Stanisław Szymaniec

Retinal Antigens Are Recognized by Antibodies Present in Sera of Patients with Multiple Sclerosis

Multiple sclerosis (MS) is frequently accompanied by visual symptoms including those related to retinal disorders. Since they may be a consequence of an autoimmune reaction, we examined whether sera of patients with diagnosed MS and changes in visual-evoked potentials contain antibodies against retinal antigens (retAgs). Immunoblot analysis revealed that MS sera recognized mainly a 46-kD antigen, a 41-kD antigen, retinal arrestin, to a smaller extent also 70-, 56-, 43-, and 36-kD proteins. Patients whose sera showed the highest reactivity with 41- and 46-kD antigens had deficiencies in visual acuity, visual fields, ophthalmoscopy, and electroretinograms. Our observation suggests that antibodies to these retAgs may play a role in the origin of ophthalmologic impairment in MS.

Cancer-associated retinopathy in patients with breast carcinoma

Introduction:Cancer-associated retinopathy (CAR) is a paraneoplastic neurological syndrome resulting in progressive loss of vision and clinical signs of retinal degeneration. It is associated with various types of cancer and is also considered to be an autoimmune disorder that involves cross-reaction between autoantibodies and retinal proteins. The aim of this study was to establish whether immunoreactivity to retinal antigens (RAs) observed in patients with breast cancer is accompanied by any visual impairments.Materials and Methods:Sera of 295 patients with diagnosed breast cancer were screened for the presence of anti-RAs antibodies using immunoblotting. Cellular immunoreactivity to RAs present in retinal extracts and to purified recoverin and arrestin was determined by means of a lymphocyte proliferation assay. Six patients with high-titer antibodies to RAs then underwent ophthalmic and neurological examinations.Results:Four serum samples contained high-titer antibodies to a 46-kDa protein, most probably retinal α-enolase, three had antibodies to a 48-kDa protein identified as retinal arrestin, while 56-, 43-, 41-, and 34-kDa antigens were recognized only by one serum sample each. Moreover, weak cellular response to all the RAs tested was observed in one patient and another patient responded only to retinal extract. Two of the examined patients displayed symptoms of CAR.Conclusions:Immunoreactivity to RAs in patients with breast cancer may also be present in cases without clinical signs of CAR.

Proinflammatory and atherogenic activity of monocytes in Type 2 diabetes

UNLABELLED Cytokines secreted by the monocyte-macrophage system play a key role in the progression of atherosclerotic lesions in Type 2 diabetes. The objectives of this study were to assess the influence of cytokine gene expression in monocytes from patients with Type 2 diabetes on direct markers of endothelial injury with regard to clinically manifest atherosclerosis. METHODS Monocytes from 58 patients with Type 2 diabetes and from 22 age-matched healthy volunteers of a control group were isolated in order to assess expression of tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6, IL-8 and IL-10 cytokines (RTPCR, Applied Biosystems). Thrombomodulin concentration was determined using a Diagnostica Stago Immunoenzymatic assay, and circulating endothelial cell numbers were assayed using immunofluorescence studies with CLB-HEC19 antibodies. RESULTS In 28 patients, TNFalpha expression in monocytes was observed. In these patients, as compared to those with undetectable levels of this cytokines expression, higher hemoglobin A(1c) (P=.012) and thrombomodulin (P=.005) concentrations were found. IL-8 expression was determined in 36 patients. Higher expression of TNFalpha (P=.048) and IL-8 (P=.049) was detected in patients with peripheral arterial disease in contrast to those free from this complication. CONCLUSION TNFalpha and IL-8 play a significant role in the proatherogenic activity of monocytes in Type 2 diabetes. The TNFalpha-connected activity of monocytes may directly determine endothelial dysfunction and injury. The location of atherosclerosis should be taken into account in the assessment of the proinflammatory activity of peripheral blood monocytes.

Antibodies to 46-kDa retinal antigen in a patient with breast carcinoma and cancer-associated retinopathy

Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome usually associated with small-cell lung carcinoma and serum autoantibodies against recoverin. We report the breast cancer woman with visual impairments and electrophysiological abnormalities characteristic of CAR. Her serum contained high-titer antibodies against α-enolase but not against other retinal proteins. This suggests that anti-enolase antibodies could be responsible for the development of CAR symptoms.

Serological characterization of anti-endotoxin serum directed against the conjugate of oligosaccharide core of Escherichia coli type R4 with tetanus toxoid

The covalent conjugate of oligosaccharide core of Escherichia coli type R4 with tetanus toxoid was prepared using reaction of reductive amination. The neoglycoconjugate was a good immunogen in rabbits yielding a high level of anti-lipopolysaccharide (LPS) antibodies of the IgG class. It was found that antiserum was able to react with the smooth LPS molecules of identical (R4) or related (R1) core type. The reactions were shown in the enzyme-linked immunosorbent assay and the immunoblotting test. Flow cytometry showed that anti-core antibodies reacted with LPS present on intact, live, smooth bacteria labelling more than 90% of cells. The anti-OS R4-TT serum used for in vitro studies showed high endotoxin neutralization activity. The serum inhibited endotoxin-induced tumor necrosis factor alpha and nitric oxide synthesis by the J-774A.1 cell line and attenuated pulmonary retention of YAC-1 cells.

Elevated levels of anti‐endotoxin antibodies in patients with bilateral idiopathic acute anterior uveitis

Purpose:  Endotoxins have been proved to be responsible for acute anterior uveitis (AAU) in animals in a well‐established experimental model of endotoxin‐induced uveitis (EIU). The purpose of our study was the detection of antibodies against endotoxins of selected enterobacteria in the serum of patients with idiopathic AAU and searching for correlations between the levels of these antibodies and the presence of HLA‐B27 antigen as well as characteristic signs of EIU such as bilaterality and the absence of spontaneous recurrences of the disease.

Selectivity of Antiproliferative Effects of Dialkyltin Compounds in Vitro and in Vivo

The inhibition of proliferation of thymocytes in vivo and in vitro is one of the earliest and most prominent biological effects caused by dialkyltin compounds. A single dose of dibutyltin dichloride (DBTC) or dioctyltin dichloride (DOTC) decreased the mitotic activity of thymocytes in mice and rats 1 to 7 days after administration. The inhibition of the mitotic rate of thymocytes was followed by a decrease of the thymus weight and thymocyte count. There was a difference in the time course of thymus atrophy induced by DOTC or glucocorticoids (Fig. 1). This difference could be explained by the additional cytolytic activity of glucocorticoids whereas the dialkyltin compounds induce the thymus atrophy solely by antiproliferative activity.