scholarly journals Hydralazine induces Z-DNA conformation in a polynucleotide and elicits anti(Z-DNA) antibodies in treated patients

1993 ◽  
Vol 294 (2) ◽  
pp. 419-425 ◽  
Author(s):  
T J Thomas ◽  
J R Seibold ◽  
L E Adams ◽  
E V Hess
Keyword(s):  
Side Effects ◽  
Antibody Production ◽  
Dna Conformation ◽  
Hypertensive Patients ◽  
Supercoiled Form ◽  
Gel Retardation Assay ◽  
High Incidence ◽  
Dna Antibodies ◽  
Z Dna ◽  
Normal Controls

We studied the effect of hydralazine, an antihypertensive drug with lupus-inducing side effects, on the conformation of poly(dG-m5dC).poly(dG-m5dC) and a plasmid with a 23 bp insert of (dG-dC)n.(dG-dC)n sequences. Using an e.l.i.s.a. with a monoclonal anti-(Z-DNA) antibody Z22, we found that hydralazine provoked the Z-DNA conformation in poly(dG-m5dC).poly(dG-m5dC) at 250-500 microM concentration. The supercoiled form of hydralazine-treated plasmid bound to Z22 in a gel-retardation assay. To examine further whether Z-DNA could act as an inciting agent in anti-nuclear antibody production in patients, we analysed 65 sera from 25 hypertensive patients taking hydralazine and found anti-(Z-DNA) antibodies in 82% of these sera. Sera from age-matched normal controls showed no binding to Z-DNA. Data on sera drawn sequentially from four hypertensive patients showed that antibodies were present after the drug treatment. These data demonstrate the presence of a high incidence of anti-(Z-DNA) antibodies in patients treated with hydralazine and suggest that a possible mechanism for the production of autoantibodies in drug-related lupus might involve the induction and stabilization of Z-DNA by drugs.

scholarly journals Polyamine-induced Z-DNA conformation in plasmids containing (dA-dC)n.(dG-dT)n inserts and increased binding of lupus autoantibodies to the Z-DNA form of plasmids

1994 ◽  
Vol 298 (2) ◽  
pp. 485-491 ◽  
Author(s):  
T J Thomas ◽  
T Thomas
Keyword(s):  
Complex Formation ◽  
Immune Complex ◽  
Dna Conformation ◽  
Circulating Dna ◽  
Inorganic Cations ◽  
Naturally Occurring ◽  
Dna Antibodies ◽  
Z Dna ◽  
Eukaryotic Genomes ◽  
Immune Complex Formation

Blocks of potential Z-DNA-forming (dA-dC)n.(dG-dT)n sequences are ubiquitous in eukaryotic genomes. We examined whether naturally occurring polyamines, putrescine, spermidine and spermine, could provoke the Z-DNA conformation in plasmids pDHf2 and pDHf14 with 23 and 60 bp inserts respectively of (dA-dC)n.(dG-dT)n sequences using an e.l.i.s.a. Spermidine and spermine could provoke Z-DNA conformation in these plasmids, but putrescine was ineffective. For pDHf2 and pDHf14, the concentration of spermidine at the midpoint of B-DNA to Z-DNA transition was 25 microM, whereas that of spermine was 16 microM. Polyamine structural specificity was evident in the ability of spermidine homologues to induce Z-DNA. Inorganic cations, Co(NH3)6(3+) and Ru(NH3)6(3+), were ineffective. Our experiments also showed increased binding of anti-DNA autoantibodies from lupus patients as well as autoimmune MRL-lpr/lpr mice to pDHf2 and pDHf14 in the presence of polyamines. These data demonstrate that small blocks of (dA-dC)n.(dG-dT)n sequences could assume the Z-DNA conformation in the presence of natural polyamines. Increased concentrations of polyamines in the sera of lupus patients might facilitate immune complex-formation involving circulating DNA and anti-Z-DNA antibodies.

scholarly journals Neutralizing Antibodies Titers and Side Effects in Response to BNT162b2 Vaccine in Healthcare Workers with and without Prior SARS-CoV-2 Infection

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 742
Author(s):  
José Javier Morales-Núñez ◽  
José Francisco Muñoz-Valle ◽  
Carlos Meza-López ◽  
Lin-Fa Wang ◽  
Andrea Carolina Machado Sulbarán ◽  
...  
Keyword(s):  
Single Dose ◽  
Side Effects ◽  
Adverse Effects ◽  
Antibody Production ◽  
Neutralizing Antibodies ◽  
Healthcare Workers ◽  
Vaccination Program ◽  
Expected Result ◽  
Neutralizing Capacity ◽  
The Usa

The main expected result of a vaccine against viruses is the ability to produce neutralizing antibodies. Currently, several vaccines against SARS-CoV-2 are being applied to prevent mortal complications, being Pfizer-BioNTech (BNT162b2) one of the first to be authorized in the USA and Mexico (11 December 2020). This study evaluated the efficacy of this vaccine on antibody production with neutralizing capacity and its side effects in healthcare workers with and without prior SARS-CoV-2 infection and in a group of unvaccinated individuals with prior COVID-19. The main findings are the production of 100% neutralizing antibodies in both groups after the second dose, well-tolerated adverse effects, the possible presence of immunosenescence, and finally, we support that a single dose of this vaccine in individuals with prior COVID-19 would be sufficient to achieve an immunization comparable to people without prior COVID-19 with a complete vaccination program (2 doses).

scholarly journals The Impact of T Cell Vaccination in Alleviating and Regulating Systemic Lupus Erythematosus Manifestation

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Liuye Huang ◽  
Yuan Yang ◽  
Yu Kuang ◽  
Dapeng Wei ◽  
Wanyi Li ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Side Effects ◽  
Lupus Erythematosus ◽  
Clinical Symptoms ◽  
Systemic Lupus ◽  
T Cell Vaccination ◽  
Dna Antibodies

Objective. Systemic lupus erythematosus (SLE) is an autoimmune disease identified by a plethora of production of autoantibodies. Autoreactive T cells may play an important role in the process. Attenuated T cell vaccination (TCV) has proven to benefit some autoimmune diseases by deleting or suppressing pathogenic T cells. However, clinical evidence for TCV in SLE is still limited. Therefore, this self-controlled study concentrates on the clinical effects of TCV on SLE patients. Methods. 16 patients were enrolled in the study; they accepted TCV regularly. SLEDAI, clinical symptoms, blood parameters including complements 3 and 4 levels, ANA, and anti-ds-DNA antibodies were tested. In addition, the side effects and drug usage were observed during the patients’ treatment and follow-up. Results. Remissions in clinical symptoms such as facial rash, vasculitis, and proteinuria were noted in most patients. There are also evident reductions in SLEDAI, anti-ds-DNA antibodies, and GC dose and increases in C3 and C4 levels, with no pathogenic side effects during treatment and follow-up. Conclusions. T cell vaccination is helpful in alleviating and regulating systemic lupus erythematosus manifestation.

scholarly journals Thalidomide as salvage therapy for chronic graft-versus-host disease

Blood ◽  
1995 ◽  
Vol 86 (9) ◽  
pp. 3604-3609 ◽  
Author(s):  
PM Parker ◽  
N Chao ◽  
A Nademanee ◽  
MR O'Donnell ◽  
GM Schmidt ◽  
...  
Keyword(s):  
Side Effects ◽  
Complete Remission ◽  
Graft Versus Host Disease ◽  
Dose Intensity ◽  
Drug Discontinuation ◽  
Effective Agent ◽  
Host Disease ◽  
Graft Versus Host ◽  
Number Of Patients ◽  
High Incidence

Thalidomide has been reported to be an effective agent for treatment of chronic graft-versus-host disease (CGVHD). To determine the efficacy of this agent in patients with refractory CGVHD a total of 80 patients who failed to respond to prednisone (PSE) or PSE and cyclosporine (CSA) were treated with thalidomide. Sixteen patients (20%) had a sustained response, 9 with a complete remission and 7 with a partial response. Twenty-nine patients (36%) had thalidomide discontinued because of side effects, which included sedation, constipation, neuritis, skin rash, and neutropenia. Side effects were reversible with drug discontinuation except for mild residual neuritis in one case. Rashes and neutropenia have not previously been reported as thalidomide side effects when used for CGVHD treatment. We conclude thalidomide is immunosuppressive and active in the treatment of CGVHD. A high incidence of reversible side effects limited dose intensity and reduced the number of patients who could benefit from treatment.

A Long-term Retrospective Follow-up Study of Patients Treated with Prophylactic Lithium Carbonate

1987 ◽  
Vol 150 (2) ◽  
pp. 175-179 ◽  
Author(s):  
C. Page ◽  
S. Benaim ◽  
F. Lappin
Keyword(s):  
Side Effects ◽  
Complete Remission ◽  
Lithium Carbonate ◽  
Favourable Outcome ◽  
Lithium Level ◽  
Follow Up Study ◽  
High Incidence ◽  
Average Serum

Patients suffering from unipolar and bipolar affective illness, who began treatment with prophylactic lithium carbonate during a 5-year period, were followed up and 59 out of 101 interviewed. Most had been taking lithium for at least 13 years: 49% had a complete remission, 41% a partial but significant response, and 10% no response. No specific individual or illness factor was found to correlate with favourable outcome, and no correlation between average serum lithium level and outcome. No side-effects could be associated specifically with the long-term use of lithium, but there was a surprisingly high incidence of clinical hypothyroidism.

Native DNA fragments photocrosslinked to psoralen binds to anti-B and anti-Z DNA antibodies

1995 ◽  
Vol 48 (3) ◽  
pp. 215-219 ◽  
Author(s):  
Sadia Arjumand ◽  
Zarina Arif ◽  
Asif Ali ◽  
Rashid Ali
Keyword(s):  
Dna Fragments ◽  
Dna Antibodies ◽  
Z Dna

scholarly journals Interleukin 6 Dependence of Anti-DNA Antibody Production: Evidence for Two Pathways of Autoantibody Formation in Pristane-induced Lupus

1998 ◽  
Vol 188 (5) ◽  
pp. 985-990 ◽  
Author(s):  
Hanno B. Richards ◽  
Minoru Satoh ◽  
Melody Shaw ◽  
Claude Libert ◽  
Valeria Poli ◽  
...  
Keyword(s):  
Disease Activity ◽  
Antibody Production ◽  
High Titer ◽  
Enzyme Linked Immunosorbent Assay ◽  
Autoantibody Production ◽  
Crithidia Luciliae ◽  
Dsdna Antibody ◽  
Dna Antibodies ◽  
Antibody Levels ◽  
Phosphate Buffered Saline

Pristane induces a lupus-like syndrome in nonautoimmune mice characterized by the development of glomerulonephritis and lupus-associated autoantibodies. This is accompanied by overproduction of interleukin (IL)-6, a cytokine linked with autoimmune phenomena. The goal of this study was to evaluate the role of IL-6 in autoantibody production in pristane-induced lupus. BALB/cAn IL-6–deficient (−/−) and –intact (+/+) mice were treated with pristane or phosphate-buffered saline, and autoantibody production was evaluated. Pristane induced high levels of immunoglobulin (Ig)G anti-single-stranded DNA, –double-stranded (ds)DNA, and -chromatin antibodies in IL-6+/+, but not IL-6−/− mice by enzyme-linked immunosorbent assay. High titer IgG anti-dsDNA antibodies also were detected in sera from +/+, but not −/−, mice by Crithidia luciliae kinetoplast staining. The onset of IgG anti-dsDNA antibody production in +/+ mice occurred >5 mo after pristane treatment, well after the onset of nephritis, suggesting that these antibodies are not directly responsible for inducing renal disease. In contrast to anti-DNA, the frequencies of anti-nRNP/Sm and anti-Su antibodies were similar in pristane-treated IL-6−/− and IL-6+/+ mice. However, levels were higher in the +/+ group. These results suggest that IgG anti-DNA and chromatin antibodies in pristane-treated mice are strictly IL-6 dependent, whereas induction of anti-nRNP/Sm and Su autoantibodies is IL-6 independent. The IL-6 dependence of anti-DNA, but not anti-nRNP/Sm, may have implications for understanding the patterns of autoantibody production in lupus. Anti-DNA antibodies are produced transiently, mainly during periods of disease activity, whereas anti-nRNP/Sm antibody levels are relatively insensitive to disease activity. This may reflect the differential IL-6 dependence of the two responses.

Effects of the O2' hydroxyl group on Z-DNA conformation: structure of Z-RNA and (araC)-[Z-DNA]

Biochemistry ◽  
1989 ◽  
Vol 28 (12) ◽  
pp. 4923-4928 ◽  
Author(s):  
Mai Kun Teng ◽  
Yen Chywan Liaw ◽  
Gijs A. Van der Marel ◽  
Jacques H. Van Boom ◽  
Andrew H. J. Wang
Keyword(s):  
Dna Conformation ◽  
Hydroxyl Group ◽  
Z Dna

Sodium and Renin in the Hypertension of Early Renal Disease

1978 ◽  
Vol 55 (s4) ◽  
pp. 301s-303s ◽  
Author(s):  
S. F. Wong ◽  
M. I. Mitchell ◽  
V. Robson ◽  
R. Wilkinson
Keyword(s):  
Blood Pressure ◽  
Renal Disease ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Renin Activity ◽  
Exchangeable Sodium ◽  
Hypertensive Patients ◽  
Body Build ◽  
Activity Response ◽  
Normal Controls

1. Plasma renin activity, response to saralasin and exchangeable sodium have been measured in 43 patients with early renal disease. 2. Blood pressure was directly proportional to plasma renin activity. However, mean plasma renin activity was lower in patients with renal disease than in normal controls. 3. Blood pressure fell in response to saralasin infusion in proportion to the pre-infusion plasma renin activity. 4. Exchangeable sodium in hypertensive patients with renal disease did not exceed that in normotensive patients in contrast to earlier reports. Discrepancies may arise from the difficulty in interpreting measured exchangeable sodium in relation to body build.

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