Quote from Dr. Garrett Smith on November 19, 2018, 6:34 pm

Serum Retinol-Binding Protein 4 Concentration and Its Ratio to Serum Retinol Are Associated with Obesity and Metabolic Syndrome Components in Children https://academic.oup.com/jcem/article/92/11/4359/2598752

Concept: Think of the RAR/RXRs as a screw that has the Philips-style slot, and that also has the extra channel so that a slothead screwdriver can be used, but is not optimal. The screw can be manipulated with multiple different tools. It is meant to be manipulated with DHA and ARA, that's the Philips head. Vitamin A is the slothead, which can be used, but is not optimal, yet it can "do some of the job" (fix blindness and xeropthalmia) that the other tool can do. Then, there are the nasty things that can also brute force turn the screw, like using pliers to grab the head of the screw and turn (this is like glyphosate and other compounds that are demonstrably bad for us and also are ligands for the RAR/RXRs). Yes, the screw is turned, but there's a lot of damage. If too many screws are being turned all the time, the screws get damaged and the body stops making as many of them to turn (downregulation, a known defense mechanism against overstimulation). This messes up the whole system.  On the other hand, things in the research that "potentiate" or "synergize" or "re-sensitize" the RAR/RXR are likely kicking out the VA or other toxic compounds from the receptor, allowing it to reset (upregulate?) and become active again to work properly. Then the studies show "benefit" from VA again in the short-term, while again, it will destroy the same stuff in the long-term.

Important...shows how tissue toxicity can occur in spite of extremely low serum VA:  http://www.jbc.org/content/270/2/866.long

"RXR serves as the common heterodimerization partner for peroxisome proliferator-associated receptor (PPAR), "activated" Vitamin D3 receptor, thyroid hormone receptor (TR), and all-trans-retinoic acid receptor (RAR) (39,40). RXR and RAR are structurally and functionally distinct." https://books.google.com/books?id=SO7dBgAAQBAJ&pg=PT49&lpg=PT49&dq=rar+rxr+overstimulation&source=bl&ots=i1r8k1T0ML&sig=HQfJ6zGMh-7i-APnQVoKaVqw5DA&hl=en&sa=X&ved=2ahUKEwii1OWGhPzeAhVnwVQKHe8hBzcQ6AEwDHoECAEQAQ#v=onepage&q=rar%20rxr%20overstimulation&f=false

Mine for basic info: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931982/

"Administering excess tRA will overstimulate the signaling pathway" https://books.google.com/books?id=HP9Vg2ZXZLgC&pg=PA89&lpg=PA89&dq=rar+rxr+overstimulate&source=bl&ots=XClFfyh2Pg&sig=1kuBlVd2phP-PnsKuDpTljO9LK0&hl=en&sa=X&ved=2ahUKEwjnoNuXlPzeAhWkPH0KHc28DcYQ6AEwDnoECAoQAQ#v=onepage&q=overstimulate&f=false

"Their differential spatiotemporal patterns of expression suggest that fine regional control of availability of retinoic acid (RA) to the nuclear receptors plays an important role in organization and differentiation of the nervous system. For instance, expression of CRABP I in the migrating cells that give rise to the olivary and pontine nuclei, which develop abnormally in conditions of retinoid excess, is consistent with observations from a variety of other systems indicating that CRABP I limits the access of RA to the nuclear receptors in normal physiological conditions."

"All-trans retinoic acid significantly inhibited the expression of all the tested osteoblastogenic genes and proteins except alkaline phosphatase activity. In the presence of ATRA, 50 ng/ml bone morphogenetic protein-2/7 not only completely restored but also significantly enhanced all the osteoblastogenic genes and proteins. On the 28^th day, mineralization was completely inhibited by all-trans retinoic acid." https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0078198

"high doses of ATRA induce an over stimulation of RAR-a (retinoic acid receptor),"

Ligand/receptor explanation video:  https://www.youtube.com/watch?v=zJ4oSPJevR0

"Conclusions: Our results show that RA activation of the p38 intracellular pathway was essential for its early induction of apoptosis and partially responsible for promoting differentiation. DHA prevention of this apoptosis suggests that RA effects during early development must be counterbalanced by survival factors to prevent photoreceptor death, in an interplay that might help to establish the final number of photoreceptors." https://iovs.arvojournals.org/article.aspx?articleid=2189053

"Retinoid X receptor (RXR) is a promiscuous nuclear receptor forming heterodimers with several other receptors, which activate different sets of genes." https://mcb.asm.org/content/34/7/1234

Add to duration paradox rule:  "It is possible that downregulation of these receptors would suppress the expression of many developmental genes." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046313/

Example of duration paradox rule with atherosclerosis:
better short-term: http://www.advances.umed.wroc.pl/ahead-of-print/74552.pdf
worse with time:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961421/

The body will create bodyfat (to make protective RBP) around tissues (bodyfat, fatty liver, pericardial fat) in order to both create more storage space and to make more RBP (fat makes RBP): https://www.ncbi.nlm.nih.gov/pubmed/21645024

Look at Acne Vulgaris and Acne Rosacea section, and hypervitaminosis K (doesn't exist) section: https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/hypervitaminosis

The action of Vitamin K in hypervitaminosis A:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1258540/

VA depletes cellular Mg and reduces cellular energy production: https://www.ncbi.nlm.nih.gov/pubmed/9851825
Magnesium: https://www.ncbi.nlm.nih.gov/pubmed/19271422 , https://www.ncbi.nlm.nih.gov/pubmed/22364157

Serum retinyl esters are positively correlated with analyzed total liver vitamin A reserves collected from US adults at time of death https://academic.oup.com/ajcn/article-abstract/108/5/997/5201552 (note, no one outside of the research world tests retinyl esters, coincidence?)

Lithium and VA:  http://www.bloodjournal.org/content/120/21/2614?sso-checked=true , https://www.ncbi.nlm.nih.gov/pubmed/16408307

Higher levels of retinol, retinyl esters, and urine RBP in dogs with kidney stones:  https://www.ncbi.nlm.nih.gov/pubmed/14633234

Clinical Implications of Serum Retinol-Binding Protein (RBP) 4 in Asthmatic Children https://www.jacionline.org/article/S0091-6749(07)03025-4/abstract

Binding of the Active Vitamin A Metabolite Retinoic Acid to the Major Cows Milk Allergen Bos d 5 Down-Regulates T-Cell Responses (Vitamin A in dairy SUPPRESSES the immune system!) https://www.jacionline.org/article/S0091-6749(15)03076-6/abstract

Evaluation of thyroid function tests of acne vulgaris patients treated with systemic isotretinoin. https://www.ncbi.nlm.nih.gov/pubmed/27425198

Free fatty acids and endotoxins aggravate: https://www.researchgate.net/profile/Peter_Scott26/publication/5927591_A_Subpopulation_of_Macrophages_Infiltrates_Hypertrophic_Adipose_Tissue_and_Is_Activated_by_Free_Fatty_Acids_via_Toll-like_Receptors_2_and_4_and_JNK-dependent_Pathways/links/56ec178f08aed740cbb6111c.pdf , https://www.ncbi.nlm.nih.gov/pubmed/19122198 ,

Butyrate & SCFAs aggravate: https://www.ncbi.nlm.nih.gov/pubmed/27151945 , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942363/ , https://www.sciencedirect.com/science/article/pii/S0014299918302607 ,

Synergy between LPS (bacterial endotoxin) and retinoic acid: https://academic.oup.com/jn/article/131/10/2628/4686565

Bacterial endotoxin (LPS)-induced expression of COX-1 and COX-2 mRNA in human monocytic (THP-1) cells. (LPS activates COX1 and COX2):  https://www.researchgate.net/figure/Bacterial-endotoxin-LPS-induced-expression-of-COX-1-and-COX-2-mRNA-in-human-monocytic_fig3_8576526

Health risks related to high intake of preformed retinol (vitamin A) in the Nordic countries (includes doses of VA known to cause acute and chronic toxicity): http://folk.uio.no/runeb/pdf%20filer/Vitamin%20A%20toxicity.PDF

All-trans retinoic acid induces COX-2 and prostaglandin E2 synthesis: https://www.ncbi.nlm.nih.gov/pubmed/17204142

Summary of many of the above studies put together:

https://www.ncbi.nlm.nih.gov/pubmed/2100739 - "Brain uptake of substrates other than glucose has been demonstrated in neonatal but not fetal animals in vivo. This study was undertaken to investigate the ability of the fetal sheep brain to use potential alternative substrates when they were provided in increased amounts. Brain substrate uptake was measured in chronically catheterised fetal sheep during 2-h infusions of neutralised lactate (n = 12) or beta-hydroxybutyrate (n = 12). Despite large increases in fetal arterial lactate and beta-hydroxybutyrate during the respective infusions, no significant uptake of either substrate was demonstrated. However during both types of infusion, the brain arterio-venous difference for glucose decreased 30% (P less than 0.05). Since the brain arterio-venous difference for oxygen was unchanged, and blood flow to the cerebral hemispheres (measured in 11 studies) was also unchanged, the infusions appeared to cause a true decrease in brain glucose uptake. This decrease paralleled the rise in lactate concentration during lactate infusions, and the rise in lactate and butyrate concentrations during the butyrate infusions. Both substrates have metabolic actions that may inhibit brain glucose uptake. We speculate that the deleterious effects of high lactate and ketone states in the perinatal period may in part be due to inhibition of brain glucose uptake.”

Interpretation by Harry M: "Butyrate is also blocking glucose uptake in the brain, as well as activating retinoic production, inflammatory enzymes, releasing FFAs into the blood (which also activate TLR4 and cause inflammation) and then synergise with the retinoic acid."

Mechanisms of Vitamin A toxicity: https://www.ncbi.nlm.nih.gov/pubmed/1127357/

VA as a mitochondrial poison: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452429/

VA toxicity requiring a liver transplant, case study:  https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/lt.21007

Nigella sativa as protectant: https://sci-hub.tw/10.1024/0300-9831/a000121

Vitamin A messing up behavior and mood:  https://www.ncbi.nlm.nih.gov/pubmed/20659790 ,
https://www.nature.com/articles/1300998 , https://www.ncbi.nlm.nih.gov/pubmed/25578258 ,

Historical evidence of hypervitaminosis A:  http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.1009.4901&rep=rep1&type=pdf

Less Vitamin A slows progression of leukemia:  https://www.nature.com/articles/s41467-018-04150-7

More Sertoli cell damage:  https://www.researchgate.net/profile/Ramatis_De_Oliveira/publication/5413091_Retinol_and_retinoic_acid_modulate_catalase_activity_in_Sertoli_cells_by_distinct_and_gene_expression-independent_mechanisms/links/5b8f20d1299bf114b7f610bc/Retinol-and-retinoic-acid-modulate-catalase-activity-in-Sertoli-cells-by-distinct-and-gene-expression-independent-mechanisms.pdf

Coffee (possibly caffeine) and Vitamin A connections: http://www.alliedacademies.org/articles/effect-of-maternal-caffeine-and-retinoic-acid-intake-on-liver-during-pre-and-postnatal-development-of-mice-mus-musculus.html , http://file.scirp.org/pdf/NM_2015122414264517.pdf

Vitamin D supplements not helpful for osteoporosis https://www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30265-1/fulltext

Vitamin A Metabolism and Adipose Tissue Biology https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257733/ (already placed in duration paradox rule thread)

Liver damage caused by therapeutic vitamin A administration: Estimate of dose-related toxicity in 41 cases (discusses how liver biopsy is needed to show toxicity) https://www.gastrojournal.org/article/0016-5085(91)90672-8/pdf

Statins as an example of Duration Paradox rule:
http://cancerres.aacrjournals.org/content/67/9/4524
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3590479/
(easy to find the research showing statins promote cancer long-term)

DNA toxicity of carotenoids: https://www.ncbi.nlm.nih.gov/pubmed/22465157

Influence of High Protein Diets on Vitamin A Metabolism and Adrenal Hypertrophy in the Chick: https://academic.oup.com/jn/article-abstract/82/1/139/4779409

Big paper, cold exposure and more https://escholarship.org/uc/item/5rz736db

"Three generations of VAS feeding decreased atRA in most tissues of most strains, in some cases more than 50%, and maintained an order of liver = testis > kidney > white adipose tissue = serum. Neither serum retinol nor atRA reflected tissue atRA concentrations. Strain and tissue-specific differences in retinol and atRA that reflect different amounts of dietary vitamin A could have profound effects on retinoid action, and are predictive of strain dependent differences in enzymes regulating atRA synthesis and catabolism."

Lyme pdf https://academic.oup.com/jid/article-pdf/174/4/747/2431767/174-4-747.pdf , Lyme google books https://books.google.com/books?id=RajxCAAAQBAJ&pg=PA601&lpg=PA601&dq=serum+retinol+borrelia&source=bl&ots=FDsT6ra9pD&sig=pjJk5qcByu9y1syiXpb1wMvdq3w&hl=en&sa=X&ved=2ahUKEwi_kZGki9feAhWiMHwKHSJ1A5cQ6AEwBnoECAIQAQ#v=onepage&q=serum%20retinol%20borrelia&f=false

Carotenoids directly affecting Caucasian women's skin color: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517028/

Fossil evidence of VAT: https://academic.oup.com/cid/article/40/10/1454/308400

Vit A and cancer: http://europepmc.org/articles/PMC2001610

Put this in the testes/testosterone destruction thread: http://www.academia.edu/4578461/All_trans_-retinoic_acid_induces_apoptosis_in_Leydig_cells_via_activation_of_the_mitochondrial_death_pathway_and_antioxidant_enzyme_regulation

Open up abscisic acid rabbit hole: https://www.ncbi.nlm.nih.gov/pubmed/26594836 , https://www.ncbi.nlm.nih.gov/pubmed/25552429 ,

Sensory disorders linking to VA: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754244/

VA increasing effects of botox: https://www.ncbi.nlm.nih.gov/pubmed/23016532 , botox as treatment for MS: https://www.medicinenet.com/botox_to_treat_multiple_sclerosis_ms/article.htm , MS and VA connection: https://www.ncbi.nlm.nih.gov/pubmed/25149081

Pull out low A, high choline foods: https://blog.radiantlifecatalog.com/bid/63690/5-Ways-to-Get-More-Choline-in-Your-Diet-Secret-of-Radiant-Living

Circadian rhythm effects: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504648/

"Interestingly, the gut bacterial community was slightly altered by RA administration," https://www.nature.com/articles/srep25835#f6

More RBP4 = more retinol = more inflammation and disease: https://mcb.asm.org/content/32/24/5103

Ethanol/hangovers: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2830136/ , https://www.mayoclinic.org/diseases-conditions/hangovers/symptoms-causes/syc-20373012

"It has been known since the 1970s that retinyl ester bound to lipoproteins is an RBP-independent mechanism of delivering vitamin A (15). Since RBP knockout mice have primarily vision defects under vitamin A-sufficient conditions (16, 17), it is not surprising that RBP receptor knockout mice also have primarily vision defects under the same conditions (10)" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019051/

Causing long bone problems, possible cause of age-related leg bowing (example): https://www.ncbi.nlm.nih.gov/pubmed/3875458

Admitting problems with Vitamin A in skin products:  https://osmiaorganics.com/blogs/blog/rethinking-retinoids-a-modern-review

"These findings suggest that hypovitaminosis A in RA may be mediated by decreased vitamin A transport from the liver to the blood, caused by the low level of zinc dependent hepatic retinol binding protein synthesis." https://www.ncbi.nlm.nih.gov/pubmed/2591121

Vitamin E: https://www.ncbi.nlm.nih.gov/pubmed/28668878

Protein: https://www.ncbi.nlm.nih.gov/pubmed/2634036

Magnesium: https://www.ncbi.nlm.nih.gov/pubmed/19271422

Nutrients (figure 1):  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642414/

Low-carotenoid fruits: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2621.1964.tb01725.x

Selenium: https://www.ncbi.nlm.nih.gov/pubmed/19056238

Vitamin C: https://www.ncbi.nlm.nih.gov/pubmed/4040504

Same paper: https://www.sciencedirect.com/sdfe/pdf/download/eid/3-s2.0-B9780323352147000317/first-page-pdf , https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/hypervitaminosis-a , connect cyclodextrin to beta-glucan https://www.hindawi.com/journals/jnme/2012/851362/

All-trans retinoic acid selectively increases the potency of certain immunotoxins, http://jcb.rupress.org/content/jcb/125/4/743.full.pdf

ConsumerLab on toxicity of Vitamin A (last paragraph): https://www.consumerlab.com/answers/can-combining-vitamin-a-supplements-with-fish-oil-lead-to-a-vitamin-a-overdose/vitamin_A/

MS and Vitamin A:  https://multiple-sclerosis-research.blogspot.com/2013/01/vitamin-and-risk-of-ms.html

Toxicity of fish oils: http://www.jbc.org/content/89/1/437.full.pdf

Menstrual cycle and Vitamin A correlations: https://www.ncbi.nlm.nih.gov/pubmed/14976795

Pomegranate protects against endotoxin: https://www.ncbi.nlm.nih.gov/pubmed/29770393

DocosaHexenoic Acid as retinoid X-receptor ligand and uses thereof: https://patents.google.com/patent/US6355446

Connecting DHA and ARA/AA (arachidonic acid) deficiency to xerophthalmia and developmental eye issues, not VA deficiency: https://www.ncbi.nlm.nih.gov/pubmed/7769900 , https://www.popline.org/node/347765 ,

Cannabis smoke directly breaks down beta-carotene: https://www.sciencedirect.com/science/article/pii/S2214750016300439

Corticosteroids may be anti-VA (not that we want to use them): https://jamanetwork.com/journals/jamasurgery/fullarticle/390751 , https://www.ncbi.nlm.nih.gov/pubmed/2768567 , https://www.ncbi.nlm.nih.gov/books/NBK395909/

More VA and carotenoids in the part of brain affected most by Alzheimer's: https://www.ncbi.nlm.nih.gov/pubmed/15129301

Theory...short chain fatty acids are problematic (resistant starch and colon cancer): https://www.mdpi.com/2072-6643/3/10/858/htm , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029053/ , (stimulate RA production) https://www.physiology.org/doi/full/10.1152/ajpgi.00411.2015

RA and MS (also include connection between higher latitudes / less sunlight and decreased breakdown of VA): https://www.ncbi.nlm.nih.gov/pubmed/25149081

Health risks related to high intake of preformed retinol (vitamin A) in the Nordic countries.
folk.uio.no/runeb/pdf%20filer/Vitamin%20A%20toxicity.PDF (also attached).

Toward a Theory of Childhood Learning Disorders, Hyperactivity, and Aggression
https://www.hindawi.com/journals/isrn/2012/589792/

Risk assessment of vitamin A (retinol and retinyl esters) in cosmetics (also attached)
https://vkm.no/english/riskassessments/allpublications/riskassessmentofvitaminaretinolandretinylestersincosmetics.4.27ef9ca915e07938c3b2c959.html

RETINOIC ACID SYNTHESIS AND DEGRADATION
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551983/

Aloe vera gel helped reduce side effects of tretinoin:
https://www.ncbi.nlm.nih.gov/pubmed/23336746
and may also be helpful as a hair product itself (see related comment): https://www.facebook.com/DoctorAsTeacher/posts/10215860737565219
https://www.ncbi.nlm.nih.gov/pubmed/21341543 (helps fix liver damage)

Connections between alcohol dehydrogenase and Poison/"Vitamin A" breakdown:
https://academic.oup.com/jn/article/128/2/459S/4724054
http://www.jbc.org/content/274/24/16796
https://www.ncbi.nlm.nih.gov/pubmed/10358022
(also look at formaldehyde connections) https://www.cfs.gov.hk/english/programme/programme_rafs/programme_rafs_fa_02_09.html

DHA (the natural/intended ligand of RXR) connected to developmental disorders, including blindness:
https://www.developmental-delay.com/page.cfm/247
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519357/
https://www.ncbi.nlm.nih.gov/pubmed/27008858

Refsum's disease is "pseudohypervitaminosis A"
https://www.ncbi.nlm.nih.gov/pubmed/10673856
http://www.worldblindunion.org/English/VisionHealth/eyeconditions/Pages/Retinitis-Pigmentosa.aspx (phytanic acid is another ligand of RXR, avoiding it in Refsum's Disease is helpful, so not to overstimulate the RXR)

EWG on Retinol: https://www.ewg.org/skindeep/ingredient/706889/RETINOL_%28VITAMIN_A%29/

Resistant starch as colon cancer PROMOTER (connect to Bosnian anecdote of never eating cooked-then-cooled food):
http://cebp.aacrjournals.org/content/11/9/915.long

https://academic.oup.com/carcin/article/20/5/805/2529738
https://www.ncbi.nlm.nih.gov/pubmed/12738184
https://www.ncbi.nlm.nih.gov/pubmed/8566598

Free fatty acids as problematic (cause excess oxidative damage, may affect Poison/"Vitamin A"), triglycerides as OK?
https://translate.google.com/translate?sl=de&tl=en&js=y&prev=_t&hl=en&ie=UTF-8&u=https%3A%2F%2Fwww.charriau.com%2Fde%2Frohrkuhler-zur-milchvorkuhlung%2Fgehalt-an-freie-fettsauren-als-qualitatskriterium&edit-text=
http://www.webexhibits.org/butter/compounds-fatty.html (butter)
https://www.myrecipes.com/extracrispy/whats-the-difference-between-refined-and-unrefined-coconut-oil (free fatty acids removed from refined)

NAFLD and Vit A:
https://www.nature.com/articles/srep45100
https://lipidworld.biomedcentral.com/articles/10.1186/s12944-017-0566-7
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0205747
http://www.sjamf.eg.net/article.asp?issn=1110-2381;year=2018;volume=2;issue=2;spage=115;epage=122;aulast=Mourad;aid=SciJAl-AzharMedFacGirls_2018_2_2_115_241830
https://www.ncbi.nlm.nih.gov/pubmed/25948673
https://www.ncbi.nlm.nih.gov/pubmed/29286303
cherry angiomas as diagnostic for likely NAFLD: https://www.researchgate.net/publication/306254650_Cherry_angioma_has_acceptable_diagnostic_value_for_nonalcoholic_fatty_liver_disease_Diagnosis_of_fatty_liver_by_cherry_angioma
"Cherry angiomas begin to appear in middle adulthood as small, red papules on the trunk and upper extremities and increase in number with age." https://www.sciencedirect.com/topics/medicine-and-dentistry/angioma

Ascorbate and oxalate and B6 connections (I'm positive this is somehow involved in VA toxicity, as kidney stones are a well-known Hypervitaminosis A effect): https://cdn.fbsbx.com/v/t59.2708-21/37124983_10215960280977692_290005194077372416_n.pdf/ascorbic-acid-and-oxalate-slides.pdf

The body defending itself against VA in new ways: http://www.bloodjournal.org/content/bloodjournal/83/1/10.full.pdf?sso-checked=true
"(1) the remission of the disease obtained with retinoic acid (RA) treatment, whose mechanism of action consists in inducing the APL blasts to differentiate terminally; and (2) the presence in the APL blasts of an anomalous protein, the PML/RARa protein, a mutant of one of the retinoic acid receptors"
"Alternative explanations for sensitivity to RA are based on the claim that PML/RARa is localized, at least in part, in the cytoplasm. The cytoplasmic PML/RARa would constitute a barrier for RA,"
"However, in most cases of post RA therapy relapse, the promyelocytic blasts are resistant in vitro to the differentiation action of RA, which suggests that during treatment they have accumulated mutations in molecules involved in the response to RA (C. Chomienne, personal communication and our unpublished results, May 1993)."