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Biomedical subjects

B Lang

Publications and source records attributed to B Lang.

At least 109 records · Page 6Linked to original sources
PubMed1996

Neuroimmune control of interleukin-6 secretion in the murine spleen. Differential beta-adrenergic effects of electrically released endogenous norepinephrine under various endotoxin conditions.

In a previous study we demonstrated a superfusion technique which allows for investigation of nerve-immune cell interaction in murine spleen. We demonstrated that under septic-like conditions in the presence of bacteria and lipopolysaccharide (LPS), electrically induced inhibition of interleukin 6 (IL-6) secretion was attenuated by the beta-adrenergic antagonist propranolol. This effect was now investigated more closely under various endotoxin conditions in order to dissect effects of bacteria and endotoxin: (A) bacteria-rich conditions (without penicillin/streptomycin [P/S] and without LPS), (B) LPS-enriched conditions (with P/S and with LPS), and (C) bacteria-free conditions (with P/S and without LPS). Under bacteria-rich conditions, norepinephrine (Emax = 10(-6) M, p = 0.012) and isoproterenol (Emax = 10(-6) M, p = 0.048) concentration-dependently inhibited IL-6 secretion from murine spleen slices in contrast to bacteria-free conditions. In a bacteria-free environment the beta-adrenergic antagonist propranolol did not attenuate the electrically induced inhibition of splenic IL-6 secretion. The insertion of bacterial filters in front of the superfusion chambers to avoid direct contact between bacteria and cells increased the electrically-induced inhibition of IL-6 secretion (p = 0.0036). Added LPS did not change the electrically-induced release of norepinephrine from presynaptic nerve terminals in murine spleen. The study demonstrates two different beta-adrenergic effects on IL-6 secretion of murine spleen slices under bacteria-rich or bacteria-free conditions.

Adrenergic beta-Antagonists↗
PubMed1996

Autoimmunity to ion-channels and other proteins in paraneoplastic disorders.

Paraneoplastic neurological disorders are rare conditions caused by immune responses against tumour antigens that cross-react with neuronal antigens. In the past year, there have been advances in the definition of some of the antigens that are recognized by patients' antibodies, and new observations on the results of passive and active immunization against the antigens.

Animals↗
PubMed1996

Antigen processing and presentation by a mouse macrophage-like cell line expressing human HLA class II molecules.

Macrophages differ from other antigen-presenting cell types in their potential to take up, process and present particulate antigens as well as proteins and peptides. To study their influence on T cell activation we transfected the mouse macrophage-like cell line P388D1 with human genes coding for the alpha and beta chains of class II molecules (DRA*0101 and DRB1*0401 or DRB1*0404) or with a series of localized DR beta mutants. The transfected cells (TP cells) all expressed DR4 molecules on their surface. Since they stimulated some, but not all, human DR4-reactive T cell clones, some of the resident peptides are evidently similar in mouse and man. Proteins and polypeptides such as pepsin or the human acetylcholine receptor (AChR) alpha 37-181 were also processed correctly by these transfectants and then presented efficiently to other T cell clones. Nearly all the mutants tested could present to the pepsin-specific clone, establishing functional expression of the transfected DR molecules. For the more exacting AChR alpha 144-156-specific T cell clone PM-A1, we confirmed that the single Gly86--> Val mutation in the DR beta chain abolished presentation by two DR4 subtypes. If, however, this same replacement was made in a third variant that has Lys71 (rather than Arg71), the effects were less drastic. This approach could also be used to analyse the contributions of individual substitutions that confer susceptibility to rheumatoid arthritis.

Amino Acid Sequence↗
PubMed1996

Distinct patterns of immunoglobulin classes and IgG subclasses of autoantibodies in patients with inflammatory bowel disease.

OBJECTIVE: The pathophysiological significance of autoantibodies in inflammatory bowel diseases (IBD) is still unclear. To assess specific immunological abnormalities we examined the distribution and restriction of immunoglobulin classes and subclasses of anti-neutrophil cytoplasmic antibodies (ANCAs) in ulcerative colitis and of antibodies to pancreatic juice (APJs) in Crohn's disease. METHODS: We tested 62 sera of patients with ulcerative colitis and 184 sera of patients with Crohn's disease for their immunoglobulin class and IgG subclass distribution of ANCAs (in ulcerative colitis patients) and APJs (in Crohn's disease patients) by fluorescence isothiocyanate (FITC)-labelled anti-human antibodies in an immunofluorescence assay with human granulocytes or pancreas as substrate. Twenty-five patients with Wegener's granulomatosis were used for comparison. RESULTS: In ulcerative colitis ANCAs were found in 74% of the patients. They were predominantly of the IgG (96%) and IgA class (37%). In Crohn's disease APJs (present in 28% of the cases) were of the IgG (98%) and IgA class (71%). ANCAs in ulcerative colitis were of the IgG1 (73%) and IgG3 (5%) subclasses, APJs in Crohn's disease of the IgG1 (94%), IgG2 (20%) and IgG3 (2%) subclasses. The immunoglobulin class and IgG subclass distributions of ANCAs and APJs resembled the changes in total immunoglobulin classes and IgG subclasses in ulcerative colitis or Crohn's disease. CONCLUSION: The immunoglobulin classes and IgG subclasses of autoantibodies in ulcerative colitis and Crohn's disease differ from each other and from the distribution of autoantibodies in vasculitic diseases (Wegener's granulomatosis, microscopic vasculitis, systemic lupus erythematosus). These alterations reflect specific pathophysiological features of ulcerative colitis and Crohn's disease.

Adolescent↗
PubMed1996

Atrial natriuretic factor and digoxin-like immunoreactive factor in diabetic patients: their interrelation and the influence of the autonomic nervous system.

In diabetic patients, several factors contribute to volume expansion and have to be counteracted by humoral and neuronal feedback control systems. We investigated N-terminal proatrial natriuretic factor (ANF1-98) and digoxin-like immunoreactive factor (DLIF), which are two counteracting hormones, and their interrelationship, with additional consideration given to autonomic nervous function in diabetic patients. ANF1-98 and DLIF were measured in 64 diabetic patients. Autonomic nervous function was assessed using nine autonomic nervous function tests. The patients were subdivided into two groups, one with four or more (group 1) and one with less than four abnormal results in autonomic function tests (group 2). Compared with group 2, group 1 demonstrated detectable DLIF levels less often (17.2 vs. 45.7, P = 0.0195) and increased levels of ANF1-98 (mean +/- SEM: 850.0 +/- 108.8 vs. 554.8 +/- 45.9 pmol/L, P = 0.0099). However, the groups did not differ in blood pressure, daily sodium, and daily potassium excretion. The number of abnormal autonomic function tests correlated significantly with ANF1-98 (P = 0.0002). In patients with detectable DLIF, DLIF correlated with ANF1-98 (P = 0.0080). These results demonstrate close interactions between the autonomic nervous system and the two natriuretic hormones. In patients with autonomic nervous dysfunction, higher levels of ANF may possibly compensate for the lack of the natriuretic DLIF to counteract hypertension and chronic volume expansion.

Adult↗
PubMed1996

Effects of intravenous immunoglobulin on muscle weakness and calcium-channel autoantibodies in the Lambert-Eaton myasthenic syndrome.

Intravenous immunoglobulin improves many antibody-mediated autoimmune disorders, but its mode of action is unknown. We investigated its effects on muscle strength and on the serum titer of the calcium-channel autoantibodies that are likely to be pathogenic in the Lambert-Eaton myasthenic syndrome (LEMS). In a randomized, double-blind, placebo-controlled crossover trial, serial indices of limb, respiratory, and bulbar muscle strength and the serum titer of calcium-channel antibodies in nine patients were compared over an 8-week period, using the area-under-the-curve approach, following infusion on two consecutive days of immunoglobulin at 1 g/kg body weight/day (total dose 2.0 g/kg body weight) or placebo (equivalent volume of 0.3% albumin). Calcium-channel antibodies were measured by radioimmunoassay using 125I-omega-conotoxin MVIIC. Direct anti-idiotypic actions of immunoglobulin were tested in this assay. Immunoglobulin infusion was followed by significant improvements in the three strength measures (p = 0.017 to 0.038) associated with a significant decline in serum calcium-channel antibody titers (p = 0.028). Improvement peaked at 2 to 4 weeks and was declining by 8 weeks. Mean serum titers were unchanged at 1 week, however, and direct anti-idiotypic neutralization by immunoglobulin was not demonstrable in vitro. We conclude that immunoglobulin causes a short-term improvement in muscle strength in LEMS that probably results from the induced reduction in calcium-channel autoantibodies. The reduction is not due to a direct neutralizing action of the immunoglobulin, but a delayed anti-idiotypic action cannot be excluded. Improvement following intravenous immunoglobulin in other autoantibody-mediated disorders may similarly be associated with decline in levels of pathogenic autoantibodies.

Adolescent↗
PubMed1996

[10 years experience with vertical banded gastroplasty for operative therapy of morbid obesity].

Since 1985 vertical banded gastroplasty has been performed in a consecutive series of 300 morbid obese patients. Two years after operation the average weight loss was 46 kg or 67% of the initial overweight. There was one postoperative and one late death. The reintervention rate was 2% per year for the first 5 years. In the treatment of morbid obesity vertical banded gastroplasty is an effective procedure, rapid and simple to perform and without irreversible changes of the digestive tract.

Adolescent↗
PubMed1996

Dehydroepiandrosterone sulfate is positively correlated with soluble interleukin 2 receptor and soluble intercellular adhesion molecule in systemic lupus erythematosus.

OBJECTIVE: To determine whether dehydroepiandrosterone sulfate (DHEAS) is linked with soluble immune mediators in systemic lupus erythematosus (SLE). METHODS: DHEAS and various soluble immune mediators were measured by ELISA in the serum of 35 patients with SLE (26 women, 9 men) and in 41 control subjects. RESULTS: DHEAS was lower in patients with SLE compared to controls (male 1.29 +/- 0.32 vs 3.04 +/- 0.33 micrograms/ml, p < 0.001; female 0.75 +/- 0.12 vs 2.16 +/- 0.18 micrograms/ml, p < 0.001). The DHEAS reduction was in part dependent on prior glucocorticosteroid treatment (p < 0.02). After adjustment for multiple comparisons, there was significant negative correlation between steroid dose and DHEAS (RRank = -0.426, p = 0.005), but with none of the soluble immune mediators. No significant difference in the percentage of steroid treated male and female patients was found (p = 0.220). However, there was positive correlation between DHEAS and soluble interleukin 2 receptor in women, but not in men, with SLE [RRank = 0.747 (n = 26, p < 0.0001) vs RRank = -0.1333( n = 9, p = 0.366)] and between DHEAS and soluble intercellular adhesion molecule in women, but not in men, with SLE [RRank = 0.509 (n = 26, p = 0.005) vs RRank = 0.4833 (n = 9, p = 0.094)]. CONCLUSION: These data demonstrate positive interrelation between DHEAS and soluble immune mediators involved in leukocyte function and leukocyte adhesion only in female patients with SLE.

Adult↗
PubMed1996

Autonomic and sensorimotor neuropathy in patients with systemic lupus erythematosus and systemic sclerosis.

OBJECTIVE: To determine and compare the prevalence and degree of autonomic (ANP) and sensorimotor neuropathy (SNP) in patients with systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). METHODS: Thirty-one patients with SLE and 19 with SSc were investigated. Pupillary ANP was assessed by pupillometry, cardiovascular ANP using a standardized test battery, and SNP by a standardized clinical examination. RESULTS: In patients with SLE (SSc), 26% (10.5%) had a pathological pupillary latency time and 6.5% (13.7%) had an abnormal maximal pupillary area (p for the difference between latency time and maximal pupillary area in SLE = 0.040). Thus, patients with SLE had more often lesions of the pupillary parasympathetic portion of the autonomic nervous system. Overall prevalence of ANP was not different between the 2 groups; 29.0% in SLE and 21.1% in SSc for pupillary ANP and 9.7 and 15.7% for cardiovascular ANP, respectively. Overall prevalence of SNP was 6.5% in SLE and 21.1% in SSc. Disease activity was correlated with ANP (p = 0.008) and SNP (p = 0.020) in SLE. Kidney involvement was associated with more severe ANP in patients with SSc (p = 0.031). Duration of the disease did not correlate with any type of neuropathy. CONCLUSION: ANP and SNP are often present in SLE and SSc. SLE and SSc differ in the pattern of ANP and SNP, which indicates that different structures and neuropathogenic mechanisms may be involved. Patients with SLE had severe pupillary ANP, probably a sign of central nervous system involvement.

Adult↗
PubMed1995

Binding of Lambert-Eaton myasthenic syndrome IgG to synaptosomal proteins does not correlate with an inhibition of calcium uptake.

The immunochemical and functional properties of IgG fractions from patients with Lambert-Eaton myasthenic syndrome (LEMS) were examined in chick and rat synaptosomes. LEMS IgG immunoprecipitated 125I-omega conotoxin GVIA (125I-omega CgTx) labeled N-type calcium channels solubilized from both tissues, and reacted with a 65 kDa protein band in immunoblots of rat synaptosomes. Depolarization-induced 45Ca2+ influx into chick synaptosomes was partially inhibited by omega CgTx, whereas influx into rat synaptosomes was insensitive to omega CgTx. No effect of LEMS sera or IgG on 45Ca2+ uptake was apparent in either preparation.

Animals↗
PubMed1995

Immunopathology of the Lambert-Eaton myasthenic syndrome.

LEMS is an antibody-mediated autoimmune disease that can occur in isolation, or as a paraneoplastic disorder in association with SCLC (60% of patients). The underlying defect is a reduction in the quantal release of the neurotransmitter ACh from the presynaptic nerve terminal at the neuromuscular junction. Experimental evidence indicates the autoantibodies are directed against nerve terminal VGCCs causing down-regulation in the number of functional channels by cross-linkage. Functional VGCCs have been detected in SCLC cell lines. In cancer-associated LEMS it appears likely that antibodies initially provoked by tumour VGCCs cross-react with VGCCs at the nerve terminal, causing the clinical disorder. Antibodies against L-, N- and P-/Q- subtypes of the calcium channels have been identified and radioimmunoassays have been developed to help diagnose the disease. Using peptide toxin 125I-omega-CmTx MVIIC to label P-/Q-type VGCC solubilised from human cerebellum, positive antibody titres can be detected in 85% of patients. However, autoantibodies in LEMS are heterogenous; the antigenic targets include different VGCC subtypes, the intracellular beta subunit and the synaptic vesicle protein synaptotagmin. The disease phenotype may reflect the diversity and titre of these different antibodies.

Animals↗
PubMed1995

In vitro superfusion method for the investigation of nerve-immune cell interaction in murine spleen.

Immune defence mechanisms can be modulated by brain function. To study such interactions, an in vitro method was developed to examine the release of cytokines and norepinephrine (NE) after electrical stimulation. Slices of mouse spleen were placed in chambers with a volume of 80 microliters and superfused with culture medium. To characterize electrically evoked NE release and cell viability a suitable stimulation protocol was developed using of [3H]NE. As parameter for immune function, modulation of interleukin-6 (IL-6) release by the spleen cells brought about by electrical stimulation was investigated. Splenic [3H]NE overflow was calcium-dependent, tetrodotoxin-sensitive and elicited by 54 mM potassium. Electrically evoked [3H]NE release at 22 h was about 80% of the release at 5.3 h. Electrical stimulation substantially reduced IL-6 secretion at 6 h (control: 143.4 +/- 14.3 vs. electrical: 71.3 +/- 7.9 pg/ml/10(6) leukocytes, P = 0.0001). This effect was inhibited in a concentration-dependent manner by the beta-adrenergic antagonist propranolol (P = 0.0298, EC50 approx. 10(-7) M). In conclusion, this new technique allows long-term investigation of cell function in slices of murine spleen. In addition, these are the first in vitro data indicating the presence of a functional neuroimmunological link in murine lymphoid tissue.

Adrenergic beta-Antagonists↗
PubMed1995

Autoantibodies, neurotoxins and the nervous system.

Myasthenia gravis, the Lambert-Eaton myasthenic syndrome, and acquired neuromyotonia are three disorders of the neuromuscular junction or motor nerve that are caused by autoantibodies to ion channel proteins: acetylcholine receptors, voltage-gated calcium channels and voltage-gated potassium channels, respectively. The antibody titres can be measured using the relevant 125I-neurotoxins to label the extracted channels. Other disorders of the peripheral motor nerve are associated with antibodies to gangliosides. Sera with raised levels of anti-ganglioside antibodies have direct effects on the function of the distal motor nerve and motor nerve terminal. These conditions can be improved by therapies designed to reduce circulating antibodies. Antibodies that bind to neuronal surface antigens are proving to be of great clinical importance and interest in neurological disorders.

Autoantibodies↗
PubMed1995

Antigens associated with N- and L-type calcium channels in Lambert-Eaton myasthenic syndrome.

In Lambert-Eaton myasthenic syndrome neurotransmitter release is reduced by an autoimmune response directed against the calcium channel complex of the nerve terminal. Autoantibodies were detected by immunoprecipitation assays using solubilized receptors labeled with ligands selective for N-type (125I-omega conotoxin GVIA) and L-type ([3H]PN200-110) calcium channels. Sera with a high antibody titer (> 3 nM) against rat brain N-type channels contained autoantibodies that immunoprecipitated neuronal and muscle L-type channels. These IgG fractions stained a 55-kDa protein in immunoblots of purified skeletal muscle dihydropyridine receptor, suggesting that they contain autoantibodies against the beta subunit of the calcium channel. A distinct antibody population in the same fractions reacted with a nerve terminal 65-kDa protein that is unrelated to the beta subunit and displays properties similar to those of synaptotagmin.

Animals↗