Prinzmetal angina and cyproheptadine.
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Angina Pectoris, Variant↗
Biomedical subjects
J L Ambrus
Publications and source records attributed to J L Ambrus.
Hemorrheologic effects of metabolites of pentoxifylline (Trental).
Pentoxifylline (Trental) is metabolized by red blood cells and the liver into seven metabolites. Metabolites I and V have significant hemorrheologic effects. They are both similar to pentoxifylline in their activity on red blood cell membrane fluidity. Metabolite I is more active than pentoxifylline in inhibiting ADP-induced platelet aggregation. Metabolite V is more active than pentoxifylline in inhibiting epinephrine-induced platelet aggregation.
Adenosine Diphosphate↗
Calcitriol analogs cause differentiation of neoplastic cells in culture.
Several investigators are developing calcitriol (DHCC, Compound A) derivatives which have less effect on mineral metabolism and are effective in causing differentiation of neoplastic cells. In the present study we investigated three new DHCC derivatives (Compounds B, C, D) for differentiation inducing effect in human neoplastic cell lines HL-60 and U-937.
Calcitriol↗
Influence of cold storage altered red cell surface on the function of platelets.
In previous studies, we have shown that in the hemoocclusive crisis of sickle cell disease, red blood cells (RBC) develop reversible membrane changes which may represent a thrombogenic surface for platelets. As a result there is platelet activation and platelet derived procoagulant activity. Platelet activation is also enhanced when platelets come into contact with stored RBC in comparison with freshly obtained red blood cells from normal individuals. Pentoxifylline (P, Trental), a trisubstituted xanthine derivative, acts on the red cell membrane and decreases its effect on platelet activation. In addition, it may have direct platelet aggregation inhibitory effects. By decreasing red cell "stiffness", it may also increase the circulating life span of stored red blood cells. It is suggested that pentoxifylline may be explored as an additive in the preservation of RBC.
Blood Coagulation↗
Study of the mechanisms of action of sodium meclofenamic acid (Meclomen) a "double inhibitor" of the arachidonic acid cascade.
Meclofenamic acid sodium (Meclomen) was found to inhibit both the cyclooxygenase and the lipoxygenase pathways of arachidonic acid metabolism. It inhibited both 5-lipoxygenase and 15-lipoxygenase activities. Meclomen was also shown to interfere with leukotriene receptors or possibly post-receptor mechanisms. In isolated lung parenchyma strip preparations Meclomen inhibited leukotriene C4 and D4 induced contractions, but had no effect on histamine induced contractions. Ibuprofen, naproxen and indomethacin had no effect on lipoxygenases or on leukotriene receptors but were powerful inhibitors of cyclooxygenases.
Animals↗
Viral etiology of neoplastic and immune deficiency disorders.
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Animals↗
Potentiation of thrombolytic therapy by enzyme combinations and with aspirin or pentoxifylline.
Radioactively labeled human fibrin clots were placed into veins of Macaca arctoides monkeys. Thrombolysis was recorded by the disappearance of radioactivity and by angiography. Streptokinase (SK) and urokinase (UK) induced thrombolysis was potentiated by low dose aspirin (ASA) and pentoxifylline (PE). Studies on the mechanisms of action revealed that PE inhibits platelet aggregation, releases tissue plasminogen activator (t-PA) from the endothelium, increases red cell deformability and inhibits white cell adhesion. Thrombolysis by pro-urokinase (pro-UK) was potentiated by low dose SK probably because of streptokinase-plasmin activation of pro-UK to UK. Platelet aggregation inhibitory effects, disaggregation of platelet aggregate inducing effects, and the t-PA releasing activity of PE was demonstrated in patients with obstructive cardiovascular disease. Pharmacodynamic studies suggested that PE metabolites one and five are most effective from this point of view. These metabolites are currently studied in combination with thrombolytic enzymes.
Animals↗
An inexpensive method for the rapid identification of specific cDNAs from cDNA libraries.
The identification of specific cDNAs by screening filters impregnated with DNA from phage or bacterial colonies is a time-consuming and expensive undertaking. We have developed a rapid and inexpensive method for identifying specific cDNAs that involves hybridization of cDNAs to specific oligonucleotides bound to nylon filters. Using this method, we have identified specific cDNAs for a human B-cell growth factor from different cDNA libraries. The total processing time was 3 days, and 30% of the cDNAs selected by this method were correct.
Adsorption↗
Differentiation of neoplastic cells toward normal induced by vitamin D3 derivatives.
Two new analogs of 1,25 dihydroxy vitamin D3 (calcitriol, DHCC), the active metabolite of vitamin D3 (cholecalciferol (D3) are less active on calcium metabolism and less toxic than (DHCC). They had increased differentiation-inducing activity towards normal on human myeloblastic leukemia cell line HL-60 and on histiocytic lymphoma cell line U-937 consisting of monoblastoid cells. 1,2 tetradeconyl phorbol 1, 3 acetate (TPA) was used as a positive control in these experiments.
Calcitriol↗
Inhibition of IL-6 and IL-8 production in human fibroblast cell lines by 1,25 (OH)2 vitamin D3 and two of its analogs with lower calcemic activity.
In human fibroblast cultures TPA increased IL-6 and IL-8 production. This was reduced by vitamin D3 metabolites and analogs. The two analogs employed: 1,25 (OH)2-22 (E)-dehydro-24-monohomo vitamin D3 (Compound A) and 1,25 (OH)2 -22 (E)-dehydro-24 dihomo-vitamin D3 (Compound B) may be useful in the therapy of pathologic proliferative disorders including psoriasis, particularly since they are less toxic and have less effect on calcium metabolism than vitamin D3.
Calcitriol↗
Pentoxifylline and meclofenamic acid treatment reduces clinical manifestations in a murine model of AIDS.
C57/BL/6 mice infected with LP-BM5 MuLV virus developed an AIDS-like disease (MAIDS) with splenomegaly, leukopenia, thrombocytopenia, anemia, decreased numbers of helper/inducer and suppressor/cytotoxic T-cells and decreased production of interferon alpha. We have shown previously that HIV-associated Kaposi's sarcoma tissue contains high levels of prostaglandin E2 (PgE2), and this inhibits interferon synthesis through a cAMP-dependent second-messenger process. In this study we treated groups of MAIDS-infected mice with combinations of pentoxifylline, an agent which increases cAMP and inhibits phosphodiesterases, and sodium meclofenamic acid, a PgE2 inhibitor. Treated mice showed: 1) significantly higher total leukocyte and platelet counts, 2) higher total L3T4+ (helper/inducer) and Lyt-2+ (suppressor-cytotoxic) T-cell population. Pathologic examination also showed significantly less hepatosplenomegaly and lymphadenopathy in animals treated with pentoxifylline and meclofenamic acid. Partly, PgE2-induced suppression of interferon alpha production may mediate expression of retrovirus infection in this murine model of AIDS.
Acquired Immunodeficiency Syndrome↗
Identification of a cDNA for a human high-molecular-weight B-cell growth factor.
Proliferation is necessary for many of the phenotypic changes that occur during B-cell maturation. Further differentiation of mature B cells into plasma cells or memory B cells requires additional rounds of proliferation. In this manuscript, we describe a cDNA for a human B-cell growth factor we call high-molecular-weight B-cell growth factor (HMW-BCGF). Purified HMW-BCGF has been shown to induce B-cell proliferation, inhibit immunoglobulin secretion, and selectively expand certain B-cell subpopulations. Studies using antibodies to HMW-BCGF and its receptor have suggested that HMW-BCGF, while produced by T cells and some malignant B cells, acts predominantly on normal and malignant B cells. The HMW-BCGF cDNA was identified by expression cloning using a monoclonal antibody and polyclonal antisera to HMW-BCGF. Protein produced from the cDNA induced B-cell proliferation, inhibited immunoglobulin secretion, and was recognized in immunoblots by anti-HMW-BCGF antibodies. The amino acid sequence of HMW-BCGF deduced from the cDNA predicts a secreted protein of 53 kDa with three potential N-linked glycosylation sites. The identification of this cDNA will allow further studies examining physiologic roles of this cytokine. We propose to call it interleukin 14.
Amino Acid Sequence↗
The alpha-interferon system in patients undergoing renal transplantation and treated with cyclosporine and prednisone.
The interferon system was investigated in 65 normal control patients and ten patients with chronic renal disease, approximately a half year after renal transplantation and treatment with prednisone and cyclosporine. In previous studies, comparable doses of prednisone had no effect on the interferon system. It was assumed that the changes observed were primarily the result of cyclosporine therapy. In contrast with normal persons, low levels of interferon-alpha (IFN-alpha) were found in the circulation of patients. It was thought that this may be related to low grade infections in immunosuppressed persons. In patients, the IFN-alpha synthesizing capacity of leukocytes was significantly decreased. IFN-alpha inhibitor level was slightly increased in two patients. Inhibition of IFN-alpha (IFN-alpha) synthesizing capacity may be part of the immunosuppression mechanism of action of cyclosporine in patients undergoing transplant.
Adolescent↗
Differentiation of acute promyelocytic leukemia cell induced by 1,25-dihydroxyvitamin D3 and pentoxifylline (Trental).
Human promyelocytic leukemia cell line HL-60 in tissue culture was treated with various concentrations of 1,25-dihydroxyvitamin D3, (D3) pentoxifylline (Px) or in combinations. Differentiation to normal granulocytes or monocytes was evaluated by nitroblue tetrazolium (NBT) reducing capacity and morphologic criteria. (D3) produced monocytic differentiation, but sub-differentiation inducing doses of (Px) had no effect. In previous studies we found higher doses of (Px) to produce granulocytic differentiation in vitro and in vivo.
Calcitriol↗
"Stiff red cell syndrome". A review of the treatment of sickle cell disease with pentoxifylline.
Pentoxifylline has been used extensively to improve microcirculation, particularly in peripheral vascular disease. Pentoxifylline appears to act by increasing red cell flexibility and inhibiting platelet aggregation and white cell adhesion. For that reason, experimental and clinical studies were initiated to explore its possible usefulness in the prevention of vaso-occlusive crises in sickle cell diseases. The current status of such studies is reviewed.
Animals↗
Pentoxifylline in treatment of acquired immunodeficiency syndrome?
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Acquired Immunodeficiency Syndrome↗
Effect of red blood cells from patients with sickle cell disease on platelet factor 3 release.
Red cells from two SS genotype and two SA genotype patients were sampled. When the samples were deoxygenated and mixed with platelet-rich plasma, they caused the release of platelet factor 3 as recorded in a coagulometer. This phenomenon was not present in control blood samples from normal individuals. Membrane changes in abnormal red cells during hypoxia may be responsible in part for platelet activation and its role in vasoocclusive crisis. Vasoocclusive crisis could be prevented by increasing the red cell membrane fluidity and inhibiting the platelet aggregation with pentoxifylline.
Adult↗
Studies on tumor induced angiogenesis.
Methods were developed to test angiogenic response to human tumor implants and various biologic agents in the cornea of rabbits and non-human primates (Macaca arctoides). Crude PDGF preparations were found to have significant angiogenic effect. Purified, recombinant PDGF preparations were also effective inhibitors (e.g. pentoxifylline (Px) (which also were found to release PgI2 and t-PA) inhibited human tumor implant induced angiogenesis and reduced spontaneous metastases in 3 transplantable murine tumors (Furth-Columbia Wilms' tumor in Furth-Wistar rats, C-1300 neuroblastoma in A/J mice and HM-Kim mammary carcinoma in Wistar rats) but not in the NIH adenocarcinoma in Balb/c mice. Sodium diethyldithiocarbamate (DDTC), a metal complexing agent with special affinity to copper and anti-thyroid as well as, immune stimulating activity was shown to be anti-angiogenic and to potentiate the effect of Px. The anti-fibrinolytic agents epsilon amino caproic acid (EACA) and tranaxamic acid (t-AMCHA) were anti-angiogenic. DDTC and Px were synergistic from this point of view.
Adenocarcinoma↗