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J Oppenheim

Publications and source records attributed to J Oppenheim.

At least 19 recordsLinked to original sources
PubMed2002

The fibrinolytic receptor for urokinase activates the G protein-coupled chemotactic receptor FPRL1/LXA4R.

The function of urokinase and its receptor is essential for cell migration in pathological conditions, as shown by the analysis of knockout mice phenotypes. How a protease of a fibrinolytic pathway can induce migration is not understood and no link between this protease and migration-promoting G protein-coupled receptors has been described. We now show that FPRL1/LXA4R, a G protein-coupled receptor for a number of polypeptides and for the endogenous lipoxin A4 (LXA4), is the link between urokinase-type plasminogen activator (uPA) and migration as it directly interacts with an activated, soluble, cleaved form of uPA receptor (uPAR) (D2D3(88-274)) to induce chemotaxis. In this article we show that (i) both uPAR and FPRL1/LXA4R are necessary for the chemotactic activity of uPA whereas FPRL1/LXA4R is sufficient to mediate D2D3(88-274)-induced cell migration. (ii) Inhibition or desensitization of FPRL1/LXA4R by antibodies or specific ligands specifically prevents chemotaxis induced by D2D3(88-274) in THP-1 cells and human peripheral blood monocytes. (iii) Desensitization of FPRL1/LXA4R prevents the activation of tyrosine kinase Hck induced by D2D3(88-274). (iv) D2D3(88-274) directly binds to FPRL1/LXA4R and is competed by two specific FPRL1/LXA4R agonists, the synthetic MMK-1 peptide and a stable analog of LXA4. Thus, a naturally produced cleaved form of uPAR is a unique endogenous chemotactic agonist for FPRL1/LXA4R receptor and its activity can be antagonized by specific ligands. These results provide the first direct link, to our knowledge, between the fibrinolytic machinery and the inflammatory response, demonstrating that uPA-derived peptide fragments can activate a specific chemotactic receptor.

Animals↗
PubMed2001

Shikonin, a component of antiinflammatory Chinese herbal medicine, selectively blocks chemokine binding to CC chemokine receptor-1.

Shikonin is a chemically characterized component of traditional Chinese herbal medicine and has been shown to possess antiinflammatory activities. We ascertained that shikonin blocked radiolabelled Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) and macrophage inflammatory protein-1 (MIP-1alpha) binding to human monocytes with IC50 values of 3.58 x 10(-6) and 2.57 x 10(-6) M, respectively. In contrast, up to 1.7 x 10(-5) M of shikonin failed to inhibit stromal cell-derived factor-1 (SDF-1alpha) binding to the cells. Additionally, shikonin blocked RANTES and MIP-1alpha binding to stable CC chemokine receptor-1 (CCR1) transfected human embryonic kidney (HEK)/293 cells with IC50 values of 2.63 x 10(-6) and 2.57 x 10(-6) M, respectively. However, shikonin inhibited neither RANTES nor MIP-1alpha binding to CCR5 transfected HEK/293 cells. Shikonin also did not inhibit monocyte chemoattractant protein-1 (MCP-1) binding to CCR2 cells, eotaxin binding to CCR3 cells, interferon-inducible T cell alpha-chemoattractant (I-TAC) binding to CXCR3 cells and SDF-1alpha binding to CXCR4 cells. Additionally, shikonin inhibited RANTES-induced CCR1 cell migration, but did not inhibit CCR1 cell migration induced by epidermal growth factor (EGF). Our study suggests shikonin may be a target for the future design of more potent, highly selective therapeutics that could be useful antiinflammatory agents for selectively blocking the binding of CCR1 ligands.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

"Mad" or "bad"? Evaluating the decision to hospitalize SED youth using qualitative data.

This study examines variables associated with positive and negative hospitalization outcomes of seriously emotionally disturbed (SED) youth, and proposes that the context of the decision-making process that takes place before hospitalization plays a role in determining outcomes. Qualitative data from 13 case histories were analyzed to determine the effects of hospitalization after a 2-year follow-up period. Several indicators that have predicted negative outcomes in earlier studies are supported here, including bizarre symptom patterns, educational impairment, and additional hospitalization during the follow-up period. There was agreement in fewer than half of the cases among research clinicians, the subject, or the subject's family regarding the outcome. Findings demonstrate the advantages of qualitative methods in determining the manner in which definitions of mental health influence hospitalization outcomes, suggesting that mental health categories are not a priori categories in the subjects' or families' minds. The social context of the decision to hospitalize is found to be a contributing factor in hospitalization outcomes.

Adolescent↗
PubMed1996

The role of cytokines in cancer.

The role of cytokines was intensively discussed over the course of a two and a half day meeting sponsored by the US-JAPAN Cancer Cooperative Research Program of the Office of International Affairs, National Cancer Institute and held at The National Institutes of Health, Bethesda, Maryland on 15-17 January 1996. Most of the first day was devoted to a discussion of the role of cytokines in modulating angiogenesis and the consequent effect of this on tumor growth and metastases. This was followed by sessions on the effect of various cytokines in enhancing or suppressing immunological responses to tumors. Several presentations focused on the direct inhibitory or growth promoting effects of cytokines on tumor growth. The final session consisted of a comparison of the efficacy of different approaches to tumor vaccination including gene therapy, enhanced antigen presentation, use of polymeric carriers or of DNA vectors. For background information the reader is referred to appropriate chapters on the role of cytokines in neoplastic diseases (Oppenheim JJ, Rossio JL, Gearing AJH, eds. In Clinical Application of Cytokines: Role of Pathogenesis, Diagnosis and Therapy. Oxford University Press, New York, 1993 [1]).

Acquired Immunodeficiency Syndrome↗
PubMed1995

Bone marrow-derived murine mast cells migrate, but do not degranulate, in response to chemokines.

We have determined that several chemokines induce mast cell migration in vitro. This directed migration is dependent on the presence of particular extracellular matrix proteins and the activation status of the cells. Mast cell haptotactic responses were observed in response to various chemokines on vitronectin-, laminin-, and fibronectin-coated filters. Unstimulated mast cells were chemoattracted only by monocyte chemotactic protein-1 and RANTES on vitronectin-coated and, to a lesser extent, laminin-coated filters, whereas IgE-activated mast cells migrated in response to monocyte chemotactic protein-1, regulated on activation normal T expressed and secreted, platelet factor-4, and macrophage inflammatory protein-1 alpha on all three matrix proteins. No significant migration was observed on collagen type IV-coated or uncoated filters. Mast cell migration in response to chemokines on extracellular matrices and its enhancement by IgE-dependent activation provide a mechanism by which cells may be drawn to sites of inflammation. Chemokine-induced mast cell recruitment may be particularly relevant in host defense responses to parasitic infections, allergic reactions, Jones-Mote reactions, and in wound healing.

Animals↗
PubMed1995

CD8+ and CD45RA+ human peripheral blood lymphocytes are potent sources of macrophage inflammatory protein 1 alpha, interleukin-8 and RANTES.

The chemokines macrophage inflammatory protein 1 alpha (MIP 1 alpha), interleukin-8 (IL-8) and RANTES are potent regulators of leukocyte trafficking. Examination of chemokine secretion by human peripheral blood lymphocytes after stimulation with anti-CD3 or phorbol 12, 13 myristate acetate and ionomycin showed CD8+ cells were the dominant source of MIP 1 alpha and RANTES. Although production of MIP 1 alpha and IL-8 were similar in pharmacologically stimulated CD4+ CD45RA+, CD4+ CD45RO+, and CD8+ CD45RA+ cells, the largest amounts of MIP 1 alpha and RANTES were secreted by CD8+ CD45RO+ lymphocytes. A parallel pattern of prolonged chemokine mRNA expression for at least 18 h after activation was observed in the T cells subsets. These results confirm that human T lymphocytes have a unique capacity for secretion of these three chemokines. In addition, CD8+ cells have an unrecognized role in recruiting cells to sites of inflammation, and adult human CD45RA+ cells have a physiologically significant secretory capacity.

Blotting, Northern↗
PubMed1992

Mammalian mitochondrial chaperonin 60 functions as a single toroidal ring.

Chaperonins are thought to participate in the process of protein folding in bacteria and in eukaryotic mitochondria and chloroplasts. While some chaperonins are relatively well characterized, the structures of the mammalian chaperonins are unknown. We have expressed a mammalian mitochondrial chaperonin 60 in Escherichia coli and purified the recombinant protein to homogeneity. Structural and biochemical analyses of this protein establish a single toroidal structure of seven subunits, in contrast to the homologous bacterial, fungal, and plant chaperonin 60s, which have double toroidal structures comprising two layers of seven identical subjects each. The recombinant mammalian chaperonin 60, together with the mammalian chaperonin 10 (but not with bacterial chaperonin 10), facilitates the formation of catalytically active ribulose-bisphosphate carboxylase from an unfolded state in the presence of K+ and MgATP. Analysis of the partial reactions involved in this in vitro reconstitution reveals that the single toroid of chaperonin 60 can form stable complexes with both unfolded or partially folded [35S]ribulose-bisphosphate carboxylase and mitochondrial (but not bacterial) chaperonin 10 in the presence of MgATP. We conclude that the minimal functional unit of chaperonin 60 is a single hepatmeric toroid.

Adenosine Triphosphate↗
PubMed1991

Isolation and properties of the RepA1 protein of the IncFII replicon, RepFIC.

The initiator protein RepA1 of the IncFII replicon RepFIC derived from the enterotoxin plasmid EntP307 has been cloned under the control of the lambda PL promoter. This has enabled us to overproduce this protein and study its properties. Here we show that RepA1 is a soluble basic protein with an experimentally determined molecular weight of 40,000. Deletion analysis indicates that the overproduced protein originates from the open reading frame which we previously designated as coding for RepA1. We have also shown that the replication function of the replicon RepFIC depends on the intact RepA1 coding frame.

Amino Acid Sequence↗
PubMed1991

The Bacillus subtilis sin gene, a regulator of alternate developmental processes, codes for a DNA-binding protein.

The sin gene of Bacillus subtilis encodes a dual-function regulatory protein, Sin, which is a negative as well as a positive regulator of alternate developmental processes that are induced at the end of vegetative growth in response to nutrient depletion. Sin has been purified to homogeneity by using a simple two-step procedure. It was found to bind to the developmentally regulated aprE (alkaline protease) gene at two sites in vitro. The stronger Sin-binding site (SBS-1) is located more than 200 bp upstream from the transcription start site. It is required for Sin repression of aprE expression in vivo, as strains bearing SBS-1 deletions were not affected by the sin gene. The second, weaker Sin-binding site lies on a DNA fragment that contains the aprE promoter. Results of DNase I, exonuclease III, and dimethyl sulfate footprinting analysis of SBS-1 suggested that Sin binding involves two adjacent binding sites which appear to contain two different partial dyad symmetries. An analysis of the predicted amino acid sequence of Sin revealed a potential leucine zipper protein dimerization motif which is flanked by two helix-turn-helix motifs that could be involved in recognizing two different dyad symmetries.

Amino Acid Sequence↗
PubMed1990

Biochemical characterization of Plasmodium falciparum hemozoin.

Hemozoin, the pigment granule which develops within the blood stage food vacuole of the malaria parasite Plasmodium falciparum, was biochemically characterized. Hemozoin was found to be composed of 65% protein, 16% ferriprotoporphyrin-IX (hematin), 6% carbohydrate, and trace amounts of lipid and nucleic acids. The overwhelming majority of the protein component is a mixture of native and denatured human globin non-covalently associated with the metalloporphyrin. Immunoelectron microscopy, employing anti-human hemoglobin as a probe, identified in situ association of hemoglobin with hemozoin. Hemozoin produced within diabetic blood had a higher proportion of carbohydrate, suggesting that the carbohydrate component comes from non-enzymatic glycosylation of hemoglobin.

Animals↗
PubMed1989

Immunocytochemical localization of the [3H]estradiol-binding protein in rat pancreatic acinar cells.

Significant amounts of an estradiol-binding protein (EBP) are present in pancreatic acinar cells. This protein differs from the one found in female reproductive tissues and secondary sex organs (which is commonly referred to as estrogen receptor). EBP has now been purified from rat pancreas and was used as an antigen to induce polyclonal antibodies in rabbits. The antiserum obtained was purified initially by ammonium sulfate fractionation and then still further by interaction with a protein fraction from pancreas that was devoid of estradiol-binding activity. The latter procedure was used to precipitate nonspecific immunoglobulin Gs. Western blot analysis demonstrated that the anti-EBP antibody reacted specifically with a doublet of protein bands having mol wt of 64K and 66K. When this purified antibody was used as an immunocytochemical probe in conjunction with protein-A-gold, acinar cells were labeled on the surface of the endoplasmic reticulum, on the plasma membrane, and in mitochondria. This specific labeling pattern was not observed when preimmune serum was used. No labeling was observed over the nucleus, Golgi apparatus, or zymogen granules with purified anti-EBP antibodies. The unexpected distribution of EBP in both the endoplasmic reticulum and mitochondria is discussed.

Animals↗
PubMed1986

Proportional anterior commissure area in humans and monkeys.

Behavioral testing following division of the corpus callosum has shown that the anterior commissure can transfer information related to visual tasks interhemispherically in nonhuman primates but not in humans. We have found that the ratio of anterior commissure cross-sectional area to total neocortical commissural area is significantly greater for rhesus monkeys than for humans. This difference persists when the proportions are weighted for these structures' known differences in axon density. We hypothesize that this interspecies dissimilarity reflects a difference in the distribution of interhemispheric communication and may explain the behavioral differences observed after callosal section.

Adult↗
PubMed1980

Implementation of adjuvant therapy for breast cancer in the St. Louis Metropolitan area: 1976-1977.

In order to determine the extent of implementation of adjuvant chemotherapy for stage II carcinoma of the breast in the St. Louis area, records of all patients with stage II carcinoma of the breast treated with standard or modified radical mastectomy in five different St. Louis hospitals were reviewed. Between July 1, 1976, and July 1, 1977 (17 months after publication of preliminary L-PAM results and 4 months after publication of preliminary L-PAM results and 4 months after publication of preliminary CMF results), 73% of 24 premenopausal patients and 55% of 58 postmenopausal patients received adjuvant chemotherapy. Ten percent of premenopausal and 31% of postmenopausal patients received therapy other than CMF or L-PAM. Compared to premenopausal patients in university-affiliated hospitals, premenopausal patients in community hospitals tended to receive radiation therapy more commonly and chemotherapy alone less often (P < 0.1). Compared to postmenopausal patients in university-affiliated hospitals, postmenopausal patients in community hospitals more commonly received chemotherapy alone, and less often received no adjuvant therapy (P < 0.05). We conclude that results of adjuvant chemotherapy trials can be rapidly implemented into standard practice both in university-affiliated and community hospitals. Since 12 of 52 patients receiving adjuvant chemotherapy in fact received nonstandard, unpublished regimens, improvements in phase IV drug development may be required to prevent potentially deleterious modifications of published recommendations.

Adult↗