Overexpression of SOCS-2 and SOCS-3 genes reverses erythroid overgrowth and IGF-I hypersensitivity of primary polycythemia vera (PV) cells.

Polycythemia vera (PV), an acquired, chronic, clonal disorder arising in a multipotential hematopoietic progenitor cell, is characterized by hyperplasia of three major myeloid lineages, with a pronounced increase in cells of the erythroid lineage. Erythroid progenitor cells in PV are strikingly hypersensitive to insulin-like growth factor-I (IGF-I); this effect is specific and is mediated through the IGF-I receptor. To investigate the possibility that in PV the increase in number of erythroid progenitors and their hypersensitivity to IGF-I result from a defect in negative regulation of cytokine activity, we examined the expression of members of the SOCS gene family.

A comprehensive information resource on traditional, complementary, and alternative medicine: toward an international collaboration.

Objectives: A prototype for a comprehensive information resource for traditional complementary and alternative medicine (TCAM) has been developed to fill the considerable needs of a broad audience for worldwide access to TCAM information. The proposed resource is to be a comprehensive, vocabulary-controlled, integrated, standardized, multimedia information resource for TCAM. It will facilitate international cooperation, promote synergistic development of individual resources, promote dissemination of TCAM knowledge, and map the interrelationships among the TCAM traditions.

Hypersensitivity of circulating progenitor cells to megakaryocyte growth and development factor (PEG-rHu MGDF) in essential thrombocythemia.

Hematopoietic progenitor cells in 2 myeloproliferative disorders, juvenile chronic myelomonocytic leukemia and polycythemia vera, are known to be hypersensitive to cytokines that control normal progenitor cell proliferation, differentiation, and survival in their respective granulocyte/macrophage and erythroid lineages. Because thrombopoietin controls these functions in the normal megakaryocytic lineage, we asked the question: Are megakaryocytic progenitor cells in the myeloproliferative disorder essential thrombocythemia (ET) hypersensitive to thrombopoietin? Peripheral blood mononuclear cells from patients with ET, or secondary (reactive) thrombocytosis (2 degrees T), or healthy volunteers were grown in strictly serum-free agarose culture containing interleukin 3 (IL-3) and all-trans-retinoic acid, with various concentrations of PEG-rHu megakaryocyte growth and development factor (MGDF). The concentration of cytokine at half-maximum colony number served as a measure of progenitor cell sensitivity.

Madingley, Madding, Mad scenarios: an exercise in futurology.

The Madingley scenarios were created to suggest potential contrasting futures (around year 2020) that could develop from the same driving forces. Those contrasting futures are named 'Trust their Guidance' and 'Find my Way', respectively. Trust their Guidance depicts a world where institutions have succeeded in adapting to the changing world and have strengthened their power and control on nations.

Factors that shape alternative medicine: the role of the alternative medicine research community.

The documented prevalence of alternative medicine practices in the United States warrants a critical evaluation of this field. Although adequate scientific evaluation is needed, it is doubtful that such research will take place unless other factors are taken into account that remain overlooked. We have previously proposed a conceptual definition of alternative medicine practices and outlined those sociological, political, economic, and regulatory factors independent of the alternative healthcare community that could potentially hamper the optimal evaluation of alternative medicine.

Is the scientific publishing of complementary and alternative medicine objective?

Bias expressed by conventional journals against the field of "alternative," "integrative," or "complementary" medicine has been said to drive the appearance of new journals dedicated to this field. We examined two examples of recent articles on complementary and alternative medicine that appeared in two major medical journals in 1998. One is an editorial on the risks of alternative medicine, published in The New England Journal of Medicine and the other is a study on Therapeutic Touch, published in the Journal of the American Medical Association.

Progress in complementary and alternative medicine: contribution of the National Institutes of Health and the Food and Drug Administration.

Since the creation of the Office of Alternative Medicine (OAM) at the National Institutes of Health (NIH), progress has been made in the evaluation and, where appropriate, the clinical and scientific acceptance of "complementary and alternative" medicine (CAM). This progress is due in part to initiatives jointly conducted by the NIH and the U.S.

Methodologic considerations for research in traditional (alternative) medicine.

The widepsread use, in the United States and other western countries, of alternative medical practices often derived from traditional systems of health has intensified the need to evaluate their safety and effectiveness. These practices tend to generate polarized attitudes of either acceptance or rejections. Opponents reject them because, they claim, good scientific research has not supported their use.

Circulating erythroid progenitors in polycythemia vera are hypersensitive to insulin-like growth factor-1 in vitro: studies in an improved serum-free medium.

We have investigated the question of erythropoietin (Epo) hypersensitivity versus Epo independence as the basis for the endogenous erythroid bursts (EEBs) that develop in cultures without added Epo from hematopoietic cells of polycythemia vera (PV) patients. Using an improved serum-free (SF) medium containing interleukin (IL)-3, but no insulin-like growth factor-1 (IGF-1), and devoid of contaminants that influence erythropoiesis, we compared circulating normal and PV early erythroid progenitors (BFU-E) with respect to their responses in vitro to recombinant human (rHu) Epo. Cultures were seeded with Ficoll-Hypaque density-separated peripheral blood (PB) mononuclear cells (MNCs), and erythroid bursts, together with their component colonies of > or = 50 cells, were scored in situ at 13 to 16 days of culture.

Superoxide dismutase halts cycling of murine erythroid progenitor cells prior to S phase in vitro and possibly in vivo.

Mice of the C57BL/6 (B6) strain show a much lower proportion of marrow erythroid progenitor cells (BFU-E) in DNA synthesis in vivo than mice of the congeneic B6S strain. However, when assayed in vitro marrow cells from both strains show high proportions of BFU-E in S-phase. BFU-E from normal B6 mice have been previously shown to be specifically inhibited from entering S-phase in vitro by the antioxidant enzyme superoxide dismutase (SOD), however, in this study we have found that BFU-E taken from the marrow of B6S mice or B6 mice which have been subjected to bleeding are insensitive to SOD inhibition in vitro.

Superoxide dismutase specifically inhibits erythroid cell DNA synthesis and proliferation.

The antioxidant enzyme superoxide dismutase (SOD) was previously shown to inhibit both the proliferation of murine erythroid DA-1 cells growing in the presence of Interleukin-3 (IL-3) and the DNA synthesis of marrow erythroid progenitor cells (BFU-E) in vitro. We show here that the inhibition of marrow cell DNA synthesis by SOD is specific for BFU-E and erythroid precursors (CFU-E), with other myeloid progenitors (CFU-GM) and stem cells (CFU-S) being unaffected, and IL-3 blocks the inhibitory effects of SOD on BFU-E in a dose-dependent manner. Extending earlier observations on the effects of SOD on cell proliferation, it was found that SOD was capable of inhibiting DA-1 cell proliferation supported by either IL-3 or erythropoietin (epo), but had no effect on IL-3 dependent FDCP-1 cells, nor on epo-dependent HCD-57 cells.

Purification of an inhibitor of erythroid progenitor cell cycling and antagonist to interleukin 3 from mouse marrow cell supernatants and its identification as cytosolic superoxide dismutase.

We have isolated a protein from media conditioned by a murine marrow-derived cell line (PB6) and from mouse marrow supernatants that antagonizes interleukin 3-dependent proliferation of cells in culture and reversibly inhibits DNA synthesis of erythroid progenitor cells (BFU-E) in vitro. This protein, p16 (monomer Mr = 16 kD on SDS-PAGE), was purified to homogeneity and amino acid sequencing of a polypeptide fragment yielded a sequence identical to that of murine cytosolic Cu,Zn-containing superoxide dismutase (SOD). The identification of p16 as SOD was confirmed by the detection of SOD enzymatic activity in pure p16 fractions, and when a commercial human erythrocytic SOD preparation was tested it showed the same cell inhibitory activities as p16.

Interleukin 3 opposes the action of negative regulatory protein (NRP) and of transforming growth factor-beta (TGF-beta) in their inhibition of DNA synthesis of the erythroid stem cell BFU-E.

DNA synthesis of the early erythropoietic progenitor cell (erythroid burst-forming unit, BFU-E) is inhibited by a growth factor that we have called negative regulatory protein (NRP). This protein appears to act during the S-phase of the cell cycle and to be specific to the BFU-E. It is nontoxic and its action is readily reversible by washing the cells.

Depressed PMNC blastogenic response in patients with cancer of the head and neck: a study of IL-2 production, IL-2 consumption, and IL-2 receptor expression.

Approximately two thirds of patients with head and neck cancer have been shown to have peripheral mononuclear cells that exhibit a lowered blastogenic response to the T-cell mitogens, concanavalin A and phytohemagglutinin. To investigate the possible mechanisms of this phenomenon, we measured the amount of activated T-cell lymphokine interleukin-2 present in the supernatant of concanavalin A- or phytohemagglutinin-stimulated peripheral mononuclear cells taken from patients with squamous cell carcinoma of the upper aerodigestive tract. Concentrations were found that were similar to those of healthy subjects.

Negative regulation of DNA synthesis in early erythropoietic progenitor cells (BFU-E) by a protein purified from the medium of C57BL/6 mouse marrow cells.

During studies on the influence of Fv-2 on the cycle state of the erythroid burst-forming unit (BFU-E), an activity was found in bone marrow supernatants from C57BL/6 (B6) mice that shut down DNA synthesis of the BFU-E in vitro. It acted within minutes, its action was completely reversed by a single wash, and it appeared specific to the BFU-E. The activity-causing substance, being macromolecular, heat stable, and trypsin-sensitive, was evidently a protein and was named negative regulatory protein.

Treatment of oro-facial herpes simplex infections with acyclovir: a review.

The treatment of herpes simplex virus (HSV) infections in the past has been largely unsuccessful. Introduction of the drug acyclovir has been a positive development. Acyclovir has been extensively studied in the treatment of a a variety of HSV infections in immunocompromised patients and in otherwise healthy patients.

Effects of heparin on in vitro immune parameters.

The effects of heparin on several in vitro immune functions [blastogenesis, interleukin-2(IL-2) production] were investigated. The addition of heparin to human peripheral mononuclear cells stimulated with phytohemagglutinin or pokeweed mitogen significantly increased the blastogenic response of these cells. Peak IL-2 concentrations in the supernatant of heparin-containing cultures were two- to fourfold higher than in heparin-free cultures.