Relation between serum IgA concentration and haptoglobin type.
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Biomedical subjects
Publications and source records attributed to J Delanghe.
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We investigated the components of biological variation, including seasonality, in plasma haptoglobin (Hp) levels and the relationships between plasma Hp and interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6), sIL-2R, fibrinogen (Fb) and absolute number of peripheral blood mononuclear cells, such as leukocytes, neutrophils, monocytes, lymphocytes, CD4+, CD8+, CD25+ T cells and CD20+ B cells. Monthly blood samples were taken from 26 normal volunteers during one calendar year. The estimated inter- and intra-individual C.V. values for plasma Hp were 27.9% and 20.0%, respectively; the index of individuality was 0.72. No significant seasonal rhythms could be detected in plasma Hp levels. The yearly mean values in plasma Hp were significantly and positively related to those in plasma Fb, absolute number of leukocytes, neutrophils, CD4+ T cells and the CD4+/CD8+ T cell ratio. 49.0% of the variance in the yearly mean values of plasma Hp could be explained by variances in serum IL-6 and number of CD4+ (positively related) and CD8+ (negatively related) T cells. There were significant and positive time relationships between plasma Hp, on the one hand, and plasma Fb, sIL-6R, sIL-2R and number of leukocytes, neutrophils and monocytes, on the other. A smaller part of the within-subject variability in plasma Hp (i.e. 6.0%) could be explained by serum sIL-6R and sIL-2R. It is concluded that there are (1) important between-subject differences in the homeostatic setpoints of plasma Hp, which are related to those in plasma Fb and in immune status and (2) significant within-subject, time relationships between plasma Hp and indicators of immune activation and plasma Fb.
The distribution of chromium (Cr) among the proteins in plasma of three continuous ambulatory peritoneal dialysis (CAPD) patients and in dialysis solutions was studied with 'in vitro' and 'in vivo' 51Cr-labelled plasma. Radiolabelling allows the kinetics of newly added Cr to be investigated. The separation of the proteins was achieved by ion exchange fast protein liquid chromatography, ensuring quantitative recoveries of the 51Cr activity, transferrin and albumin. In all fractions the proteins were qualitatively characterised by iso electric focusing. The concentrations of transferrin and albumin were determined by nephelometry. The 51Cr distribution among the plasma proteins was similar for the three patients. The 51Cr activity was mainly bound to transferrin and, in the beginning of the incubation, in a lesser degree also to albumin. After 1-6 h a shift was observed of the 51Cr from albumin to an unidentified low molar mass complex (+/- 5000 Da). Two 51Cr species showed up in the subsequently drained dialysate, but they could not be identified.
The MN blood group has been linked with blood pressure levels and sodium-lithium counter-transport in red blood cells of normotensives. The aim of the study was to compare the distribution of MN phenotypes according to age at diagnosis of essential hypertension and to investigate the relationship between MN phenotypes, severity of complications and therapeutic needs. MN blood group polymorphism was studied in 386 Caucasians with established essential arterial hypertension, treated for at least one year. In 285 healthy normotensive blood donors, blood pressure was measured and MN blood group was typed. MN blood groups were typed with polyclonal antisera and confirmed with monoclonal antisera. MN blood group phenotype frequencies in hypertensives were 0.207 (MM), 0.601 (MN), and 0.192 (NN), which differs (P < 0.000002) from the distribution in the controls: 0.270 (MM), 0.540 (MN) and 0.189 (NN). The relative MN phenotype frequency was strongly over-represented (P < 0.05). Age at detection of hypertension was significantly lower for MN patients (P < 0.0005). With increasing age of detection, the relative frequency of MN phenotype gradually decreases from 0.73 in those detected before age 40 to 0.50 for patients detected after 60. This observation holds true for both male and female hypertensive. Furthermore, hypertensives with a MM blood group had a lower (P < 0.05) prevalence of cerebrovascular accidents. In controls, blood pressure was comparable for the three MN phenotypes. The present study suggests that the MN phenotype is a genetic factor associated with early detection of essential hypertension.
Previous studies have suggested that depression and suicide are related to alterations in total cholesterol serum concentrations, and that an altered distribution of haptoglobin (Hp) phenotypes in major depression indicates that variation on chromosome 16 may be associated with that illness. Lecithin:cholesterol acyl transferase (LCAT, EC 2.3.1.43), the enzyme that catalyzes the esterifying reaction of cholesterol in serum, is located close to the Hp gene. This study examined the serum concentrations of total and free cholesterol and the esterified cholesterol ratio in 26 healthy controls, 47 unipolar depressed subjects (16 minor, 14 simple major and 17 melancholic depressed subjects) and 12 relatives of melancholic subjects. Depressed subjects (regardless of subtype) and relatives of depressed subjects had a significantly lower esterified cholesterol ratio than normal controls. No significant differences in total or free cholesterol concentrations were found between the above study groups. In depressed subjects, there were no significant relationships between the esterified cholesterol ratio, total or free cholesterol and postdexamethasone adrenocorticotropic or cortisol values, Hp phenotypes, severity of illness or suicidal symptoms. It is hypothesized that lower esterification in serum cholesterol may constitute a vulnerability factor for depression through alterations in cell membrane microviscosity.
OBJECTIVE: Studies from the authors' laboratory have shown that major depression is accompanied by significantly increased plasma concentrations of positive acute-phase proteins such as haptoglobin. Haptoglobin is characterized by a molecular variation with three known phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2). This study investigated haptoglobin plasma levels and phenotype and gene frequencies in unipolar major depression. METHOD: Haptoglobin plasma levels of 22 healthy volunteers, 32 patients with minor depression, and 72 patients with major depression were determined by means of a laser nephelometric method. Haptoglobin phenotyping of these 126 subjects and 200 healthy blood donors was also carried out. RESULTS: The patients with major depression exhibited significantly higher haptoglobin plasma levels than the healthy comparison subjects and the patients with minor depression. Subjects with the haptoglobin phenotype Hp 2-2 had significantly lower haptoglobin levels than the phenotype Hp 1-1 and Hp 2-1 carriers. The frequencies of haptoglobin phenotypes Hp 2-1 (61.1%) and Hp 2-2 (20.8%) in the patients with major depression were significantly higher and lower, respectively, than the frequencies in the normal population (i.e., the blood donors: 48.0% and 37.0%, respectively). The frequency of the Hp-1 gene was significantly greater in the patients with major depression (48.6%) than in the normal population (39.0%). CONCLUSIONS: Major depression is characterized by a hyperhaptoglobinemia that is largely independent of haptoglobin phenotypes. This altered distribution of haptoglobin phenotypes and genes suggests that genetic variation on chromosome 16 may be associated with that illness.
Twelve consecutive patients undergoing elective cardiac surgery were perfused with the Cobe Optima hollow fibre oxygenator. Gas transfer characteristics and blood handling were studied. The device had a maximum oxygen transfer of 315 ml/minute. The average shunt fraction was 4.5%, and was not influenced by blood-flow rate. Mean platelet count declined slightly to 91% of the baseline at the end of the study period. Haemolysis was evaluated by monitoring serum-free haemoglobin, serum haptoglobin and serum haemopexin. The evolution was as follows: free haemoglobin increased from 14 +/- 5 mg/100 ml to 85 +/- 0.8/100 ml (p = 0.01) at the end of bypass; haptoglobin decreased from 1.33 +/- 0.90 g/l to 0.89 +/- 0.15 g/l (p = 0.01); and haemopexin decreased from 0.84 +/- 0.13 g/l to 0.74 +/- 0.15 g/l (p = nonsignificant). In all patients the residual capacity of serum haptoglobin to protect against haemolysis was satisfactory. All patients had an uneventful postoperative course.
One hundred healthy Caucasian medical students (age 22 +/- 1 years) were vaccinated with a recombinant hepatitis B vaccine and their haptoglobin types were determined. A relationship between haptoglobin type and immune response to the vaccine was observed. Subjects with a 2-2 haptoglobin phenotype produced significantly lower hepatitis B antibody titres than those having a 1-1 or 2-1 haptoglobin phenotype. The haptoglobin phenotypes not only influenced the magnitude but also the kinetics of the anti-HBs response. For all haptoglobin types, haptoglobin concentration and immune response to the vaccine behaved independently.
Overall leukocyte counts decrease during certain forms of hemodialysis, but little information is available on the intradialytic evolution of phagocytic metabolic function, especially during dialysis with dialyzers not affecting the number of circulating phagocytes. This study evaluated the phagocytic capacity of granulocytes and monocytes to generate CO2 out of glucose under basic unchallenged conditions and after stimulation with latex or zymosan, before and after 15, 60 and 240 minutes of dialysis with reused cuprophan, AN69S, polysulphone, polymethylmethacrylate and hemophan hemodialyzers. Phagocytic metabolic function was assessed in whole blood on the basis of 14CO2-production from labelled glucose during the phagocytic process. There were no changes in basic unchallenged CO2-production with any of the dialyzers. Reactivity to latex and zymosan, expressed per number of phagocytes, showed no decrease, irrespective of the membrane type. For polymethylmethacrylate and reused cuprophan, a slight but significant increase in metabolic reactivity was observed in response to latex and zymosan. The test employed may give a screening picture of the phagocytic reaction to contact with dialyzers and membranes and thus of their degree of biocompatibility towards the phagocyte system.
We present a six-year follow-up of a boy with a novel type of hypolipoproteinemia, with clinical and biochemical features distinct from classical hypoalphalipoproteinemias. There were abnormally low concentrations of total and high-density lipoprotein (HDL) cholesterol, apolipoprotein (apo) B, apo A-I, and apo A-II, and the phospholipids were decreased. The most striking abnormality was an extra fraction containing mainly phospholipids and apo A-I in the HDL3 subfraction. This fraction is reminiscent of concentric 20- to 50-nm-diameter lamellar phospholipid liposomes. Plasma lecithin:cholesterol acyltransferase activity was strongly decreased. We noted a persisting polyclonal hypergammaglobulinemia, hematological abnormalities (hemolytic anemia and thrombocytopenia), and a progressive splenomegaly. After the five-year follow-up, the patient had recurrent severe infections; moderate hematuria and proteinuria developed gradually. Treatment with corticosteroids and immunoglobulins improved thrombocytopenia and hypolipoproteinemia. These clinical and biochemical findings differ from those in the known primary and secondary hypo-alpha-lipoproteinemia syndromes. Although investigation of the relatives suggests a familial predisposition for hypo-alpha-lipoproteinemia, the subject's condition can be regarded as acquired.
Sensitive and highly specific ELISA assays were developed to determine humoral immune response against actin and myosin in 122 patients suffering from various cardiovascular diseases: acute viral myocarditis (n = 10, MYO), acute myocardial infarction (n = 28, AMI), valve surgery (n = 35, VALVE), coronary bypass surgery (n = 35, CABG), and peripheral vascular surgery (n = 14, VASC). Anti-actin and anti-myosin antibodies were determined on admission and serially during a period of 90 days. Anti-actin and anti-myosin immune response (IgG, IgM) was expressed comparing absorbance of the patients' serum with a reference serum. In the different patient groups significantly (P less than 0.01) higher anti-actin and anti-myosin antibody concentrations were found on admission compared with age-matched control groups. During follow-up, all patient groups except the vascular surgery group showed a significant immune response against actin and myosin, with an immune response ratio (peak/admission) for AMA IgG and IgM respectively of 2.12 and 2.40 in the VALVE group, 1.30 and 1.99 in the CABG group, 1.42 and 1.48 in the AMI group and 1.66 and 1.25 in the MYO group; and for AAA IgG and IgM respectively of 1.57 and 3.00 in the VALVE group, 1.54 and 1.64 in the CABG group, 1.25 and 1.07 in the AMI group, and 1.42 and 1.42 in the MYO group. A significant correlation between pre-cardiac injury and peak post-cardiac injury anti-myosin and anti-actin autoantibody levels could be demonstrated suggesting that pre-injury sensitization to these antigens plays an important role in evoking post-cardiac injury immune response.(ABSTRACT TRUNCATED AT 250 WORDS)
A recently introduced turbidimetric immunoassay using shell/core particles for determination of myoglobin (Turbiquant Myoglobin, Behringwerke, Marburg, Germany) was evaluated on the Behring Turbitimer analyzer. Intra-assay CV varied between 1.0% and 3.2%; interassay CV was between 2.0% and 3.6%. Linear results were obtained between 2.8 nmol/L and 36.7 nmol/L. Manual dilution in saline solution allowed measurement of myoglobin concentrations up to 25,400 nmol/L. In the tested range, no high-dose 'hook' effect was observed. Haemolysis interfered with the assay when haemoglobin concentrations exceeded 2 g/L. The occurrence of error codes due to the presence of triglycerides was shown to depend on particle size. Repeat assays on diluted samples were necessary at triglyceride concentrations of 2.3 mmol/L for post-prandial chylomicrons (200-1000 nm), and at 11-31 mmol/L for very-low density lipoprotein-triglycerides (80-200 nm). No significant interferences of haptoglobin, bilirubin, iodine containing contrast media, and rheumatoid factors were detected for the assay. Treatment of lipaemic samples with Lipoclean (Behringwerke) resulted in lower myoglobin values. Simultaneously drawn serum and heparin-plasma samples gave comparable myoglobin results. However, values obtained in EDTA- or citrate-treated plasma samples occasionally differed significantly from serum values. The upper reference limit for myoglobin concentration was 4.2 nmol/L. The turbidimetric assay correlated well with a radioimmunoassay (Byk-Sangtec; r = 0.892) and with the automated nephelometric assay (Behringwerke; r = 0.944). Values obtained by turbidimetry were comparable to those obtained by the latex agglutination test (Behringwerke).
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Creatine kinase brain isoenzyme (CK-BB) was determined in cerebrospinal fluid of 150 neonates by a newly developed immunoenzymatic assay. Newborns with a documented neurologic disorder (intraventricular hemorrhage, postasphyxial encephalopathy, central nervous system infection, or persistent periventricular intraparenchymal echodensities) showed markedly higher concentrations of immunoreactive CK-BB than did the normal newborns or those with subarachnoid hemorrhage. In neonates with seizures the data suggest that the underlying neurologic disorder accounts for the higher CK-BB values and not the seizures per se. High concentrations of CK-BB in the neonatal period were followed by poor short-term outcome.
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The selective multi-protein analyser Behring Nephelometer was examined according to the ECCLS guidelines in a multicentre evaluation involving five laboratories. IgG, IgA, IgM, C-reactive protein, C3c, C4, apolipoprotein A-I and B were measured in serum, and albumin and IgG were measured in cerebrospinal fluid. All values obtained were included in the evaluation without correcting for outliers. The trial, which lasted three months and involved over 20,000 analyses, basically yielded the following results: 1. The precision was generally better than that of comparative procedures. For the majority of methods, the between-day coefficients of variation were below 4.5%. The highest coefficient of variation was 7.2% (for C-reactive protein) and the lowest 1.35% (for C3c). 2. The fraction of assigned values of control materials varied between 0.95 and 1.08. 3. Good agreement was found with results from the comparison procedures: Beckman ICS, Behring Laser Nephelometer, Hyland Laser Nephelometer. 4. No carry-over effects were observed. 5. No interferences were observed for IgG, IgA and IgM determinations using hyperbilirubinaemic or haemolytic samples. In contrast lipaemic samples and some with monoclonal immunoglobulin M showed an influence on the immunoephelometric reaction. 6. Because of the large measuring range, it is necessary to repeat analyses only in extremely rare cases. 7. During the entire evaluation period no instrument malfunctions or interruptions occurred. As a result of its reliability, the Behring Nephelometer is well suited for routine operation and emergency analyses in medium and large-sized laboratories.
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