Neutrophil infiltration into inflammatory sites is one of the hallmarks of acute inflammation. Locally produced chemotactic factors are presumed to mediate the sequence of events leading to the infiltration at inflammatory sites.... more
Neutrophil infiltration into inflammatory sites is one of the hallmarks of acute inflammation. Locally produced chemotactic factors are presumed to mediate the sequence of events leading to the infiltration at inflammatory sites. Interleukin-8 (IL-8), a novel leukocyte chemotactic activating cytokine (chemokine), is produced by various types of cells upon stimulation with inflammatory stimuli and exerts a variety of functions on leukocytes, particularly, neutrophils in vitro. However, no definitive evidence has been presented on its role in recruiting and activating neutrophils in the lesions of various types of inflammatory reactions. We administered a highly specific neutralizing antibody against IL-8 in several types of acute inflammatory reactions, including lipopolysaccharide (LPS)-induced dermatitis, LPS/IL-1-induced arthritis, lung reperfusion injury, and acute immune complex-type glomerulonephritis. Anti-IL-8 treatment prevented neutrophil-dependent tissue damage as well as ...
Systemic lupus erythematosus is an autoimmune disease of unknown etiology. Research efforts of the last few years have mainly focused on basic molecular and cellular pathogenetic processes of the disease. Consequently, this paper reviews... more
Systemic lupus erythematosus is an autoimmune disease of unknown etiology. Research efforts of the last few years have mainly focused on basic molecular and cellular pathogenetic processes of the disease. Consequently, this paper reviews the etiopathogenetic hallmarks, such as ...
ABSTRACT The distribution of intravenously injected A-layer protein and lipopolysaccharide (LPS) purified from the outer surface of the fish pathogen Aeromonas salmonicida, was studied in Atlantic salmon. Radiolabelling was achieved by... more
ABSTRACT The distribution of intravenously injected A-layer protein and lipopolysaccharide (LPS) purified from the outer surface of the fish pathogen Aeromonas salmonicida, was studied in Atlantic salmon. Radiolabelling was achieved by conjugating the antigens to tyramine cellobiose (TC) or fluorescein isothiocyanate (FITC) which were radioiodinated either before or after conjugation. Since both TC and FITC are trapped intralysosomally at the cellular site of uptake, the ligands are advantageous in studies on tissue distribution of antigens. Injection of TC-A-layer protein and TC-LPS resulted in high specific radioactivity (cpm g−1tissue) in both head kidney and trunk kidney. In contrast, only low specific radioactivity was recovered in spleen, heart and liver. Surprisingly, use of FITC-LPS as the antigen changed the uptake to be high in both spleen and head kidney. Radiolabelled (125I-TC-) LPS and A-protein, administered by a dorsal aorta catheterisation technique, were cleared from the blood within 24 h. In immunised fish, the antibody activity against the A-layer protein was diminished even within 10 min after administration, in contrast to the level of anti-LPS antibodies which remained high. These results suggest that immune-complex formation took place at least with the A-layer protein, but the uptake of A-layer protein in the various tissues did not differ significantly in vaccinated (A. salmonicida bacterin) and non-vaccinated fish.
Immunosensors are affinity ligand-based biosensor solid-state devices in which the immunochemical reaction is coupled to a transducer. The fundamental basis of all immunosensors is the specificity of the molecular recognition of antigens... more
Immunosensors are affinity ligand-based biosensor solid-state devices in which the immunochemical reaction is coupled to a transducer. The fundamental basis of all immunosensors is the specificity of the molecular recognition of antigens by antibodies to form a stable complex. This is similar to the immunoassay methodology. Immunosensors can be categorized based on the detection principle applied. The main developments are electrochemical, optical, and microgravimetric immunosensors. In contrast to immunoassay, modern transducer technology enables the label-free detection and quantification of the immune complex. The analysis of trace substances in environmental science, pharmaceutical and food industries is a challenge since many of these applications demand a continuous monitoring mode. The use of immunosensors in these applications is most appropriate. Similarly, a series of clinical problems may be solved by continuous monitoring of certain analytes. Clinical chemists should take advantage of immunosensors in clinical diagnostics. There are many recent developments in the immunosensor field which have potential impacts. The future role of this technique in intralaboratory, as well as bedside testing, will become even more important as the clinical laboratory is faced with increasing pressure to contain costs.
Afro-Ecuadorian individuals from an area where Onchocerca volvulus is hyperendemic have been monitored for infection over the past 16 years. To determine whether in utero exposure to O. volvulus biases a child's subsequent immune... more
Afro-Ecuadorian individuals from an area where Onchocerca volvulus is hyperendemic have been monitored for infection over the past 16 years. To determine whether in utero exposure to O. volvulus biases a child's subsequent immune responses, children (9 to 16 years old) for whom the mother's infection status was known were chosen for study. Children of infected mothers (n = 19) had significantly higher levels of skin microfilariae than children of uninfected mothers (n = 13; P = 0.021). While the serum levels of O. volvulus-specific immunoglobulin G (IgG), IgG subclasses, and IgE showed no significant differences between the two groups of children, peripheral blood mononuclear cells of children of infected mothers produced higher levels of Th2-type cytokines to several parasite antigens and lower levels of Th1-type cytokines to nonparasite antigens than those of children of uninfected mothers. Thus, in utero exposure to O. volvulus has a long-term effect on the child's su...
The aim of this study was to investigate the effect of increased number and frequency of vaccination on immune complex deposition in the choroid plexus and glomeruli of non-nephrectomized and unilateral nephrectomized mice. Fifty-five... more
The aim of this study was to investigate the effect of increased number and frequency of vaccination on immune complex deposition in the choroid plexus and glomeruli of non-nephrectomized and unilateral nephrectomized mice. Fifty-five non-nephrectomized, 40 nephrectomized, and 7 control Swiss albino mice were used. Half of each group was vaccinated only with diphtheria-tetanus and the other half with multiple vaccines, which are used in pediatric practice. Each group was divided into subgroups, which were vaccinated with increasing frequency. No immune deposits were detected in the choroid plexus of any vaccinated mice. There were immune deposits in glomeruli in 2 of 55 (3.6%) of the non-nephrectomized and in 3 of 40 (7.5%) of the nephrectomized mice (P=0.199). The difference between the diphtheria-tetanus and multiple vaccine groups in non-nephrectomized (P=0.236) and nephrectomized (P=1.000) mice was not significant. A significant positive correlation between increased frequency of vaccination and glomerular immune complex deposition 8 weeks after the last immunization was detected in the multiple vaccine group of nephrectomized mice (P=0.048, r=0.447). Our results suggest that the large number and frequent doses of vaccines would not lead to immune complex deposition in choroid plexus and do not significantly increase the deposition of immune complexes in glomeruli in unilateral nephrectomized mice compared with non-nephrectomized mice.
Sjögren's syndrome is one of the most frequent autoimmune diseases. It is a chronic and systemic disorder predominantly found in women, and is characterized by the appearance of a lymphocytic inflammatory infiltrate, with dryness of... more
Sjögren's syndrome is one of the most frequent autoimmune diseases. It is a chronic and systemic disorder predominantly found in women, and is characterized by the appearance of a lymphocytic inflammatory infiltrate, with dryness of the oral cavity and eyes, secondary to involvement of the salivary and lacrimal glands. The underlying causal mechanism involves a number of factors and has not been clearly established, though an autoimmune response is known to be triggered, with the accumulation of immune complexes in the gland acini that interfere with gland function. In the oral cavity, xerostomia or hyposialia is the most disabling manifestation for patients, and is accompanied by rapidly progressing caries, candidiasis and an important worsening of buccodental health. The most important complication is a 44-fold increase in the risk of developing non-Hodgkin lymphoma, compared with the general population. The treatment of Sjögren's syndrome is limited to symptomatic managem...
Background. FcgRIIa is a low affinity receptor that has two co-dominantly expressed alleles, R131 and H131, which differ in their ability to bind immunoglo- bulin G (IgG) subclasses. Cells expressing H131 bind more efficiently complexed... more
Background. FcgRIIa is a low affinity receptor that has two co-dominantly expressed alleles, R131 and H131, which differ in their ability to bind immunoglo- bulin G (IgG) subclasses. Cells expressing H131 bind more efficiently complexed IgG2 and IgG3 than those expressing the R131 variant. The FcgRIIa polymorph- ism has been shown to be associated with lupus nephritis. Here we evaluated
The convalescence phase of severe meningococcal sepsis is complicated by immune complex reactions with arthritis being the commonest. No standard guidelines exist for management of such complications, but non-steroidal anti-inflammatory... more
The convalescence phase of severe meningococcal sepsis is complicated by immune complex reactions with arthritis being the commonest. No standard guidelines exist for management of such complications, but non-steroidal anti-inflammatory drugs and steroids have been used with varying success. We report excellent response to intravenous immunoglobulin in a child with immune complex reaction following meningococcal sepsis.
The Silent Information Regulatory proteins, Sir3 and Sir4, and the telomeric repeat-binding protein RAP1 are required for the chromatin-mediated gene repression observed at yeast telomeric regions. All three proteins are localized by... more
The Silent Information Regulatory proteins, Sir3 and Sir4, and the telomeric repeat-binding protein RAP1 are required for the chromatin-mediated gene repression observed at yeast telomeric regions. All three proteins are localized by immunofluorescence staining to foci near the nuclear periphery suggesting a relationship between subnuclear localization and silencing. We present several lines of immunological and biochemical evidence that Sir3, Sir4, and RAP1 interact in intact yeast cells. First, immunolocalization of Sir3 to foci at the yeast nuclear periphery is lost in rap1 mutants carrying deletions for either the terminal 28 or 165 amino acids of RAP1. Second, the perinuclear localization of both Sir3 and RAP1 is disrupted by overproduction of the COOH terminus of Sir4. Third, overproduction of the Sir4 COOH terminus alters the solubility properties of both Sir3 and full-length Sir4. Finally, we demonstrate that RAP1 and Sir4 coprecipitate in immune complexes using either anti-...
Due to its structure, the glomerular capillary has a filtration function since it is interposed between the blood stream and the urinary space exposed to circulating plasma proteins, which are likely to form a deposit. The role of renal... more
Due to its structure, the glomerular capillary has a filtration function since it is interposed between the blood stream and the urinary space exposed to circulating plasma proteins, which are likely to form a deposit. The role of renal biopsy is to diagnose glomerulonephritis and systemic autoimmune diseases, on the basis of two samples: one for light microscopy and the other for immunofluorescence (IF). Electron microscopy has specific indications. IF is necessary to identify immune deposits. Renal biopsy has made possible the identification and characterization of lesions such as those related to the new viral diseases that emerged over the last decade: cryoglobulinemia and hepatitis C virus (HCV), the BK virus, the positivity of the C4d marker in humoural rejection of transplants, glomerular lesions due to monoclonal immunoglobulin. Besides, the recent molecular biology techniques as applied in renal transplantation are likely to improve the matching donors/recipients, and to tr...
Background. In small vessel vasculitis and its renal- limited form, idiopathic crescentic glomerulonephritis, renal damage is characterized by pauci-immune necro- tizing crescentic glomerulonephritis (CGN) without histological evidence of... more
Background. In small vessel vasculitis and its renal- limited form, idiopathic crescentic glomerulonephritis, renal damage is characterized by pauci-immune necro- tizing crescentic glomerulonephritis (CGN) without histological evidence of immunoglobulin (Ig) deposi- tion. In some patients, however, significant amounts of immune deposits may be detected. Therefore, we evaluated the clinical significance of these immune deposits in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune
In a prospective study of 200 non-cirrhotic portal fibrosis (NCPF) patients, 7% had mild proteinuria and their renal biopsies showed mild mesangial proliferative glomerulonephritis (mes-PGN). The remaining 93% biopsies were normal.... more
In a prospective study of 200 non-cirrhotic portal fibrosis (NCPF) patients, 7% had mild proteinuria and their renal biopsies showed mild mesangial proliferative glomerulonephritis (mes-PGN). The remaining 93% biopsies were normal. However, following the insertion of a spleno-renal shunt (SRS) for portal hypertension 32% of these patients developed nephrotic syndrome in five years. Renal histology revealed mesangiocapillary glomerulonephritis (MCGN) (18.5%), mes-PGN (9%), minimal change nephropathy (3%), and chronic sclerosing GN (1.5%). Immunofluorescence showed granular deposition of IgA and C3. IgA2 was the predominant form of Ig in the glomerular deposits, indicating that IgA in the immune complexes was derived from the gastrointestinal tract. Electron microscopy revealed electron dense deposits in the mesangium. In contrast to the NCPF patients who underwent a SRS for portal hypertension, the 200 patients in our study who underwent spleno-renal shunting because of extra hepatic portal obstruction did not have renal disease, nor did they develop renal disease during the five-year post-operative follow-up. Fifty percent of the glomerulonephritis (GN) in the NCPF group progressed to renal failure in five years; 46.6% continued to have proteinuria. Low serum complement, C3 (40%) and circulating immune complexes (14.8%) were detected in the glomerulonephritis group. Our study shows that: (i) there is a high rate of the occurrence of GN following SRS in NCPF patients, but not in those with normal livers; (ii) the type of GN is primarily IgA nephropathy; and (iii) the GN could be the result of defective hepatic reticuloendothelial function in the NCPF group that is worsened by the shunting procedure.