The mechanisms of action of intravenous immunoglobulin (IVIg) in autoimmune diseases include modulation of cytokine levels. We examined therefore whether direct infusion of abnormally high levels of ...13 different cytokines or cytokine-inhibitors within 5 different IVIg preparations have any role in modulation of their levels. None of the measured cytokines in any of the IVIg preparations tested were above the normal levels, and regarding some no traces could be detected. Hence, modulation of cytokine levels following IVIg therapy involves other mechanisms such as interference with their secretion or cytokine-specific blocking antibodies, rather than direct infusion of cytokines.
The aim of this study was to examine the presence of antibodies to GM1 and sulfatide in various IVIg preparations. Five brands of commercially available human IVIg (Sandoglobulin, Isiven, Cytogam, ...Omrigam and Cutter) were examined and compared. Serial dilutions of each of the above preparations were prepared at a working range of 0.009 to 25.0 mg/ml IVIg, and screened by a standard 96-well microplate EIA for autoantibodies to the ganglioside GM1 and to the glycolipid sulfatide. The various IVIg preparations (Omrigam, Cytogam, Sandoglobulin, Isiven), except for Cutter IVIg, contained low to medium titers of the autoantibodies tested. Omrigam and Cytogam IVIg contained low titer of antibodies to GM1, and medium-titer of antibodies to sulfatide, whereas Sandoglobulin and Isiven contained only low-titer of autoantibodies to sulfatide. The presence of natural autoantibodies to myelin in human sera may explain the presence of the tested antibodies within IVIg preparations. Measurements of antibodies to ganglioside and glycolipid in sera of Guillain-Barré patients immediately following IVIg, would probably not reveal antibody decrease. Alternatively, long-term (several weeks) follow-up of titers might result in their modification due to inhibition of antibodies production by IVIg.
Factor XI deficiency is an hereditary coagulopathy that is usually associated with milder tendency to bleeding with comparison to hemophilia A. While the failure of stable fibrin clot formation may ...lead to bleeding, it is speculated that the same process may provide a protection against thrombosis of injured arteries due to atherosclerotic plaque rupture. Whereas 2 studies indicate that hemophiliacs have decreased mortality rate from cardiovascular diseases, there is no similar data regarding factor XI deficiency patients. In here we report about 3 patients with severe factor XI deficiency who have a long-standing history of thromboembolic phenomena: 2 patients with myocardial infarctions, and one patient with transient ischemic attacks. We discuss the possible role of factor XI in thrombosis, and whether its deficiency may protect patients from thromboembolic phenomena.
The aim of this study was to determine whether treatment of patients with immune thrombocytopenic purpura (ITP) with intravenous immunoglobulin (IVIg) is associated with a modification in the ...antiplatelet glycoprotein (GP) antibodies (Abs). Fourteen patients with ITP (11 females and 3 males, mean age 36.6 years, range 18-72) received one to four IVIg treatment courses. The preparation used was ISIVEN that was given in a dose of 2 g/kg body weight in a 5-day schedule and in monthly intervals. Levels of IgG, IgM and IgA isotypes of Abs to GPs IIb/IIIa and Ib/IX were measured before the treatment, and before and after each treatment course. Two patients did not respond to IVIg, 6 had a temporary response, 5 had a sustained response and 1 patient responded well to the treatment but was lost to follow-up. The patients had a high prevalence of serum Abs directed against GPs IIb/IIIa and Ib/IX before the treatment, and the mean IgG isotype levels of both Abs increased after each treatment course, and decreased again before the following course began. Whenever high Ab levels of either isotype (> 10 U/ml) were detected before the treatment, they were significantly decreased before the last treatment course. The elevated levels of IgG Abs to IIb/IIIa and Ib/IX after every course are probably a result of displacement of these Abs from Fc receptors by the IVIg, rather than of exogenous infusion of these Abs contained within the IVIg, whereas the decrease in high Ab levels after a few treatment courses results from the immunomodulatory effects of IVIg: suppression of Ab formation, and the presence of anti-idiotypes.
Any chronic inflammatory condition of the middle ear may bring about bone destruction. Today, in the antibiotic era, this destruction concerns mostly the ossicular chain. Any one of the ossicles or ...all of them together may be partially damaged or completely destroyed (Sadé et al, 1981). Hearing is usually impaired if the stapes or the incus or both of them are damaged. To overcome the resulting hearing deficit, various surgical techniques, using various materials, have been introduced, with various degrees of success. The most problematic situation encountered surgically is the one in which the stapes is missing, and it is with this situation that the present study deals. The surgical solution so far advocated has been in the form of a surgical bridge or columella between the mobile footplate and the drum. The columella (Fig. 1) is made out of bone or some non-organic biocompatible material. Often, however, this solution is not very successful, for two reasons: A. Instability of the columella (prosthesis) is often unavoidable because of its slim attachment to the footplate; B. Biologically, an incompatibility between the drum and the prosthesis is all too often present, when the latter is made of plastic materials. These columellas have been found, sooner of later, to extrude. It is the purpose of this communication to report a new technique and a new concept, which tries to overcome the above shortcomings, using a different type of stapes-replacing prosthesis.
This is a description of a new stapes replacement prosthesis (SRP), which we term "Tabor". The prosthesis has two parts--the lower part is made of a broad inorganic, biocompatible material (Teflon) ...base, which fits and covers most of the footplate, ensuring maximal stability. The upper part of the prosthesis is made of autograft or homograft bone--usually a malleus head, the contact of which with the drum prevents extrusion. Eleven out of 12 ears operated with this prosthesis were successful--the average postoperative air conduction going up 33 dB (15-50), leaving an average of 18 dB (5-30) air-bone gap. The bone conduction also improved, from an average of 21 dB (10-30) to an average of 14 dB (10-25).
The effects that three different growth inhibitory cytokines exert on expression and function of members of the Jun family were studied in this work. M1 myeloblastic cells were chosen for this ...purpose because of their high growth sensitivity to interleukin 6 (IL-6), transforming growth factor beta 1 and alpha- and beta-interferons. It is reported here that IL-6 elevated the junB and c-jun mRNA levels and induced the formation of a novel DNA-protein complex with high sequence specificity to 12-O-tetradecanoylphorbol-13-acetate response element (TRE) oligonucleotides. This IL-6 induced TRE binding complex was abolished by anti-Jun specific antibodies and was efficiently competed by an oligonucleotide that comprises the mouse homologue of a previously described human c-myc negative DNA element. It persisted in cells for at least 48 h after IL-6 treatment and failed to be induced by alpha- and beta-interferons or by transforming growth factor beta 1, which affected differently the pattern of jun mRNA expression. To further explore regulatory and functional aspects of this induced TRE binding activity, an IL-6 resistant M1 clone was isolated and further analyzed. This clone carried a postreceptor deficiency that abrogated completely the growth inhibitory responses to IL-6 but did not interfere with the induction of two differentiation related cell surface markers. Interestingly, the IL-6 resistant clone had lost two molecular responses to IL-6, induction of TRE binding activity and suppression of the c-myc gene. The data correlate the IL-6 induced AP1 activity with the suppression of c-myc and growth inhibition.
