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1.
J Biol Chem ; 299(1): 102757, 2023 01.
Article in English | MEDLINE | ID: mdl-36460099

ABSTRACT

Antiestrogens (AEs) are used to treat all stages of estrogen receptor (ER)-positive breast cancer. Selective estrogen receptor modulators such as tamoxifen have tissue-specific partial agonist activity, while selective estrogen receptor downregulators such as fulvestrant (ICI182,780) display a more complete antiestrogenic profile. We have previously observed that fulvestrant-induced ERα SUMOylation contributes to transcriptional suppression, but whether this effect is seen with other AEs and is specific to ERα is unclear. Here we show that several AEs induce SUMOylation of ERα, but not ERß, at different levels. Swapping domains between ERα and ERß indicates that the ERα identity of the ligand-binding domain helices 3 and 4 (H3-H4 region), which contribute to the static part of the activation function-2 (AF-2) cofactor binding groove, is sufficient to confer fulvestrant-induced SUMOylation to ERß. This region does not contain lysine residues unique to ERα, suggesting that ERα-specific residues in H3-H4 determine the capacity of the AE-bound ERα ligand-binding domain to recruit the SUMOylation machinery. We also show that the SUMO E3 ligase protein inhibitor of activated STAT 1 increases SUMOylation of ERα and of ERß containing the H3-H4 region of ERα, but not of ERß. Together, these results shed new light on the molecular basis for the differential capacity of selective estrogen receptor modulators and selective estrogen receptor downregulators to suppress transcription by ERα.


Subject(s)
Breast Neoplasms , Estrogen Receptor alpha , Humans , Female , Estrogen Receptor alpha/metabolism , Estrogen Receptor Modulators/pharmacology , Receptors, Estrogen/metabolism , Fulvestrant/pharmacology , Furylfuramide , Selective Estrogen Receptor Modulators/pharmacology , Sumoylation , Ligands , Estrogen Antagonists/pharmacology , Tamoxifen/pharmacology , Breast Neoplasms/metabolism , Estrogen Receptor beta/genetics , Estrogen Receptor beta/metabolism , Estradiol/pharmacology
2.
JMIR Med Inform ; 4(2): e21, 2016 Jun 15.
Article in English | MEDLINE | ID: mdl-27307046

ABSTRACT

BACKGROUND: Picture archiving and communication system (PACS) is a well-known imaging informatics application in health care organizations, specifically designed for the radiology department. Health care providers have exhibited willingness toward evaluating PACS in hospitals to ascertain the critical success and failure of the technology, considering that evaluation is a basic requirement. OBJECTIVE: This study aimed at evaluating the success of a PACS in a regional teaching hospital of Kuwait, from users' perspectives, using information systems success criteria. METHODS: An in-depth study was conducted by using quantitative and qualitative methods. This mixed-method study was based on: (1) questionnaires, distributed to all radiologists and technologists and (2) interviews, conducted with PACS administrators. RESULTS: In all, 60 questionnaires were received from the respondents. These included 39 radiologists (75% response rate) and 21 technologists (62% response rate), with the results showing almost three-quarters (74%, 44 of 59) of the respondents rating PACS positively and as user friendly. This study's findings revealed that the demographic data, including computer experience, was an insignificant factor, having no influence on the users' responses. The findings were further substantiated by the administrators' interview responses, which supported the benefits of PACS, indicating the need for developing a unified policy aimed at streamlining and improving the departmental workflow. CONCLUSIONS: The PACS had a positive and productive impact on the radiologists' and technologists' work performance. They were endeavoring to resolve current problems while keeping abreast of advances in PACS technology, including teleradiology and mobile image viewer, which is steadily increasing in usage in the Kuwaiti health system.

3.
Pediatr Radiol ; 36(8): 823-32, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16699764

ABSTRACT

BACKGROUND: There is increasing awareness among pediatric radiologists of the potential risks associated with ionizing radiation in medical imaging. However, it is not known whether there has been a corresponding increase in awareness among pediatricians. OBJECTIVE: To establish the level of awareness among pediatricians of the recent publicity on radiation risks in children, knowledge of the relative doses of radiological investigations, current practice regarding parent/patient discussions, and the sources of educational input. MATERIALS AND METHODS: Multiple-choice survey. RESULTS: Of 220 respondents, 105 (48%) were aware of the 2001 American Journal of Roentgenology articles on pediatric CT and radiation, though only 6% were correct in their estimate of the quoted lifetime excess cancer risk associated with radiation doses equivalent to pediatric CT. A sustained or transient increase in parent questioning regarding radiation doses had been noticed by 31%. When estimating the effective doses of various pediatric radiological investigations in chest radiograph (CXR) equivalents, 87% of all responses (and 94% of CT estimates) were underestimates. Only 15% of respondents were familiar with the ALARA principle. Only 14% of pediatricians recalled any relevant formal teaching during their specialty training. The survey response rate was 40%. CONCLUSION: Awareness of radiation protection issues among pediatricians is generally low, with widespread underestimation of relative doses and risks.


Subject(s)
Pediatrics , Radiotherapy Dosage , Radiotherapy/adverse effects , Clinical Competence , Data Collection , Humans , Informed Consent , Neoplasms, Radiation-Induced/etiology , Pediatrics/education , Radiation Protection , Risk , Surveys and Questionnaires
4.
Pediatr Radiol ; 35(4): 440-3, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15798926

ABSTRACT

Popliteal artery entrapment syndrome (PAES) is well-described in adults, but is an uncommon cause of lower-limb pain in children. We present an 11.5-year-old girl with thrombosed aneurysm of the right popliteal artery, subsequently diagnosed with bilateral type I PAES. Multimodality illustration of the radiological findings is presented.


Subject(s)
Aneurysm/diagnosis , Arterial Occlusive Diseases/diagnosis , Popliteal Artery/pathology , Thrombosis/diagnosis , Angiography , Arterial Occlusive Diseases/classification , Child , Female , Humans , Intermittent Claudication/diagnosis , Magnetic Resonance Imaging , Ultrasonography, Doppler, Duplex
5.
Pediatr Radiol ; 35(3): 330-3, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15756543

ABSTRACT

Non-traumatic atlanto-axial subluxation (Grisel's syndrome) is an uncommon complication of neck space infection or otolaryngologic procedures. It most frequently affects children, although it may occur in adults. We present a 14-year-old boy with Grisel's syndrome as a complication of infectious mononucleosis proceeding to cervical ankylosis.


Subject(s)
Atlanto-Axial Joint/diagnostic imaging , Infectious Mononucleosis/complications , Torticollis/diagnostic imaging , Adolescent , Humans , Male , Syndrome , Tomography, X-Ray Computed , Torticollis/virology
6.
Pediatr Radiol ; 35(6): 630-4, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15580341

ABSTRACT

Intracranial involvement in extramedullary hematopoiesis (EMH) is rare, but it should be suspected in patients with myelofibrosis presenting with chronic severe headache. We present a 9-year-old girl with known myelofibrosis whose headaches were unresponsive to routine treatment. CT and MRI studies of the brain showed diffuse pachymeningeal thickening. CT examinations of the chest and abdomen had demonstrated bilateral thoracic paraspinal masses caused by EMH, suggesting the possibility that the intracranial involvement might also be related to EMH. The diagnosis was confirmed by sulfur colloid isotope scan.


Subject(s)
Brain Diseases/diagnosis , Brain Diseases/etiology , Headache/etiology , Hematopoiesis, Extramedullary , Primary Myelofibrosis/diagnosis , Primary Myelofibrosis/etiology , Child , Female , Humans , Magnetic Resonance Imaging , Radiopharmaceuticals , Technetium Tc 99m Sulfur Colloid , Tomography, X-Ray Computed
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