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H Dang

Publications and source records attributed to H Dang.

90 records · Page 5Linked to original sources
PubMed1987

Autoantibodies of various specificities encoded by genes from the VH J558 family bind to foreign antigens and share idiotopes of antibodies specific for self and foreign antigens.

We examined the binding to foreign antigens and the expression of crossreactive idiotypes by a panel of 20 murine monoclonal autoantibodies encoded by V genes from the VH J558 family. 9 of 20 antibodies bound to foreign antigens such as bacterial polysaccharides, poly(Glu50, Tyr50), poly(Glu54,Lys37,Phe9), arsonate, and lysozyme, known to interact with antibodies encoded by genes from the VH J558 family. A high proportion of our panel of autoantibodies expressed crossreactive idiotypes originally borne by monoclonal rheumatoid factors, anti-Sm, and anti-DNA antibodies, all encoded by V genes from the VH J558 family. Some of these VH J558+ autoantibodies shared crossreactive idiotypes with VH J558+ antibodies directed against foreign antigens such as influenza virus hemagglutinin, poly(Glu60,Ala30,Tyr10), arsonate, and dextran. The implications of these findings are discussed with respect to the process of activation of self-reactive clones.

Animals↗
PubMed1987

Interleukin 2, T cell receptor and sex hormone studies in autoimmune mice.

Systemic lupus erythematosus (SLE) is a disease of immune dysregulation in which B cell hyperactivity and T cell deficiency are important characteristics. Sex factors also play a major role in the pathogenesis based on the physiologic effects of estrogen in promoting immunologic hyperactivity. Our findings suggest that a posttranscriptional mechanism is responsible for the functional interleukin 2 (IL-2) defect since transcription of the IL-2 message occurs after mitogenic stimulation. The proliferating cell in the MRL/lpr mouse model of lupus may be an immature T cell. The T cell receptor in these mice has a lower molecular weight than normal. This aberrant T cell receptor might be explained by a defect in glycosylation. The administration of estrogen to pregnant mice late in gestation results in offspring with a permanently altered immune system. These mice develop features of autoimmunity similar to those that occur spontaneously in genetically susceptible autoimmune mice. This phenomenon may have etiopathological significance for familial SLE.

Animals↗
PubMed1987

A common idiotype expressed on a murine anti-Sm monoclonal antibody and antibodies in SLE sera.

A rabbit anti-idiotypic antiserum made against a murine monoclonal anti-Sm autoantibody (Y2) was used in a solid-phase radioimmunoassay to investigate idiotypic cross-reactivity among anti-Sm antibodies present in sera from patients with systemic lupus erythematosus. Sera from 25 of 51 SLE patients (49%) containing anti-Sm antibodies were positive for this Y2 idiotype compared to only one of 22 normal human sera. Nine of 28 SLE patients (32%) whose sera were anti-Sm negative were also positive for the Y2 idiotype in low titre. Binding was not due to rheumatoid factor-like activity but was specific for the Y2 determinant and could be eliminated by absorption with Y2 monoclonal antibodies. The anti-idiotypic antibody blocked the ability of 12 of 25 anti-Sm positive lupus sera to bind Sm. Conversely, Sm antigen inhibited the binding of anti-idiotypic antibody in nine of 12 lupus sera.

Animals↗
PubMed1986

Monoclonal antibody specific to acid phosphatase isoenzyme 4.

Prostatic acid phosphatase isoenzyme 4 was purified by ion exchange column chromatography, followed by high pressure liquid chromatography. The highly purified enzyme was used to produce monoclonal antibody from immunized BALB/c mice. The antibody was specific to isoenzyme 4, with negligible affinity to isoenzyme 2. The specificity of the monoclonal antibody was evaluated by Western blot analysis and by inhibition of radioimmunoassay. Immunohistochemistry method using the antibody to isoenzyme 2 showed heavy staining on the cell surface in contrast to the even staining throughout the cytoplasm when monoclonal anti-isoenzyme 4 was used. These results reflect the secretory nature of isoenzyme 2 and the non-secretory nature of isoenzyme 4.

Acid Phosphatase↗
PubMed1986

Shared idiotypes and restricted immunoglobulin variable region heavy chain genes characterize murine autoantibodies of various specificities.

The study of the Ig variable region heavy chain (VH) genes used to encode antibodies specific for self-epitopes from murine hybridomas showed that three VH families are primarily utilized: VH J558, the largest family, and VH QPC52 and VH 7183, the families most proximal to the Ig joining region heavy chain genes. These monoclonal autoantibodies express cross-reactive idiotopes shared by rheumatoid factors and antibodies specific for Sm. The expression of these idiotypes is independent of major histocompatibility complex and Ig constant region heavy chain haplotypes, self-antigen specificity, and even the VH gene family utilized. Though the experiments described here are limited to murine autoantibodies, similarities exist between murine and human autoimmune diseases. Studies that aim to investigate the relationship between VH gene expression and the presence of cross-reactive idiotypes among human autoantibodies should enable us to better understand the mechanisms of autoimmunity and self-tolerance.

Animals↗
PubMed1986

Shared idiotypes and restricted VH genes among murine autoantibodies of various specificities.

The autoantibodies studied here express cross-reactive idiotypes despite the fact that they are heterogeneous with respect to combining site. Furthermore, the presence of cross-reactive idiotypes is independent of the major histocompatibility complex, VH gene usage, and isotype. Similarly, VH gene usage shows that autoantibodies are derived from a restricted number of VH gene families. This restriction is independent of antigen specificity as well as the method of induction (i.e., spontaneous vs. induction). The observation that the VH 7183 gene is predominantly used suggests that certain autoantibodies may be derived from a unique set of B cells such as the Ly1+ B cells. It has been reported that these B cells secrete a high percentage of IgM autoantibodies. The studies reported here may provide greater insight into the genetic and immunoregulatory mechanisms by which autoantibodies arise. The precise mechanisms are not known but may involve both molecular (i.e., VH gene usage) and extracellular (i.e., idiotypic recognition) events.

Animals↗
PubMed1986

Alteration of acid phosphatase isoenzyme in a human prostatic cancer cell line.

The acid phosphatase (AcP) isoenzyme in a human prostatic cancer cell line was compared to that of prostatic tissue extract by electrophoresis. The major isoenzyme by prostatic tissue extract is the AcP isoenzyme 2, while only AcP isoenzyme 4 (AcP-4) was observed in the human prostatic cancer cell line. A monoclonal antibody specific to AcP-4 was used to investigate the ultrastructural distribution of AcP-4 in a prostatic cancer cell line. The peroxidase staining pattern indicates that AcP-4 is synthesized on bound ribosomes, discharged into the cisternae of rough endoplasmic reticulum, transported to the cisternae of Golgi apparatus for concentration and packaging, and transferred to the secretory vesicles for exocytosis. It is well known that synthesis and secretion of AcP-2 are the major characteristics of the highly differentiated prostatic epithelial cells. The present data demonstrate the loss of this specific function in the prostatic cancer cell line. Instead of AcP-2, the dedifferentiated cancer cell line synthesizes and secretes AcP-4, which is a common AcP isoenzyme of many nonprostatic tissues.

Acid Phosphatase↗
PubMed1985

Monoclonal anti-poly(rA) hybridoma antibodies from an autoimmune MRL/MpJ-lpr/lpr mouse.

Three B cell hybridomas were produced by the fusion of spleen cells from a 5 month old MRL/Mp-lpr/lpr mouse with the myeloma cell line, NS-1. By competitive inhibition, all three monoclonal antibodies (MoAb) were specific for poly(rA) and were inhibited to a lesser extent by dDNA, nDNA, poly(rI) and poly(rC). Moreover, the three MoAb were not inhibited by mononucleosides and the nucleotide, ATP. Competitive inhibition, using poly(rA) of defined lengths, showed that the recognition site among the MoAb varied, one demonstrating binding of poly(rA) as small as two bases in length. This study suggests that the spontaneous autoimmune repertoire to poly(rA) is restricted as compared to other monoclonal autoantibodies to nucleic acids, but contains within itself microheterogeneity.

Animals↗
PubMed1985

Anti-idiotypic antiserum to monoclonal anti-Sm inhibits the autoantigen-induced proliferative response.

Anti-idiotypic sera were produced in BALB/c mice against three established monoclonal anti-Sm antibodies. Inhibition assays showed that the anti-idiotypic antibodies recognized determinants that were present on all three monoclonal antibodies but not on normal mouse IgG from unimmunized BALB/c mice or myeloma proteins. Normal (+/+) and autoimmune (lpr/lpr) MRL/MpJ or C3H/HeJ mice were immunized with Sm in complete Freund's adjuvant. Immune T cells from the draining lymph nodes proliferated in response to the addition of Sm in vitro. Anti-idiotypic serum added to these cultures inhibited the proliferative response by 50 to 70%, whereas normal BALB/c serum had no effect. This inhibition of proliferation was antigen specific, because the anti-idiotypic serum did not inhibit the T cell proliferative response to an irrelevant antigen, TNP-KLH, or ovalbumin. Kinetic studies showed that the anti-idiotypic serum inhibited an early event in antigen-induced proliferative response, because the addition of serum late in culture did not cause any significant reduction in proliferation. The reduced proliferative response was due to direct action of the anti-idiotypic serum on the Lyt-1+, 2- T cell population.

Animals↗
PubMed1984

The in vivo and in vitro glomerular deposition of isolated anti-double-stranded-DNA antibodies in NZB/W mice.

Employing a hydroxyapatite double-stranded (ds) DNA column for affinity chromatography, anti-ds-DNA antibodies were isolated from the sera of aging NZB/W mice. These antibodies were radiolabeled and injected intravenously into NZB/W mice at various ages. Significant deposition of radiolabeled antibodies were shown to occur in NZB/W mice 4 months of age and older. While the injected antibodies displayed heterogeneity in their isoelectric points (pI's), those antibodies which bound to the kidney were restricted to a more alkaline pI range. Glomerular cultures were prepared from NZB/W mice at various ages and incubated with radiolabeled anti-ds-DNA antibodies with restricted pI's. Antibodies having pI's between 7 and 9 bound in vitro to glomeruli obtained from 9-month-old NZB/W mice but not to glomeruli obtained from 2-month-old mice. In contrast, antibodies with pI's between 5 and 7 were unable to bind to glomeruli obtained from either age group. An exchange between free antibodies and antibodies bound to glomeruli was also demonstrated to occur in vitro. These findings suggest the presence of subpopulations of anti-ds-DNA antibodies which preferentially bind to glomeruli containing immune complexes.

Aging↗
PubMed1984

Defective LN cell proliferative response to Sm antigen in mice bearing the lpr gene.

Several normal and lpr/lpr congenic mouse strains were immunized with an autoantigen (Sm) and a conventional antigen (PPD) and tested for their respective in vitro proliferative responses. All normal strains of mice demonstrated a brisk proliferative response to Sm and PPD on days 3 and 5 of culture. Two month old mice bearing the lpr gene demonstrated a proliferative response to the two antigens only on day 3, while by day 5 of culture, the proliferative response was markedly diminished. Mixing experiments between +/+ and lpr/lpr Sm primed lymph node cells ruled out the influence of a suppressor cell within the lpr/lpr population at day 5. The inability to sustain an in vitro proliferative response to antigen in young lpr/lpr mice was not due to an overall T cell defect nor to in vitro cell death since Con A stimulation and viability were the same in cultures containing lpr/lpr and +/+ LN, cells, respectively. The primary defect may be partly attributed to a defect in interleukin-2 (IL-2) production and response. By day 5 of culture, lpr/lpr supernatants contained much lower levels of IL-2 activity compared to supernatants from +/+ cultures. The addition of exogenous IL-2 was only moderately successful in improving the response falling far below that seen when IL-2 was added to +/+ cultures. This study demonstrates a decrease in autoantigen-induced T cell proliferation in mice that spontaneously produce autoantibodies to that antigen.

Animals↗
PubMed1983

Deficient T-cell mitogen response in murine experimental autoimmune myasthenia gravis: a defect in the adherent cell population.

T-Lymphocyte number and functions are often reduced, while B-lymphocyte function is often increased in patients with autoimmune disorders. To study the mechanisms responsible for these T-cell malfunctions in autoimmunity we adapted the murine experimental autoimmune myasthenia gravis (EAMG) model. Splenocytes from C57BL/6 mice immunized with acetylcholine receptors (AChR) in complete Freund's adjuvant (CFA) produced approximately half the amount of concanavalin A (Con A)-induced interleukin 2 (IL-2) as did splenocytes of CFA-inoculated controls. Further, AChR plus CFA-immunized splenocytes showed a marked reduction in T-cell proliferative responses induced by Con A or phytohemagglutinin when compared with CFA-inoculated controls. By contrast, lipopolysaccharide-induced B-cell function is preserved. Deficient Con A splenic T-cell response is seen early after secondary inoculation with CFA or AChR in CFA. T-Cell recovery occurs in CFA-inoculated mice but not in AChR plus CFA-inoculated mice. Defective Con A splenic T-cell response seen early after secondary immunization with CFA or AChR in CFA is due to the presence of a defective splenic adherent cell population. Moreover, defective Con A splenic T-cell response seen after established autoimmunity to AChR in EAMG is also due to the presence of a defective splenic adherent cell population.

Animals↗
PubMed1983

Molecular and antigenic nature of isolated Sm.

The Sm antigen was isolated and purified from calf thymus nuclear extract by affinity chromatography. The affinity columns were made with serum antibodies from an SLE patient or an anti-Sm monoclonal antibody derived from a hybridoma cell line. Proteins eluted from these two columns had m.w. of 58,000 and 35,000 by SDS polyacrylamide gel electrophoresis. The natural conformation of this antigen appears to be 95,000 in m.w. with the 58,000 particle containing the Sm antigenic determinant. The affinity column-purified antigen detected by the human anti-Sm antibodies is also recognized by anti-Sm antibodies in murine lupus serum, as shown by solid-phase radioimmunoassay. This study 1) demonstrates the molecular and antigenic nature of the Sm antigen and 2) compares the anti-Sm binding capabilities of antibody populations present in sera from SLE patients and from MRL lpr/lpr mice.

Animals↗
PubMed1982

A comparison of anti-DNA antibodies from serum and kidney eluates of NZB x NZW F1 mice.

The qualitative aspects of anti-DNA antibodies from the serum and those eluted from the kidney of (NZB x NZW)F1 (B/W) mice were evaluated in terms of their class and subclass specificity, avidity and isoelectric profile. Serum anti-DNA binding was demonstrated in both the IgG and IgM classes. In addition, all subclasses of IgG studied (IgG1, IgG2a, and IgG2b) were shown to bind DNA. Avidity measurements indicate that the avidity of isolated serum IgG for 125I labeled DNA decreases with age in B/W mice, while the avidity of isolated serum IgM remains relatively unchanged. Anti-DNA antibodies eluted from kidneys were found to be predominantly of the IgG1 and IgG2a subclasses. Equal amounts of both high and low avidity antibodies to DNA were demonstrated in the kidney eluates at all ages studied. Furthermore, the dissociation curves of these antibodies remained relatively unchanged with age. The isoelectric spectrum of serum antibodies to DNA obtained from mice at 4 to 11 months of age demonstrated considerable heterogeneity covering the pH range of 6 to 8.5. In contrast, the anti-DNA antibodies eluted from the kidney are slightly more basic in nature having isoelectric points between 7.2 to 9.0. This study suggests that distinct subpopulations of anti-DNA antibodies exist and that these may play an important role in the development of murine lupus nephritis.

Animals↗
PubMedDate not supplied

Strangulated traumatic diaphragmatic hernia simulating a subphrenic abscess.

Traumatic diaphragmatic hernias can be difficult to diagnose because of their varied clinical and radiologic signs and because patients may not present with symptoms for months to years following the injury. We report a case of a delayed presentation of a traumatic diaphragmatic rupture through which a portion of the stomach herniated and simulated a large subphrenic abscess.

Adult↗
PubMedDate not supplied

Pooled human immunoglobulins contain anti-idiotypes with reactivity against the SLE-associated 4B4 cross-reactive idiotype.

OBJECTIVE: To identify anti-idiotype antibody activity against a regulatory anti-Sm idiotype (4B4) in pooled human IgG (IVIG). METHODS: ELISA were used to determine anti-idiotype antibody activity in IVIG. RESULTS: Anti-idiotype antibody activity to 4B4 was detected in IVIG. The anti-idiotypic activity in IVIG could be inhibited by antigen, Sm, and rabbit anti-idiotypic antiserum. The idiotypic binding activity was predominately directed against the 4B4 VH region. CONCLUSION: IVIG contains antibodies against a lupus-associated crossreactive idiotype. These antibodies represent Ab2 beta type antibodies. The anti-idiotypic activity in IVIG may be relevant to the efficacious use of IVIG in treating rheumatic diseases.

Animals↗
PubMedDate not supplied

Inappropriate apoptosis of salivary and lacrimal gland epithelium of immunodeficient NOD-scid mice.

OBJECTIVE: The lesion is Sjögren's syndrome consists of lymphocytic infiltration and has a pathology characteristic of the potential apoptotic death of salivary gland secretory epithelial cells. To examine the role of the glandular epithelial cells in the pathogenesis of autoimmune exocrinopathy, we studied Fas and Fas ligand (FasL) expression and quantitated the levels of apoptosis in salivary and lacrimal glands from NOD and NOD-scid mice, an animal model that develops a Sjögren's syndrome-like pathology. METHODS: The parotid, submandibular and lacrimal tissues of NOD, NOD-scid, and BALB/c mice were evaluated by immunohistochemical analysis for the expression of Fas and FasL. Nuclear fragmentation of DNA from the epithelial cells of exocrine tissues was evaluated by the terminal UTP nucleotide end labeling method (TUNEL). Messenger RNA was isolated from 8 and 18 week old mice and was analyzed by the reverse transcription-polymerase chain reaction (RT-PCR) for the expression of Fas and FasL. RESULTS: We found suggestive evidence that apoptosis of the secretory epithelial cells occurs in both NOD and NOD-scid mice despite the lack of T- and B-lymphocytes in the latter. FasL mRNA and cell surface protein were expressed in salivary and lacrimal gland epithelial cells from 8 and 18 week old NOD, NOD-scid, and BALB/c mice. Fas protein and mRNA were expressed only in the exocrine glands from 18 week old NOD and NOD-scid mice. Glandular secretory epithelial cell apoptosis was elevated in both NOD and NOD-scid mice, however; there was little evidence of apoptosis in the control strain of BALB/c mice. CONCLUSION: These results suggest a potential apoptotic process dependent on Fas:FasL interactions occurring in NOD-scid glandular secretory epithelial cells in the absence of lymphocytic infiltration.

Animals↗