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Biomedical subjects

J S Deng

Publications and source records attributed to J S Deng.

At least 37 records · Page 2Linked to original sources

Affinity of SSB/La nuclear antigen to small nuclear ribonucleic acids.

Anti-SSB/La antibody is one kind of antinuclear antibody and is found predominantly in patients with Sjögren's syndrome and systemic lupus erythematosus. SSB/La antigen is present in the nucleus as ribonucleoprotein in particle form and is composed of peptide and RNAs. SSB/La antigen can be partially purified through several sequential procedures including salt fractionation and ion exchange chromatography. SSB/La antigen is capable of binding to 4 RNAs from uninfected KB cells and 6 RNAs from Epstein-Barr virus transformed WiL2 cells. These RNAs can bind to SSB/La peptide in vitro and form ribonucleoprotein complexes which could be reprecipitated by anti-SSB/La antibody. SSB/La associated RNAs are labile and subjected to degradation easily. Anti-SSB/La antibody may be a useful probe to investigate the potential role of Epstein-Barr virus involvement in cutaneous pathology.

Antibodies, Antinuclear↗

A monoclonal antibody recognizing Golgi apparatus produced using affinity purified material from a patient with connective tissue disease.

Serum antibodies recognizing the Golgi apparatus have been reported in patients with connective tissue diseases, but little is known of their significance. Serum from a systemic lupus erythematosus patient with polymyositis was found to have high titers of anti-Golgi apparatus antibody. This serum recognized a 64 kD polypeptide in immunoblotting with HEp-2 cells. To verify that the 64 kD polypeptide was associated with the Golgi apparatus and to characterize which Golgi component was recognized, a monoclonal antibody was produced. IgG, isolated from this serum, was used in affinity chromatography to produce purified material which was used to generate a mouse monoclonal antibody. The monoclonal antibody had an indirect immunofluorescent pattern identical to that produced by the patient's serum, and similarly recognized a 64kD polypeptide in immunoblotting. A 59 kD polypeptide was also recognized by the monoclonal antibody, suggesting that the antigens recognized by the monoclonal and serum antibodies may be only partially identical. The antigen appears to be a glycoprotein and an integral component of the Golgi cisternae membranes.

Aged↗

Comparison of IgG subclass autoantibodies in patients with systemic lupus erythematosus and subacute cutaneous lupus erythematosus.

Circulating antinuclear antibodies and in vivo bound immunoglobulins at the dermal-epidermal junction are frequently seen in patients with lupus erythematosus. The present study was designed to examine the distribution of the IgG subclasses of in vivo skin bound IgG and circulating antinuclear antibodies (ANA) in patients with systemic lupus erythematosus (SLE) or subacute cutaneous lupus erythematosus (SCLE). Immunofluorescence studies on skin biopsies showed IgG1 to be the predominant IgG subclass in SCLE patients, present in 20 of 21 (95%) of the specimens. IgG2 was present in 4 patients (19%), IgG3 in 1 (5%), and IgG4 in 7 (33%). The frequencies of IgG2, IgG3, and IgG4 skin staining were significantly higher in the seven SLE patients who were studied: IgG1 in 7/7 (100%), IgG2 in 7/7 (100%) and IgG4 in 6/7 (86%). Immunoblot analysis for the IgG subclasses was performed on serum of 29 patients with SCLE who had antibodies to SSA/Ro antigen. Twenty-seven (93%) of these patients were positive for IgG1 anti-SSA/Ro antibody, while the frequencies for IgG2, IgG3, and IgG4 anti-SSA/Ro were very low. These studies indicate that there is a difference in the IgG subclass antibody response in patients with SLE and SCLE. The presence of more than one subclass antibody may be indicative of systemic disease.

Antibodies, Antinuclear↗

Antinuclear matrix antibody. Hidden antinuclear antibody in patients with connective tissue diseases.

A total of 435 serum samples from patients with different rheumatic diseases were screened for the presence of autoantibody to nuclear matrix components by indirect immunofluorescence on 0.1 mol/L HCl extracted HEp-2 cell and WiL2 cell substrates. A total of 28 specimens were positive in this assay. Eighteen of them were from patients with systemic lupus erythematosus (18 of 250), 2 from patients with rheumatoid arthritis (2 of 115), and 8 from patients with mixed connective tissue disease (8 of 10). Antigenic material for this antibody is resistant to DNase, partially sensitive to RNase, and sensitive to trypsin. This indicates that the antigen is composed of protein and possibly RNA. In immunoblot analysis, sera positive for this antibody in indirect immunofluorescence assay recognized different peptides. This suggests that protein peptides are the major antigenic material.

Antibodies, Antinuclear↗

Possible role of Epstein-Barr virus infection in cutaneous T-cell lymphomas.

Although cutaneous T-cell lymphoma (CTCL) is a neoplastic helper T-cell disorder of unknown etiology, prolonged antigenic stimulation has been postulated to contribute to the development of this disease. Because Epstein-Barr Virus (EBV) infection has been associated with several different lymphomas, the sera of 21 CTCL patients were examined for antibodies to EBV antigens. By using complement immunofluorescence (CIF) techniques, 13 of 21 CTCL patients had detectable antibodies to Epstein-Barr Nuclear Antigens (EBNA), whereas only five of 20 control psoriatic patients were CIF positive. When immunoblot analysis was employed, all 21 of the CTCL patients had antibodies to the EBV antigens, EBNA, whereas only 12 of the control patients had detectable antibodies to these antigens. In addition, three of 21 CTCL patients had antibodies to the EBV-associated antigen, rheumatoid arthritis nuclear antigen (RANA), as determined by double immunodiffusion, whereas none of the control sera contained anti-RANA antibodies. These results indicate that antibodies against EBV antigens are found with a higher frequency and concentration in patients with CTCL when compared to controls and suggest that EBV products might serve as a possible stimulus for the development of this malignant disease.

Adult↗

Anti-V region antibodies as "almost clonotypic" reagents for the study of cutaneous T cell lymphomas and leukemias.

Despite recent advances in the understanding of normal T lymphocyte immunobiology, there has been little progress in characterizing the non-HTLV cutaneous T-cell lymphomas and leukemias (CTCL) Mycosis Fungoides and Sezary syndrome. The two major impediments to in vitro studies of these malignancies have been the contamination of CTCL cells with normal T cells and the inability to induce a vigorous proliferative response or establish long-term cultures with standard T-cell mitogens. The ideal reagent for identifying CTCL cells in a given patient would be tumor specific. Although a monoclonal antibody to the clonotypic antigen receptor on CTCL cells would approach this ideal, it is not currently feasible to generate such antibodies for each CTCL patient. As a compromise, we chose to test an "almost clonotypic" reagent by examining whether monoclonal antibodies directed at the variable (V) region of the T-cell antigen receptor could be applied to CTCL. We identified three Sezary patients, who by standard T-cell phenotype and Southern blot analysis for clonality had a virtually pure peripheral blood population of leukemic cells (PBL). We then screened the PBL of these patients with a panel of seven commercially available monoclonal anti-V region antibodies and found one patients' cells reacted greater than 99% with alpha V beta 5. The other patients' cells were non-reactive. In addition, we utilized a solid-phase system to cross-link V beta 5 on the one CTCL patients' PBL cells, and found that they proliferated vigorously in the presence of 10 units of IL-2 and IL-4. Parallel cultures have been maintained for one month by restimulation twice a week. These findings suggest that anti-V region antibodies should prove useful for investigating the immunobiology of CTCL.

Antibodies, Monoclonal↗

Establishment of a human cutaneous T-cell lymphoma in C.B-17 SCID mice.

Investigation into the immunobiology of cutaneous T-cell lymphomas (CTCL) would be facilitated by the development of a suitable experimental system. The recent use of mice with severe combined immune deficiency (SCID) as a vehicle to study the human immune system prompted us to try to establish CTCL in SCID mice. We found that a CD4+ lymphocytic infiltrate characteristic of CTCL was maintained within patient skin grafts in place on natural killer cell depleted SCID mice for the month of observation. CTCL cells were not found outside the human skin graft. This chimeric model using SCID mice and patient lesional skin should provide a useful tool to characterize CTCL/skin microenvironmental interactions and to test new therapeutic approaches.

Animals↗

Significance and specificity of anti-SSA/Ro antibody in patients with bullous disorders.

Sera from 45 patients with pemphigus and from 25 patients with bullous pemphigoid were screened for the presence of anti-SSA/Ro autoantibody by double immunodiffusion and SSA/Ro enzyme-linked immunosorbent assay and immunoblot analysis. Totally 6 of them were found to have IgG4 subclass anti-SSA/Ro antibody by SSA/Ro enzyme-linked immunosorbent assay, and this was further confirmed by immunoblot analysis. None of these 6 patients have any evidence of symptoms or signs for connective tissue disease.

Adult↗

Comparison of IgG subclasses and complement binding activity of autoantibodies from patients with bullous pemphigoid and pemphigus.

Bullous pemphigoid and pemphigus are autoimmune disorders of skin of unknown etiology and are characterized by the presence of immunoreactants in the skin and circulating autoantibodies to skin components. The distribution of IgG subclass antibodies to intercellular substance (ICS) of pemphigus and basement membrane zone substance (BMZ) of bullous pemphigoid was analyzed by using monoclonal antibodies to human IgG subclasses. IgG4 type anti-BMZ antibody was found in the majority of patients with bullous pemphigoid (88% in skin and 96% in serum). One third to one half of bullous pemphigoid patients had IgG1 and IgG2 anti-BMZ antibodies. The majority of bullous pemphigoid skin (92%) had complement in skin, however only one third of their sera had complement binding activity in vitro. IgG1 anti-ICS antibody was the predominant one in patients with pemphigus (86% in skin and 80% in circulation). IgG4 anti-ICS antibody was seen in two thirds of specimens from pemphigus patients. IgG3 subclass antibody was more frequently seen in pemphigus than in bullous pemphigoid patients. Two-thirds of pemphigus sera were capable of activating complement in vitro. The complement binding activity was directly associated with IgG1 and/or IgG3 subclass antibodies. The possible mechanisms for the restricted IgG4 subclass antibodies in bullous pemphigoid and pemphigus are discussed.

Antibody Specificity↗

A major autoepitope is present on the amino terminus of a human SS-A/Ro polypeptide.

A human SS-A/Ro antigen is present on the polypeptide component of a particle composed of hyRNA and a 60 kD protein. We have now purified the Wil-2 cell 60 kilo dalton (kD) SS-A/Ro protein and determined its amino-terminal amino acid sequence. A synthetic peptide corresponding to residues 7 to 24 of this sequence (RoSP7-24) exhibited enzyme-linked immunosorbent assay (ELISA) binding activity with immunodiffusion-defined, monospecific anti-SS-A/Ro sera. In addition, ELISA binding of monospecific anti-SS-A/Ro sera to native SS-A/Ro antigen was partially inhibited (35%) by KLH-RoSP7-24. Sera from patients known to frequently produce precipitating anti-SS-A/Ro antibody (subacute cutaneous lupus erythematosus [SCLE], 56 patients; Sjögren's syndrome [SS], 41 patients; mothers of infants with neonatal LE [NLE], 10 individuals; infants with congenital heart block [CHB], 5 patients) were tested for reactivity to RoSP7-24 in ELISA. Overall, 38% of SCLE sera, 36% of SS sera, 50% of maternal NLE sera and 20% of CHB infant sera had anti-RoSP7-24 binding levels greater than 2 standard deviations above the mean of that of normal individuals. Of the sera which had anti-SS-A/Ro detected by double immunodiffusion and/or counterimmunoelectrophoresis, 68% of SCLE patients, 71% of SS patients, 55% of NLE mothers and 20% of CHB infants had significantly elevated RoSP7-24 ELISA binding levels. These findings strongly suggest that a major autoepitope of native human SS-A/Ro resides on the amino terminal portion of the Wil-2 SS-A/Ro 60 kD polypeptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Antinuclear↗

Localization of Ro (SS-A) antigen in the cardiac conduction system.

The presence of anti-Ro (SS-A) antibody in maternal serum has been associated with congenital heart block. Using human sera monospecific for anti-Ro (SS-A) antibodies in an indirect immunofluorescence assay, Ro (SS-A) antigen was found to be present in the nuclei of myocardial cells and cells of the cardiac conduction system. The possible relationship between the location of Ro (SS-A) antigen, anti-Ro (SS-A) antibody, and heart block is discussed.

Autoantigens↗

Comparison of commercial kits for the detection of anti-nDNA antibodies using Crithidia luciliae.

The reactions of sera from 15 selected patients with connective tissue diseases and 4 selected control people were compared with the use of five commercial kits detecting anti-nDNA antibodies by indirect immunofluorescence on Crithidia luciliae. The cases with systemic lupus erythematosus (SLE) and a related condition reacted with the kinetoplasts of the C. luciliae in each kit tested with one exception, notably a case of drug-induced LE. The four control cases selected for a trace of staining of the nuclei of C. luciliae gave negative reactions with the kinetoplasts. The titer for each individual positive serum varied from 1.36 to 2.67 (mean SG 2.04) geometric standard deviation units. The staining pattern of sera positive for anti-nDNA antibodies on C. luciliae included reactivity of the kinetoplast with or without nuclear staining. The drug-induced LE serum produced only nuclear staining with no significant kinetoplast staining, i.e., a negative test for anti-nDNA antibodies. Patient control sera stained only the nucleus when any reactivity on C. luciliae was present. Generally, there were no major differences in titers and patterns of sera when comparisons were made between manufacturers. The sera were also tested by the Farr radioimmunoassay and the latex nucleoprotein test. The results of both of these assays correlated in most cases with the C. luciliae reactions.

Antibodies, Antinuclear↗

[Establishment of a human colonic carcinoma xenograft in nude mice and its chief biological characteristics].

A human colonic cancer specimen cut into 1-2 mm3 pieces under aseptic condition was heterotransplanted hypodermically by trocar to the inguinal region of BALB/cATcL nude mice bred in our laboratory. 53 days later, a 10 X 9 X 11 mm3 tumor was obtained. The take rate was 100% (48/48). The take rate of liquid nitrogen frozen and recovered tissue pieces was also 100% (13/13). Grossly, the tumor was rich in blood supply and well encapsulated. Within the tumor, the tissue was cream-colored. G-banded chromosome analysis revealed a human chromosome pattern with the mode 70-90. Pathologic diagnosis was signet-ring cell cancer, which was identical to the surgical specimen. No change was found after maintaining 13 passages in nude mice. It was named the human colonic carcinoma xenograft XHCn/w. It provides an ideal tumor model for in vivo or in vitro experiments.

Adenocarcinoma, Mucinous↗

Correlation between ANA determinations on tissue substrate, WiL-2 cell substrate, and precipitin antibody by double diffusion.

Four hundred fifty-five sera from patients with various connective tissue diseases were screened for the presence of fluorescent antinuclear antibodies (ANA) on two different substrates-mouse kidney sections and WiL-2 cell smears-and precipitin antibodies by using WiL-2 cell extracts as an antigenic source. The antigen for the precipitin was prepared as for extractable nuclear antigen tests. Of 258 sera from systemic lupus erythematosus cases, 73% were positive for ANA on mouse kidney sections, 98% on Wil-2 cell smears, and 47% by precipitin tests. However, 33 sera which were ANA negative on mouse kidney sections were positive on WiL-2 cell smears and also positive for precipitin antibodies. WiL-2 cells used as ANA substrates increased the frequency of ANA in connective tissue diseases, and there was a strong correlation between the WiL-2 cell ANA and the presence of precipitin antibodies. Twenty-four of these 33 sera had anti-SSA/Ro antibody. Some sera containing anti-SSB/La or anti-nRNP antibodies were ANA negative on mouse kidney sections, but all were positive on WiL-2 cells.

Antibodies↗

Specificity of the hydrochloric-acid-modified Crithidia luciliae immunofluorescence assay for detection of antibody to native DNA.

The Crithidia luciliae immunofluorescence (CLIF) assay is widely used to detect antibodies to native dsDNA in the diagnosis and management of systemic lupus erythematosus (SLE). However, sera from patients with SLE, rheumatoid arthritis, systemic sclerosis, drug-induced lupus erythematosus, and Sjogren's syndrome have given false-positive CLIF results. The frequency was 5% for SLE, 16% for drug-induced LE, and 5% for rheumatoid arthritis. Such false positivity was effectively eliminated by pretreatment of Crithidia luciliae smears with 0.1 N HCl. Hydrochloric acid pretreatment of Crithidia luciliae smears renders the CLIF test more specific for the detection of anti-dsDNA antibodies, without sacrificing its sensitivity and specificity. In the future, modification of routine Crithidia luciliae immunofluorescence with 0.1 N HCl pretreatment is recommended.

Antibodies, Antinuclear↗

Anti-SS-A antibodies and fetal outcome in maternal systemic lupus erythematosus.

In 155 women with systemic lupus erythematosus, there were no significant differences in the rates of fertility or adverse fetal outcome between the 47 (30%) with serum anti-SS-A antibody and the 108 without anti-SS-A, except in the frequency of congenital heart block. This complication occurred in 6 of 96 pregnancies in women with anti-SS-A and was associated with high-titer maternal antibody. The overall risk of a woman with lupus having an infant with congenital heart block was estimated to be 1:60, but the risk was considerably higher (1:20) if anti-SS-A antibody was present.

Abortion, Spontaneous↗