Neutrophil maturation occurs in well defined morphological stages that correlate with the acquisition of molecular markers associated with neutrophil function. A variety of factors are known to play a role in terminal neutrophil maturation, including the vitamin A derivative, retinoic acid. Retinoic acid can directly modulate gene expression via binding ...

In order to investigate the direct effects of retinoids on normal adult hematopoietic progenitors, purified CD34+ cells were seeded in serum-free cultures in the presence of pharmacological (10(-6)) M or physiological (10(-12)) M concentrations of all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA) plus combinations of specific cytokines. ...

The mechanisms underlying the growth-inhibitory effect of retinoids on normal human B lymphocytes are not well understood. We addressed this issue by examining the effect of retinoic acid on the cell cycle machinery involved in G1/S transition. When retinoic acid was administered to B cells stimulated into mid to late ...

Retinoic acids, structurally related to vitamin A, inhibit the in vitro proliferation of different types of normal and neoplastic cells. The effects of all-trans, 9-cis, and 13-cis retinoic acids were tested on mitochondria isolated from rat liver. All the compounds were able to induce the membrane permeability transition observed as ...

Laser desorption ionization (LDI)- and matrix-assisted laser desorption ionization (MALDI)-mass spectrometry (LDI-MS, MALDI-MS) at 337-nm laser wavelength were used to analyze retinol (vitamin A), retinoic acid, and retinal and their analogs 3-hydroxyretinol, 3-hydroxyretinoic acid, 3-hydroxyretinal, 4-oxoretinol, 4-oxoretinoic acid, 4-oxoretinal, 3,4-didehydroretinol (vitamin A(2)), 3,4-didehydroretinoic acid, 3,4-didehydroretinal, acycloretinol, acycloretinoic acid, and acycloretinal. ...

Retinoids, natural or synthetic substances which have vitamin A activity, have a well-known reputation for their antitumour and differention-inducing activity in vitro and in vivo. More than 1500 retinoids have been tested so far but very few of them have been entered into clinical trials because of their side-effects. All-trans-N-(4-hydroxyphenyl)retinamide ...

Vitamin A is an intrinsic modulator of proliferation and differentiation in human epidermis, and may be destroyed by ultraviolet radiation (UVR) impinging on the skin. To identify the deleterious effects of a perturbed cellular vitamin A status, we investigated the endogenous retinoid concentrations and the metabolism of [3H]retinol and all-trans ...

13-cis retinoic acid (RA) is a causative agent for human/monkey retinoic acid embryopathy (RAE), in which the most common type of malformation is microtia or anotia. In the present study, malformed ears of monkey fetuses exposed to RA during early embryogenesis were analyzed and revealed a subtype of defects., i.e., ...

We investigated the biological effects of five all-trans retinoic acid derivatives, bearing heterocyclic ring systems in the side chain. Growth assays performed on submerged human fibroblast and keratinocyte cultures revealed that (E)4-[2-(5-terbuthyl-thiophen-2-yl)propenyl]benzoic acid (compound 5) is the best compound among the studied derivatives for it exhibits a weaker antiproliferative activity ...

Retinoic acid receptor alpha (RARalpha) is the target of several chromosomal translocations associated with acute promyelocytic leukemias (APLs). These rearrangements fuse RARalpha to different partner genes creating the chimeric proteins: PML-RARalpha, PLZF-RARalpha, and NPM-RARalpha. Although the vast majority of APLs respond to retinoic acid therapy, those associated with PLZF-RARalpha are ...

We have shown previously that retinoids induce apolipoprotein (apo) A-I gene expression in cultured cynomolgus hepatocytes and do not have an effect on apo B-100 synthesis. In the present study, the effect of retinoids on apolipoprotein(a) (apo(a)) synthesis in cultured hepatocytes was investigated. The addition of all-trans retinoic acid (at-RA) ...

Some members of the human alcohol dehydrogenase (ADH) family possess retinol dehydrogenase activity and may thus function in production of the active nuclear receptor ligand retinoic acid. Many diverse natural forms of retinol exist including all-trans-retinol (vitamin A(1)), 9-cis-retinol, 3,4-didehydroretinol (vitamin A(2)), 4-oxo-retinol, and 4-hydroxy-retinol as well as their respective ...

We have previously demonstrated that gene expression of the hepatocyte nuclear factor 3alpha (HNF-3alpha) transcription factor is activated during retinoic-acid-induced differentiation of F9 embryonal carcinoma cells (A. Jacob et al. (1994). Nucleic Acids Res. 22, 2126-2133). We have extended these studies and now show that HNF-3alpha mRNA is induced approximately ...

The combined use of retinoic acid and chemotherapy has led to an important improvement of cure rates in acute promyelocytic leukemia. Retinoic acid forces terminal maturation of the malignant cells and this application represents the first generally accepted differentiation-based therapy in leukemia. Unfortunately, similar approaches have failed in other types ...

A new bleaching protocol for skin hyperpigmentation with a higher concentration of all-trans retinoic acid (atRA) aqueous gel than those commercially available is introduced. AtRA aqueous gel (0.1%) was applied topically twice a day along with 4% hydroquinone, 7% lactic acid ointment to oriental patients with hyperpigmented lesions such as ...

Retinoic acid has manifold effects on pancreatic beta-cells. Previously we reported that retinoic acid increases glucokinase activity and messenger RNA (mRNA) levels in the insulinoma cell line RIN-m5F; however, we could not rule out the possibility that the effect of retinoic acid on RIN-m5F glucokinase was inherent to the cell ...

Retinoic acid syndrome is a serious condition that may complicate the treatment of acute promyelocytic leukaemia patients. This syndrome may be treated effectively with high-dose corticosteroid therapy and, as a result, many patients with acute promyelocytic leukaemia receive dexamethasone at some point during treatment. We investigated whether dexamethasone would also ...

Control of retinoic acid synthesis in vertebrate organisms is undoubtedly important for regulating the numerous retinoid signaling events which occur during development. The mechanisms which accomplish this task involve enzymes such as class I aldehyde dehydrogenase (ALDH1), which has recently been found to be conserved from amphibians to mammals and ...

Because retinyl palmitate was reported to be more stable to oxidation than retinol, we wondered if retinyl palmitate was also more resistant to photolysis as compared to free alcohol. We investigated the resistance of ethanolic solutions of retinol, retinyl palmitate, or both to air oxidation and (or) photolysis using fluorescent ...

Determination of the left-right position (situs) of visceral organs involves lefty, nodal and Pitx2 genes that are specifically expressed on the left side of the embryo. We demonstrate that the expression of these genes is prevented by the addition of a retinoic acid receptor pan-antagonist to cultured headfold stage mouse ...

Differentiation therapy using retinoic acids (RAs) or 1alpha25-dihydroxyvitamin D3 (D3) is an attractive alternative to chemotherapy in acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). However, with the exception of RA therapy for acute promyelocytic leukaemia (APL), RAs and D3 are not potent enough at doses that can be tolerated ...

Solar radiation contains ultraviolet B (280-315 nm) and ultraviolet A (ultraviolet AII, 315-340 nm; ultraviolet AI, 340-400 nm) wavebands. Ultraviolet B is known to suppress certain aspects of cell mediated immunity. Using three ultraviolet lamps (the broad-band ultraviolet B TL-12, the narrow-band ultraviolet B TL-01 and an ultraviolet AI source), ...

The discovery of the oncogene and the mechanism by which these genetic changes create malignant transformation has provided new opportunities for drug development. Suramin is the first drug shown to exert its anticancer activity by blocking autocrine loops involved in malignant transformation. Phenylacetate and related aromatic fatty acids are potent ...

The remarkable success of retinoic acid in the treatment of acute promyelocytic leukemias and the subsequent discovery that mutant forms of a retinoid acid receptor (RARalpha) are invariably associated with this disease has generated considerable interest among both clinicians and basic scientists. Studies both in cell culture and in transgenic ...

Apo-carotenoids with different numbers of conjugated double bonds are formed upon eccentric cleavage of carotenoids. These compounds may exhibit biological activities similar to those of the parent carotenoids or their central cleavage products, the retinoids. 11-Apo-canthaxanthin-11-oic acid, 13-apo-canthaxanthin-13-oic acid, and 14'-apo-canthaxanthin-14'-oic acid, carrying 2, 3, or 5 conjugated double bonds ...

Despite the high effectiveness of various P-glycoprotein (P-gp) modulating substances in vitro their clinical value e.g. for combination treatment of acute myelogenous leukemias (AML) remains still unclear. This might be explainable by recent findings that other factors than P-gp (e.g. the multidrug resistance associated protein (MRP)) may also be involved ...

Mammalian class I aldehyde dehydrogenase (ALDH1) has been implicated as a retinal dehydrogenase in the biosynthesis of retinoic acid, a modulator of gene expression and cell differentiation. As the first step towards studying the regulation of ALDH1 and its physiological role in the biosynthesis of retinoic acid, mouse ALDH1 cDNA ...

The recent availability of tazarotene, the first receptor-selective retinoid, provides a much-needed addition to the therapeutic armamentarium for mild-to-moderate plaque psoriasis. Tazarotene gel offers a welcome combination of good efficacy and cosmetic acceptability, with minimal risk of systemic adverse effects. The selectivity of tazarotene for the beta and gamma subtypes ...

BACKGROUND: Accumulation of the cytosine arabinoside (ara-C) metabolite ara-C-triphosphate (ara-CTP) in leukemic blast cells is considered to be the main determinant of ara-C cytotoxicity in vitro and in vivo. Retinoids such as all-trans-retinoic acid (ATRA) have been shown to increase the sensitivity of acute myelogenous leukemic (AML) blast cells to ...

We have previously shown that daily application of 0.05% retinoic acid to the backs of lightly pigmented, hairless HRA:Skh-2 mice increases melanogenesis resulting from exposure to solar-simulated ultraviolet radiation. In this study we show that as early as 1 wk following commencement of treatment, there is a 2- fold increase ...

1. Effects of arachidonic acid, prostaglandins, retinol, retinoic acid and cholecalciferol on xenobiotic oxidations catalysed by 12 recombinant human cytochrome P450 (P450 or CYP) enzymes and by human liver microsomes have been investigated. 2. Arachidonic acid (50 microM) significantly inhibited CYP1A1- and 1A2-dependent 7-ethoxycoumarin O-deethylations, CYP2C8-dependent taxol 6alpha-hydroxylation and CYP2C19-dependent ...

A series of high affinity retinoic acid receptor (RAR) antagonists were prepared based upon the known antagonist AGN 193109 (2). Introduction of various phenyl groups revealed a preference for substitution at the para-position relative to the meta-site. Antagonists with the highest affinities for the RARs possessed hydrophobic groups, however, the ...

In order for nuclear retinoic acid receptors to mediate retinoid signaling, the ligand retinoic acid must first be produced from its vitamin A precursor retinal. Biochemical studies have shown that retinal can be metabolized in vitro to retinoic acid by members of the aldehyde dehydrogenase enzyme family, including ALDH1. Here ...

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by hypergranular leukemic cells, bleeding diathesis and t(15; 17) translocation. The t(15; 17) translocation leads to the production of the PML-RAR alpha fusion protein which plays a vital role in the pathogenesis of APL by arresting normal ...

Retinoic acid exerts pleiotropic effects by acting through two families of nuclear receptors, RAR and RXR. All-trans and 9-cis retinoic acid bind RARs, whereas 9-cis retinoic acid binds and activates only the RXRs. To understand the role of human liver cytosolic aldehyde dehydrogenase (ALDH1) in retinoic acid synthesis, we examined ...

The uptake and metabolism of retinol was compared in squamous cell carcinoma lines, SCC12b and SCC13, and in normal human keratinocytes (NHK). Long chain fatty acid esters of retinol and 3,4-didehydroretinol were the predominant metabolites formed in both cell types. Lesser amounts of unesterified retinol, 3,4-didehydroretinol, and their respective active ...

The results of the present study showed that administration of 13-cis-retinoic acid or retinol acetate for 6 weeks reduced the diameter of the seminiferous tubules in the testes of <I>Gerbillus chessemani</I>. Also, a decrease in the Leydig cell count was observed. However, the ratio of spermatogenesis was decreased only by ...

OBJECTIVE: In order to circumvent the tolerance problems encountered with topical application of retinoic acid - a biologically active metabolite of vitamin A - we performed in various models a series of experiments aimed at assessing the bio-availability of topical retinaldehyde and its conversion into either retinoid stores or biologically ...

Dietary deprivation and gene disruption studies clearly demonstrate that biologically active retinoids, such as retinoic acid (RA), are essential for numerous developmental programs. Similar ontogenic processes are also affected by retinoic acid excess, suggesting that the effects of retinoid administration reflect normal retinoid-dependent events. In the mouse, exogenous retinoic acid ...

Neurofibromin and p120 GTPase activating protein (p120 GAP) down-regulate the activity of cellular Ras proteins. How the activity of these two proteins is controlled is not yet clear. In this study, we analyzed the effects of eight nutritionally relevant fatty acids on GTPase stimulatory activity of full-length neurofibromin and p120 ...

BACKGROUND: Retinaldehyde is a key molecule in the metabolism of vitamin A by keratinocytes. In order to evaluate its range of topical activity in acne, its comedolytic effect was compared to that of retinoic acid in the same vehicle, in the rhino mouse model. METHODS: The animals were treated on ...

Suramin is an anti-neoplastic drug. Its actions include the inhibition of binding of urokinase-type plasminogen activator (uPA) to its receptor, an event which may prevent cartilage breakdown. The aim of this work was to determine the effect of suramin on cartilage resorption. Cartilage expiants, stimulated with interleukin-1alpha, tumour necrosis factor-alpha ...

Vitamin A derivatives (retinoids) play a key role in mammalian development and cell differentiation. Isomers of retinoic acid, the main active metabolite of vitamin A, activate retinoid receptors that act as ligand-dependent transcription factors and affect gene expression. White and brown adipose tissues are major sites of storage of vitamin ...

Retinoic acid receptor (RAR) is a ligand-dependent transcription factor that regulates the expression of genes involved in cell growth, differentiation, and development. Binding of the retinoic acid hormone to RAR is accompanied by conformational changes in the protein which induce transactivation or transrepression of the target genes. In this paper ...

BACKGROUND: Studies comparing purported antiaging compounds are rare. OBJECTIVE: To compare in a randomized, placebo-controlled double-blind study 10% glycolic acid (GA), 2% 2-hydroxy-5-octanoyl benzoic acid (beta-lipohydroxy acid, LSA) and 0.05% all-trans-retinoic acid (RA). METHODS: Women volunteers treated one forearm twice daily with one of the active products and the other ...

Vitamin A and related compounds, also known as retinoids are thought to play a role in the development of head and neck cancer. We measured levels of the major retinoids, retinol, all-trans retinoic acid, 13-cis retinoic acid and 13-cis-4-oxo retinoic acid in plasma of head and neck cancer patients in ...

The effect of retinoids on spermatogenesis in adult male gerbils (Gerbillus cheesemani) was studied using light and electron microscopy. Treatment with either 13-cis-retinoic acid or retinol acetate was given for 6 weeks and their effects were compared with controls. It was found that 13-cis-retinoic acid induced almost complete cessation of ...

Using 1H NMR two diastereoisomers of the ethacrynic acid glutathione conjugate (EASG) as well as ethacrynic acid (EA) could be distinguished and quantified individually. Chemically prepared EASG consists of equal amounts of both diastereoisomers. GSTP1-1 stereospecifically catalyzes formation of one of the diastereoisomers (A). The GSTP1-1 mutant C47S and GSTA1-1 ...

This two-part series provides an up-to-date summary of the various chemopreventive agents currently in development and testing. Part 1, published in last month's issue, focused on the retinoids, such as all-trans-retinoic acid (ATRA [Vesanoid]), 9-cis-retinoic acid (9cRA), and isotretinoin (Accutane), and the carotenoids, such as beta-carotene and lycopene, and other ...

OBJECTIVE: We compared the activity and tolerance profile of a 0.05% retinaldehyde cream with a 0.05% retinoic acid cream and the retinaldehyde vehicle in patients with photodamaged skin of the face. METHODS: A silicone replica of the left crow's feet area was taken at baseline and at weeks 18 and ...