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Biomedical subjects

E Raz

Publications and source records attributed to E Raz.

89 records · Page 5Linked to original sources
PubMed1989

Anti-DNA antibodies bind directly to renal antigens and induce kidney dysfunction in the isolated perfused rat kidney.

The pathogenesis of SLE is commonly attributed to the deposition of circulating immune complexes consisting of DNA and anti-DNA autoantibodies. However, recent work has shown multiple cross-reactions between anti-DNA antibodies and a variety of cellular and extracellular Ag. To test the possibility that these antibodies interact directly with glomerular Ag and induce kidney dysfunction, we applied mouse and human anti-DNA IgG to the isolated perfused rat kidney. The NZB/NZW mouse monoclonal anti-DNA bound to glomerular Ag with a concomitant induction of proteinuria and a decrease in inulin clearance. The albumin excretion was 2301 +/- 734 micrograms/min at 160 min of perfusion, as compared with 85 +/- 21 micrograms/min in controls (p less than 0.001). The inulin clearance was reduced to 0.17 +/- 0.02 ml/min as compared with 0.28 +/- 0.09 ml/min in controls (p less than 0.05). Polyclonal anti-DNA IgG obtained from patients with lupus nephritis bound to rat glomeruli and induced albumin excretion of 542 +/- 217 micrograms/min at 160 min of perfusion, as compared with 163 +/- 77 micrograms/min in controls (p = NS). The addition of plasma as a source of C to the human IgG increased the proteinuria markedly (albumin excretion of 1115 +/- 195 micrograms/min at 160 min of perfusion, p less than 0.02), probably due to C activation. Preincubation of the reactive mouse and human IgG with DNA completely abolished their binding to renal tissue and its physiologic consequences. These results suggest that direct binding of anti-DNA antibodies to renal Ag may play an important role in the induction of lupus nephritis.

Adolescent↗
PubMed1989

Cerebrovascular accident and myocardial infarction associated with anticardiolipin antibodies in a young woman with systemic lupus erythematosus.

A 26 year old woman with systemic lupus erythematosus, including malar rash, photosensitivity, and arthritis, developed a cerebrovascular accident and acute myocardial infarction. High titres to antinuclear factor, anti-DNA antibodies, positive Venereal Disease Research Laboratory (VDRL) test, and anticardiolipin antibodies were found in her serum. A possible association between the presence of anticardiolipin antibodies and the two major thrombotic events is discussed.

Adult↗
PubMed1989

Improvement of immune-complex nephritis associated with hepatitis B surface antigen excess.

A case of hypocomplementemic membranoproliferative glomerulonephritis was studied during remission of nephrosis induced by high doses of corticosteroids. Hepatitis B surface antigen (HBsAg) and immune complexes were detected in serum and glomeruli. Anti-hepatitis-B surface antibody, undetectable in serum by conventional radioimmunoassays was identified in circulating immune complexes (CIC). On two occasions, improvement in renal function coincided paradoxically with an extreme increase in serum HBsAg levels as well as with marked elevation of CIC. We suggest that, as previously observed in animal models of glomerulonephritis, extreme antigen excess may inhibit glomerular deposition of immune complexes.

Antigen-Antibody Complex↗
PubMed1989

Prolonged pyrexia and lung metastases. A rare presentation of an occult epithelioid sarcoma.

A 31-year-old patient presenting with fever of unknown origin, night sweats and weight loss, associated later with pulmonary nodules, is described. Multiple invasive diagnostic procedures, including exploratory laparotomy and open-lung biopsy, suggested a benign inflammatory granulomatous disease. Metastatic epithelioid sarcoma was ultimately diagnosed after biopsy of an enlarging groin mass. Epithelioid sarcoma should be considered in the differential diagnosis of prolonged fever, associated with granulomas of obscure etiology.

Adult↗
PubMed1988

Antinuclear antibody-negative systemic lupus erythematosus (SLE) and severe renal involvement: close correlation between disease activity and appearance of circulating anticoagulant.

A 16-year-old girl meeting the criteria for SLE is described. Salient features of the clinical course included active glomerulonephritis with dense subepithelial deposits on electron microscopy, pulmonary embolism, axillary vein thrombosis, arthritis, serositis and fever. Disease activity correlated with the presence of lupus anticoagulant as measured by VDRL and partial thromboplastin time (PTT). Her serum was consistently negative to ANA, anti-DS-DNA, anti-SS-DNA, ENA, anti-Ro, anti-La, and LE cells for the entire 4-year course. She responded remarkably to prednisone and azathioprine. Reappearance of VDRL and elevated PTT preceded exacerbation of disease activity and served as a serological guide for modifying medical treatment.

Adolescent↗
PubMed1987

Evaluation of diagnostic accuracy in the clinical setting.

The admission diagnoses of 183 patients seen in the Emergency Room by 14 residents in surgery were compared with the discharge diagnoses of the same patients. The degree of accuracy of the admission diagnosis was rated by an experienced surgeon on a 0 to 4 scale for each patient, and the average diagnostic accuracy score was calculated for each resident. The residents' scores ranged from 2.0-3.3 (mean 2.6). The average diagnostic accuracy score was shown to be a discriminative measure. It correlated significantly with the quality of the initial diagnostic hypotheses, as measured by a written open-ended clinical simulation, but not with the success of the residents on the remaining parts of the written clinical simulation, with their peer and preceptor ratings, nor with the length of their training prior to testing.

Abdomen↗
PubMed1986

Effects of systemic glucocorticoids on the degradation of glycosaminoglycans in the mandibular condylar cartilage of newborn mice.

This investigation studied the early in vivo effects of triamcinolone hexacetonide, a potent fluorinated analogue of cortisol, on the degradation of sulfated proteoglycans in condylar cartilage of newborn mice. While determining the rate of [35S]sulfate release in test and control specimens, it became evident that in hormone-treated animals there was a dose-dependent retardation of the isotope clearance. Further, triamcinolone was found to have increased the half-life of condylar glycosaminoglycans (GAGs) from 16 h in control animals to 31.4 h in hormone-treated ones. Dexamethasone, another fluorinated analogue of cortisol, and progesterone evoked a similar effect. On the other hand, hydrocortisone and cortisone induced a much milder effect, whereas the non-glucocorticoid steroid deoxycorticosterone did not affect the turnover of radiosulfate in this tissue. Clearance of the isotope from the serum was faster in the hormone-treated animals. Further, the hormone led to a decrease in the overall content of GAGs, a feature that lasted for 24 h. These data tend to imply that, concomitant with the inhibitory effects of glucocorticoids on proteoglycan synthesis in cartilage, they also induce a transient depressive effect upon the degradation of proteoglycans and thereby interfere with the normal growth and development of this cartilage.

Animals↗
PubMed1982

Studies on hormonal regulation of the growth of the craniofacial skeleton: II. Effects of a glucocorticoid hormone on sulfate incorporation by neonatal condylar cartilage.

Condylar cartilage of neonatal mice served as an experimental model to study the early in vivo effects of a single dose of a fluorinated synthetic analogue of cortisol on sulfate incorporation and matrix metachromasia. Twenty-four hours after the administration of triamcinolone hexacetonide condyles incorporated significantly less 35SO4, a feature that followed a dose-response relationship. Dexamethasone, another fluorinated synthetic analogue of cortisol, evoked a similar effect, as did triamcinolone. On the other hand, corticosterone, the natural glucocorticoid in rodents, induced a markedly milder effect, whereas hydrocortisone lacked it altogether. Progesterone, a nonglucocorticoid steroid hormone, induced a reverse effect as it was found to increase 35SO4 incorporation into condylar cartilage. The hormonal inhibitory effect upon 35SO4 incorporation persisted, for the most part, for 2 days, and thereafter the sulfation process appeared to have returned to normal values. Of interest was the finding that the latter response was not accompanied by distinct changes in the degree of matrix metachromasia when measured at the chrondroblastic zone. It, therefore, seems possible, though not as yet proved, that concomitant with the transient inhibitory effects on 35SO4 incorporation, the hormone also induced changes in the degradative processes within the cartilage matrix.

Animals↗
PubMed1981

Retardative effects of a corticosteroid hormone upon chondrocyte growth in the mandibular condyle of neonatal mice.

This study examined the influence of triamcinolone hexacetonide, a long-acting synthetic analog of cortisol on the proliferative activity and subsequent development of chondroprogenitor cells in condylar cartilage of neonatal mice. It became evident that a single injection of relatively low doses of the hormone significantly reduced the uptake and incorporation of [3H]thymidine followed by a significant decrease in the number of young cartilage cells. A unique feature was the fact that at the same time condyles of triamcinolone-treated mice revealed an increase in the number of mesenchyme-like cells within the condylar chondroprogenitor zone. High values of correlation were noted between the inhibitory effects of the hormone upon the incorporation of [3H]thymidine, the number of mitotic figures (within the chondroprogenitor zone), and the dimension of the chondroblastic zone. This study indicates that in young animals fluorinated corticosteroid hormones possess a significant bivalent inhibitory effect upon both the proliferative activity of chondroprogenitor cells as well as upon capacity of the latter cells to differentiate into chondroblasts. In so doing, corticosteroids adversely affect the normal process of endochondral bone formation in one of the prominent growth centers within the craniofacial skeleton. Thus, in the developing animal, corticosteroids impair the growing mandible from expressing its inherent morphogenetic pattern.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Developmental control by the Drosophila EGF receptor homolog DER.

The identification of receptor tyrosine kinases in Drosophila has provided an opportunity to study the requirement for these proteins during the development of a multicellular organism. Genetic analysis of the function of the Drosophila epidermal growth factor (EGF) receptor homolog (DER) has revealed an extremely diverse set of roles for this protein throughout the life cycle of the organism, for example in eye development and in the establishment of dorsoventral polarity in the oocyte. We discuss the possible basis for the pleiotropic activity of DER, and the similarities and differences in the function of the homologous proteins in other invertebrates and vertebrates.

Animals↗
PubMedDate not supplied

DNA-Based immunization for asthma.

BACKGROUND: Immunostimulatory DNA sequences (ISS) containing a CpG motif are able to inhibit Th2-mediated airway eosinophilia and bronchial hyperresponsiveness in a mouse model of asthma. METHODS: To determine the optimal frequency and timing of intervention with ISS in inhibiting Th2 cytokine production and airway eosinophilia, we used ISS administration protocols which differed in the frequency (one vs. two doses), route (systemic vs. mucosal) and timing of ISS administration (before or together with antigen) in a mouse model of ovalbumin-induced eosinophilic airway inflammation. RESULTS: ISS induced Th1 cytokine production (IFN-gamma) and effectively inhibited Th2 cytokine production (IL-5) as well as eosinophilic inflammation when ISS was administered before or coadministered with inhaled allergen challenge. Although ISS was effective when coadministered with inhaled allergen, it was most effective when administered once 6 days prior to allergen challenge. Mucosal (intranasal and intratracheal) delivery of ISS was as effective as systemic (intraperitoneal) ISS delivery in inhibiting airway eosinophilia and switching cytokine responses from a Th2 to a Th1 response. CONCLUSIONS: ISS is most effective in inhibiting airway eosinophilia when administered as a single dose 6 days prior to antigen inhalation. However, ISS can also significantly inhibit eosinophilic inflammation, when coadministered with antigen inhalation. Thus, ISS administered prior or together with allergen should be considered as a novel method of allergen-based immunotherapy.

Allergens↗
PubMedDate not supplied

Inhibition of IgE antibody formation by plasmid DNA immunization is mediated by both CD4+ and CD8+ T cells.

BACKGROUND: We previously showed that immunization of mice with plasmid DNA (pDNA) encoding the Escherichia coli beta-galactosidase gene (pCMV-LacZ) induces a Th1 response, whereas beta-galactosidase (beta-gal) in saline or alum induces a Th2 response. Furthermore, the Th1 response dominates over the Th2 response and downregulates preexisiting IgE antibody formation. Here, we determined by passive transfer of CD4+ or CD8+ lymphocytes and by immunizing beta2-microglobulin knockout (beta2-M KO) mice whether CD4+ and/or CD8+ cells from pDNA-immunized mice suppress IgE antibody production. METHODS: BALB/c mice were injected with either CD4+ or CD8+ lymphocytes from naive beta-gal-in-alum or pCMV-LacZ-immunized mice, then immunized with beta-gal in alum, and the IgE antibody formation was determined. Second, C57BL/6 wild-type (WT) or beta2-M KO mice were immunized with beta-gal orpCMV-LacZ, and the IgE antibody production was assessed. RESULTS: Passive transfer of both CD4+ and CD8+ lymphocytes from pDNA-immunized mice suppressed the IgE antibody response by 90% compared to transfer of CD4+ T cells from naive or beta-galin-alum immunized mice. beta2-M KO mice produced 3 times more IgE than the WT control mice both in the primary and secondary response. CONCLUSION: Both CD4+ and CD8+ subsets of T cells from pDNA-immunized mice can suppress IgE antibody production by affecting the primary response and/or by propagating the Th1 memory response in a passive cell transfer system. Immunization with pDNA-encoding allergens may be an effective new form of immunotherapy for atopic diseases.

Animals↗