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Biomedical subjects

D Sredni

Publications and source records attributed to D Sredni.

6 recordsLinked to original sources

A dominant negative bone morphogenetic protein 4 receptor causes neuralization in Xenopus ectoderm.

Injection of DN-BR mRNA encoding a dominant negative type I receptor for bone morphogenetic protein 4 (BMP4) converted prospective ectoderm into neural tissue in Xenopus animal cap explants, in the absence of expression of mesodermal marker genes. The injected caps expressed a general neural marker NCAM and the forebrain marker opsin. Coinjection of wild-type BMP4 receptor mRNA completely reversed the neuralization by DN-BR. No expression of known neuralizing factors, i.e., noggin and follistatin, was detected in the DN-BR-injected animal caps. Furthermore, neuralization elicited by noggin or 3m, a LIM domain mutant of Xlim-1, was substantially inhibited by co-injection of BMP4 mRNA. Since BMP4 is expressed in the prospective ectoderm during gastrulation, our results suggest that the ventralizing factor BMP4 acts also as a physiological inhibitor of neuralization in the development of Xenopus ectoderm.

Animals

Induction of IL-10 gene expression in human keratinocytes by UVB exposure in vivo and in vitro.

Numerous studies have demonstrated that ultraviolet B (UVB) irradiation has profound effects on the skin and systemic immune systems. Because many of the effects of UVB result in suppression of contact sensitivity responses and because IL-10 induces a Th2 rather than a Th1 response, we sought to determine whether UVB irradiation induces IL-10 transcription and subsequent protein secretion by human epidermal cells. Skin of nine volunteers was exposed to UVB or sham irradiation, and epidermal cell suspensions were prepared from suction blister roofs 24 h thereafter. mRNA was extracted using oligo dT-coated magnetic beads, and IL-10 cDNA was amplified with a sensitive RT-PCR technique. We found that IL-10 was constitutively expressed by epidermal cells in 5 of 9 volunteers and that IL-10 message was up-regulated by UVB exposure in all experiments. Since epidermis consists of a heterogeneous cell population with distinct cytokine profiles, we determined whether UVB caused enhanced IL-10 transcription and protein secretion in human keratinocyte cultures. In these experiments, IL-10 was constitutively expressed by keratinocytes and UVB up-regulated IL-10 gene expression in a dose-dependent manner 24 h after in vitro irradiation, coinciding with IL-10 protein secretion into the culture supernatants. Taken together, the findings indicate that UVB irradiation induces IL-10 in human keratinocytes and suggest that keratinocyte-derived IL-10 may be an important component of the immunosuppression that results from UVB irradiation.

Adult

Interleukin-3-like activity levels in pregnant women: possible modulation by progesterone.

Human interleukin-3-like activity (IL-3-LA), a factor possessing similar characteristics to interleukin-3 and having clony stimulating factor (CSF) activity, has recently been defined. In the present study, IL-3-LA levels in the sera of women before and after delivery were examined. The results indicate a significant increase in IL-3-LA levels in women before delivery as compared to IL-3-LA levels after delivery or to non-pregnant healthy women. The ability of mononuclear cells from women before and after delivery to produce IL-3-LA was similar to that of mononuclear cells from cord blood. In addition, the effect of progesterone on in vitro IL-3-LA production was examined and a stimulatory dose-dependent effect was observed. These observations point to the hypothesis that during pregnancy IL-3-LA levels are modulated by progesterone. With placental loss, the IL-3-LA in the sera decreases, although the mononuclear cells previously affected by the hormone continue to produce cytokines.

Female

The putative role of cytokines in the induction of primary anti-phospholipid syndrome in mice.

Antiphospholipid syndrome (APLS) is characterized by thrombocytopenia, thromboembolic phenomena and recurrent fetal loss, associated with anti-cardiolipin antibodies (ACA) and/or lupus anticoagulant. The syndrome may be primary or may be associated with other conditions such as systemic lupus erythematosus (SLE). In this study we induced primary APLS following immunization of BALB/c mice with a human monoclonal ACA (H-3). Analysis of the cytokine profile of the mice with experimental APLS indicated low production of IL-2, IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) by concanavalin A (Con A)-stimulated splenocytes of H-3 immunized mice. It seems that the low levels of IL-3 and GM-CSF have a potential role in the fetal loss of the APLS. Whatever the mechanism of IL-3 and GM-CSF in preventing fetal loss, these results may have therapeutic bearing on the reproductive outcome in women and other species with APLS.

Animals

Stimulation of human T cell colony growth by a lymphocyte colony enhancement factor derived from lymphocyte subpopulations.

Blood mononuclear cells (MNC) develop into T cell colonies when the cells are sensitized with PHA and seeded in a two-layer soft agar system. Conditioned medium (CM) derived from MNC enhanced lymphocyte colony formation when it was added to the culture system. CFU-TL appear to be stimulated into colony formation by molecules secreted by lymphocyte subpopulations contained in the seeded cells. In this study, human peripheral blood MNC were fractionated by a battery of techniques into adherent, E+, CD4+, CD8+, B and null cells. CM was prepared from each of the subpopulations and its effects on T cell colony growth assayed. All the lymphocyte subpopulations were found to generate lymphocyte colony enhancement factor (LCEF). After several purification procedures, CM prepared from CD4 and CD8+, displayed LCEF activity corresponding to proteins of molecular weight 30-40 and 100-140 kD.

Antigens, CD