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H Slor

Publications and source records attributed to H Slor.

At least 19 recordsLinked to original sources

Association of AUUUA-binding protein with A+U-rich mRNA during nucleo-cytoplasmic transport.

Resealed nuclear envelope (NE) vesicles from rat liver containing entrapped exogenous RNA were used to study the effect of adenosine+uridine binding factor (AUBF), present in cytosolic cell extracts, on ATP-dependent transport of A+U-rich RNA (AU+RNA) and A+U-free RNA (AU-RNA) across the NE. This factor specifically binds to A+U-rich sequences present in the 3' untranslated regions of lymphokine and cytokine mRNAs, containing overlapping AUUUA boxes (granulocyte-macrophage colony stimulating factor, interleukin-3). Addition of AUBF to the extravesicular compartment markedly increased the efflux of the in vitro transcribed, capped and polyadenylated AU+ RNAs. Export of entrapped AU- control RNA, such as beta-globin RNA, was not affected by AUBF, in contrast to chimeric AU+ beta-globin RNA containing the A+U-rich sequence of human interferon-alpha mRNA (6 reiterated AUUUA motifs). Competition experiments revealed that AUBF enhances the affinity of poly(A)-containing AU+ RNAs to the NE poly(A)-binding component (poly(A)-recognizing mRNA carrier p106), and thereby accelerates nuclear export of these RNAs. We could demonstrate that AUBF added to the extravesicular space forms stable complexes with polyadenylated AU+ RNA with relative molecular masses of about 45,000, 62,000 and 70,000 inside the vesicles or during ATP-dependent export. In addition we determined that AUBF may affect mRNA stability by protecting A+U-rich RNA against degradation by trans-acting, nuclear matrix-associated and A+U-specific endoribonuclease V.

Adenosine

Diversity and pattern of inheritance of autoantibodies in families with multiple cases of systemic lupus erythematosus.

The pattern of inheritance of autoantibodies in eight families chosen from a pool of 110 families of patients with systemic lupus erythematosus (SLE) is described. In all the eight families at least two members were already affected by SLE. In total, 19 patients and 43 first degree relatives were examined. The inheritance of a large set of antinuclear antibodies (for example, DNA, Sm, RNP, Ro, La, histones) and 16/6 idiotype seemed to be related to some unknown genetic factors but not related to HLA. The presence of numerous antinuclear autoantibodies in the serum of a subject was not necessarily associated with overt disease. The incidence of the 16/6 idiotype among patients and their relatives was low. It is not yet clear whether the 'autoantibody burden' is greater in families with multiple cases of SLE than in families with single cases.

Antibody Diversity

The effects of incubation temperature and coating procedure on the measurement of antibodies to cardiolipin.

Many laboratories have established ELISAs for the the routine detection of anti-cardiolipin antibodies (ACA). Earlier studies had indicated that assay incubation at 37 degrees C may interfere with the antigen binding capacity of these antibodies. We have reexamined this phenomenon by comparing ACA titers obtained when incubations are performed at either 37 degrees C or at room temperature (RT). In addition, the effect of coating antigen in aqueous or organic solution was compared. The sera tested included a set of recognized ACA standards and samples from 19 patients with SLE, two with primary anti-phospholipid syndrome, 71 patients with a variety of autoimmune and non-autoimmune disorders and 210 blood bank controls. The results show that while some sera do perform better under either incubation temperature there was no correlation between ACA titers and incubation temperature on a population basis either for IgG or IgM isotypes. This was seen both for positive standards and patient sera. For IgG ACA a similar phenomenon was seen if the microplates were coated with cardiolipin either in sodium carbonate or ethanol. For IgM ACA there was a significant increase in ACA titers at RT when cardiolipin was coated in ethanol. The data suggest that for most sera neither the antigen coating medium nor the assay incubation temperature are important variables in the determination of IgG ACA. Factors contributing to the influence of either variable in individual sera could not be identified.

Analysis of Variance

Antinuclear autoantibodies in healthy nonpregnant and pregnant women and their offspring.

Antinuclear autoantibodies have previously been detected in sera of healthy women although less frequently than in sera of women with autoimmune disorders. The effect of pregnancy on antinuclear autoantibody production in healthy women is as yet debatable. We present four studies in which, by employing the ELISA method, we evaluated the presence of six antinuclear autoantibodies (anti-ds DNA, anti-ss DNA, anti-poly(I), anti-cardiolipin, anti-Sm, and anti-RNP) in the sera of more than 1,000 healthy pregnant and nonpregnant women, including 196 pairs of matched maternal and cord blood sera. In all four studies healthy pregnant women did not demonstrate significantly higher prevalence rates of various serum antinuclear autoantibodies as compared to healthy non-pregnant women. All detected autoantibodies were of the IgM isotype. In only one infant (born to a healthy seronegative mother) was an autoantibody (IgM anti-ss DNA) detected. This may indicate that in certain circumstances the fetus is capable of self-production of autoantibodies.

Adolescent

Anti-Sm-RNP activity in sera of patients with rheumatic and autoimmune diseases.

The sera of various rheumatic and autoimmune diseases were examined for the presence of anti-RNP/Sm activity. An enzyme-linked immunosorbent assay (ELISA) was employed. Anti-RNP Ab's were detected in 18%, 20%, 28%, 16% of the sera of SLE, myasthenia gravis (MG), rheumatoid arthritis (RA) and thyroid diseases respectively. The anti-RNP Ab's belonged to the IgG and IgM isotypes. Most of the IgG anti-Sm antibodies were detected in SLE sera, but they were found also in two sera of MG and in one sera of RA patients. IgM anti-Sm antibodies were not found in SLE sera, but they were detected in low titer in MG, RA and autoimmune thyroid diseases. The activity against RNP and/or Sm was further confirmed by employing immunoblotting assays. In none of the patients, except those with SLE, was any clinical manifestation of SLE noted. The mere presence of anti-Sm antibodies of the IgG isotypes is not sufficient for the development of SLE, however, its presence is highly specific for SLE.

Adult

Shuttling of the autoantigen La between nucleus and cell surface after uv irradiation of human keratinocytes.

During the past years we have established that the nuclear autoantigen La shuttles between the nucleus and the cytoplasm in tumor cells after inhibition of transcription or virus infection. We reinvestigated this shuttling using primary human keratinocytes from both healthy donors and patients with xeroderma pigmentosum. Ultraviolet irradiation resulted in both an inhibition of transcription and a translocation of La protein from the nucleus to the cytoplasm. After a prolonged inhibition of transcription La protein relocated into the nucleus and assembled with nuclear storage regions. The uv-induced shuttling included a translocation to the cell surface, where La protein colocalized with epidermal growth factor receptors.

Autoantigens

Antinuclear and related autoantibodies in sera of healthy subjects with IgA deficiency.

The sera of 49 healthy IgA-deficient (SIgAD) subjects were evaluated for the presence of autoantibodies directed against 10 different nuclear and cytoskeletal antigens, as well as for the presence of the common lupus anti-DNA idiotype (16/6 Id). Twenty-nine sera were from IgG subclass-deficient subjects (4 = IgG2, 25 = IgG3), and 25 from normal healthy subjects, used as controls. The incidence of antinuclear but not anti-cytoskeletal antibodies were found to be significantly greater in the SIgAD group, as compared to the IgG-deficient subjects and the normal controls. Overall, 39% of SIgAD sera demonstrated polyreactivity, namely reactivity against more than one nuclear antigen. The incidence of specific antibody detection ranged from 37% against cardiolipin to 12% against RNP in the IgA-deficient group, albeit not with statistical significance in all cases when compared to the control group. Isotype evaluation of the antinuclear and related antibodies in the SIgAD group showed a greater tendency towards IgG. This increased incidence of autoantibody production in SIgAD may preceed the development of an overt autoimmune disease in the future.

Agammaglobulinemia

Detection of antimitochondrial antibodies: characterization by enzyme immunoassay and immunoblotting.

Mitochondrial antigens were purified from rat liver and characterized by immunoblotting. Sera from 19 well defined patients with primary biliary cirrhosis (PBC) reacted with two mitochondrial polypeptides of 68 Kd and 45 Kd. Antibodies to these antigens were not detected in any of the sera of patients with cirrhosis of the liver, chronic active hepatitis or other autoimmune diseases. The two polypeptides were derived from the soluble fraction of the mitochondrial matrix. An enzyme-linked immunosorbent assay (ELISA) employing these rat liver mitochondrial antigens is described. Positive results were obtained with all except one PBC sera (95%), five out of 47 patients with cirrhosis (11%), one out of 20 patients with chronic active hepatitis (5%), and two out of 19 patients with various autoimmune disorders (11%). The titers detected in PBC were markedly higher than those recorded in patients with other liver and autoimmune diseases. Strong correlation was found between immunoblotting and the ELISA in determining antimitochondrial antibodies. The ELISA presented is easily performed and seems to be a useful diagnostic tool for antimitochondrial antibodies in patients with PBC.

Adolescent

The detection of anti-Sm-RNP activity in sera of patients with monoclonal gammopathies.

The sera of 141 patients with monoclonal gammopathies were examined for the presence of anti-RNP and anti-Sm activities. An enzyme-linked immunosorbent assay (ELISA) was employed. Thirty-two sera were found to bind RNP while 16 bound to Sm. The anti-Sm and anti-RNP antibodies were found in sera of patients with IgG, IgM and IgA gammopathies. The activity against RNP and/or Sm was confirmed further by using purified immunoglobulins, employing competition assays and immunoblotting. Anti-Sm antibodies are regarded as being highly specific for SLE, yet none of the patients whose serum was found to contain high titres of anti-Sm/anti-RNP antibodies presented with symptoms related to SLE or other rheumatic diseases. Our results of a high incidence of anti-ribonucleoproteins activity in the serum of patients with monoclonal gammopathies support previous reports of autoantibody properties characteristic of these immunoglobulins.

Antibodies, Antinuclear

Natural autoantibodies in the serum of healthy women--a five-year follow-up.

Autoantibodies are often found among healthy individuals. The significance of these findings, regarding the potential development of overt autoimmune disease and the severity of such an eventuality, is as yet unclear. In order to elucidate these issues 506 healthy women were screened and 60 women of child-bearing age were found to posses high titres of various anti-nuclear antibodies. After a 5-year follow-up, 57 of these 60 women were found to have autoantibodies to a variety of autoantigens. Seven of the women had some symptoms that could be associated with the presence of the antibodies (i.e. arthritis, multiple abortions, Raynaud's phenomenon), however, none exhibited overt clinical signs of an autoimmune disease. Our study may point to the fact that in normal subjects (women aged 22-44 years) high titres of natural autoantibodies are not necessarily indicative of a high risk of developing an overt autoimmune condition, at least for a follow-up period of 5 years.

Adult

Autoantibody production by patients infected with Leishmania.

Sera from 29 patients with visceral leishmaniasis and 14 patients with cutaneous leishmaniasis were tested against a panel of nine nuclear antigens employing an enzyme-linked immunosorbent assay (ELISA). Anti- Sm, RNP, SS-A and SS-B antibodies were present in high titres in 83, 86, 36 and 73 per cent of the patients with visceral leishmaniasis and in 7, 14, 25 and 25 per cent of the patients with cutaneous leishmaniasis. One serum from a patient with visceral leishmaniasis which reacted strongly with Sm, RNP, SS-A and SS-B was examined by immunoblotting on extractable nuclear antigen from Hela cells. This serum binds to nine different antigenic bands (16, 23, 29, 30, 40, 50, 58, 100 and 115 kD). These same antigens were recognized by serum from a patient with systemic lupus erythematosus. The binding of visceral leishmaniasis serum antibodies to ribonucleoproteins was inhibited by prior incubation of serum with either leishmanial membrane antigens, from four different species of Leishmania, or intact cells of Leishmania donovani, implying molecular resemblance between common leishmanial antigens and ribonuclear antigens. It seems that appearance of autoantibodies to ribonucleoproteins in sera of patients infected with Leishmania is not only due to simply polyclonal activation of lymphocytes, but is also the result of a molecular mimicry between leishmanial antigens and ribonucleoproteins.

Antibodies, Antinuclear