(Rubiaceae, Ophiorrhizeae), a new species from Vietnam.

is described as a new species endemic to Central Vietnam. It is morphologically closest to in having setose hairs on the abaxial leaf surface and a pedunculate head-like inflorescence but differs from the latter by a number of characteristics: shorter stem, 3-lobed stipules, narrowly lanceolate leaf blades with a cuneate-oblique base and 20-22 pairs of secondary veins, 3.5-4.

A new species of (Araceae) from Vietnam.

is described as a new species endemic to Vietnam. It is unique in the genus in having an oblong-elliptic spathe limb with an obtuse apex and yellowish-greenish filiform staminodes with a down-curved acumen. The ecology, distribution and assessment of the conservation status of the new taxon, as well as a key to all known species in Vietnam, are provided.

Targeting PRMT1-mediated FLT3 methylation disrupts maintenance of MLL-rearranged acute lymphoblastic leukemia.

Relapse remains the main cause of MLL-rearranged (MLL-r) acute lymphoblastic leukemia (ALL) treatment failure resulting from persistence of drug-resistant clones after conventional chemotherapy treatment or targeted therapy. Thus, defining mechanisms underlying MLL-r ALL maintenance is critical for developing effective therapy. PRMT1, which deposits an asymmetric dimethylarginine mark on histone/non-histone proteins, is reportedly overexpressed in various cancers.

Targeting cell membrane HDM2: A novel therapeutic approach for acute myeloid leukemia.

The E3 ligase human double minute 2 (HDM2) regulates the activity of the tumor suppressor protein p53. A p53-independent HDM2 expression has been reported on the membrane of cancer cells but not on that of normal cells. Herein, we first showed that membrane HDM2 (mHDM2) is exclusively expressed on human and mouse AML blasts, including leukemia stem cell (LSC)-enriched subpopulations, but not on normal hematopoietic stem cells (HSCs).

Autophagy mediates proteolysis of NPM1 and HEXIM1 and sensitivity to BET inhibition in AML cells.

The mechanisms underlying activation of the BET pathway in AML cells remain poorly understood. We have discovered that autophagy is activated in acute leukemia cells expressing mutant nucleophosmin 1 (NPMc+) or MLL-fusion proteins. Autophagy activation results in the degradation of NPM1 and HEXIM1, two negative regulators of BET pathway activation.

Expression and Role of the ErbB3-Binding Protein 1 in Acute Myelogenous Leukemic Cells.

Purpose: The ErbB3-binding protein 1 (Ebp1) has been implicated in diverse cancers as having either oncogenic or tumor suppressor activities. The present study was undertaken to determine the effects of Ebp1 expression in AML cells and to determine the mechanisms by which Ebp1 promotes cell proliferation in these cells.

Experimental Design: The expression of Ebp1 was studied in mononuclear cells obtained from the peripheral blood of 54 patients with AML by Western blot analysis.

Reversibility of Defective Hematopoiesis Caused by Telomere Shortening in Telomerase Knockout Mice.

Telomere shortening is common in bone marrow failure syndromes such as dyskeratosis congenita (DC), aplastic anemia (AA) and myelodysplastic syndromes (MDS). However, improved knowledge of the lineage-specific consequences of telomere erosion and restoration of telomere length in hematopoietic progenitors is required to advance therapeutic approaches. We have employed a reversible murine model of telomerase deficiency to compare the dependence of erythroid and myeloid lineage differentiation on telomerase activity.

Identification and genetic manipulation of human and mouse oesophageal stem cells.

Objective: Human oesophageal stem cell research is hampered by the lack of an optimal assay system to study self-renewal and differentiation. We aimed to identify and characterise human and mouse oesophageal stem/progenitor cells by establishing 3-dimensional organotypic sphere culture systems for both species.

Design: Primary oesophageal epithelial cells were freshly isolated and fluorescence-activated cell sorting (FACS)-sorted from human and mouse oesophagus and 3-dimensional organotypic sphere culture systems were developed.

Regulation of ribosomal RNA synthesis in T cells: requirement for GTP and Ebp1.

Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil, an effective immunosuppressive drug. Both MPA and mycophenolate mofetil are highly specific inhibitors of guanine nucleotide synthesis and of T-cell activation. However, the mechanism by which guanine nucleotide depletion suppresses T-cell activation is unknown.

Regulation of ribosomal gene expression in cancer.

The ability of a cell to undergo malignant transformation is both associated with and dependent on a concomitant increase in protein synthesis due to increased cell division rates and biosynthetic activities. Protein synthesis, in turn, depends upon the synthesis of ribosomes and thus ultimately on the transcription of ribosomal RNA by RNA polymerase I that occurs in the nucleolus. Enlargement of nucleoli has long been considered a hallmark of the malignant cell, but it is only recently that the rate of synthesis of rRNA in the nucleolus has been recognized as both a critical regulator of cellular proliferation and a potential target for therapeutic intervention.

Interaction of TIF-90 and filamin A in the regulation of rRNA synthesis in leukemic cells.

The transcription initiation factor I (TIF-IA) is an important regulator of the synthesis of ribosomal RNA (rRNA) through its facilitation of the recruitment of RNA polymerase I (Pol I) to the ribosomal DNA promoter. Activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, which occurs commonly in acute myelogenous leukemia, enhances rRNA synthesis through TIF-IA stabilization and phosphorylation. We have discovered that TIF-IA coexists with a splicing isoform, TIF-90, which is expressed preferentially in the nucleolus and at higher levels in proliferating and transformed hematopoietic cells.

Akt activation enhances ribosomal RNA synthesis through casein kinase II and TIF-IA.

Transcription initiation factor I (TIF-IA) plays an essential role in regulating ribosomal RNA (rRNA) synthesis by tethering RNA polymerase I (Pol I) to the rDNA promoter. We have found that activated Akt enhances rRNA synthesis through the phosphorylation of casein kinase IIα (CK2α) on a threonine residue near its N terminus. CK2 in turn phosphorylates TIF-IA, thereby increasing rDNA transcription.

Rat prostate explants in serum-free organ culture: a comparison of two media and gas mixtures.

Background: Urologists are looking for a way to easily discriminate between aggressive and very slow-growing prostate tumors. A sound way to appreciate such developing activities would be to identify an appropriate cell marker in prostate explants maintained in a defined culture system.

Methods: Different biological parameters were compared in rat prostate explants cultured for 5 days in rich CMRL or basic Leibovitz's L-15 medium, unsupplemented with serum, under a mixture of either 95% air/5% CO2 or 50% N2/45% O2/5% CO2.

Kinin receptors in the diabetic mouse.

It has been proposed that kinins are important inflammatory mediators involved in the pathogenesis of several diseases. In the present study, we attempted to determine the effects of kinins in a type I diabetic mouse model, using in vitro assays. Injection of streptozotocin (STZ) to the C57BL/Ks mdb mice causes an insulitis (inflammation of Langerhans islets) that leads to the diabetic condition.

Pharmacological profiles of the human and rabbit B1 receptors.

Twenty-two peptides related to kinins were used (i) to examine some chemical features required for the human and rabbit B1 receptor activation or blockade and (ii) to establish the existence of a correlation between the pharmacological spectrum of the B1 receptor obtained on the rabbit aorta (rbA) and the human umbilical vein (hUV). The apparent affinities of these peptides were measured in vitro using classical bioassays and are expressed in terms of pD2 (for agonists) or pA2 values (for antagonists). Selectivity for the B1 receptor was demonstrated by testing the peptides against the effect of bradykinin (BK) on the hUV and the rabbit jugular vein (rbJV), two preparations containing B2 receptor-mediating vasoconstriction.

Antagonists for kinin B1 and B2 receptors in the mouse.

Contractile responses to B1 and B2 receptor agonists have been demonstrated in the mouse stomach; the mouse urinary bladder responds only to B2 receptor agonists. These tissues were used in this study to investigate the antagonistic effect of four B2 receptor antagonists, namely, DArg[Hyp3,DPhe7,Leu8]BK (BK, bradykinin), HOE-140, WIN 64338, and FR-173657 (B2 receptor antagonists), as well as three B1 kinin receptor antagonists; [Leu8]desArg9BK, Lys[Leu8]desArg9BK, and AcLys[D beta Nal7,Ile8]desArg9BK, were investigated. Results shown indicate that DArg[Hyp3,DPhe7,Leu8]BK is a partial agonist, while HOE-140 and FR-173657 are pure antagonists, devoid of direct myotropic effects, and quite selective for the B2 receptor.

Neurokinin receptors (NK1, NK2) in the mouse: a pharmacological study.

Experiments were performed on strips of mouse stomach and urinary bladder to characterize the receptors involved in the contractile responses of these tissues to neurokinins (substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and neuropeptide gamma (NP gamma). The neurokinin receptors were characterized by using assays with selective agonists as well as peptide and nonpeptide antagonists and by applying the two Schild criteria for receptor classification, namely, the order of potency of agonists and the apparent affinity of competitive antagonists. The mouse stomach contains primarily NK1 and NK2 functional sites and possibly some NK3 receptors, whereas the urinary bladder possesses only the NK2 receptor.

Pharmacological heterogeneity of neurotensin receptors: an in vitro study.

Neurotensin (NT), a linear tridecapeptide, has been shown to exert a variety of biological effects in the periphery and in the central nervous system. The aim of the present study was to characterize the NT receptors mediating the contractions of two isolated organs, the rat stomach strip and the guinea pig ileum. More than 20 compounds, peptides, nonpeptides, or pseudopeptides, were tested for their agonistic and antagonistic effects against NT and a series of potent analogs or fragments.

The effects of insulin, transferrin and androgens on rat prostate explants in serum-free organ culture.

A model previously developed in our laboratory to culture rat prostate explants in serum-free chemically-defined medium was used to evaluate the direct influence of potential regulators. The aim of the present work was to verify the effects of insulin (I) and transferrin (Tr), two hormones considered as essential in other serum-free culture systems, and three androgenic hormones, since the prostate is known to be androgen-dependent. Explants of rat prostate were cultured for five days in serum-free Leibovitz's L-15 medium (37 degrees C, 95% air-5% CO2).

Structure-activity studies of B1 receptor-related peptides. Antagonists.

We tested several peptides related to des-Arg9-bradykinin as stimulants or inhibitors of B1 (rabbit aorta, human umbilical vein) and B2 (rabbit jugular vein, guinea pig ileum, human umbilical vein) receptors. We also incubated the compounds with purified angiotensin-converting enzyme from rabbit lung to test their resistance to degradation. We evaluated apparent affinities (in terms of the affinity constant pA2) of compounds and their potential residual agonistic activities (alpha E).

Receptors for kinins: from classical pharmacology to molecular biology.

In the past 20 years, we have focused our efforts on the study of kinin receptors involved in contraction or relaxation of vascular smooth muscle. Initial studies on rabbit vessels led to the discovery of two kinin receptors, B1 and B2, mediating contraction of the rabbit aorta (B1) and the rabbit jugular vein (B2). Studies on dog vessels contributed to the identification of B2 receptors in arterial endothelium promoting the release of NO and the relaxation of arterial smooth muscles; further studies on dog renal vessels led to the demonstration of B2 receptors in endothelia and in the smooth muscle, mediating relaxation through NO (endothelia) and prostanoids (smooth muscle).

Receptors for kinins: from classical pharmacology to molecular biology.

In the past twenty years, we have focused our efforts on the study of kinin receptors involved in contraction or relaxation of vascular smooth muscle. Initial studies on rabbit vessels led to the discovery of two kinin receptors, B1 and B2, mediating contraction of the rabbit aorta (B1) and the rabbit jugular vein (B2). Studies on dog vessels contributed to the identification of B2 receptors in arterial endothelium promoting the release of NO and the relaxation of arterial smooth muscles; further studies on dog renal vessels led to the demonstration of B2 receptors in endothelia and in the smooth muscle, mediating relaxation through NO (endothelia) and prostanoids (smooth muscle).

Pharmacological characterization of SR 142801: a new non-peptide antagonist of the neurokinin NK-3 receptor.

Pharmacological and biochemical assays were performed to characterize SR 142801, a new NK-3 receptor antagonist, and its [R]-enantiomer, SR 142806. The compounds were tested (1) in the guinea pig isolated ileum stimulated with [MePhe7]NKB (NK-3 system) in order to evaluate onset and duration of action and to estimate the apparent affinity of the antagonist in terms of pA2 at 140 min after application; (2) in 6 selected monoreceptor systems, the rabbit (rb) vena cava for the NK-1rb receptor, the rabbit pulmonary artery and the hamster (hs) urinary bladder for the NK-2rb and NK-2hs receptors, the rat (r) portal vein for the NK-3r receptor, and in two multireceptor systems adequately treated with NK-1 or NK-2 receptor antagonists to obtain monoreceptor-mediated biological responses (the rat urinary bladder treated with SR 48968 for evaluating the NK-1r and the guinea pig-gp-ileum treated with CP-99994 for measuring the antagonist affinity on the NK-3gp receptor), in order to evaluate the antagonist selectivity, and (3) in various plasma membrane preparations containing NK-3-binding sites from rats, guinea pigs, and man. The data presented indicate that SR 142801 is a potent, fairly selective non-peptide antagonist of the functional (pA2 9.

Receptors for kinins in the human isolated umbilical vein.

1. The human umbilical vein has been found to contract in response to bradykinin (BK) and desArg9BK. 2.