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K S Tung

Publications and source records attributed to K S Tung.

At least 19 recordsLinked to original sources
PubMed1992

Tolerance mechanism in experimental ovarian and gastric autoimmune diseases.

Neonatal splenocytes, neonatal thymocytes, or phenotypically mature adult thymocytes, transferred from normal BALB/c mice to syngeneic athymic nu/nu (or SCID) mice, led to autoimmune oophoritis and autoimmune gastritis, with corresponding serum autoantibodies, in the recipients. The overall disease incidence was 73%; the pathology ranged from mild to severe, with complete loss of ovarian follicles and gastric parietal cells. CD4+ neonatal spleen cells and CD4+ CD8- adult thymocytes were required for autoimmune disease induction. Adult spleen cells did not elicit disease, but they prevented disease when co-transferred with neonatal spleen cells. However, in confirmation of an earlier report by Sakaguchi et al., (J. Exp. Med. 161:72, 1985), a subset of adult splenic T cells expressing a low level of CD5 molecules elicited similar autoimmune diseases. Thus, self-reactive T cells responsible for autoimmune disease of the stomach and ovary are not effectively deleted in the thymus, and they exist in the peripheral lymphoid organs of normal mice. We conclude that the functional expression of the self-reactive T cells is ontogenetically regulated; whereas T cells in the neonatal mice readily elicited autoimmune diseases in nu/nu recipients, regulatory cells may render self-reactive T cells in the normal adults unresponsive.

Animals↗
PubMed1992

Lupus nephritis in a pediatric renal transplant recipient.

A case of aggressive lupus nephritis in a pediatric renal transplant patient is described. She initially presented with end-stage glomerulonephritis for which an underlying etiology could not be determined. Ten months after cadaveric renal transplantation, systemic lupus erythematosus was diagnosed, when she developed diffuse proliferative glomerulonephritis in association with antinuclear antibody, anti-double-stranded DNA antibody and extrarenal manifestations of lupus. It is plausible that she developed recurrent rather than de novo lupus nephritis following transplantation. Reactivation of lupus nephritis in a renal transplant is unusual in adults, and is previously unreported in children.

Antibodies↗
PubMed1992

SRN1, a yeast gene involved in RNA processing, is identical to HEX2/REG1, a negative regulator in glucose repression.

The yeast RNA1 gene encodes a cytosolic protein that affects pre-tRNA splicing, pre-rRNA processing, the production of mRNA, and the export of RNA from the nucleus to the cytosol. In an attempt to understand how the RNA1 protein affects such a diverse set of processes, we sought second-site suppressors of a mutation, rna1-1, of the RNA1 locus. Mutations in a single complementation group were obtained. These lesions proved to be in the same gene, SRN1, identified previously in a search for second-site suppressors of mutations that affect the removal of intervening sequences from pre-mRNAs. The SRN1 gene was mapped, cloned, and sequenced. DNA sequence analysis and the phenotype of disruption mutations showed that, surprisingly, SRN1 is identical to HEX2/REG1, a gene that negatively regulates glucose-repressible genes. Interestingly, SRN1 is not a negative regulator of RNA1 at the transcriptional, translational, or protein stability level. However, SRN1 does regulate the level of two newly discovered antigens, p43 and p70, one of which is not glucose repressible. These studies for the first time link RNA processing and carbon catabolite repression.

Amino Acid Sequence↗
PubMed1992

Autoimmune disease of the ovary induced by a ZP3 peptide from the mouse zona pellucida.

We describe a novel experimental system in mice for the study of ovarian autoimmune disease, a condition encountered in women with premature ovarian failure. The ovarian autoimmune disease is induced in B6AF1 mice by a 15-amino acid peptide (Cys-Ser-Asn-Ser-Ser-Ser-Ser-Gln-Phe-Gln-Ile-His-Gly-Pro-Arg) from mouse ZP3, the sperm-binding component of the zona pellucida that surrounds growing and mature oocytes. Whereas the peptide induces both T cell and antibody responses, adoptive transfer of CD4+ T cell lines derived from affected animals causes oophoritis without observable antibodies to the zona pellucida peptide. The primacy of the T cell response in the pathogenesis of disease is further substantiated by defining oophoritogenic peptides as small as eight amino acids (Asn-Ser-Ser-Ser-Ser-Gln-Phe-Gln) that do not elicit an antibody response to the full-length ZP3 peptide. The identification of a well characterized peptide as a causative agent of autoimmune oophoritis should facilitate understanding of the pathogenesis of this T cell-mediated autoimmune disease. Because the proteins of the zona pellucida are conserved among mammals (the mouse and human ZP3 proteins are 67% identical), this murine model may lead to better understanding of the pathogenesis of human autoimmune oophoritis.

Amino Acid Sequence↗
PubMed1991

Effector and regulatory cells in autoimmune oophoritis elicited by neonatal thymectomy.

(C57BL/6 x A/J)F1 (B6AF1) mice thymectomized between days 1 and 4 of age develop autoimmune oophoritis (D3TX oophoritis) 4 to 6 wk later. Oophoritis can be adoptively transferred to young recipients, and the disease in D3TX mice is prevented by reconstitution with normal adult spleen cells. The present study was further defined the nature of the effector and suppressor cells. Contrary to an earlier report, oophoritis is transferred to syngeneic and not allogeneic recipients. The spleen cells from D3TX mice when stimulated in vitro with Con A, also transfer oophoritis to adult recipients. The effector cells are CD4+: oophoritis transfer is abrogated by CD4 antibody and not by CD8 antibody and C. Spleen cells from D3TX male mice transfer disease less efficiently than female cells, thus endogenous ovarian Ag may be required for activation of effector T cells. T cells from normal adult spleen that suppress D3TX oophoritis also appear to be of CD4+ phenotype. These cells are likely to be derived from adult thymus because adult thymocytes also suppress D3TX disease. We were unable to substantiate the earlier claim that suppressor cells in normal mice are ovarian Ag specific. Thus male and female spleen cells suppress disease with comparable efficiency, and deprivation of endogenous ovarian Ag by neonatal ovariectomy of cell donors had no observable effect on disease suppression.

Animals↗
PubMed1991

Differential staining of human alpha beta and gamma delta T cells by the fluorescein conjugate of an anti-CD3 monoclonal antibody.

The enumeration of total T cells, an important function of the clinical immunology laboratory, utilizes antibodies to CD3, the macromolecular complex associated with the antigen-specific receptors of T cells. We compared the ability of some commonly employed commercial anti-CD3 reagents to stain human peripheral blood lymphocytes. Surprisingly, the fluorescein isothiocyanate (FITC) conjugate of Coulter clone T3 (FITC-T3) stained most T cells brightly, but selectively stained gamma delta T cells very dimly or not at all. In contrast, the other anti-CD3 reagents studied (FITC-Leu 4, PE-T3, PE-Leu 4, and indirectly labelled T3 and Leu 4) stained all T cells equivalently. Dual-colour flow cytometric analysis with FITC-T3 and PE-Leu 4 readily demonstrated a FITC-T3-/PE-Leu 4+ population of T cells. This unique population stained dimly or not at all with a combination of anti-CD4 and anti-CD8 monoclonal antibodies and positively with the pan-gamma delta T cell antibody TCR delta 1. Moreover, an excellent correlation was found between the number of FITC-T3-/PE-Leu 4+ cells and the number of TCR delta 1+ cells in 32 normal individuals. Thus, the FITC-T3-/PE-Leu 4+ phenotype accurately marks all gamma delta T cells. In contrast to FITC-T3, both PE-conjugated and unconjugated T3 stained gamma delta T cells brightly. Therefore, T3 binds to an epitope present on all T cells, but fluoresceinylation specifically attenuates this antibody's ability to bind to gamma delta T cells. These findings indicate that the use of FITC-T3 can result in a significant and variable underestimation of peripheral blood T cell number and demonstrate further that the CD3 complexes of human alpha beta and gamma delta T cells are significantly different.

Adult↗
PubMed1991

Immunologic basis of reproductive failure.

This article has reviewed the immunologic factors of human infertility and some of the animal models that have provided experimental evidence for the better understanding of these disorders. It is clear that definitive evidence for human autoimmune diseases of the gonads is still lacking. However, recent findings in infertile men represent tangible support for this possibility and should stimulate further studies. Insofar as these diseases are relatively rare, meaningful clinical investigations can best come from a multicenter effort based on patients with well-defined clinical and laboratory profiles. To arrive at a firmer immunologic basis for these human diseases, it will be helpful to extrapolate from experimental studies. For both testicular and ovarian diseases, it will be desirable to refine the methods for quantifying humoral and cellular immune responses to the organ-specific autoantigens in the testis and ovary. Immunohistochemical localization of immune reactants is likely to be successful when performed early in the disease process and on tissue from patients with active disease. The nature of the immune deposits in testes will need to be confirmed by the classic approach of elution of antibody from the tissue with dissociating agents, followed by quantitation. The large quantity of tissue required for study can come from orchiectomy specimens from infertile men with unilateral vasal stenosis. In addition to immunologic reactions that lead to inflammation, future studies should take into consideration the possible existence of autoantibodies that react against hormone receptors or other functional ligands involved in ovarian or testicular physiology. Despite the paucity of evidence for human autoimmune diseases of the gonads, the likelihood of existence of these diseases is also supported by the ease with which experimental autoimmune disease of the gonads can be induced. We have described the experimental models of gonadal autoimmune diseases in detail, since analysis of these diseases has led to some unique contributions to immunopathology research and the physiology of the gonads. It is anticipated that future studies will characterize the target antigens as well as the local and systemic mechanisms that prevent autoimmune disease of the gonads in normal individuals. Moreover, it is anticipated that the model of neonatal thymectomy and oophoritis/orchitis will help to define the intricate interplay among thymic function, tolerance mechanisms, and autoimmunity. It is important to emphasize that research on the maternal-fetal immunologic relationship is a rapidly moving and controversial field. Although we have tried to point out controversial areas, the reader may wish to consult several excellent recent reviews. The anatomy and function of the hemochorial placenta and decidua are extraordinarily complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Abortion, Spontaneous↗
PubMed1979

Histoplasmosis. Association with circulating immune complexes, eosinophilia, and mesangiopathic glomerulonephritis.

A patient with disseminated histoplasmosis, eosinophilia, and transient mesangiopathic glomerulonephritis stimulated a search for the presence of circulating immune complexes. Serum samples obtained on the fifth and 11th hospital days were strongly positive for ciculating immune complexes by both the Raji cell radioassay and the C1q solid phase assay. During the course of complete clinical recovery without therapy, both assays were weakly positive for circulating immune complexes on day 33. On day 56 they were negative. Using this case as a prototype, possible mechanisms for the renal immunopathology and the eosinophilic response are discussed with reference to the immunological perturbations thay may be observed in systemic mycotic infection.

Adult↗
PubMed1979

Immunobiological consequence of immunization of female mice with homologous spermatozoa: induction of infertility.

Female Swiss Webster mice were immunized intraperitoneally with mouse epididymal spermatozoa or with phosphate buffered saline (PBS) and their fertility was compared by (1) incidence and size of litters, (2) number of uterine implantation sites, and (3) incidence and number of fertilized eggs in the oviducts. Statistically significant reduction in fertility was noted following two courses of injections of spermatozoa; 12% of mice injected with spermatozoa had litters compared with 80% of mice injected with PBS. The infertility did not seem to be related to a failure in fertilization since the two groups of mice had a similar incidence and number of fertilized eggs in the oviducts. All female mice were found to have a "natural' anti-acrosomal antibody. Following immunization with spermatozoa, antibodies to "postacrosomal' region, the main piece and the midpiece of the tail, as well as cytotoxic antisperm antibodies, appeared. Anti-LDH-X antibody was not detected. However, correlation was not found between infertility and antisperm antibodies or sperm granulomata that developed in the peritoneal cavities. It is concluded that female mice receiving repeated i.p, injections of mouse spermatozoa become infertile and that the infertility is related to interference with events after fertilization.

Animals↗
PubMed1979

Circulating immune complexes in Lyme arthritis. Detection by the 125I-C1q binding, C1q solid phase, and Raji cell assays.

We have found immunoglobulin (Ig) G-containing material consistent with immune complexes in the sera of patients with Lyme arthritis. It was detected in 29 of 55 sera (55%) from 31 patients by at least one of three assays: (125)I-C1q binding, C1q solid phase, or Raji cell. The presence of reactive material correlated with clinical aspects of disease activity; it was found early in the illness, was most prominent in sera from the sickest patients, was infrequent during remissions, and often fluctuated in parallel with changes in clinical status. The results in the two C1q assays showed a strong positive correlation (P<0.001). They were each elevated in 45% of the sera and were usually concordant (85%). In contrast, the Raji cell assay was less frequently positive and often discordant with the C1q assays. In sucrose density gradients, putative circulating immune complexes sedimented near 19S; they, too, were detected best by the two assays based on C1q binding. An additional 7S component was found in some sera by the (125)I-C1q binding assay. Serum complement was often above the range of normal in patients with mild disease and normal in patients with severe disease but did not correlate significantly with levels of circulating immune complexes. IgM and IgG rheumatoid factors were not detectable. These findings support a role for immune complexes in the pathogenesis of Lyme arthritis. Their measurement, by either the (125)I-C1q binding assay or by the C1q solid phase assay, often provides a sensitive index of disease activity. Moreover, the complexes are likely sources of disease-related antigens for further study of this new disorder.

Adolescent↗
PubMed1979

Glomerulonephritis in procainamide induced lupus erythematosus: report of a case and review of the literature.

A 61-year-old man developed clinical lupus syndrome with positive antinuclear antibody, positive lupus erythematosus (LE) cell preparation, and diffuse proliferative glomerulonephritis following 26 months of procainamide therapy. He was treated sequentially with prednisone and azathioprine (2 weeks), decreasing doses of prednisone alone (21 months), and no immunosuppressive drugs (10 months). Coincidental with this treatment, the immunopathology of the glomerulonephritis improved dramatically, dramatically, renal function returned almost to normal, and both antinuclear antibody and LE cell preparation became negative. The course of this patient's renal disease contrasts sharply with diffuse proliferative glomerulonephritis of idiopathic systemic lupus, and suggests that this rare complication of procainamide therapy may have a favorable course.

Azathioprine↗
PubMed1978

Allergic orchitis lesions are adoptively transferred from vasoligated guinea pigs to syngeneic recipients.

Histopathology typical of allergic orchitis developed in testes of inbred guinea pigs 16 months after vasoligation. A similar histopathology was found in unoperated testes after unilateral vasoligation. Peritoneal exudate cells from vasoligated guinea pigs transferred identical lesions to syngeneic recipients. The testicular lesions in long-term vasoligated guinea pigs have an immunological basis.

Animals↗
PubMed1978

Hemolytic-uremic syndrome after shigellosis. Relation to endotoxemia and circulating immune complexes.

To investigate three possible causes of the acute hemolysis in the hemolytic-uremic syndrome, we studied prospectively 207 children and 34 adults with shigellosis in Bangladesh. Nineteen children showed acute hemolytic anemia, a leukemoid reaction, thrombocytopenia and oliguria; nine other had, in addition, a serum urea nitrogen level of over 100 mg per diciliter. Eight of the nine had pseudomembranous colitis, and six of the nine died. The frequency of bacteremia was similar in all grades of shigellosis. Circulating immune complexes were found in 10 of 20 patients with uncomplicated shigellosis and in four of six with severe hemolytic-uremic syndrome. Limulus assay for endotoxemia was positive in nine of 18 patients with hemolysis (50 per cent) and three of 61 with uncomplicated shigellosis (5 per cent) (P less than 0.001). These data support the hypothesis that severe colitis in shigellosis is associated with circulating endotoxin from the colon producing coagulopathy, renal microangiopathy and hemolytic anemia.

Adolescent↗
PubMed1978

Decrease in circulating immune complexes during hemodialysis.

Raji cell radioimmunoassay and Clq solid phase radioimmunoassay were used to determine serially circulating immune complexes in a patient with rapidly progressive glomerulonephritis who was receiving hemodialysis therapy. Initiation of hemodialysis was associated with a significant decrease in detectable immune complexes which, in turn, was associated with improvement and stabilization of renal function. We suggest that hemodialysis may remove immune complexes from the circulation and that it could be of therapeutic benefit in selected patients with presumed immune complex-mediated glomerulonephritis.

Adolescent↗