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PubMed1987

The pathologic and immunologic response to inhaled trimellitic anhydride in rats.

Trimellitic anhydride (TMA) is a chemical intermediate used in the paint and plastics industry. Inhalation of TMA can induce four types of syndromes in TMA workers; three are immunologically based whereas the fourth, an irritant syndrome, is nonimmunologic. To evaluate the potential inhalation hazard of TMA under controlled conditions, Sprague-Dawley rats were exposed 6 hr/day via inhalation to target concentrations of 0, 10, 30, 100, and 300 micrograms/m3 for varying durations. Two sets of rats received either 5 or 10 exposures and were terminated. A third set received 10 exposures, and was held 12 days and terminated. A fourth set received 10 exposures, and was held 12 days, challenged with a single 6-hr exposure, and terminated. A fifth set received 10 exposures, and was held 12 weeks and terminated. There were no effects after 5 exposures; however, after 10 exposures the following parameters were increased in a concentration-related manner: absolute and relative lung weights, external hemorrhagic lung foci, alveolar macrophage accumulation, alveolar hemorrhage, pneumonitis, and lung and mediastinal lymph node nonspecific IgG and complement (C3). The rats exposed and rested 12 days were nearly recovered from these effects; however, rats rested 12 days and subsequently challenged exhibited lesions similar to those seen immediately following exposure. Exposed rats rested 12 weeks were completely normal in all of the above parameters. The timing and nature of the lung lesions, along with the presence of lung IgG and complement, are consistent with some of the known aspects of TMA-induced lesions in humans, and are reflective of results obtained from other hypersensitivity pneumonitis models.

Administration, Inhalation↗

PubMed1978

Serum proteins in heavily burnt patients.

Several serum proteins, such as prealbumin, protease inhibitors, immunoglobulins, metalloproteins and inflammatory glycoproteins were determined in the sera of heavily burnt patients by radial immunodiffusion. An increase of acute phase reactant glycoproteins (orsomucoid, haptoglobin, haemopexin, C-reactive protein), C3-complement, immunoglobulins, prealbumin and of the protease inhibitors (a1-antitrypsin, a2-macroglobulin) was found. For some proteins, such as prealbumin, haemopexin, immunoglobulins, this increase was preceeded by a decrease on days 3 to 5 post-burn. The time course of the increase was variable, faster for some patients and slower for others: orosomucoid, C-reactive protein, C3-complement reached peak values between days 6 and 8; immunoglobulins and hemopexin decreased then towards normal values. No significant increase was found for ceruloplasmin, transferrin, beta2-glycoprotein, a2-SH glycoprotein and GC-globulin. It is proposed that the selective overproduction of the above mentioned proteins may be related to the stimulation of acute-phase reactant protein synthesis by the liver as a result of tissue breakdown produced by the circulating proteases and especially by elastases and collagenases as was shown previously (Miskulin et al., 1978; Moati et al., 1978a).

Blood Proteins↗

PubMedDate not supplied

Opsonic activity of human ascitic fluid: a potentially important protective mechanism against spontaneous bacterial peritonitis.

The opsonic activity of 60 ascitic fluids from 47 patients was measured using a standard opsonophagocytic assay. Curve analysis of the opsonic activity compared to the ascitic fluid concentration of total protein, total hemolytic complement, C3 and C4 yielded correlation coefficients of 0.84 (p less than 0.001), 0.84 (p less than 0.001), 0.94 (p less than 0.001) and 0.92 (p less than 0.001), respectively. There appeared to be a threshold of concentration for each protein below which there was no killing of bacteria. Cirrhotic ascites had significantly (all p less than 0.001) lower concentrations of total protein and complement and less opsonic activity than noncirrhotic ascites (including malignant, cardiac and miscellaneous types). Perhaps it is the dilution of crucial antimicrobial proteins below a threshold which predisposes to spontaneous bacterial peritonitis.

Ascites↗

PubMed1982

Induction of the acute-phase protein serum amyloid P in experimental Chagas' disease.

Serum amyloid P protein (SAP), which shares several structural properties with C-reactive protein, has been recently identified as an acute-phase reactant in mice. In this study, the systemic inflammatory response of mice to infection with Trypanosoma cruzi was characterized with respect to induction of SAP as well as to stage-specific alterations on complement C3 and C4 levels. The SAP response depended on the dose and infectivity of the parasites. Kinetic data indicated a close temporal relationship between the onset of parasitemia and induction of SAP. The levels of SAP were maximally enhanced (1,050%) by the time parasitemia started to regress, and the response remained elevated as the infection entered the latency phase. The decline in parasitemia was paralleled by a significant reduction in C3 levels. A reciprocal relationship between the extent of parasitemia and SAP/C3 levels became apparent when these parameters were compared in individual inbred mice during the time of decreasing parasitemia.

Amyloid↗

PubMed1987

Sub-MICs of cefuroxime and ciprofloxacin influence interaction of complement and immunoglobulins with Klebsiella pneumoniae.

Growth of encapsulated (K+) and nonencapsulated (K-) Klebsiella pneumoniae strains in media containing sub-MICs of either cefuroxime or ciprofloxacin resulted in cell elongation but had little effect on the outer membrane protein or lipopolysaccharide profiles. Exposure to serum complement increased the surface hydrophobicity of a K- strain but failed to interact or to increase the surface hydrophobicity of the K+ strains. However, after growth of the K+ strains in sub-MICs of the antibiotics, complement increased their surface hydrophobicity and complement C3 was detected bound to their surface. Antisera raised against a K-O- strain agglutinated the K+ strains grown in the presence but not in the absence of cefuroxime or ciprofloxacin. These findings suggest that the filamentous morphology induced by these antibiotics influences the distribution or amount of capsular polysaccharide such that cell envelope components previously masked by the capsule become accessible to complement and immunoglobulins.

Agglutination Tests↗

PubMed1998

Humoral and cell-mediated immunity in malnourished children in Ghana.

OBJECTIVE: To examine the relationship between immunological variables and the different types and severity of malnutrition in Ghanaian children. DESIGN: Case-control study. SETTING: The study was done at Princess Marie Louise Hospital, Accra, Ghana. SUBJECTS: One hundred and seventy children, aged 8-36 months, were recruited at the clinical ward and public health service section of the hospital: 61 normal children, 49 moderately malnourished (underweight) children and 60 severely malnourished children (19 kwashiorkor, 30 marasmus, and 11 marasmic kwashiorkor children). METHOD: The children underwent clinical observations, anthropometric measurements and blood sampling for biochemical analysis to evaluate their nutritional and immunological status. Serum immunoglobulins (IgA subclasses, IgG subclasses and IgM), complements (C3 and C4) and lymphocyte subpopulations (T cells, B cells, CD4+, CD8+, NK cells and HLADR) were determined for the assessment of humoral and cell-mediated immunity. RESULTS: Serum levels of IgA1, IgA2 and C4 tended to be higher in severely malnourished children than in normal children, while serum level of C3 and the proportion of B cells were significantly lower in the severely malnourished children than in the normal children (P < 0.05). There were no notable differences in most immunological parameters among the three severely malnourished groups. No differences were observed in the immunological parameters except for the proportion of B cells between normal and moderately malnourished children. Factor analysis revealed that C3 levels were positively correlated with a factor which was strongly associated with weight-for-height z-score and biochemical indicators for evaluating protein nutrition. In addition, IgA2, IgG1 and IgM levels were positively correlated with a factor which was associated with C-reactive protein. CONCLUSION: Several immunological variables responded positively or negatively with the different levels of severity of malnutrition, but most variables did not on the different types of malnutrition. The changes of C3 level were more associated with the severity of malnutrition.

Antibody Formation↗

PubMed1988

Serum immunoglobulin and complement levels in patients with sickle cell anaemia from eastern province of Saudi Arabia.

Serum immunoglobulin (IgG, IgA, IgM) and complement (C3, C4) levels were determined in 61 sickle cell anaemia patients of various age groups and both sexes in their steady state by nephelometry. Serum IgG was found to be consistently elevated in 46% cases of all age groups. Increase in the levels of IgA, IgM and in the complement values (C3, C4) was also observed. Although the mechanism responsible for these variations was unclear, however, this study gave an idea about the general pattern of serum immunoglobulin and complement levels in sickle cell anaemia patients from the Eastern Province of Saudi Arabia.

Adolescent↗

PubMed1998

Mechanisms of severe, immediate reactions to iodinated contrast material.

PURPOSE: To measure and elucidate the mechanisms of presumed mediators of unexpected severe, immediate reactions to iodinated contrast materials. MATERIALS AND METHODS: In a multicenter study, 20 patients with mild to severe reactions to iodinated contrast material and 20 control subjects without reactions were evaluated. Ionic contrast material was associated with 18 (90%) of 20 reactions. Concentrations of plasma histamine, tryptase, urinary methylhistamine, specific immunoglobulin E (IgE) against ioxitalamate or ioxaglate, and the anaphylatoxins C3a and C4a were measured with radioimmunoassays; complement C3 and C4 levels were measured with nephelometry. RESULTS: Histamine levels were increased in 14 patients; tryptase levels, in 16; and methylhistamine levels, in six. Histamine and tryptase values correlated with the severity of the reaction (P < .02 and P < .004, respectively). Significantly higher levels of specific IgE against ioxaglate (P < .005) and ioxitalamate (P = .045) were found in patients. No differences were found for complement fractions. Skin test results in two patients with life-threatening reactions were positive for the administered contrast material. CONCLUSION: Histamine release and mast cell triggering are related to severe reactions. An IgE-related mechanism is strongly suspected. Radiologists should be trained to identify and treat anaphylactic shock in patients who react to iodinated contrast material.

Adult↗

PubMed2004

Significance of postoperative adjuvant immunochemotherapy after curative resection of colorectal cancers: identification of responders incorporating the age factor.

To identify responders when protein-bound polysaccharide (PSK) is used in adjuvant immunochemotherapy after curative resection of colorectal cancers, we examined the host and tumor factors that affect the prognosis incorporating the age factor. A total of 101 patients who had undergone macroscopic curative resection of colorectal cancer were treated with mitomycin C + fluoropyrimidine oral antineoplastics + PSK (MFP therapy) for two years in principle. These cases were divided into two age groups of <65 years [n=55; 54.8 +/- 8.3 years (mean +/- SD)] and > or =65 years (n=46; 69.1 +/- 3.3 years). Host factors including humoral factors (complement C3 and C4), immunosuppressive acidic protein (IAP), lymphocyte transformation (cellular factors) induced by various mitogens [phytohemagglutinin (PHA), pokeweed mitogen (PWM), and PSK], and tumor markers (CEA, CA19-9) were measured. The cases were divided by the cut-off value of each parameter into > or = cut-off value and < cut-off value groups, and the 5-year survival rates were compared. The cut-off values obtained for these parameters and the tumor factor (Dukes class) were subjected to multivariate analysis to identify the markers that affect prognosis. The 5-year mortality rate was 74.5% in the <65 age group and 56.8% in the > or =65 age group, with a tendency of better prognosis in the <65 age group (p=0.1109). Compared to the <65 age group, the > or =65 age group showed higher levels of C3 (2-way ANOVA: p=0.0582), C4 (p=0.0009) and IAP (p=0.0110) over time, but lower PSK-induced stimulation index (SI) as an indicator of cellular immunity) (p=0.0001) and PHA-induced SI (p=0.2650) over time. These results indicated that compared to patients aged <65 years, patients aged > or =65 years were characterized by lowered cellular immunity in addition to augmented complement production and an aggravated immunosuppressive state, suggesting the presence of some differences in host immune function with aging. Using the Cox proportional hazard model, the prognostic determinant was found to be Dukes C in the <65 age group, and CEA level in the > or =65 age group. The present results suggested that analysis of prognostic determinants of this therapy should take into account the age factor. Especially in elderly subjects, responders to PSK may be identified using the preoperative CEA value.

Adult↗

PubMed1987

Distinct sets of acute phase plasma proteins are stimulated by separate human hepatocyte-stimulating factors and monokines in rat hepatoma cells.

A subline of the rat hepatoma (H-35) cells has been identified which responds to hepatocyte-stimulating factors (HSFs) of human squamous carcinoma cells by increased synthesis of all major rat acute phase plasma proteins. The regulation occurs at the level of mRNA. Two HSFs (HSF-I and HSF-II) have been purified from conditioned medium of the squamous carcinoma cells. HSF-I is a protein with an Mr = 18,000 and pI 5.5, and HSF-II is a glycoprotein with an Mr = 34,000 and a broad, neutral to basic charge. In H-35 cells, HSF-I predominantly stimulates the synthesis of complement C3 and haptoglobin and acts synergistically with dexamethasone to stimulate alpha 1-acid glycoprotein. HSF-II stimulates cysteine protease inhibitor, alpha 1-antichymotrypsin, alpha 1-antitrypsin, fibrinogen, and hemopexin, and acts synergistically with dexamethasone to stimulate alpha 2-macroglobulin. Each HSF is between 10 and 100 times less effective in regulating proteins of the other set. Human tumor necrosis factor and interleukin-1 increase complement C3, haptoglobin, and alpha 1-acid glycoprotein, as does HSF-I, but are unable to modulate any of the other acute phase proteins. The monokines differ from HSF-I is their low activity in HepG2 cells and rat hepatocytes.

Acute-Phase Proteins↗

PubMed1990

Antimicrobial proteins of maternal and cord sera and human milk in relation to maternal nutritional status.

Antimicrobial proteins in maternal and cord sera and sequential samples of human milk were studied in a group of 60 Chinese women to determine the degrees of passive immunity transferred from women of different nutritional status to their infants. Maternal malnutrition was characterized by low values for wt/ht2 and serum total protein and albumin. Maternal immunoglobulin (IgG) concentrations were not significantly different between well- and malnourished groups prepartum but were significantly different postpartum. Mean concentrations of cord IgG and lysozyme from well- and malnourished groups were not statistically different. During the first 7 d of lactation and most stages thereafter, mean concentrations of IgA; complements C3 and C4, and lysozyme in milk from the malnourished group were only half of those of the well-nourished group. Antimicrobial proteins transferred via milk to newborns may be influenced by the mother's nutritional status.

Blood Proteins↗

PubMed1984

Crossed immunoelectrophoresis for the detection of split products of the third complement component in dengue hemorrhagic fever. II. In vitro activation by dengue viral antigen.

The ability of dengue viral antigen(s) from different sources, and performed antigen-antibody complexes, to activate the third component of human complement (C3) in vitro was demonstrated by using split products of human C3. Dengue type 2 viral antigen(s) from suckling mouse brain and from infected monocytes activated C3 via the alternative pathway, while performed soluble dengue-2 antibody complex activated mainly the classical pathway. The implications of this finding for the pathogenesis of dengue hemorrhagic fever are discussed.

Animals↗

PubMed1980

Synovial fluid in seronegative juvenile rheumatoid arthritis: studies of immunoglobulins, complements, and alpha 2-macroglobulin.

Synovial fluid of 20 children with seronegative juvenile rheumatoid arthritis (JRA) and 20 patients with other joint pathology was examined for levels of total hemolytic complement and selected components, immune complexes, and alpha 2-macroglobulin (alpha 2-M). When adjusted for total protein, synovial levels of total hemolytic complement, C3, C4, and alpha 2-M did not differ significantly in the two groups. The concentrations of IgM and IgG were elevated in the JRA synovial fluid, but immune complexes were not increased when compared with non-JRA group as determined by the Raji cell technique. alpha 2-M activity against substrates of C1 esterase was absent. therefore, evidence of specific increase in immune complexes and complement activation was sought but not found, suggesting that they may not be a major factor in the pathogenesis of seronegative, pauciarticular JRA.

Adolescent↗

PubMed1990

Complement component 3 (C3) genetics and diabetes mellitus.

Complement component 3 (C3) phenotype and allele frequencies were defined in 312 patients with type-1 diabetes (insulin-dependent diabetes mellitus), 256 patients with type-2 diabetes (non-insulin-dependent diabetes mellitus), 114 apparently non-diabetic first-degree relatives of type-1 diabetics, in 10 families (29 members) with a familial history of type-1 or type-2 diabetes, in 181 patients with coronary heart disease and 255 subjects with arterial hypertension. 512 blood donors served as controls. All persons investigated were Europeans. There is no evidence that genes linked to C3 influence susceptibility to type-1 and type-2 diabetes and to their late complications as well as to atherosclerosis and essential hypertension. The distribution of apolipoprotein E phenotypes in patients and controls was likewise not significantly different. The combined evaluation of data from linked genes (C3 and apo E) could not improve the results. Deductions of C3 as a genetic disease marker have to be interpreted with caution.

Alleles↗

PubMed1986

Effects of acidotropic compounds on the secretory pathway: inhibition of secretion and processing of the third and fourth components of complement.

Acidotropic compounds (also termed lysosomotropic) such as chloroquine and amantadine interfered with processing of the single-chain precursors to the third and fourth components of complement (C3 and C4) by the human hepatoma-derived cell line HepG2. When these compounds were added to culture medium, the precursors of C3 and C4 became the major secretory forms in contrast to the normal secretion of C3 and C4 as their mature forms. In addition, secretion of C3, C4, and total protein was inhibited by these compounds. Our results indicate that lysosomotropic agents, in addition to their well recognized effects on lysosomes and endosomes, inhibit functions of the secretory pathway.

Amantadine↗

PubMed1996

Inheritance of serum autoantibody, reduced serum IgA and autoimmune disease in a canine breeding colony.

Immunological parameters were examined in 113 English cocker spaniel dogs from two breeding kennels. Dogs from kennel 1 (n = 86) were grouped as having idiopathic cardiomyopathy (n = 19), autoimmune or other disease (n = 7) or being clinically normal (n = 60). Dogs from kennel 2 (n = 27) were all clinically normal and used for comparative purposes. There was a high incidence of serum antinuclear antibody (ANA) amongst all groups from kennel 1 (39/82 dogs tested), with anti-thyroglobulin and anti-erythrocyte antibodies also recorded in a dog with systemic lupus erythematosus. Thirty percent of dogs with idiopathic cardiomyopathy had anti-mitochondrial antibody. Thirteen dogs from kennel 1 had reduced serum IgA (< or = 0.3 mg/ml), but there was no consistent abnormality in the concentration of serum IgG, IgM, complement C3 or C4 in these thirteen dogs, or other dogs from this kennel. No immunological abnormality was recorded in dogs from kennel 2. Pedigree analysis of dogs from kennel 1 revealed inheritance of autoimmune disease, serum ANA and low serum IgA within several breeding lines. Inheritance of idiopathic cardiomyopathy was recorded through three generations and a strong association demonstrated between the presence of this disorder and a particular complement C4 phenotype (C4: 4).

Animals↗

PubMed1992

Cerebellar granular layer degeneration in small cell lung cancer: paraneoplastic cerebellopathy or artifact?

The aim of our study was to ascertain whether granular cell degeneration represents uniquely an artifactual or a supravital event in patients with oat cell carcinoma. The material includes 52 cases of small cell lung cancer (SCLC). Formalin fixed and paraffin embedded representative cerebellar slides were stained routinely (HE, Klüver-Barrera), and some of them served as material for immunohistochemical study. The following antibodies were used: anti-ferritin, anti-GFAP, anti-IgG and anti-C3 complement fraction. Finally 5 cases out of our material could be diagnosed as paraneoplastic cerebellar degeneration (PCD), on the basis of lack of metastases within the CNS and concomitant intensive loss of Purkinje and granule cells. Clinically the cerebellar syndrome was disclosed in 3 cases. In the granular layer prevalence of microglial cell reaction was noted. GFAP-labeled astroglia were not demonstrated in the same intensity. Antisera to the C3 complement fraction showed moderate staining of Purkinje cell cytoplasm and in some cases also of granule cells. IgG immunostaining was disclosed in Purkinje cell cytoplasm and in 4 cases also in granule cell nuclei. The immunopathological changes presently observed and glial cell proliferation could be evidence for a nonartifactual origin of PCD.

Adult↗

PubMed1978

Antinuclear antibodies in juvenile chronic arthritis.

One hundred patients with juvenile chronic arthritis (JCA) were studied with respect to granulocyte-specific and organ-nonspecific antinuclear antibodies (GS- and ON-ANA) in relation to clinical features of disease. Seventy-two were girls and 28 boys. Sixty-seven patients had IgG ANA, 31 IgM, 10 IgA, 6 IgD, 19 IgE and 35 had ANA, which fixed complement C3. Sixteen of 17 sera containing IgG GS-ANA were from girls. The prevalence of IgG GS-ANA increased with the number of joints affected. No patient with the acute febrile type of the disease had IgG GS-ANA or CS fixing ANA. The prevalence of IgG ON-ANA did not differ significantly in the mono-, pauci-, polyarticular and acute febrile types of JCA. Patients showing clinical activity more frequently had IgG and IgM ANA and C3 fixing ANA. The high titers of ANA were most often seen in girls. Chronic uveitis occurred in 10 of the patients and IgG ANA were present in sera from all of these.

Adolescent↗