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Biomedical subjects

M R Daha

Publications and source records attributed to M R Daha.

At least 397 records · Page 22Linked to original sources
PubMed1985

Activation and inhibition of Hageman factor-dependent pathways and the complement system in uncomplicated bacteremia or bacterial shock.

Levels of components of the contact activation, coagulation, and complement systems and their main inhibitors were measured in 45 critically ill patients during 61 episodes of uncomplicated bacteremia or bacterial shock. Levels of Hageman factor (factor XII), prekallikrein, high-molecular-weight kininogen, factor XI, factor VII, total hemolytic complement, alternative pathway activity, and C3 were within the normal range during uncomplicated bacteremia (n = 29), but during fatal bacterial shock (n = 13) a significant decrease by 40%-50% was observed in all measurements. During nonfatal bacterial shock (n = 19) a moderate decrease was observed in most of these measurements. The capacity of plasma to inactivate kallikrein was significantly higher during bacteremia than during bacterial shock because of a significant increase in the level of C1 esterase inhibitor. Levels of antithrombin III and alpha 2-macroglobulin were below normal in all groups. Thus increased inhibition of the contact activation and complement systems is beneficial during bacteremia.

Angiotensin III↗
PubMed1985

Is the renal kallikrein system relevant to sodium sensitivity in patients with essential hypertension.

In twenty-five outpatients with essential hypertension, the relevance of renal kallikrein excretion for inter-individual differences in the blood pressure response to changes in dietary sodium intake was investigated. The patients were studied during 2 weeks of high (300 mmol) and 2 weeks of low (50-100 mmol) sodium intake. In addition there were two control periods of normal sodium intake, one lasting 4 weeks at the beginning and one lasting 2 weeks at the end of the study. Blood pressure, body weight and 24 h urinary sodium and kallikrein excretion were measured at the end of all periods. At the end of the first control period, 1 mg furosemide per kg body weight was administered intravenously, and the urinary excretion of kallikrein and sodium were measured 30 and 120 min later. The difference in mean arterial pressure (delta MAP) between high and low sodium intake ranged from + 18 to -8 mmHg. The eight patients with a delta MAP greater than 10 mmHg were regarded as salt-sensitive. They were older and had a higher initial blood pressure than salt-insensitive patients. For all patients, urinary kallikrein excretion at the end of the low sodium period (123(SEM 20.3) micrograms 24 h-1) was significantly higher than at the end of the first control period (96(SEM 16.3) micrograms 24 h-1, P less than 0.01) and at the end of the high sodium period (96(SEM 23.7) micrograms 24(-1), P less than 0.01). When compared with salt-insensitive patients, salt-sensitives had lower levels of urinary kallikrein excretion and a blunted kallikrein response to dietary sodium restriction and furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Binding and activation of human precursor C1 by soluble aggregates of human and rabbit IgG.

The capacities of soluble human and rabbit IgG aggregates to bind and to activate human C1 were compared. Aggregates prepared by incubation of purified IgG at 63 degrees C were fractionated by gel filtration and hemolytic assays were used to measure the binding and activation of isolated human precursor C1. The C1 binding and activation capacities of both human and rabbit IgG aggregates were highly dependent on their size. Human IgG aggregates had a slightly higher binding avidity for human C1 than rabbit IgG aggregates of comparable size, but no clear differences were found between their capacities to activate C1. Experiments with nonaggregated IgG also indicated that although human IgG binds human C1 somewhat more avidly, human and rabbit IgG do not differ in their capacities to initiate fluid-phase activation of the human classical complement pathway.

Animals↗
PubMed1985

Opsonic activity of cord blood sera against various species of microorganism.

The results of the present study on the opsonic activity of cord blood serum against various microorganisms (Staphylococcus aureus, Escherichia coli, and group B streptococci) show that the activity of cord blood serum in promoting IgG-mediated ingestion is equal to that of sera of healthy adults. This implies that IgG concentrations, as assessed by immunochemical methods, in cord blood and adult sera represent functionally similar IgG activities. Ingestion of microorganisms involving complement-dependent opsonization was found to be of the same level for cord blood and adult sera, when the opsonization occurred via the classical pathway of complement activation. However, due to decreased concentrations of factors B, P, and D in cord blood serum, optimal opsonization of microorganisms requiring the alternative pathway of complement was impaired. Taken together, these results indicate that an opsonic defect of cord blood serum affects mainly microorganisms requiring opsonization via the alternative pathway of complement.

Blood Bactericidal Activity↗
PubMed1985

IgM immune complexes, lymphocytotoxins, and rheumatoid factors in renal transplant recipients with CMV disease.

In studying 127 consecutive adult recipients of cadaver renal transplants, we found that the 23 patients who developed CMV disease produced IgM immune complexes as measured by a polyethyleneglycol precipitation (PEG) assay which coincided with symptoms of their illness. In addition to anti-CMV antibodies, PEG precipitated apparently non-specific antibodies such as lymphocytotoxins and rheumatoid factor (RF). The lymphocytotoxins were IgM antibodies that were not directed against HLA antigens and lysed granulocytes as well as lymphocytes but not platelets at 22 degrees C. Lymphocytotoxin production was correlated with HLA-DR 3 and 7 and with graft dysfunction during the CMV disease. The RF also were predominantly IgM antibodies that were detectable for only 3-8 weeks. The production of RF coincided with the initial rise in IgG anti-CMV antibody activity and some reacted with the Fab fragments of IgG raising the possibility that they could modulate the cellular or humoral immune response to CMV. Patients with RF tended to have severe CMV infections with pneumonia and graft dysfunction.

Adult↗
PubMed1985

In vivo degradation of rat C1q induced by intravenous injection of soluble IgG aggregates.

Immune complexes are able to bind and activate the first component of complement, C1. Upon activation of C1, C1r and C1s are rapidly inactivated by C1-In which also forms a complex with these two subcomponents, resulting in their release from C1-immune aggregate complexes. The fate of C1q after the binding C1 to immune complexes in vivo is not clear and, therefore the clearance of radiolabelled rat C1q was investigated in normal rats and in rats receiving soluble aggregated human IgG. 125I-labelled rat C1q was cleared with a half-life (T 1/2) of 12.4 hr in normal rats. Injection of AIgG into rats that had previously received 125I-C1q accelerated the clearance of 125I-C1q, resulting, finally, in a T 1/2 of 53 min. The levels of circulating endogenous C1q were also followed using haemolytic titrations and immunochemical measurements. Directly after injection of AIgG into rats, there was a rapid decrease in C1q haemolytic activity to less than 25% of the initial value after 10 min. The rate of disappearance of C1q antigen, was, however, much slower, the lowest concentration being 30% at 2 hr. C1q haemolytic activity and the C1q antigen level returned to virtually normal values after 24 hr. Plasma samples were taken at different time intervals after the injection of AIgG and subjected to gel filtration on Sephacryl S-400 columns. It was found that, in the 10 min samples, C1q antigen and C1q haemolytic activity, each with an estimated molecular weight (MW) of 400,000, were detected together. In addition, there was C1q antigen with a MW of less than 69,000 without C1q haemolytic activity. SDS-PAGE analysis of the various serum samples indicated that the low MW C1q antigen had an apparent MW of 25,000. Measurement of uptake of 125I-C1q in various organs indicated that the main site of clearance of 125I-C1q is the liver.

Animals↗
PubMed1985

Reduction of the complement activation capacity of soluble IgG aggregates and immune complexes by IgM-rheumatoid factor.

The influence of IgM-rheumatoid factor (IgM-RF) on the activation of isolated C1 by soluble IgG aggregates (AIgG) and immune complexes was studied. IgM preparations obtained from the sera of four patients with seropositive rheumatoid arthritis markedly reduced the C1 activation capacity of AIgG, especially when large aggregates were tested. The results of parallel experiments with radiolabelled AIgG indicated that this inhibitory effect of IgM-RF was accompanied by a very large increase of the aggregate size. A comparable IgM preparation isolated from pooled normal human serum influenced neither the size nor the C1 activation capacity of AIgG. The inhibitory effect of IgM-RF on C1 activation was also demonstrated for soluble tetanus-anti-tetanus immune complexes. Thus, in spite of the established C activation ability of IgM-RF and the fact that, in general, larger IgG aggregates and immune complexes activate C1 more efficiently, cross-linking and size enlargement of soluble IgG complexes and aggregates by IgM-RF lead to a decrease of the C1 activation capacity. As a consequence, IgM-RF may reduce plasma complement activation by soluble IgG complexes in the circulation of patients with seropositive rheumatic diseases.

Antigen-Antibody Complex↗
PubMed1985

IgA containing immune complexes in rheumatoid vasculitis and in active rheumatoid disease.

Serum and synovial fluid (SF) from 68 patients with rheumatoid arthritis (RA) were studied for the presence of immune complexes (IC) and the results correlated with extraarticular features and/or disease activity. IC were measured by the 125I Clq binding assay (ClqBA) and with one detecting IgG, IgA, C3 or C4 in IC. Disease activity correlated significantly with IgG or IgA containing and Clq binding IC. The IgA containing IC were found only in 25% of the patients, including all but one case of rheumatoid vasculitis, but otherwise only in seropositive active RA. C3 and C4 IC did not correlated with disease activity, seropositivity or vasculitis. IC in serum did not correlate with SF levels, but C4 containing IC were more frequent in SF (60%) than in serum (30%). Thus serum IC did not reflect SF levels. Patients with vasculitis showed more IC in the sera than in SF.

Adolescent↗
PubMed1984

Fc- and complement receptor-dependent degradation of soluble immune complexes and stable immunoglobulin aggregates by guinea pig monocytes, peritoneal macrophages, and Kupffer cells.

The degradation of soluble immune complexes (ICx) and stable soluble immunoglobulin aggregates was studied in vitro. To obtain insight into the capacity of phagocytes from different organs to degrade soluble ICx we studied monocytes, peritoneal macrophages, and Kupffer cells. Peritoneal macrophages and Kupffer cells degrade similar amounts of aggregated guinea pig IgG2 (AIgG) and ICx per cell. Monocytes were at least ten times less effective than peritoneal macrophages and Kupffer cells. The presence of normal guinea pig serum as a source of complement enhanced the degradation of ICx and AIgG by peritoneal macrophages and monocytes. There was, however, a diminished degradation of ICx and AIgG by freshly isolated Kupffer cells in the presence of complement. After culturing of the Kupffer cells for 40 hours, there was an increase in the density of C3b receptors and a concomitant reversal of inhibition of AIgG degradation in the presence of complement. It can be concluded from the present experiments that the capacities of peritoneal macrophages and Kupffer cells to degrade soluble ICx and AIgG are comparable and that monocytes are much less active than peritoneal macrophages and Kupffer cells.

Animals↗
PubMed1984

Analysis of lymphoid and dendritic cells in human lymph node, tonsil and spleen. A study using monoclonal and heterologous antibodies.

The distribution of lymphoid and dendritic cells in human reactive lymph nodes, tonsils and spleens was examined by means of an indirect immunoperoxidase technique, using a panel of monoclonal and heterologous antibodies. The antibodies used were directed against antigens present on T cell subsets (Leu1, leu2a, Leu3a, TA1, OKT6), various types of B cells (BA1, BA2, HLA-DR, CR1) and cells of the mononuclear phagocyte system (alpha HM1, TA1, CR1, OKM1, NA 1/34). In the lymph node and tonsil Leu3a-positive cells (T-helper/inducer phenotype) and Leu2a-positive cells (T-suppressor/cytotoxic phenotype) are found in the thymus-dependent or T-cell area; in the spleen Leu3a-positive cells are found mostly in the periarteriolar lymphocyte sheath (PALS), while Leu2a-positive T-suppressor/cytotoxic cells are almost completely restricted to the cords of Billroth in the red pulp. The cells in the mantle zone of germinal centres and in the primary follicles in lymph nodes, tonsils and spleens have B-cell properties (BA1-, HLA-DR-, and CR1-positive). The cells in the germinal centres show a similar staining pattern (HLA-DR-, and partly CR1-positive). Follicles and T-cell-dependent areas have specific dendritic cells, each with a specific staining pattern: the dendritic reticulum cell (DRC) of the follicle stain with CR1, HLA-DR, BA2 and alpha HM1; the interdigitating cell of the T-cell areas in the lymph node, tonsil and spleen stain with HLA-DR and BA1. Moreover, large dendritic OKT6-positive cells are found in the T-cell areas of some of the peripheral lymph nodes, and are probably Langerhans cells. It is concluded that human lymph nodes and tonsils have an identical compartimentalisation, clearly differing from the spleen in cellular organization.

Antibodies, Monoclonal↗
PubMed1984

Circulating and mesangial secretory component-binding IgA-1 in primary IgA nephropathy.

In a prospective study of 38 patients who presented with hematuria of renal origin, 15 patients were found to have primary IgA nephropathy and 23 had other renal disorders. Sera and renal biopsy specimens of these patients were studied for the presence of macromolecular IgA1 and IgA2 using monoclonal antibodies, and the presence of J-chain as demonstrated either by immunofluorescence or its capacity to bind free secretory component. Circulating macromolecular IgA was found exclusively in the sera of patients (80%) with primary IgA nephropathy. In these sera the polymer/monomer ratio for IgA1 (0.64 +/- 0.13) was significantly higher than for normal human serum (0.39 +/- 0.01) (P less than 0.001), while no differences were found for IgA2. The polymeric IgA1 was isolated from serum by gel chromatography and was shown to have the capacity to bind free secretory component. Direct two-color immunofluorescence studies revealed the presence of only IgA1 in the mesangial deposits and also its capacity to bind free secretory component. We conclude (1) that demonstration of circulating macromolecular IgA in patients with renal hematuria is of diagnostic value and (2) that antigenetic similarities between the circulating and the mesangial macromolecular IgA suggest that dimeric IgA1 is deposited in the mesangium of patients with primary IgA nephropathy.

Antibodies, Monoclonal↗
PubMed1984

Excretion of urokallikrein in renal transplant patients. Relation to graft rejection, renal function, and blood pressure.

The relation between urinary kallikrein excretion ( Ukal ) and rejection, graft function, and blood pressure was studied in 45 renal transplant recipients. Ukal was assayed by means of an enzymatic (amidolytic) method, as well as with a specific radioimmunoassay. In a group of 10 patients studied longitudinally from the day of transplantation till day 35 +/- 3, an increase in urinary amidolytic activity without a concomitant increase in kallikrein antigen excretion was found to precede 11 out of 14 rejection episodes. This increased amidolytic activity generally persisted for several days. It was demonstrated by chromatography using an immunoadsorbent column of antiurokallikrein that the rejection-associated esterase, or esterases, differed from urokallikrein . In 35 outpatient recipients with stable graft function, Ukal excretion was decreased compared with that of healthy controls (42 +/- 7.5 vs. 107.5 +/- 7.3 micrograms/24 hr by radioimmunoassay and 0.70 +/- 0.08 vs. 1.10 +/- 0.07 U/24 hr, using the amidolytic method); for these patients a significant correlation between Ukal excretion and creatinine clearance was found (P less than 0.02). Both in transplant recipients and in controls there was a close correlation between the results of the two Ukal assays (P less than 0.001). No significant relation between Ukal excretion and blood pressure was found, either for patients or for controls. It is concluded that acute graft rejection is accompanied by an increased excretion of nonurokallikrein esterase(s). The lower Ukal excretion in patients with stable renal function seems to be related to their reduced renal function. No relation between Ukal excretion and blood pressure levels was found.

Adolescent↗
PubMed1984

Direct and indirect measurement of urinary kallikrein excretion in patients with essential hypertension and normotensives: relation to age and plasma renin and aldosterone levels.

The relevance of age and activity of the renin-angiotensin-aldosterone system to the excretion of urinary kallikrein (Ukal) was studied in twenty-five patients with essential hypertension and forty normotensive controls. The age range for both study groups was 20-60 years. Ukal was measured by radioimmunoassay and by an amidolytic assay. Results of both assays correlated closely (r = 0.93, n = 65, P less than 0.001). For all hypertensives Ukal excretion was not significantly different from that of controls. However, older hypertensives (greater than 40 years, n = 13) had a significantly lower Ukal excretion than normotensives of the same age (n = 20) (radioimmunoassay 67.2 (SEM 7.2) v. 105.1 (SEM 8.4) micrograms (24 h)-1; and amidolytic method 0.84 (SEM 0.10) v. 1.13 (SEM 0.08) U (24 h)-1). No correlation was found between Ukal excretion and plasma renin or aldosterone. In fact, the aldosterone level was highest in older hypertensives. In conclusion, the lower Ukal excretion in hypertensives over 40 is likely to be secondary to the long-standing high blood pressure. Under basal conditions, Ukal excretion seems little influenced by the activity of the renin-angiotensin-aldosterone system.

Adult↗
PubMed1984

Binding and activation of the first complement component by soluble immune complexes: effect of complex size and composition.

The interaction between soluble immune complexes and the first component of complement (C1) was studied. Complexes were prepared from purified bovine thyroglobulin (BTg) or tetanus toxoid (TT) and immunospecific IgG antibodies. Purified human precursor C1 was incubated with dilutions of the preparations, and the inhibition of C1 haemolytic activity was determined as a measure of C1-binding. The activation of C1 was assessed by measuring the amount of C4 consumed by generated C1. The molar antibody/antigen (Ab/Ag) ratio of BTg--anti-BTg mixtures strongly influenced their C1-binding and C1-activating capacities: mixtures with high Ab/Ag ratios were by far the most efficient. On the other hand, the Ab/Ag ratio had only a limited influence on the activity of TT--anti-TT complexes. The effect of complex size was investigated by ultracentrifugation of antibody-antigen mixtures on calibrated sucrose density gradients followed by C1-binding and -activation experiments with the fractions obtained. For both types of immune complex, the C1-binding and -activating capacities increased markedly with increasing complex size. Thus, both the size and the Ab/Ag ratio of soluble immune complexes influence their capacity to activate the classical complement pathway. The effect of the Ab/Ag ratio, however, may also be dependent on the antigen molecule(s) present in the complexes.

Animals↗
PubMed1984

Immunoglobulin production by human peripheral lymphocytes induced by anti-C3 receptor antibodies.

The exact function of receptors for C3b (CR1), which are present on B lymphocytes, is not clear. The present studies were performed to determine the influence of heterologous anti-CR1 on the production of IgM, IgG, and IgA by human peripheral B lymphocytes in vitro. Anti-CR1, raised in rabbits by immunization with purified erythrocyte CR1, was rendered immunospecific and was converted to F(ab')2 and Fab' by enzyme digestion. Pre-immune F(ab')2 and Fab' served as controls. Normal human blood T lymphocytes and T cell-depleted mononuclear cells were cultured for 6 days in RPMI medium and 10% heated fetal calf serum with a low dose (7 micrograms/ml) of pokeweed mitogen (PWM) alone or with PWM and F(ab')2-anti-CR1. In control experiments the effects of F(ab')2-anti-CR1 without PWM and of pre-immune F(ab')2, Fab'-anti-CR1 and pre-immune Fab' in combination with PWM were also tested. When PWM and F(ab')2-anti-CR1 were present simultaneously, 4.3 X 10(3), 2.5 X 10(3), and 1.8 X 10(3) ng/ml of IgM, IgG, and IgA were synthesized, respectively, in cultures containing 4.5 X 10(5) mononuclear blood cells. All other combinations resulted in synthesis of less than 250 ng/ml of each class of Ig. The presence of purified CR1 in the cultures containing PWM and F(ab')2-anti-CR1 caused a dose-dependent decrease of Ig synthesis. By culturing B cells isolated by E-C3b rosetting with T cells and monocytes, the anti-CR1 responding population was demonstrated to be mainly in the CR1-rich B cell fraction. Fab'-anti-CR1 at high doses was also able to stimulate Ig production in the presence of low concentrations of PWM. These data suggest that triggering of CR1 on B cells results in modulation of antibody production and that triggering of CR1 with more than one antibody is required for an optimal response.

Animals↗