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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 28-year old woman developed juvenile lung cancer. Cockayne syndrome, one of the progeroid syndromes, was suspected because of mental retardation, renal disfunction, photosensitivity, and the characteristic physical appearance such as low set ears, microcephaly, senile face, short stature, and cachectic habitus. We tried chemotherapy with gefitinib and docetaxel, but they were ineffective and she was found to have multiple extraocular muscle metastasis. CT scan showed carcinomatous lymphangiosis findings, her respiratory condition worsened gradually and she died about 7 months after the diagnosis of lung cancer. Some progeroid syndromes are known for their high incidence of juvenile cancres, and the responsible genes are gradually coming to light. However, concerning the relationship between lung cancer and progeroid syndromes, our investigations revealed only one case report of Werner syndrome, one of the progeroid syndromes, accompanied by lung cancer. Progeroid syndromes with lung cancer are thought to be very rare. We expect collection of data on cases like the present case will help to clarify the mechanism of aging and carcinogenesis.
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PMID:[A case of juvenile lung cancer with suspected progeroid syndrome and mental retardation]. 1741 42

Use of diagnostic imaging studies for evaluation of pregnant patients with medical conditions not related to pregnancy poses a persistent and recurring dilemma. Although a theoretical risk of carcinogenesis exists, there are no known risks for development of congenital malformations or mental retardation in a fetus exposed to ionizing radiation at the levels typically used for diagnostic imaging. An understanding of the effects of ionizing radiation on the fetus at different gestational stages and the estimated exposure dose received by the fetus from various imaging modalities facilitates appropriate choices for diagnostic imaging of pregnant patients with nonobstetric conditions. Other aspects of imaging besides radiation (ie, contrast agents) also carry potential for fetal injury and must be taken into consideration. Imaging algorithms based on a review of the current literature have been developed for specific nonobstetric conditions: pulmonary embolism, acute appendicitis, urolithiasis, biliary disease, and trauma. Imaging modalities that do not use ionizing radiation (ie, ultrasonography and magnetic resonance imaging) are preferred for pregnant patients. If ionizing radiation is used, one must adhere to the principle of using a dose that is as low as reasonably achievable after a discussion of risks versus benefits with the patient.
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PMID:Imaging the pregnant patient for nonobstetric conditions: algorithms and radiation dose considerations. 1802 13

The biological effects of radiation result primarily from damage to DNA. There are three effects of concern to the radiologist that determine the need for radiation protection and the dose principle of ALARA (As Low As Reasonably Achievable). (1) Heritable effects. These were thought to be most important in the 1950s, but concern has declined in recent years. The current ICRP risk estimate is very small at 0.2%/Sv. (2) Effects on the developing embryo and fetus include weight retardation, congenital anomalies, microcephaly and mental retardation. During the sensitive period of 8 to 15 weeks of gestation, the risk estimate for mental retardation is very high at 40%/Sv, but because it is a deterministic effect, there is likely to be a threshold of about 200 mSv. (3) Carcinogenesis is considered to be the most important consequence of low doses of radiation, with a risk of fatal cancer of about 5%/Sv, and is therefore of most concern in radiology. Our knowledge of radiation carcinogenesis comes principally from the 60-year study of the A-bomb survivors. The use of radiation for diagnostic purposes has increased dramatically in recent years. The annual collective population dose has increased by 750% since 1980 to 930,000 person Sv. One of the principal reasons is the burgeoning use of CT scans. In 2006, more than 60 million CT scans were performed in the U.S., with about 6 million of them in children. As a rule of thumb, an abdominal CT scan in a 1-year-old child results in a life-time mortality risk of about one in a thousand. While the risk to the individual is small and acceptable when the scan is clinically justified, even a small risk when multiplied by an increasingly large number is likely to produce a significant public health concern. It is for this reason that every effort should be made to reduce the doses associated with procedures such as CT scans, particularly in children, in the spirit of ALARA.
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PMID:Radiation biology for pediatric radiologists. 1908 23

Over the past 50 years, our laboratory has provided consultations dealing with the risks of various environmental toxicant exposures during pregnancy. These contacts were primarily by telephone or written communications. Since the year 2000, the primary source of consultations has been via the internet. In 2007, the pregnancy website of the Health Physics Society received 1,299,672 visits. The contacts who downloaded information totaled 620,035. After reading the website information, 1442 individuals who were still concerned contacted me directly. Unfortunately, we have learned that many physicians and other counselors are not prepared to counsel patients concerning radiation risks. Approximately, 8% of the website contacts, who had consulted a professional, were provided inaccurate information that could have resulted in an unnecessary interruption of a wanted pregnancy. Research from our and other investigators' laboratories has provided radiation risk data that are the basis for properly counseling contacts with radiation exposures. Mammalian animal research has been an important source of information that improves the quality and accuracy of estimating the reproductive and developmental risks of ionizing radiation in humans. What are the reproductive and developmental risks of in utero ionizing radiation exposure? 1. Birth defects, mental retardation, and other neurobehavioral effects, growth retardation, and embryonic death are deterministic effects (threshold effects). This indicates that these effects have a no adverse effect level (NOAEL). Almost all diagnostic radiological procedures provide exposures that are below the NOAEL for these developmental effects. 2. For the embryo to be deleteriously affected by ionizing radiation when the mother is exposed to a diagnostic study, the embryo has to be exposed above the NOAEL to increase the risk of deterministic effects. This rarely happens when the pregnant women have x-ray studies of the head, neck, chest or extremities. 3. During the preimplantation and preorganogenesis stages of embryonic development, the embryo is least likely to be malformed by the effects of ionizing radiation because the cells of the very young embryo are omnipotential and can replace adjacent cells that have been deleteriously affected. This early period of development has been designated as "the all-or-none period." 4. Protraction and fractionation of exposures of ionizing radiation to the embryo decrease the magnitude of the deleterious effects of deterministic effects. 5. The increased risk of cancer following high exposures to ionizing radiation exposure to adult populations has been demonstrated in the atomic bomb survivor population. Radiation-induced carcinogenesis is assumed to be a stochastic effect (nonthreshold effect) so that there is theoretically a risk at low exposures. Whereas there is no question that high exposures of ionizing radiation can increase the risk of cancer, the magnitude of the risk of cancer from embryonic exposures following diagnostic radiological procedures is very controversial. Recent publications and analyses indicate that the risk is lower for the irradiated embryo than the irradiated child, which surprised many scientists interested in this subject, and that there may be no increased carcinogenic risk from diagnostic radiological studies. Examples of appropriate and inappropriate counseling will be presented to demonstrate how counseling can save lives and change family histories. The reader is referred to the Health Physics Society website to obtain many examples of the answers to questions posed by women and men who have been exposed to radiation (www.hps.org). Then click on ATE (ask the expert).
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PMID:Saving lives and changing family histories: appropriate counseling of pregnant women and men and women of reproductive age, concerning the risk of diagnostic radiation exposures during and before pregnancy. 1912 55

The histone demethylase PHF8 has been implicated in multiple pathological disorders, including X-linked mental retardation and tumorigenesis. However, it is not clear how the abundance and function of PHF8 are regulated. Here, we report that PHF8 physically associates with the deubiquitinase USP7. Specifically, we demonstrated that USP7 promotes deubiquitination and stabilization of PHF8, leading to the upregulation of a group of genes, including cyclin A2, that are critical for cell growth and proliferation. The USP7-encoding gene was also transcriptionally regulated by PHF8, via positive feedback. USP7 was overexpressed in breast carcinomas, and the level of expression positively correlated with expression of PHF8 and cyclin A2 and with the histological grade of breast cancer. We showed that USP7 promotes breast carcinogenesis by stabilizing PHF8 and upregulating cyclin A2 and that the interaction between USP7 and PHF8 is augmented during DNA damage. Moreover, USP7-promoted PHF8 stabilization conferred cellular resistance to genotoxic insults and was required for the recruitment of BLM and KU70, which are both essential for DNA double-strand break repair. Our study mechanistically links USP7 to epigenetic regulation and DNA repair. Moreover, these data support the pursuit of USP7 and PHF8 as potential targets for breast cancer intervention, especially in combination with chemo- or radiotherapies.
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PMID:Stabilization of histone demethylase PHF8 by USP7 promotes breast carcinogenesis. 2718 83

Recent data from the Kollins lab ('Cannabinoid exposure and altered DNA methylation in rat and human sperm' Epigenetics 2018; 13: 1208-1221) indicated epigenetic effects of cannabis use on sperm in man parallel those in rats and showed substantial shifts in both hypo- and hyper-DNA methylation with the latter predominating. This provides one likely mechanism for the transgenerational transmission of epigenomic instability with sperm as the vector. It therefore contributes important pathophysiological insights into the probable mechanisms underlying the epidemiology of prenatal cannabis exposure potentially explaining diverse features of cannabis-related teratology including effects on the neuraxis, cardiovasculature, immune stimulation, secondary genomic instability and carcinogenesis related to both adult and pediatric cancers. The potentially inheritable and therefore multigenerational nature of these defects needs to be carefully considered in the light of recent teratological and neurobehavioural trends in diverse jurisdictions such as the USA nationally, Hawaii, Colorado, Canada, France and Australia, particularly relating to mental retardation, age-related morbidity and oncogenesis including inheritable cancerogenesis. Increasing demonstrations that the epigenome can respond directly and in real time and retain memories of environmental exposures of many kinds implies that the genome-epigenome is much more sensitive to environmental toxicants than has been generally realized. Issues of long-term multigenerational inheritance amplify these concerns. Further research particularly on the epigenomic toxicology of many cannabinoids is also required.
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PMID:Impacts of cannabinoid epigenetics on human development: reflections on Murphy et. al. 'cannabinoid exposure and altered DNA methylation in rat and human sperm' epigenetics 2018; 13: 1208-1221. 3129 13

The stem cells of neurogenesis and carcinogenesis share many properties, including proliferative rate, an extensive replicative potential, the potential to generate different cell types of a given tissue, and an ability to independently migrate to a damaged area. This is also evidenced by the common molecular principles regulating key processes associated with cell division and apoptosis. Autosomal recessive primary microcephaly (MCPH) is a neurogenic mitotic disorder that is characterized by decreased brain size and mental retardation. Until now, a total of 25 genes have been identified that are known to be associated with MCPH. The inactivation (yin) of most MCPH genes leads to neurogenesis defects, while the upregulation (yang) of some MCPH genes is associated with different kinds of carcinogenesis. Here, we try to summarize the roles of MCPH genes in these two diseases and explore the underlying mechanisms, which will help us to explore new, attractive approaches to targeting tumor cells that are resistant to the current therapies.
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PMID:The Yin and Yang of Autosomal Recessive Primary Microcephaly Genes: Insights from Neurogenesis and Carcinogenesis. 3212 80

Previous studies in a mouse model have indicated the anticancer potential of boiled Moringa oleifera pod (bMO)-supplemented diets; however, its molecular mechanisms are still unclear. Therefore, the present study aimed to explore the protein expression profiles responsible for the suppressive effect of bMO supplementation on azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced mouse colon carcinogenesis. Analysis by gel electrophoresis and liquid chromatography-tandem mass spectrophotometry demonstrated that there were 125 proteins that were differentially expressed in mouse colon tissues between 14 experimental groups of mice. The differentially expressed proteins are involved in various biological processes, such as signal transduction, metabolism, transcription and translation. Venn diagram analysis of the differentially expressed proteins was performed in six selected mouse groups, including negative control, positive control mice induced by AOM/DSS, the AOM/DSS groups receiving preventive or therapeutic bMO diets and their bMO-supplemented control groups. This analysis identified 7 proteins; 60S acidic ribosomal protein P1 (Rplp1), fragile X mental retardation, cystatin 9, round spermatids protein, zinc finger protein 638, protein phosphatase 2C (Ppm1g) and unnamed protein product as being potentially associated with the preventive and therapeutic effects of bMO in AOM/DSS-induced mouse colon cancer. Analysis based on the search tool for interactions of chemicals (STITCH) database predicted that Rplp1 interacted with the apoptotic and inflammatory pathways, whereas Ppm1g was associated only with inflammatory networks. This proteomic analysis revealed candidate proteins that are responsible for the effects of bMO supplementation, potentially by regulating apoptotic and inflammatory signaling networks in colorectal cancer prevention and therapy.
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PMID:Protein expression profiles that underpin the preventive and therapeutic potential of Moringa oleifera Lam against azoxymethane and dextran sodium sulfate-induced mouse colon carcinogenesis. 3272 22


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