Serum immunoglobulin levels in rhinoscleroma contacts.
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Complement C3↗
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Short term effect of atorvastatin and vitamin E on serum levels of C3, a sensitive marker of the risk of myocardial infarction in men.
C3 complement is produced in response to macrophage activation and is a reliable marker of the risk of myocardial infarction in men. This study was designed to ascertain whether the treatment with atorvastatin, a powerful cholesterol lowering drug, and/or vitamin E, a natural antioxidant, may induce a short term decrease in serum C3 in subjects with persistently elevated levels. From an initial random sample of 1100 men aged 55-64 years, 140 subjects with 3 consecutive C3 measurements in the high tertile (>1.19 g/l) were selected. Those with total cholesterol <5.56 mmol/l were double blindly randomized in groups 1 (placebo, N = 28, G1) and 2 (vitamin E 600 IU/day, N= 30, G2). The subjects with total cholesterol values >5.56 mmol/l were randomized in groups 3 (placebo, N= 30, G3), 4 (atorvastatin 10 mg/day, N = 27, G4) and 5 (atorvastatin 10 mg/day + vitamin E 600 IU/day, N = 25, G5). After 3 months C3 levels were substantially unchanged in the first 4 groups, while in G5 a very significant decrement occurred: -0.070 g/l (5.2%); 95% CI 0.043-0.098; p <0.0001. "Normal" levels of C3 (< 1.19 g/l) were reached by 28% of G5 subjects. In G2 and G5 vitamin E levels increased by 60 and 36%, while in G4 they decreased by 23% (p < 0.0001), paralleling cholesterol and triglyceride fall. In all groups a progressive decrease in HDL cholesterol occurred (-17%, p < 0.0001). In conclusion, treatment with atorvastatin plus vitamin E for three months can lower persistently elevated C3 levels.
Anticholesteremic Agents↗
Structural biology: origins of chemical biodefence.
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Complement Activation↗
The comorbid association of migraine with osteoarthritis and hypertension: complement C3F and Berkson's bias.
Migraine is known to have a major genetic component and has been associated with a wide variety of comorbid disorders including arthritis and heart disease. Since migraine and some of its comorbid disorders involve inflammation, complement C3, a protein involved in acute inflammation, was selected for analysis as a candidate gene in an ongoing study of the genetic basis of migraine. Polymorphism frequencies for complement C3F (0.19) and C3S (0.81) in a sample of 137 unrelated migraineurs were found to be consistent with a control group as well as previous population studies, indicating that this common polymorphism has no association with migraine susceptibility. However, C3F positive individuals with migraine were found to have an increased incidence of osteoarthritis (Chi square = 10.06; p < 0.0008) and hypertension (Chi square = 5.18; p < 0.01). Therefore, the data in the present study indicate that certain migraine comorbidities that have been reported in the literature may result from Berkson's bias as opposed to a shared pathophysiological variation in the C3 gene.
Comorbidity↗
Complement activation directly induced by Helicobacter pylori.
BACKGROUND AND AIMS: Helicobacter pylori is a frequent gram-negative colonizer of the human stomach. Its interaction with complement may be involved in the pathogenesis of chronic gastritis, and was mechanistically studied in vitro. METHODS: Four H. pylori strains, 2 cytotoxin-associated genes (cag)A+ and 2 cagA-, were isolated from infected patients. Bacteria or purified H. pylori lipopolysaccharides (LPSs) were incubated with nonimmune serum at 37 degrees C; the activation products C3b/iC3b/C3c (C3bc) and terminal complement complex (TCC) were then quantified by immunoassays. The serum sensitivity of 1 strain (L01, cagA+) was tested by counting the numbers of colony-forming units. RESULTS: All strains and LPSs generated large amounts of C3bc and TCC. Blocking of the classic complement pathway by the calcium chelator ethylene glycol tetraacetic acid (EGTA) markedly reduced the complement products, suggesting that H. pylori and its LPSs directly engage the classic activation pathway. H. pylori was shown to be serum sensitive, but 30% or more nonimmune serum was necessary to induce marked killing. After 5 minutes, swelled bacteria coated with C3bc and TCC were shown. CONCLUSIONS: H. pylori is complement sensitive and activates the classic pathway even in the absence of specific antibodies. Released cell wall constituents such as LPSs can activate complement and may explain why this bacterium induces gastric pathology without invading the mucosa.
Antibodies, Bacterial↗
Effects of pulsatile and nonpulsatile perfusion mode during extracorporeal circulation--a comparative clinical study.
In a prospective randomized study with 80 male patients scheduled for aorto-coronary bypass grafting we investigated the influence of pulsatile and nonpulsatile perfusion mode on cell count (leukocytes, platelets, hematocrit), concentrations of thromboxane (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), plasma hemoglobin, PMN-elastase, complement C3a, clotting factor XII, lactate, plasmatic inhibitors (C1-INH, AT-III, alpha 2-antiplasmin), arterio-venous oxygen difference (AVDO2) and hemodynamic parameters. Changes in hematocrit were similar in both groups, whereas plasma hemoglobin concentration was significantly higher with pulsatile perfusion. Platelet count paralleled changes in hematocrit and was not influenced by the perfusion mode. Leukocyte count as well as concentrations of PMN-elastase and C3a showed a strong increase during cardiopulmonary bypass, but there were no significant differences between the two groups. Similar changes of the concentrations of TXB2 and 6-keto-PGF1 alpha were noted irrespective of the perfusion mode applied. The observed alterations in the concentrations of clotting factor XII, alpha 2-antiplasmin, AT-III and C1-INH largely paralleled hematocrit changes in either flow mode. Significant differences between the two groups were found with lactate: with nonpulsatile perfusion there was a slight but continuous increase, while with pulsatile flow lactate levels remained unchanged. There was no evidence for a better oxygen uptake (AVDO2) with pulsatile perfusion. Pulsatile perfusion seems to be advantageous to tissue perfusion, however, at the cost of a higher rate of hemolysis. We cannot confirm further salutary effects of the pulsatile perfusion mode with the 1-pump-system on cellular and humoral blood constituents.(ABSTRACT TRUNCATED AT 250 WORDS)
6-Ketoprostaglandin F1 alpha↗
Light concentric exercise and heavy eccentric muscle loading: effects on CK, MRI and markers of inflammation.
The consequences of a single bout of heavy eccentric exercise with and without repeated concentric exercises on MRI images, serum CK levels and markers of inflammation were studied. Two groups (ECC and ECCON), each consisting of 18 male volunteers, performed 70 eccentic contractions of the quadriceps femoris muscle. The study group (ECCON) performed additional concentric contractions on a dynamometer (Cybex II+) one day before and two hours, 1, 2, 3, 6 and 9 days after eccentric loading. Serum levels of creatine kinase (CK) were examined as a function of time, and correlated with measurements of magnetic resonance imaging (MRI) of the involved muscle groups. T2-weighted images of the thigh muscles were studied. Serum C-reactive protein, complement factors C3c and C4, haptoglobin and transferrin were measured as markers of inflammation. Additional concentric contractions (ECCON group) significantly increased CK, compared to the ECC group. However, it has no apparent effect on MRI signal intensity changes, which were of equal magnitude in the loaded vastus intermedius and deep parts of the vastus lateralis in both groups. Likewise, the serum markers of inflammation of the exercised muscles appeared to be absent. Based on MRI-images, additional concentric contractions had no statistically significant effect on muscle damage and breakdown of connective tissue. The five-fold increase in CK in the ECCON group could be a reflection of "massaging out" of the CK from the muscles into the circulation by additional concentric exercises. However, it could also be an indication for a superior sensitivity of assessing muscle fiber damage in comparison to the MRI.
Adult↗
Pyrethroids used indoors--immune status of humans exposed to pyrethroids following a pest control operation--a one year follow-up study.
A multiparametric analysis of immune components was performed in blood and serum of 61 voluntary persons before and after (1 day, 3 days, 4-6 months, 10-12 months) a professional pest control operation (PCO) using pyrethroids. Following parameters were included in the study (1) immunological parameters of the humoral defence, i.e. immunoglobulins of the classes A, G, M and E, complement components C3c and C4, acute phase proteins such as acid alpha 1-glycoprotein, haptoglobin, C-reactive protein; (2) mediators and receptors of immunity, i.e. neopterin, soluble interleukin-2 receptor (sIL-2R), soluble interleukin-6 receptor (sIL-6R), soluble tumor necrosis factor receptor (sTNF RII); (3) immunological markers of the cellular defence, i.e. white blood cell counts and lymphocyte (sub)populations such as total lymphocytes (CD2), mature lymphocytes (CD3), T-helper/inducer cells (CD4), T-suppressor/cytotoxic cells (CD8), B-cells (CD20), natural killer cells (CD56), as well as the ratio of CD4/CD8. The medians of all investigated immune components found before and for all time intervals after pyrethroid application were within the reference interval with respect to the total collective. Within this physiological range the investigated parameters showed a trend to lower values predominantly during the early phase (1 and 3 days) after PCO, partially being significant. Significant decreases were no more present in the late phase (6 to 12 month) after PCO indicating reversibility. Atopics did not differ in the immune response after PCO as compared to non-atopics. Obtained results suggest a modulation of immune components after a correct performed PCO within the physiological range towards lower values during the first days. However these immune changes are considered to be subtle and underlying compensatory mechanisms of immunoregulation.
Air Pollution, Indoor↗
Immune status of children with phenylketonuria.
OBJECTIVE: To determine the effect of differences in plasma phenylalanine (Phe) concentrations (< 363 umol/L, 363 to 605 umol/L, and > 605 umol/L) on hematological and immunological parameters in 22 children with phenylketonuria (PKU). METHODS: Children with PKU were divided into one of three groups based on fasting plasma Phe levels. Hematologic and immunologic parameters of the children with PKU were compared between the groups and also compared with published values from age-matched children without PKU. RESULTS: Hematologic and immunologic parameters did not differ among children with different plasma Phe concentrations. Specifically, no significant differences between groups of PKU children with differing plasma Phe levels were found for plasma levels of albumin, hemoglobin, amino acids, IgM, complement C3, interleukins 1 and 2, erythrocyte, leukocyte and differential cell counts, hematocrit, percentages and numbers of CD4+, CD8+, CD3+ and total lymphocytes, or CD4 to CD8 ratio. Mean plasma IgG and IgA concentrations of the PKU children were, however, significantly lower than values from similar aged children. Moreover, positive correlations were obtained between plasma albumin and percentages and numbers of CD3+ and CD4+, between plasma IgG and interleukins 1 and 2, and between intakes of energy, protein, iron and plasma IgG levels. No correlations were found between plasma Phe and immunological parameters. CONCLUSION: While differences in plasma Phe concentrations up to concentrations of 866 umol/L do not appear to affect selected immune system parameters, further studies are needed to investigate the relationship between dietary nutrient intake, nutritional status, antibody biosynthesis and cytokine production. Assessment of plasma and cell membrane lipids and trace mineral status of PKU children would be helpful to determine if relationships exist between these nutrients and antibody production.
Adolescent↗
Evaluation of essential amino acids and keto acids in uremic patients on low-protein diet.
The effectiveness of a mixture of five analogues of essential amino acids and the remaining four essential amino acids as compared to a preceeding treatment period of the nine essential amino acids was evaluated in 16 chronic uremic patients fed a low-protein diet. During amino acid analogues supplementation, there was a tendency for blood urea nitrogen to fall whereas creatinine did not change. Serum phosphate decreased in most patients, whereas serum calcium rose in some subjects. Protein metabolism, as judged by serum transferrin, Clq, C3c, total complement activity, was improved. Furthermore, the concentrations of prealbumin and retinol-binding protein, which are elevated in uremia, showed a further increase that might favor a vitamin A intoxication.
Adult↗
Progesterone regulation of estradiol-induced rat uterine secretory protein, complement C3.
Previously, using DNA sequencing, Northern and Southern analysis, and immunohistochemical data, we identified an estrogen-stimulated secretory protein as the third component of complement (C3). In this study, we demonstrate that progesterone modulated the estradiol regulation of C3 in immature rats as well as during the normal reproductive cycle. C3 was most abundant during estrus and reached its lowest concentration in diestrus. Immunoprecipitations reveal that progesterone prevented the estradiol-stimulated increase in radiolabeled C3 both in the media and tissue. The mechanism for the progesterone inhibition of estrogen-stimulated C3 appeared to be at the level of transcription or possibly mRNA stability since progesterone blocked the estradiol-stimulated increase in C3 mRNA.
Animals↗
Progesterone and RU486 regulation of uterine complement C3 after prior induction with estradiol.
Previous results demonstrated that progesterone (P4) given simultaneously with estradiol (E2) prevented stimulation by E2 of complement C3 expression in the immature rat uterus. Northern blot analysis revealed that simultaneous administration of P4 was able to prevent the E2-stimulated increase in C3 mRNA concentration in the luminal epithelial cells. The purpose of the present investigation was to determine whether progesterone modulates C3 expression after the gene has been induced by prior administration of E2 and also to determine the reversibility of this effect by the concomitant administration of RU38486, 17 beta-hydroxy-11 beta-[4-dimethylaminophenyl]estra-4,9,-dien-3-one (RU486). This regulation was studied by examination of protein synthesis as well as mRNA concentrations. Immature 21-day-old female rats were treated with E2 for 2 days (1 microgram/day), followed 24 h later by P4 (500 micrograms) or vehicle. Uteri were removed 6, 9, and 18 h after progesterone treatment and the radiolabeled secreted proteins were analyzed by SDS-PAGE and immunoprecipitation using a goat anti-rat C3 antibody. In animals treated with vehicle, E2-stimulated C3 synthesis remained elevated at 6 and 9 h and returned to control values by 18 h. In contrast, the administration of P4 resulted in a decrease in C3 synthesis at 6 and 9 h with the greatest decrease observed at 9 h. Similar results were obtained when C3 mRNA concentrations were examined. E2-stimulated C3 mRNA concentrations were decreased in rats treated with progesterone compared to those treated with vehicle alone.2
Animals↗
Comparison of three commercially available hollow fiber oxygenators: gas transfer performance and biocompatibility.
The new generation of oxygenators have improved blood flow pathways that enable reduction in priming volume and, thus, hemodilution during cardiopulmonary bypass (CPB). We evaluated three oxygenators and two sizes of venous reservoirs in relation to priming volume, gas transfer, and blood activation. To compare priming volume, gas transfer, and biocompatibility of three hollow fiber oxygenators and two different size venous reservoirs, 60 patients were randomly allocated in groups to undergo cardiopulmonary bypass. In each group, an oxygenator with a different surface area and priming volume was used: 1.8 m2 and 220 ml (group 1, n = 23), 2.2 m2 and 290 ml (group 2, n = 20), and 2.5 m2 and 270 ml (group 3, n = 17). In groups 1 and 3, a large soft shell (1900 ml) venous reservoir was used, whereas in group 2, a smaller soft shell (600 ml) venous reservoir was used. Gas transfer was assessed by calculating the oxygen transfer rate for each group and per square meter for each oxygenator group. Partial arterial oxygen pressure (paO2) and partial arterial carbon dioxide pressure (paCO2) between the groups were assessed with forward stepwise regression analysis. Biocompatibility was evaluated through measurement of platelet numbers, complement activation products (C3b/c), coagulation (thrombin anti-thrombin III complex), and fibrinolysis (plasmin anti-plasmin complex). No differences were found in oxygen transfer rate per group. However, when correcting the oxygen transfer rate for surface area, group 1 demonstrated a higher oxygen transfer rate compared with group 2 (p < 0.05) at an FiO2 of 40 and 60% and compared with group 3 at an FiO2 of 60 and 70%. The regression analysis showed that the average arterial PO2 was the highest in group 3, i.e., 79.2 mm Hg higher than in group 1 (p < 0.001) and 73.5 mm Hg higher than in group 2 (p < 0.001). Group 3 also had the lowest average arterial pCO2, 0.57 mm Hg lower than in group 1 (p = 0.004) and 0.81 mm Hg lower than in group 2 (p < 0.001). During CPB, platelet numbers decreased significantly in all groups (p < 0.001), without differences between the groups. C3b/c levels increased in all groups during CPB. At cessation of CPB the C3b/c level in group 2 (398 nmol/L(-1)) was significantly higher compared to group 1(251 nmol/L(-1); p < 0.05) and group 3 (303 nmol/L(-1); p < 0.05). Thrombin anti-thrombin III complexes and plasmin anti-plasmin complex complexes increased during CPB to significantly high levels at cessation of CPB, but there were no differences between the groups. The oxygenator with the smallest surface area and lowest priming volume (group 1) had the highest oxygen transfer rate per square meter and showed the least blood damage, as depicted by complement activation. The oxygenator with the largest blood contact surface area and improved geometric configuration (group 3) showed the lowest oxygen transfer rate per square meter. However, this oxygenator elevated oxygen partial pressure the most and reduced carbon dioxide partial pressure the most. In group 2, where a smaller venous reservoir was used, the highest blood activation was observed.
Aged↗
A4 protein in Alzheimer's disease: primary and secondary cellular events in extracellular amyloid deposition.
This study was designed to investigate the role of serum proteins, microglia, glial fibrillary acidic protein (GFAP) positive cells and dystrophic neurites in the genesis of cerebral amyloid. Using A4 protein antisera, we found an amorphous non-congophilic, form of plaque, which was not seen in Bielschowsky silver staining or Bodian impregnations. GFAP-positive glial cells, cells immunolabelled for some macrophage markers and dystrophic neurites were detected in congophilic plaques with crystalline amyloid, but not in the amorphous, non-congophilic plaques. The presence of alpha l-antichymotrypsin, complement factors and P component, but not of common serum proteins in both the amorphous and congophilic plaques, indicates that these three proteins may have a pathogenetic role in amyloid formation. Amorphous plaques may be the earlier forms of plaque and consequently, the presence of reactive cells and dystrophic neurites may be secondary phenomena.
Alzheimer Disease↗
The expression of retrovirus-like particles in psoriasis.
Retrovirus-like particles have been isolated from patients with psoriasis. Antigens crossreacting with the major internal proteins pso p27, of these particles have been demonstrated in the wall of dermal vessels and in a subfraction of cells in psoriatic lesions. The antigen has also been observed in blood lymphocytes from psoriatic patients. Pso p27 antigen and anti-pso p27 antibodies are present as complement-activating immune complexes in psoriatic scale and in the blood of patients with psoriasis and psoriatic arthritis. The potential contribution of the circulating immune complexes to the inflammatory process in psoriasis is discussed.
Antigens↗
Bullous systemic lupus erythematosus: revised criteria for diagnosis.
Blistering in systemic lupus erythematosus has been divided into three groups. A specific subgroup of 'bullous systemic lupus erythematosus' has been defined by Gammon et al. on the basis of a number of criteria. From our experience of seven patients with bullous systemic lupus erythematosus, and after reviewing the literature, we suggest that the current classification is too narrow. Our patients displayed clinical and immunohistological (based on direct and indirect immunofluorescence and Western immunoblotting) heterogeneity. Sera from two patients bound to epidermal epitopes in sodium chloride-split skin, but immunoblotting was negative. In neither of these patients could the target antigen be type VII collagen, the only antigen identified as pathogenic in this disease. Patients with epidermal binding should not be excluded from a diagnosis of bullous systemic lupus erythematosus. SLE is a disease in which there is a genetic predisposition to form antibodies to type VII collagen, along with other autoantibodies, many of which may be implicated in blistering. We suggest that the criteria for the diagnosis of BSLE should be revised. We define this disease as an acquired subepidermal blistering disease in a patient with SLE, in which immune reactants are present at the basement membrane zone on either direct or indirect immunofluorescence.
Adult↗
Diffuse intraepidermal deposition of immunoreactants on direct immunofluorescence: a clue to the early diagnosis of epidermal necrolysis.
BACKGROUND: Toxic epidermal necrolysis is a distinctive disorder that is readily identified clinically and histologically in advanced cases. Early on, however, toxic epidermal necrolysis may be difficult to identify. Some consider fixed drug eruption a limited form of toxic epidermal necrolysis. METHODS: Direct immunofluorescence was performed on biopsy material of erythematous skin lesions. RESULTS: Diffuse deposition of immunoreactants in the midmalpighian layer was noted. This finding has not been encountered in other disorders studied in our immunopathology laboratory. CONCLUSIONS: Diffuse immunoreactant deposition in the mid-epidermis should suggest a diagnosis of epidermal necrolysis either from toxic epidermal necrolysis or fixed drug eruption. Additional cases will need to be assessed to document the usefulness of this pattern for prospective diagnosis.
Aged↗
Granulocyte elastase indicates silent male genital tract inflammation and appropriate anti-inflammatory treatment.
Diagnosis of male genital inflammations plays a significant role in andrology. Although genital infections are often silent, they can severely impair male fertility. In the seminal plasma of 305 patients, immunoglobulins IgG, IgA, complement factor C3C, coeruloplasmin and the number of peroxidase-positive cells were determined in addition to conventional semen parameters and microbiological investigations. A leukocyte esterase dipstick test was also carried out. All these parameters were correlated with the granulocyte elastase determined by an enzyme immunoassay. A highly significant correlation between elastase concentrations and the other parameters indicating inflammation was observed. After anti-inflammatory treatment, elastase concentrations decreased markedly. The results showed that exact quantification of granulocyte elastase is a very specific and sensitive method to distinguish inflammatory from non-inflammatory male adnexal affections, which is appropriate for control of anti-inflammatory treatment and facilitates the diagnosis of inflammatory processes in andrology.
Adolescent↗