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Biomedical subjects

N Talal

Publications and source records attributed to N Talal.

At least 253 records · Page 14Linked to original sources
PubMed1976

Antibody-dependent cell-mediated cytotoxicity in selected autoimmune diseases.

Antibody-dependent cell-mediated cytotoxicity mediated by peripheral blood lymphocytes was studied in patients with systemic lupus erythematosus, polyarteritis nodosa. Sjogren's syndrome, and rheumatoid arthritis. The target cells were chicken erythrocytes coated with rabbit anti-chicken erythrocyte antibody. Antibody-dependent cell-mediated cytotoxic activity was normal in Sjogren's syndrome and rheumatoid arthritis but significantly decreased (P is less than 0.001) in active systemic lupus erythematosus and in two patients with polyarteritis nodosa. A partial regeneration of antibody-dependent cell-mediated cytotoxic activity was obtained by treatment with pronase and DNase followed by overnight incubation. Sera from patients with systemic lupus erythematosus inhibited antibody-dependent cell-mediated cytotoxic activity of normal lymphocytes. The inhibitory activity was studied by specific immunoadsorption and sucrose density geadient ultracentrifugation. Removal of IgG but not IgM greatly reduced inhibition. Inhibitory factors were present in 7S and heavier fractions containing IgG. Five systemic lupus erythematosus patients were studied serially to determine if improvement in clinical status could be correlated with a decrease in serum inhibitory factors as studied by inhibition of normal antibody-dependent cell-mediated cytotoxicity. Indeed, a greater serum inhibitory capacity was found in each patient during periods of greater disease activity.

Adult↗
PubMed1976

Immunologic regulation of spontaneous antibodies to DNA and RNA I. Significance of IgM and IgG antibodies in SLE patients and asymptomatic relatives.

Nine individuals from four families of patients with systemic lupus erythematosus (SLE) were studied by sucrose density gradient fractionation and filter radioimmunoassay for the presence of 19S IgM and 7S IgG antibodies to DNA, poly rA, and poly rA-poly rU. One individual in each family was totally asymptomatic, and at least one had actively systemic lupus erythematosus (SLE). The results indicate: (1) a correlation between 7S antibody to DNA and RNA and active SLE, and (2) the presence of 19S antibody to RNA in the asymptomatic relatives. These findings suggest that SLE may be a disorder of immunological regulation. The distribution of antibodies between IgM and IgG is closely related to disease severity. the asymptomatic relatives may have a partial regulatory abnormality resulting in the limited production of IgM antibodies to RNA. SLE patients may have a more complex failure of regulation permitting the additional synthesis of IgG antibodies to DNA and RNA.

Adolescent↗
PubMed1976

Hyperactive T-cell function in young NZB mice; increased proliferative responses to allogenic cells.

The one-way mixed lymphocyte reaction was employed to study proliferative responses to antigens by mature, immunocompetent T cells from NZB mice 3 weeks to 4 months old. Compared to cells from control mice of the same H-2 type, thymus, spleen and lymph node cells from NZB mice were hyperactive in this response. The results are discussed in relation to possible effects of chronic stimulation by endogenous type C leukaemia virus upon differentiation of functional T cells or upon regulation by T cells of other T-cell functions, including augmentation of antibody responses.

Animals↗
PubMed1976

In vitro effect of thymosin on T-lymphocyte rosette formation in rheumatic diseases.

The in vitro effect of calf thymosin fraction 5 on T-rosette forming cells (E-RFC) was studied in Sjögren's syndrome (SS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). The baseline percent E-RFC in sixteen normal controls was67-2 +/- 6-9. E-RFC was significantly decreased in SLE (42-6 +/- 17-0, P less than 0-0001) and SS (51-8 +/- 16-9, P less than 0-002) but not in RA (59-7 +/- 14-1). Ten of twenty-five SS patients and two of eleven RA patients had less than 50% E-RFC, and all showed a significant increase after incubation with thymosin (+ 16-5 +/- 6-5%, P less than 0-0001, and + 11 +/- 4-9%, P less than 0-001, respectively). Eleven of sixteen SLE patients had less than 50% E-RFC. Their response to thymosin was less dramatic but still statistically significant (+ 5-3 +/- 6-0%, P = 0-03). There was no response to thymosin in control subjects or in patients with baseline E-RFC greater than 50%. No increase in E-RFC was seen after incubation with calf spleen fraction 5 or known stimulators of cyclic-AMP. Sera from four active SLE patients, as well as the supernatant obtained from overnight culture of the lymphocytes from one SLE patients, were able to block T-rosette formation by normal lymphocytes, even after exposure to thymosin. Two 'blocking' sera were fractionated by sucrose density gradient ultracentrifucation. In one, the blocking capacity was found to reside in the 19S region containing IgM. In the second, the blocking capacity was in the 7S region containing IgG. Four 'blocking' lupus sera were depleted of IgG or IgM by immunoabsorption with goat anti-human IgG or goat anti-human IgM sepharose 4B. The blocking ability in three sera was partially decreased by depletion of either IgG or IgM, and in a fourth, only by removing IgG. The percent of lymphocytes staining with fluorescein labelled goat anti-human immunoglobulin antisera was increased in SLE patients (35-9 +/- 20-2 vs 21-7 +/- 5-9 in controls, P = 0-02). After overnight culture, the percent of staining cells decreased to normal values. These results suggest that thymosin can stimulate the differentiation of T-lymphocytes in patients with SS, SLE, and RA when the baseline E-RFC is decreased. Furthermore, the decreased percent E-RFC in SLE is probably due to cell-bound anti-lymphocyte antibodies that block sheep erythrocyte receptors on the T-cell and, possibly, thymosin receptors on undifferentiated lymphocytes.

Adolescent↗
PubMed1975

Beta2 microglobulin and lymphocytic infiltration in Sjögren's syndrome.

We measured salivary beta2 microglobulin concentrations in 49 patients evaluated for Sjögren's syndrome with a labial salivary-gland biopsy. The salivary concentration was elevated and a significant correlation (P less than 0.001) was found between the concentration and the degree of inflammation seen in the biopsy. Serum concentrations were increased in 135 patients with Sjögren's syndrome. Striking elevations were seen in patients with associated renal or lymphoproliferative complications. Three patients have an increase in serum beta2 microglobulin concentration in association with exacerbation of their disease, and six a decrease after clinically efficacious therapy. These data indicate that determination of beta2 microglobulin in saiva may provide a simple, noninvasive technic for estimation of the degree of local inflammation in autoimmune disease.

Adrenal Cortex Hormones↗
PubMed1975

Elevated salivary and synovial fluid beta2-microglobulin in Sjogren's syndrome and rheumatoid arthritis.

Beta2-Microglobulin is normally present in low concentrations in serum and other bodily fluids. By use of a radioimmunoassay, elevated concentrations of beta2--microglobulin were found in saliva and synovial fluid from patients with Sjogren's syndrome and rheumatoid arthritis, autoimmune inflammatory diseases that attack and destroy the salivary glands and articular tissues, respectively. Elevated beta2-microglobulin concentrations decreased in the saliva of two patients who simultaneously showed a clinical response to systemic treatment. Measurement of beta2-microglobulin in inflammatory fluids may offer a simple method of quantifying local activity in autoimmune states.

Arthritis, Rheumatoid↗
PubMed1975

The oral component of Sjögren's syndrome.

This study reports the results of an interdisciplinary approach to the diagnosis of Sjögren's syndrome in 100 patients. Ocular and systemic diagnoses and oral features from the history and physical examination are correlated with measurements of stimulated parotid flow rate and labial salivary gland histopathology. A new diagnostic criterion is introduced whereby labial salivary gland focus scores are used to establish the presence of the oral component of Sjögren's syndrome in place of the subjective evaluation of xerostomia. The differential diagnosis of the oral clinical features of Sjögren's syndrome and the clinical management of the oral component of this disease are discussed.

Adolescent↗
PubMed1975

Anti-nucleic acid antibodies in systemic lupus erythematosus patients and their families. Incidence and correlation with lymphocytotoxic antibodies.

Anti-RNA antibodies were found in 82% of 28 systemic lupus erythematosus (SLE) probands and in 16% of 124 of their family members. The incidence in 76 control family members was only 5%. In the SLE family members, the antibodies were found exclusively in 21% of the 94 close household contacts of the probands. The incidence of anti-native DNA (nDNA) antibodies was 68% for the SLE probands. The incidence of anti-nDNA antibodies in close household contacts of the probands was 6%, which was not significantly different from the 1% incidence found in control families. Lymphocytotoxic antibodies occurred in 57% of the SLE family members as a whole and in 68% of the close household contacts. In the SLE probands, lymphocytotoxic antibodies correlated with anti-single-stranded RNA (poly A) and anti-nDNA but not with anti-double-stranded RNA (poly A-poly U). On the other hand, lymphocytotoxic antibodies in the household contacts correlated with anti-double-stranded RNA (poly A-poly U) but not with anti-poly A or anti-nDNA. The anti-RNA antibodies were present in consanguineous household contacts but not in nonconsanguineous household contacts. These findings strengthen the hypothesis that both an environmental agent, possibly a virus, as well as the genetic response are important in the pathogenesis of SLE. Family members may therefore be a logical population in whom to search for specific antibodies to a viral agent.

Adult↗
PubMed1975

Independent appearance of anti-thymocyte and anti-RNA antibodies in NZB/NZW F1 mice.

NZB and NZB/NZW (B/W) mice were studied for natural thymocytoxic autoantibody(NTA) and antibody to reovirus RNA by cytotoxicity and radioimmunoassay respectively.NZB mice developed NTA by 2-3 months of age. RNA antibodies appeared later if atall. NTA and anti-RNA were present in B/W mice starting at 4-5 months and increased in frequency with age. Either activity could appear first and could be present without the other. Thus, all four possible patterns of autoantibody occurrence were found. NTA and anti-RNA in 12-month B/W sera were separable by sucrose density gradient ultracentrifugation; NTA is a 19S IgM antibody whereas anti-RNA is 7S.

Animals↗
PubMed1975

Antibodies binding polyriboadenylic acid in systemic lupus erythematosus. Immunochemical characterization and isolation by affinity chromatography.

Antibodies specific for polyriboadenylic acid (poly rA) are present in sera from patients with systemic lupus erythematosus and from NZB/NZW F1 mice. The specificity of these antibodies was established by inhibition of [3H]poly rA binding and by affinity chromatography. Poly rA binding was associated with the 19S and 7S regions when serum was fractionated by sucrose density gradient untracentrifugation. Young NZB/NZW F1 mice (1-5 months) had only 19S anti-poly rA, whereas old NZB/NZW F1 mice (2 years) had activity in both 19S and 7S regions, suggesting a possible age-dependent switching mechanism in the spontaneous development of antibodies to nucleic acids. The gamma-globulin fraction from an SLE patient was subjected to affinity chromatography on a column of poly rA covalently linked to Sepharose. An enriched population of IgG antibodies binding only poly rA, but not native or denatured DNA, was isolated in this manner. This procedure may have broad biological applicability for the preparation of isolated immunospecific anti-nucleic acid antibodies.

Age Factors↗
PubMed1975

Evidence for an abnormal microenvironment in the thymus of New Zealand black mice.

The proliferative response of NZB and DBA/2 thymocytes and spleen cells to allogeneic cells and mitogens was studied in intact and lethally irradiated bone marrow-repopulated syngeneic recipients. The major findings were complete recovery of function in NZB spleen cells and premature recovery in thymocytes compared to the control DBA/2 strain. This recovery was not influenced by the administration of thymosin to the recipients, and was not due to functional thymocytes present in the donor marrow inoculum. These results suggest normal or increased support of T cell differentiation by the radioresistant thymus in 4-month-old NZB mice. Thymic epithelial cell products regulating T cell maturation may be disordered or unbalanced but do not appear to be broadly deficient at this age.

Animals↗