to NS-1. The use of subfragments of the NS-1 protein allowed localization of the antigenic domains in the carboxy-terminal region of the protein.

Antibodies, Viral↗

An improved diagnostic assay for Lambert-Eaton myasthenic syndrome.

A new immunoprecipitation assay has been established for detecting antibodies to voltage-gated calcium channels (VGCCs) in Lambert-Eaton myasthenic syndrome (LEMS), using 125I-omega-conotoxin MVIIC, which binds to P-type VGCCs, to label extracts of human cerebellum. Fifty six of 66 serum samples (85%) from patients with clinically and electrophysiologically definite LEMS were positive for the presence of VGCC antibodies, defined as a titre > 3 SD above the mean for the healthy controls (n = 10). All disease controls (n = 40) were negative. This sensitive immunoassay should prove valuable in the diagnosis of LEMS.

Aged↗

Local vs Systemic Antibiotics to Decrease Wound Complications following Vertical Banded Gastroplasty: Results of a Prospective Randomized Trial.

BACKGROUND: Obesity is generally regarded as one factor predisposing to wound infection. Most reports of infection rates range from I to 16% for similar procedures. In our department the wound infection rate for morbidly obese patients was 12% without perioperative antibiotics. METHODS: In a prospective randomized study we compared local gentamicin-collagen fleece application in the subcutaneous layer with patients receiving a perioperative single I.V. dose of amoxicillin-clavulanic acid 2.2 g. We examined the results of different perioperative management of antibiotics on 50 morbidly obese patients who underwent vertical banded gastroplasty from March 1993 to August 1994. The fascial, subcutaneous and skin closure technique were identical in the two groups. For both groups we used a closed-suction system to drain the bottom of the deep subcutaneous layer. On the third postoperative day, the subcutaneous drains were removed. Patients stayed in hospital an average of 10 days. They had follow-up visits after 1, 3 and 6 months, and then yearly. RESULTS: None of the 50 patients developed a wound infection, hematoma, or seroma in the hospital. During the follow-up (median 6 months), no patient developed a wound abscess. CONCLUSIONS: We believe that perioperative antibiotic management is an important factor in obtaining a low infection rate.

Journal Article↗

Solute transport across the tonoplast of barely mesophyll vacuoles: Mg2+ determines the specificity, and ATP lipophilic amino acids the activity of the amino acid carrier.

After stimulation with ATP and in the absence of divalent cations, isolated barely mesophyll vacuoles exhibited massive solute fluxes across the tonoplast, measured either as efflux of endogenous solutes or as uptake of radioactive-labeled compounds. Transported solutes were ions (particularly K+, NO3-, Cl-) and amino acids (for example, ala, arg, asp, gln, leu, met). Addition of Mg2+ in excess of added ATP inhibited fluxes of inorganic ions and of positively charged amino acids, but not, or to a smaller extent, those of neutral amino acids. Thus, Mg2+ increased the specificity of the carrier for amino acids such as alanine and glutamine. All ATP-stimulated transport processes were sensitive towards inhibition by lipophilic amino acids, for example by leucine and phenylalanine. After stimulation with sulfhydryl reagents, the inhibitory properties of Mg2+ and lipophilic amino acids were lost. These data concur with the hypothesis of a single transporter which exhibits a channel-like structure with a low degree of substrate selectivity in the absence of Mg2+, and which functions as a neutral amino acid carrier in the presence of Mg2+.

Adenosine Triphosphate↗

Anti-neutrophil cytoplasm antibodies (ANCA) in rheumatoid arthritis: relationship to HLA-DR phenotypes, rheumatoid factor, anti-nuclear antibodies and disease severity.

To investigate a possible relationship between the presence of anti-neutrophil cytoplasm antibodies (ANCA), rheumatoid factors (RF), anti-nuclear antibodies (ANA), disease severity and HLA-DR phenotypes, 46 consecutive ANCA+ and 48 ANCA-, clinically well-documented RA patients were studied for RF, ANA and HLA-DR phenotypes. The 46 ANCA+ patients showed predominantly an atypical perinuclear staining pattern (89%). ANCA positivity was associated with higher RF titres (P < 0.005) and advanced functional Steinbrocker grades III/IV (P < 0.015). ANCA+ patients were also more often positive for ANA than ANCA- patients (P < 0.008). There was no correlation between ANCA positivity and certain HLA-DR phenotypes although the frequency of DR4+ (67% vs 52%) and, in particular, of DR4+ blanks (phenotypically homozygous) was increased in ANCA+ as compared to ANCA- patients (20% vs 8%). DR4-DR1-RA patients were twice as frequent in the ANCA- than in the ANCA+ group (22.9% vs 8.7%). Correspondingly, the DR4+DR1- phenotype was increased among ANCA+ RA patients. Regarding functional Steinbrocker grades, the DR4+ phenotypes were slightly but not significantly increased in grades III and IV whereas ANCA positivity was significantly associated with severe functional Steinbrocker grades III/IV (66% ANCA+ vs 39% ANCA-, P < 0.015). ANCA positivity identified a population of RA patients with a long-standing and severe clinical course of the disease. There was no correlation between ANCA positivity and certain HLA-DR phenotypes.

Adult↗

Heterogeneity of calcium channel autoantibodies detected using a small-cell lung cancer line derived from a Lambert-Eaton myasthenic syndrome patient.

We investigated the heterogeneity of anti-voltage-gated calcium channel (VGCC) antibodies in the Lambert-Eaton myasthenic syndrome (LEMS) using a small-cell lung carcinoma line (MB) derived from an LEMS patient. Four of 13 LEMS patients had raised titers of anti-125I-omega-conotoxin-labeled (N-type) VGCCs, measured by radioimmunoassay using line MB as the source of antigen. Antagonists for L-type (nitrendipine and nifedipine) and N-type (omega-conotoxin) VGCCs inhibited K(+)-stimulated (voltage-dependent) Ca2+ flux into this line--by 22% for L-type and 2% for N-type at maximum concentration. Inhibition by the LEMS IgGs, by contrast, ranged from 46 to 78% at a concentration of 2 mg/ml. These differing effects on Ca2+ flux inhibition by LEMS IgGs on the one hand and by L- and N-type channel antagonists on the other, taken together with the observation that many of the sera failed to react with omega-conotoxin-labeled (N-type) channels in the immunoprecipitation assay, suggest that in many LEMS patients the autoantibodies target other VGCC subtypes besides L- or N-types, and that these are important in inducing the myasthenic disorder.

Autoantibodies↗

Biochemical analysis of breast cyst fluid as a possible predictor of breast carcinoma development.

The occurrence of breast cancer in patients with gross cystic disease is 2-5 times higher as compared to control group of women. During 3 years, 183 cyst fluid samples were analyzed in 129 females, in 30 patients of them the samples were analysed repeatedly. The distribution of the Na+/K+ ratio, considered as the measure of cancer risk, was found to be bimodal. In repeated analyses the type I cyst fluid markedly predominated (Na+/K+ < or = 4.0). A direct dependence on this ratio was found in the concentration of glucose, albumin, carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and its specific form, TPS; an indirect dependence was found for the level of uric acid, phosphates, alkaline phosphatase (ALP) and alpha-amylase (AMS). The predominance of apocrine metaplasia cells released into the cyst fluid is characteristic of type I cysts. A definitive assessment of significance of these parameters will be enabled by a long-term follow-up of the disease in the respective patients.

Adult↗

Early diagnosis of breast cancer dissemination by tumor markers follow-up and method of prediction.

A mathematical model of prediction of progression was tested in patients with breast cancer employing long-term monitoring of tumor markers CEA, CA 15-3, MCA and TPA, erythrocyte sedimentation rate (FW), and the enzymes gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) and lactate dehydrogenase (LD) in serum. At the same time, specificity, sensitivity, lead time and positive predictive value were evaluated along with false positivity for all these parameters and their combinations. A model was proposed for the follow-up of patients with breast cancer after the completion of basic therapy.

Antigens, Tumor-Associated, Carbohydrate↗

Cross-linking of presynaptic calcium channels: a mechanism of action for Lambert-Eaton myasthenic syndrome antibodies at the mouse neuromuscular junction.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of neuromuscular transmission. Immunoglobulin G (IgG) autoantibodies act presynaptically to cause functional loss of Ca2+ channels by down-regulation. This in turn causes reduced release of acetylcholine in response to nerve stimulation (i.e. reduced quantal content). We show here that in vitro application of LEMS IgG for 24 h was as effective in causing reduced quantal content in mice as injecting animals with the antibody for 2 days. Furthermore, incubation with divalent (F(ab')2) fragments also significantly reduced quantal content. However, monovalent (Fab) fragments were without significant effect. No antibody or antibody fragment preparation affected spontaneous release. Whole LEMS IgG and F(ab')2 (but not Fab) fragments also inhibited K(+)-evoked 45Ca2+ flux in a small cell carcinoma cell line. These findings present functional evidence that LEMS IgG-induced down-regulation of nerve terminal Ca2+ channels arises due to antibody cross-linking of these channels.

Acetylcholine↗

Susceptibility to relapsing polychondritis is associated with HLA-DR4.

OBJECTIVE: To determine the frequency of HLA class II antigens in Caucasian central European patients with relapsing polychondritis (RP). METHODS: HLA class I, DR, and DQ specificities were identified in 41 patients with RP, and the frequencies were compared with those in 204 healthy, unrelated control subjects. HLA typing was performed using the standard complement-dependent microcytotoxicity assay. HLA-DR genotyping of 12 DR4-positive RP patients and 57 controls was performed by allele-specific oligonucleotide probing after amplification of genomic DNA by polymerase chain reaction. RESULTS: A significant increase in DR4 antigen frequency was found in the patients (56.1%) as compared with that in healthy controls (25.5%) (Pcorr < 0.001). Genotyping of DR4-positive patients and controls revealed no predominance of any DR4 subtype. CONCLUSION: There are important clinical similarities and overlaps between RP and rheumatoid arthritis (RA). In RA, the association with DR4 has been well established. Our findings show that although there is a DR4 association with RP, the situation is sufficiently distinct from that of RA to imply considerable differences in pathogenesis of the two conditions.

Alleles↗