Kinetic studies of the association of complement components and IgG-coated latex particles incubated in normal or complement-activated human serum.
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Calcium↗
Biomedical subjects
R Hällgren
Publications and source records attributed to R Hällgren.
Serum beta 2-microglobulin in patients with bronchial carcinoma and controls.
We measured serum levels of beta 2-microglobulin in 467 patients mainly with suspected pulmonary malignancy. By applying serum concentrations of 3.0 mg/liter as the normal upper limit, we found elevated levels in 21% of the patients with verified bronchial carcinoma (n = 230) and in 11% of the patients with lung diseases of infectious, inflammatory, or other origins but without proven malignancy. A rise in serum beta 2-microglobulin levels with advancing age was demonstrated in cancer patients and controls. No significant differences in serum concentrations were seen between cancer patients subgrouped according to the WHO clssification. Serial measurements on cancer patients generally revealed increasing serum-beta 2-microglobulin with time. The most striking elevations during tumor growth were observed in patients with small cell anaplastic or epidermoid carcinoma. After surgical removal of the lung tumor, no decrease of beta 2-microglobulin was found. Patients who at admission had low circulating levels of beta 2-microglobulin (less than 1.5 mg/liter) had a better prognosis than those with serum beta 2-microglobulin greater than 3.0 mg/liter. The mechanism behind elevated beta 2-microglobulin in bronchial carcinoma and the variation of this protein during progression of the cancer disease is unknown. One possible interpretation is that levels increase as a consequence of an increased cell turnover in tumor tissue in combination with an enhanced immune response secondary to the malignant process.
Adult↗
Elevated levels of circulating pancreatic polypeptide in inflammatory and infectious disorders.
Circulating levels of pancreatic polypeptide (PP) were found to be elevated when compared to healthy controls in 54% of patients with chronic inflammatory connective tissue disorders (SLE, rheumatoid arthritis, scleroderma, mixed connective tissue disease and temporal arteritis) and in 96% of patients with acute viral or bacterial infections. Significant positive correlations were obtained between the serum values of PP and those of haptoglobin or orosomucoid. Accompanying successful anti-inflammatory treatment of patients with autoimmune disorders, a reduction of PP levels was observed. The findings suggest that the magnitude of increase in PP was associated with the degree of the inflammatory activity. Raised PP levels may contribute to the alterations in carbohydrate and lipid metabolism observed during active inflammatory diseases in man.
Acute Disease↗
Serum and urinary myoglobin in alcoholics.
The serum levels of myoglobin were measured in 106 male alcoholics. Subnormal levels were found in 31% of the alcoholics with no alcohol consumption for the last 2--4 weeks, while none of them had elevated levels. Of the alcoholics on ambulatory control and with varying current alcohol intake. 18% had increased levels compared to healthy controls. Serial myoglobin levels were determined in 19 patients following the cessation of heavy drinking sprees. Despite the fact that none of the patients had clinical evidence of acute myopathy, marked myoglobin elevations were noted in five patients; their serum levels gradually declined and normalized with 4--7 days. Comparing the three groups, similar frequencies of subnormal or elevated serum CK levels were observed. Myoglobin levels were not raised due to impaired glomerular filtration rates. No correlation was found between serum myoglobin and laboratory signs of liver affection. Although hypophosphatemia, hypomagnesemia and hypokalemia were occasionally noted, decreased serum electrolytes did not have any relation to elevated serum myoglobin. A transient, slightly increased urinary excretion of myoglobin parallel with increased excretion of beta 2-microglobulin was observed in 2/17 alcoholics, suggesting that instances of myoglobinuria in alcoholics with heavy recent drinking may be due to a transient minor tubular dysfunction.
Adult↗
Effect of hyaluronic acid on phagocytosis of opsonized latex particles.
In an in vitro model system using isolated human granulocytes high molecular weight hyaluronic acid stimulated the initial rate of phagocytosis of complement-opsonized latex particles. This specific quality was dependent on the molecular size and occurred at low concentrations (1-10 mg/l) of hyaluronic acid. However, at high concentrations (> 100 mg/l) hyaluronic acid inhibited the initial rate of phagocytosis of both IgG- and complement-opsonized particles. The latter effect was shared with chrondoitin sulphate, heparan sulphate and heparin. The results suggest that hyaluronic acid may be instrumental in controlling inflammatory processes.
Chondroitin Sulfates↗
Cerebrospinal fluid ferritin in patients with cerebral infarction or bleeding.
By the use of a radioimmunoassay, ferritin was detected in the cerebrospinal fluid (CSF) of apparently healthy individuals at a mean concentration of 5.1 arb U/l, i.e. a level about 5% of the mean normal serum-ferritin concentration. Fourteen patients with acute cerebrovascular stroke or transient ischemic attacks (one case) were followed by serial determinations of CSF-ferritin during 2 weeks or more from onset of symptoms. After cerebral stroke all patients exhibited an increase of CSF-ferritin with peak levels between 4 and 6 days from admission. Those three patients in whom computed tomography showed cerebral bleeding had the highest peak CSF-ferritin was 28 +/- 11 arb U/l in the patients who had cerebral infarction without signs of bleeding. In seven patients CSF-ferritin returned to the control range after 2 weeks. The extent of the rise of ferritin in CSF could not be explained by damaged blood-CSF barrier. We suggest that the increment of ferritin in CSF of patients with cerebrovascular lesions may reflect an inflammatory response within the brain possibly mediated by macrophages.
Adolescent↗
Sequential studies on serum-levels of lysozyme, lactoferrin and eosinophil cationic protein in alcoholics after alcohol withdrawal.
12 male alcoholics were followed for 16 d after alcohol withdrawal with respect to the number of the different circulating blood cells and to serum levels of leucocyte markers such as beta 2-microglobulin, eosinophil cationic protein (ECP), lactoferrin and lysozyme. The results suggest a direct toxic effect of ethanol on the neutrophil granulocytes as indicated by high S-lactoferrin levels. Relatively low levels of S-lysozyme as compared to S-lactoferrin could suggest a reduced activity of the monocytes/macrophages. The eosinophils and lymphocytes seemed quite unaffected by ethanol. Increased haematopoietic activity after withdrawal was indicated by increasing cell numbers in the peripheral blood and by increasing serum levels of lactoferrin and lysozyme. The increasing monocyte/macrophage activity after withdrawal as suggested by S-lysozyme levels was closely related (P less than 0.001) to the increased thrombopoietic activity as evaluated by peripheral thrombocyte counts. This latter finding could point to a direct relationship between monocyte/macrophage activity and thrombocyte production.
Adult↗
Neutrophil function in infection-prone children.
Seven variables connected with the function of the neutrophil granulocyte were studied in 24 children who had undue susceptibilities to infections. The phagocytosis rate of IgG-coated latex particles by the patients' neutrophils was significantly reduced compared with an age-matched control group. The chemokinetic effect of patients' sera on normal polymorphonuclear neutrophil leucocytes was reduced too, especially in heated (56 degrees C, 30 min) serum. Spontaneous chemotactic activity in the patients' sera was significantly lower than in sera from healthy adults and from the age-matched control group. A functional index based on the 7 variables of neutrophil function was constructed. The score of the functional index was correlated to the severity of the patients' clinical condition and discriminated well between normal children and those with undue susceptibility to infections.
Adolescent↗
Regulation of granulocyte function by hyaluronic acid. In vitro and in vivo effects on phagocytosis, locomotion, and metabolism.
Hyaluronic acid (HA) stimulated the function of polymorphonucler leukocytes (PMN) both in vitro and in vivo. Stimulation in vitro was achieved by the incubation of PMN and HA in heparinized whole blood at concentrations of HA between 5 and 500 microgram/liter. The stimulation of the PMN function was demonstrated by an increase rate of phagocytosis of complement- and/or immunoglobulin (Ig)G-coated latex particles, increased adherence to nylon wool, increased random migration and chemotactic response, increased chemiluminescence during phagocytosis, and raised levels of intracellular ATP. The effect of HA in vivo was demonstrated, after subcutaneous administration of HA (5-20 mg) to healthy volunteers, by an enhanced rate of phagocytosis of the subsequently isolated neutrophils. The duration of the effect of one administration was approximately 1 wk with maximum effect on days 2-4. HA injections to patients with increased susceptibility to bacterial infections and impaired neutrophil function demonstrated an enhanced neutrophil function also in these individuals. HA may therefore be a new principle by which resistance to infections can be enhanced.
Adenosine Triphosphate↗
Diagnosis, size estimation and prediction of acute myocardial infarction from S-myoglobin observations. A system analysis to assess the influence of various sources of variability.
Three different ways of using S-myoglobin observations for early diagnosis of acute myocardial infarction have been investigated by computer simulation techniques, viz. classification based on (i) single determination in relation to a decision limit, (ii) the peak serum concentration value, (iii) estimated or predicted value of infarct size from serial serum concentration determinations. The results of the in numero experiments indicate that it is possible to define optimal conditions with regard to time, period and frequency of observation, as well as to assess requirements on pre-analytical/analytical variation. The optimal time for a single observation should be about 10-12 h after onset of symptoms. The influence of pre-analytical/analytical variation is not very critical in this connection and the quality requirements are achievable in the clinical chemical laboratory today (total CV about 0.10). The peak serum value has good diagnostic power, but does not provide a good index of infarct size, no matter how good the analytical quality may be. It should be possible to predict infarct size from early serial S-myoglobin observations. A coefficient of pre-analytical/analytical variation below 0.05 is then required in addition to frequent blood specimen collection from admission up to peak time of the serum concentration curve.
Humans↗
Kinetic measurement of the interaction of rheumatoid factor with IgG-coated latex particles and the influence of the first component of human complement.
Interaction between isolated rheumatoid factor (RF) of the IgM class or sera from patients with rheumatoid arthritis (RA) and IgG-coated latex particles has been studied kinetically by means of standard aggregometer equipment. The agglutination of particles mediated by isolated RF or RA-sera is inhibited by fresh normal human serum (NHS). The RF-inhibiting principle is heat-labile and recovered in the high molecular weight fractions of NHS separated on a G-200 column. Partially purified first component of complement, C1, also inhibits RF-mediated particle agglutination and disintegrates preformed RF-IgG-latex particle agglutinates. Addition of C1 to heated (56 degrees C, 30 min) NHS restores its RF-inhibiting activity. The most probable basis of this serum activity is competition between C1 with higher affinity for IgG bound to particles and RF. After about 5 min of incubation of NHS with IgG-latex particles the RF-inhibiting activity is gradually lost and interpreted to mean that C1 during the activation of the complement system is discharged from IgG bound to particles. The RF-inhibiting activity of NHS gradually decreases by incubation of serum with increasing doses of activators of the classical complement pathway probably due to the inability of activated C1 to hinder RF-interaction with IgG-particles. The presence in certain RA-sera of C1 in mainly activated form explains why such sera, even if they are fresh are able to agglutinate IgG-particles.
Complement Activation↗
Hyaluronic acid stimulates neutrophil function in vitro and in vivo. A review of experimental results and a presentation of a preliminary clinical trial.
Hyaluronic acid (HA) stimulates normal neutrophil function both in vitro and in vivo Stimulation was also achieved by subcutaneous administration of HA to patients with extreme susceptibility to bacterial infections. Clinical improvement of some patients was obtained in connection to the administration. It is premature at this time to conclude any therapeutic effect of HA in patients with extreme infection propensity. The data presented here, however, for certain merit further investigation on this matter.
Adult↗
Effects of serum and cations on the selective release of granular proteins from human netrophils during phagocytosis.
The extracellular release from human neutrophils of the primary (azurophil) granule constituents, myeloperoxidase (MPO), chymotrypsin-like cationic protein (CCP), collagenase and lysozyme, and the secondary (specific) granule constituents, lactoferrin and lysozyme, was measured during ingestion of staphylococcus protein-A-IgG complexes. In buffer, lactoferrin release was consistently higher than that of the other protein. In serum, lactoferrin release increased concomitantly with ingestion, whereas the rate of lysozyme and especially of MPO release were stimulated to a higher degree than ingestion. Magnesium (0.5--2 mM) was more potent than calcium (0.5--2 mM) in promoting release but these cations worked synergistically. Zinc (0.5--4 mM) was found to be a potent and selective inhibitor of collagenase release. Manganese (0.25--4 mM), which inhibited the ingestion of SpA-IgG complexes, also inhibited release of CCP, collagenase, lysozyme and MPO, but actually stimulated lactoferrin release. The data suggests that lactoferrin and lysozyme may be confined to distinct granule populations or else released in a different fashion from the granules. When the effects on release of primary granule proteins are concerned it is suggested that the dissociation of binding of various agents to an anionic granule matrix may be affected differently by various cations.
Blood↗
Serum beta2-microglobulin in women with breast cancer and in age-matched, non-hospitalized controls.
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Adult↗
Enhancement of factor XII dependent reactions by eosinophil cationic protein.
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Blood Coagulation↗
Serum ferritin during inflammation. A study on myocardial infarction.
The ferritin level in serum was investigated in 9 patients with myocardial infarction, all with a history of chest pain of less than 4 hours before admission. A significant rise in serum ferritin level was found in 8 patients. The rise was generally smaller than that seen in acute infection and not significantly correlated to the size of infarction, as estimated from changes in serum levels of myoglobin, ASAT and LDH. The rise started after a mean of 30 hours, the peak being reached within a week (M 4.3 days). Serum ferritin then fell to 120--300% (M 190) of the initial level, where it remained. An initial rise in serum iron levels was unexpectedly seen within 12 hours in 7 patients.
Aged↗
Blood eosinophils and eosinophil cationic protein after acute myocardial infarction or corticosteroid administration.
Measurements of eosinophil cationic protein in serum (S-ECP) have been made in patients with acute myocardial infarction. In spite of low numbers of blood eosinophils in the acute phase of the disease S-ECP levels fluctuated widely with often markedly raised levels. Peak levels of S-ECP were significantly correlated (P less than 0.001) to peak numbers of blood eosinophils, although the former usually occurred within the first 2-3 d of illness and the latter usually after the sixth day. Intravenous injection of 0.5 g methylprednisolone in healthy individuals reduced blood eosinophil counts for at least 24 h, but S-ECP levels remained within normal limits. These results suggest that ECP is released from eosinophils in vivo. The raised levels of S-ECP in patients with acute myocardial infarction are probably due to the active participation of eosinophils in the inflammatory process.
Acute Disease↗
Plasma levels of somatostatin-like immunoreactivity-independence of kidney function.
Plasma levels of somatostatin-like immunoreactivity (SLI) and gastrin were determined by radioimmunoassay in patients with varying degrees of renal dysfunction. The plasma SLI was not increased in patients with end-stage renal failure as compared to healthy controls. In patients with varying degrees of renal insufficiency no significant correlation was found between the plasma SLI and kidney function as estimated by the 51Cr-EDTA-clearance rate. In uraemic patients a significant inverse correlation was found between plasma SLI and plasma gastrin.
Adolescent↗