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Biomedical subjects

I Green

Publications and source records attributed to I Green.

At least 55 records · Page 3Linked to original sources
PubMed1986

Induction of c-myc expression early in the course of B-cell activation: studies in normal humans and patients with systemic lupus erythematosus.

The proliferative response of B lymphocytes to stimulation with anti-IgM antibodies and B-cell growth factors was studied in 27 patients with systemic lupus erythematosus (SLE) and 17 normal donors. In addition, the expression of messenger RNA of the proto-oncogene c-myc was also studied in B cells from SLE patients and normal donors. The proliferative response of lupus B cells to anti-IgM and B-cell growth factors as compared to normal B cells demonstrated a wide range of responses, 10 were lower than normal and 8 were either normal or supernormal. As compared to normals, expression of B-cell c-myc RNA from SLE patients was either normal or depressed. In general in patients with SLE there was a positive correlation between levels of c-myc expression and the degree of proliferation in B-cells after stimulation with anti-IgM and B-cell growth factors.

Adolescent↗
PubMed1985

Pharmacologic suppression of the fetal adrenal gland in utero. Attempted prevention of abnormal external genital masculinization in suspected congenital adrenal hyperplasia.

21-Hydroxylase deficiency results in congenital adrenal hyperplasia and leads to masculinization of the external genitalia of affected females. This complication could be avoided if fetal adrenal gland function were suppressed. A woman with mild 21-hydroxylase deficiency whose previous female child had classic congenital adrenal hyperplasia with masculinization was given dexamethasone beginning at the tenth week of gestation. Maternal estriol and cortisol values indicated rapid and sustained fetal and maternal adrenal gland suppression. At 39 weeks' gestation, the patient was spontaneously delivered of a female neonate with normal external genitalia. Postnatal tests indicated the infant was a single heterozygote for 21-hydroxylase deficiency. This study demonstrates prolonged suppression of the fetal adrenal gland with dexamethasone and suggests it might prevent abnormal masculinization in fetuses with severe congenital adrenal hyperplasia.

Adrenal Cortex↗
PubMed1985

Abnormalities in autologous mixed lymphocyte reaction-activated immunologic processes in systemic lupus erythematosus and their possible correction by interleukin 2.

The autologous mixed lymphocyte reaction (AMLR) represents the activation, proliferation and differentiation of T cells in response to signals from autologous non-T cells. Upon stimulation by autologous non-T cells, OKT4+ cells produce interleukin 2 (IL2); cells contained within both OKT4+ and OKT8+ cell populations can also be activated by autologous non-T cells to become sensitive to IL2. Once these activated OKT4+ and OKT8+ cells are exposed to IL2 produced by OKT4+ cells, they will proliferate and go on to differentiate into effector cells. Patients with systemic lupus erythematosus (SLE) have a defect in the AMLR. The ability of OKT4+ cells to produce IL2 in the AMLR is impaired. Upon triggering with autologous non-T cells, their OKT8+ cells become sensitive to proliferative signals of IL2; however, their OKT4+ cells fail to express IL2 receptors. These defects are a consistent feature in patients with SLE. AMLR-induced immunologic processes which require cell interactions between OKT4+ cell subpopulations are not correctable even by the addition of normal IL2. However, the immunologic processes mediated through OKT4+-OKT8+ cell interactions can be corrected with normal IL2. The latter finding suggests that the partial correction of the AMLR-induced immunologic processes with IL2 might lead to suppressed B cell hyperactivity of patients with SLE.

Adult↗
PubMed1985

Establishment of status epilepticus by limbic system stimulation in previously unstimulated rats.

A syndrome of convulsive status epilepticus developed in 4 of 18 rats which had been treated with continuous sine wave stimulation incrementally raised to 40 microA through limbic system electrodes. The syndrome was characterized by recurrent behavioral seizures, continuous EEG spiking, and marked neuropathology. In three other animals, the stimulation treatment produced a syndrome of nonconvulsive status epilepticus manifested by an electrophysiologic record of continuous seizure activity, without accompanying tonic-clonic movements. The poststimulatory effect was correlated with the animals' response to the stimulation, and was independent of whether the electrode was positioned in the hippocampus or amygdala. If an animal developed repeated convulsive seizures during the stimulation, such seizures were likely to persist after the stimulation offset. These results indicate that persistent limbic system activation can produce a syndrome of recurrent seizures similar to that caused by either neurotoxic drugs or by limbic system activation in kindled rats.

Amygdala↗
PubMed1985

Adherence of Candida to cultured vascular endothelial cells: mechanisms of attachment and endothelial cell penetration.

To elucidate the pathogenesis of hematogenous Candida infections, we developed an in vitro model of Candida adherence to and penetration of human endothelial cells. We enhanced or inhibited adherence in order to probe mechanisms of attachment. Adherence of Candida albicans showed a linear relation to Candida inoculum (range, 10(2)-10(5) cfu, r = .99, P less than .01) and exceeded that of less virulent Candida species and that of Saccharomyces cerevisiae (P less than .01). Candida immune serum blocked attachment (greater than 95% inhibition; P less than .001), however, this activity was abolished by immunoprecipitation of immune serum with C. albicans mannan (P less than .001) and was unaffected by immunoprecipitation with S. cerevisiae mannan or by adsorption with particulate chitin. Adherence was diminished by exposing C. albicans to heat (greater than 99% inhibition; P less than .01), UV light (98% inhibition; P less than .01), or sodium periodate (greater than 72% inhibition; P less than .01). An extract from heat-exposed C. albicans blocked adherence (greater than 51% inhibition; P less than .001). Transmission electron microscopy demonstrated that viable or killed Candida organisms were attached to endothelial cells, were enveloped by membrane processes from the endothelial cell surface, and were incorporated into the endothelial cells within phagosomes. Cytochalasin B blocked incorporation without blocking surface attachment.

Adhesiveness↗
PubMed1985

Effects of UV radiation on autoimmune strains of mice: increased mortality and accelerated autoimmunity in BXSB male mice.

Systemic lupus erythematosus is an immunologically mediated autoimmune disease which has been reported to be aggravated by certain environmental agents such as ultraviolet irradiation (UV). To further investigate this interaction, we examined the consequences of UV exposure on the autoimmune process of several strains of autoimmune mice. Strains of age- and sex-matched, 3- to 4-month old, autoimmune (MRL-lpr/lpr, (NZB X NZW)F1, BXSB) and nonautoimmune (BALB/c, B10.A) mice were shaved and exposed to an acute (2 h daily X 7 days) and a chronic (3 h/weekly X 4 weeks) dose of UV (FS40 lamps, 2 mJ/cm2/s). UV-induced changes in survival, autoantibody production, splenic B-cell activity, and target organ pathology were examined. After an acute UV exposure there were (10/15) deaths in the UV BXSB males and (4/15) in the UV BXSB females, compared to (1/15) in the non-UV BXSB male group and (0/15) in the non-UV BXSB females. No deaths occurred in the other UV autoimmune or nonautoimmune groups. Likewise, chronic UV resulted in increased UV BXSB male mortality (13/15) compared to UV BXSB females (2/15) and non-UV BXSB males and females. No deaths occurred in the other autoimmune (MRL-lpr/lpr, (NZB X NZW)F1) or nonautoimmune (BALB/c, B10.A) strains, after chronic UV exposure. Equivalent doses of Mylar-filtered FS40 UV (UVB deleted) resulted in no deaths in the UV BXSB male group. Acute and chronic UV also resulted in a significant increase in serum single-stranded DNA antibody production, splenic polyclonal B-cell activity, and renal glomerular inflammatory changes in the UV BXSB male mice. Thus, UV resulted in premature death and accelerated autoimmunity in UV BXSB males and may serve as a useful model for phototoxicity in autoimmunity.

Animals↗
PubMed1984

Silica-stimulated monocytes release fibroblast proliferation factors identical to interleukin 1. A potential role for interleukin 1 in the pathogenesis of silicosis.

Previous study strongly suggests that silicotic fibrosis is mediated by macrophages and their soluble mediators. The biochemical properties of the mediators involved in silicotic fibrosis, however, are as yet ill defined. The current study, therefore, determined whether human monocyte-macrophages treated with fibrogenic silica dust released factors capable of activating fibroblasts as measured by an increase in fibroblast proliferation. Silica, but not nonfibrogenic diamond dust, stimulated the release of fibroblast proliferation factors. Moreover, the level of fibroblast proliferation activity was comparable with the level of thymocyte proliferation (interleukin-1) activity in the same culture supernatants. The factors responsible for these seemingly diverse activities were found to behave identically when analyzed by gel filtration chromatography, size exclusion chromatography, isoelectrofocusing, ion exchange chromatography, and hydrophobic chromatography. Moreover, the response of these factors to four different proteases and heat (56 degrees C) was also identical, which shows that their comigration on various separation media could not be explained by noncovalent interaction between otherwise unrelated species. The data demonstrate that a monocyte-derived thymocyte proliferation factor having the molecular properties of interleukin 1 is capable of regulating fibroblast proliferation. In silicosis and other fibrotic diseases, the local release of interleukin 1 may contribute to abnormal connective tissue deposition by stimulating fibroblast proliferation, and thereby, amplifying other signals stimulating the synthesis of connective tissue components.

Cells, Cultured↗
PubMed1984

The effect of in vitro UV irradiation on the production of IL 1 by murine macrophages and P388D1 cells.

Ultraviolet irradiation (UV) exposure may lead to the development of multiple immunologic defects. One such defect is a dysfunction of normal antigen-presenting cell (APC) activation of T lymphocytes after whole body or in vitro UV. Although the mechanism of this interaction is not clearly defined, several possibilities have been suggested. One proposal is that UV may inhibit or abrogate the APC IL 1 signal and thus prevent normal T cell activation. To investigate this possibility further, we examined the functional consequences of UV on murine peritoneal adherent cell (PAC) activation of a cloned antigen-specific T cell hybridoma (A2.2.E10). In agreement with previous reports, we found a marked UV-induced inhibition of PAC activation of A2.2.E10 after sublethal UV. To correlate this UV-APC dysfunction with UV alterations of IL 1 production, both the IL 1-producing murine macrophage cell line P388D1 and normal murine PAC were exposed to various amounts of in vitro UV and the 24-hr post-UV IL 1 activity production of these cells was determined. The results surprisingly indicated that certain amounts of sublethal UV may actually augment the production of IL 1 activity, by using a dose range that clearly inhibits antigen presentation. This UV-induced activity was cycloheximide-sensitive, suggesting that de novo protein synthesis rather than release from cells was responsible for the increased IL 1 activity. In addition, the UV-induced IL 1 activity had a m.w. of 14K, consistent with previous reports, and demonstrated pyrogen activity when tested in the rabbit pyrogen assay. Thus UV clearly inhibits normal APC function; however, this may not be due to abrogation of IL 1 production, but rather the result of UV toxicity for other complex events involved in antigen presentation.

Animals↗
PubMed1983

The effect of in vitro and in vivo UV irradiation on the production of ETAF activity by human and murine keratinocytes.

Cultured epidermal cells and keratinocytes produce a potent hormone-like factor called epidermal cell-derived thymocyte-activating factor (ETAF). ETAF appears to be similar if not identical to a monocyte-derived lymphokine, known as interleukin 1 (IL-1). These two cytokines are able to amplify a diverse number of proliferative and inflammatory processes. Several recent investigations have suggested that UV-induced immunosuppression may be due in part to the inhibition of IL-1/ETAF production by monocytes and keratinocytes, respectively. We therefore decided to directly study the effects of various doses of in vitro and in vivo UV radiation (UVR) on the production of ETAF by normal murine epidermal cells and a murine (Pam 212) and a human (SCC) keratinocyte cell line. Our results surprisingly demonstrated an increase in both the extracellular and the intracellular ETAF activity of the murine epidermal, Pam 212, and SCC after sublethal amounts of in vitro UVR. Likewise, increased ETAF activity of murine epidermal cells was detected after sublethal doses of in vivo UVR. The UV-induced ETAF activity was cycloheximide-sensitive, suggesting that de novo synthesis of ETAF rather than cell membrane leakage was responsible for the increased ETAF activity. The fact that UV irradiation can increase ETAF activity by keratinocytes could have important local and systemic consequences for the host and may provide an efficient, contaminant-free method for generating ETAF activity for further biochemical and immunologic studies.

Animals↗
PubMed1983

Functional activity of a transformed thymic epithelial cell line.

In an attempt to obtain pure populations of nonlymphoid thymic cells, monolayers of thymic cells enriched for low-density cells were transformed with SV40. This paper describes the characteristics of the initial cell lines which resulted from this approach. These cell lines appeared to be of epithelial origin by morphologic criteria (extensive surface microvilli and pronounced intercellular tight functions) and by biochemical analysis, since they possessed mouse keratin proteins. They did not possess I-region-associated antigens on their surface, markers that have been detected on normal thymic epithelium. Functionally, these transformed cell lines secreted a factor capable of inducing thymocytes to mature to functional cytotoxic effector cells directed against allogeneic stimulators. This factor did not appear to be interleukin 1, interleukin 2, or colony-stimulating factor; did not result in thymocyte proliferation; and did not affect peripheral T cells. The cell lines described in this report should prove useful in delineating the steps by which immature T cells acquire their immunocompetence in the thymus.

Animals↗
PubMed1982

Ia antigen-bearing B cell tumor lines can present protein antigen and alloantigen in a major histocompatibility complex-restricted fashion to antigen-reactive T cells.

Several Ia-positive BALB/c B cell tumor lines were screened for their ability to present alloantigen and protein antigens to alloreactive and antigen-reactive T cells. Of six Ia-positive tumor lines studied, three were found to be effective as antigen presenting cells (APC). Indeed, on a per cell basis, one of the stimulatory lines, A20.3, was substantially more effective than whole spleen cells. The other three lines, although Ia-positive, were nonstimulatory. A20.3 was chosen for further study. This tumor appeared to behave like the conventional APC because (a) the tumor cells presented alloantigen, (b) they presented protein antigen in an MHC-restricted fashion to both primed donor T cells and to long-term continuous T cell lines, (c) alloantigen presentation was blocked by the inclusion of an anti-Ia antibody in the culture system, and (d) A20.3 cells could be effectively pulsed with antigen, although the continuous presence of antigen in the culture system resulted in a superior response. The addition of an exogenous source of interleukin 1 proved necessary to obtain an alloreactive but not an antigen-specific T cell response, although its inclusion did enhance the magnitude of antigen-stimulated proliferation. These tumor cells should prove useful in studying the biochemical events that occur during antigen processing and the requirements for T cell triggering by processed antigen in association with Ia molecules.

Animals↗
PubMed1982

Immune responses to hapten-modified self and their regulation in normal individuals and patients with systemic lupus erythematosus.

Purified T cells from normal subjects and patients with systemic lupus erythematosus (SLE) were studied for their abilities to respond to hapten modified self antigens and to antigens on autologous non T cells. Primary and secondary proliferative T cell responses to trinitrophenyl modified (TNP) non T cells were markedly impaired in patients with active SLE as compared with normal subjects or patients with inactive SLE. In contrast, patients with active SLE had significantly stronger cytotoxic activity against TNP modified autologous non T cells. Patients with active SLE had impaired proliferative responses to nonmodified autologous non T cells (auto-MLR). A significant negative correlation was observed between the degree of the auto-MLR and the degree of cytotoxic ability against TNP modified autologous cells in patients with SLE. This observation suggests that cells capable of proliferating in the auto-MLR might regulate the generation of cytotoxic T cell responses against modified self. We then analyzed the ability of anti T cell antibodies from patients with active SLE to preferentially interfere with this naturally occurring suppressor T cell function.

Antigens↗
PubMed1982

Plasmodium falciparum malaria. An amelanotic melanoma cell line bears receptors for the knob ligand on infected erythrocytes.

Erythrocytes infected with Plasmodium falciparum trophozoites and schizonts are not seen in the peripheral circulation because they attach to venular endothelium via knoblike structures on the infected erythrocyte membrane. We have recently shown that erythrocytes containing P. falciparum trophozoites and schizonts likewise attach to cultured human venous endothelial cells via knobs. In search of a more practical target cell for large scale binding studies designed to characterize and isolate the knob ligand, we tested various normal cells and continuous cell lines for their ability to bind P. falciparum-infected erythrocytes. Of the 18 cell types tested, binding of infected erythrocytes was observed to a human amelanotic melanoma cell line and amnion epithelial cells as well as to human aortic and umbilical vein endothelial cells. 96-100% of amelanotic melanoma cells bound 17+/-4 (+/-1 SEM) infected erythrocytes per positive cell, whereas fewer endothelial cells (4-59%) and amnion epithelial cells (8-19%) were capable of binding 12+/-5 and 4+/-1 infected erythrocytes per positive cell, respectively. Further studies designed to compare the mechanism of binding to the amelanotic melanoma cell line and endothelial cells showed the following results. First, that adhesion of infected erythrocytes to these two cell types was parasite stage-specific in that only erythrocytes containing late ring forms, trophozoites, and schizonts bound. Erythrocytes containing early ring forms, which do not attach to venular endothelium in vivo, did not bind to either cell type. Second, erythrocytes infected with trophozoites and schizonts of P. vivax or a knobless strain of P. falciparum, both of which continue to circulate in vivo, did not bind to either target cell type. Third, transmission electron microscopy showed that infected erythrocytes attached to the amelanotic melanoma cells via knobs. We conclude that cultured human endothelial cells and an amelanotic melanoma cell line share common determinants on their surface and that the mechanism of binding to these two different cell types is similar. The amelanotic melanoma cell line offers a useful substitute for endothelial cells in binding studies requiring large numbers of target cells.

Amnion↗