Recent Progress in Orphan Nuclear Hormone Receptors

Moore, David D.,Lee, Yoon-Kwang,Tzameli, Iphigenia,Zavacki, Ann Marie The Korea Science and Technology Center 1998 BMB Reports Vol.31 No.5

The nuclear hormone receptor superfamily currently includes approximately equal numbers of conventional receptors and orphan receptors, which do not have known ligands. Here, we review recent progress from this laboratory on three orphans, two of which are moving from orphan to conventional receptor status. Perhaps the most unusual is CAR, which is a constitutive transactivator in the absence of ligands but becomes transcriptionally inactive in the presence of its ligands, which are androgen metabolites. The response of CAR to its ligands is thus opposite to that of the conventional receptor paradigm. RIP14 (also known as FXR) is activated by both all-trans retinoic acid and a synthetic retinoid previously though to specifically target the retinoic acid receptors (RARs), and thus appears to be a novel retinoid receptor. Finally, SHP is a novel orphan that lacks a DNA binding domain and interacts with a number of other receptor superfamily members. While it generally inhibits its targets, including CAR, the retinoid X receptor (RXR), and the estrogen receptor (ER), it stimulates transactivation by the orphan SF-1.

Colorectal Cancer Treatment and Survival: the Experience of Major Public Hospitals in South Australia over three Decades

Roder, David,Karapetis, Christos S,Wattchow, David,Moore, James,Singhal, Nimit,Joshi, Rohit,Keefe, Dorothy,Fusco, Kellie,Powell, Kate,Eckert, Marion,Price, Timothy J Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

Background: Registry data from four major public hospitals indicate trends in clinical care and survival from colorectal cancer over three decades, from 1980 to 2010. Materials and Methods: Kaplan-Meier productlimit estimates and Cox proportional hazards models were used to investigate disease-specific survival and multiple logistic regression analyses to explore first-round treatment trends. Results: Five-year survivals increased from 48% for 1980-1986 to 63% for 2005-2010 diagnoses. Survival increases applied to each ACPS stage (Australian Clinico-Pathological Stage), and particularly stage C (an increase from 38% to 68%). Risk of death from colorectal cancer halved (hazards ratio: 0.50 (0.45, 0.56)) over the study period after adjusting for age, sex, stage, differentiation, primary sub-site, health administrative region, and measures of socioeconomic status and geographic remoteness. Decreases in stage were not observed. Survivals did not vary by sex or place of residence, suggesting reasonable equity in service access and outcomes. Of staged cases, 91% were treated surgically with lower surgical rates for older ages and more advanced stage. Proportions of surgical cases having adjuvant therapy during primary courses of treatment increased for all stages and were highest for stage C (an increase from 5% in 1980-1986 to 63% for 2005-2010). Radiotherapy was more common for rectal than colonic cases. Proportions of rectal cases receiving radiotherapy increased, particularly for stage C where the increase was from 8% in 1980-1986 to 60% in 2005-2010. The percentage of stage C colorectal cases less than 70 years of age having systemic therapy as part of their first treatment round increased from 3% in 1980-1986 to 81% by 1995-2010. Based on survey data on uptake of adjuvant therapy among those offered this care, it is likely that all these younger patients were offered systemic treatment. Conclusions: We conclude that pronounced increases in survivals from colorectal cancer have occurred at major public hospitals in South Australia due to increases in stage-specific survivals. Use of adjuvant therapies has increased and the patterns of change accord with clinical guideline recommendations. Reasons for sub-optimal use of radiotherapy for rectal cases warrant further investigation, including the potential for limited rural access to impede uptake of treatments at metropolitan-based radiotherapy centres.

Metastatic Colorectal Cancer Treatment and Survival: the Experience of Major Public Hospitals in South Australia Over Three Decades

Roder, David,Karapetis, Christos S,Wattchow, David,Moore, James,Singhal, Nimit,Joshi, Rohit,Keefe, Dorothy,Fusco, Kellie,Buranyi-Trevarton, Dianne,Sharplin, Greg,Price, Timothy J Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.14

Background: Registry data from four major public hospitals indicate trends over three decades from 1980 to 2010 in treatment and survival from colorectal cancer with distant metastases at diagnosis (TNM stage IV). Materials and Methods: Kaplan-Meier product-limit estimates and Cox proportional hazards models for investigating disease-specific survival and multiple logistic regression analyses for indicating first-round treatment trends. Results: Two-year survivals increased from 10% for 1980-84 to 35% for 2005-10 diagnoses. Corresponding increases in five-year survivals were from 3% to 16%. Time-to-event risk of colorectal cancer death approximately halved (hazards ratio: 0.48 (0.40, 0.59) after adjusting for demographic factors, tumour differentiation, and primary sub-site. Survivals were not found to differ by place of residence, suggesting reasonable equity in service provision. About 74% of cases were treated surgically and this proportion increased over time. Proportions having systemic therapy and/or radiotherapy increased from 12% in 1980-84 to 61% for 2005-10. Radiotherapy was more common for rectal than colonic cases (39% vs 7% in 2005-10). Of the cases diagnosed in 2005-10 when less than 70 years of age, the percentage having radiotherapy and/or systemic therapy was 79% for colorectal, 74% for colon and 86% for rectum (&RS)) cancers. Corresponding proportions having: systemic therapies were 75%, 71% and 81% respectively; radiotherapy were 24%, 10% and 46% respectively; and surgery were 75%, 78% and 71% respectively. Based on survey data on uptake of offered therapies, it is likely that of these younger cases, 85% would have been offered systemic treatment and among rectum (&RS) cases, about 63% would have been offered radiotherapy. Conclusions: Pronounced increases in survivals from metastatic colorectal cancer have occurred, in keeping with improved systemic therapies and surgical interventions. Use of radiotherapy and/or systemic therapy has increased markedly and patterns of change accord with clinical guideline recommendations.

Obstructing colorectal cancer: a population-based review of colonic stenting in Queensland, Australia

Keogh Cian,Moore Julie,Cossio Danica,Smith Nick,Clark David A. 대한대장항문학회 2024 Annals of Coloproctolgy Vol.40 No.3

Purpose: Stenting is a useful treatment option for malignant colonic obstruction, but its role remains unclear. This study was designed to establish how stents have been used in Queensland, Australia, and to review outcomes. Methods: Patients diagnosed with colorectal cancer in Queensland from January 1, 2008, to December 31, 2014, who underwent colonic stent insertion were reviewed. Primary outcomes of 5-year survival, 30-day mortality, and overall length of survival were calculated. The secondary outcomes included patient and tumor factors, and stoma rates. Results: In total, 319 patients were included, and distant metastases were identified in 183 patients (57.4%). The 30-day mortality rate was 6.6% (n=21), and the 5-year survival was 11.9% (n=38). Median survival was 11 months (interquartile range, 4–27 months). A further operation (hazard ratio [HR], 0.19; P<0.001) and chemotherapy and/or radiotherapy (HR, 0.718; P=0.046) reduced the risk of 5-year mortality. The presence of distant metastases (HR, 2.052; P<0.001) and a comorbidity score of 3 or more (HR, 1.572; P=0.20) increased mortality. Surgery was associated with a reduced risk of mortality even in patients with metastatic disease (HR, 0.14; P<0.001). Twenty-two patients (6.9%) ended the study period with a stoma. Conclusion: Colorectal stenting was used in Queensland in several diverse scenarios, in both localized and metastatic disease. Surgery had a survival advantage, even in patients with metastatic disease. There was no survival difference according to whether patients were socioeconomically disadvantaged, diagnosed in a major city or not, or treated at private or public hospitals. Stenting proved a valid treatment option with low stoma rates.

Safety of Autologous Umbilical Cord Blood Therapy for Acquired Sensorineural Hearing Loss in Children

Linda S. Baumgartner,Ernest Moore,David Shook,Steven Messina,Mary Clare Day,Jennifer Green,Rajesh Nandy,Michael Seidman,James E. Baumgartner 대한청각학회 2018 Journal of Audiology & Otology Vol.22 No.4

Background and Objectives: Sensorineural hearing loss (SNHL) in children is associated with neurocognitive morbidity. The cause of SNHL is a loss of hair cells in the organ of Corti. There are currently no reparative treatments for SNHL. Numerous studies suggest that cord blood mononuclear cells (human umbilical cord blood, hUCB) allow at least partial restoration of SNHL by enabling repair of a damaged organ of Corti. Our objective is to determine if hUCB is a safe treatment for moderate to severe acquired SNHL in children. Subjects and Methods: Eleven children aged 6 months to 6 years with moderate to severe acquired SNHL were treated with intravenous autologous hUCB. The cell dose ranged from 8 to 30 million cells/kg body weight. Safety was assessed by measuring systemic hemodynamics during hUCB infusion. Infusion-related toxicity was evaluated by measuring neurologic, hepatic, renal and pulmonary function before and after infusion. Auditory function, auditory verbal language assessments and MRI with diffusion tensor imaging (DTI) were obtained before and after treatment. Results: All patients survived, and there were no adverse events. No infusionrelated changes in hemodynamics occurred. No infusion-related toxicity was recorded. Five subjects experienced a reduction in auditory brainstem response (ABR) thresholds. Four of those 5 subjects also experienced an improvement in cochlear nerve latencies. Comparison of MRI with DTI sequences obtained before and after treatment revealed increased fractional anisotropy in the primary auditory cortex in three of five subjects with reduced ABR thresholds. Statistically significant (p<0.05) reductions in ABR thresholds were identified. Conclusions: TIntravenous hUCB is feasible and safe in children with SNHL.

Temperature distribution in a full-scale steel framed building subject to a natural fire

František Wald,Magdalena Chladná,David Moore,Aldina Santiago,Tom Lennon 국제구조공학회 2006 Steel and Composite Structures, An International J Vol.6 No.2

Current fire design codes for determining the temperature within the structural elements that form part of a complete building are based on isolated member tests subjected to the standard fire. However, the standard time-temperature response bears little relation to real fires and doesn’t include the effects of differing ventilation conditions or the influence of the thermal properties of compartment linings. The degree to which temperature uniformity is present in real compartments is not addressed and direct flame impingement may also have an influence, which is not considered. It is clear that the complex thermal environmental that occurs within a real building subject to a natural fire can only be addressed using realistic full-scale tests. To study global structural and thermal behaviour, a research project was conducted on the eight storey steel frame building at the Building Research Establishment’s Cardington laboratory. The fire compartment was 11 m long by 7 m wide. A fire load of 40 kg/m2 was applied together with 100% of the permanent actions and variable permanent actions and 56% of live actions. This paper summarises the experimental programme and presents the time-temperature development in the fire compartment and in the main supporting structural elements. Comparisons are also made between the test results and the temperatures predicted by the structural fire Eurocodes.

Outcomes and Use of Therapeutic Drug Monitoring in Multidrug-Resistant Tuberculosis Patients Treated in Virginia, 2009-2014

Heysell, Scott K.,Moore, Jane L.,Peloquin, Charles A.,Ashkin, David,Houpt, Eric R. The Korean Academy of Tuberculosis and Respiratory 2015 Tuberculosis and Respiratory Diseases Vol.78 No.2

Background: Reports of therapeutic drug monitoring (TDM) for second-line medications to treat multidrug-resistant tuberculosis (MDR-TB) remain limited. Methods: A retrospective cohort from the Virginia state tuberculosis (TB) registry, 2009-2014, was analyzed for TDM usage in MDR-TB. Drug concentrations, measured at time of estimated peak ($C_{max}$), were compared to expected ranges. Results: Of 10 patients with MDR-TB, 8 (80%) had TDM for at least one drug (maximum 6 drugs). Second-line drugs tested were cycloserine in seven patients (mean $C_{2hr}$, $16.6{\pm}10.2{\mu}g/mL$; 4 [57%] below expected range); moxifloxacin in five (mean $C_{2hr}$, $3.2{\pm}1.5{\mu}g/mL$; 1 [20%] below); capreomycin in five (mean $C_{2hr}$, $21.5{\pm}14.0{\mu}g/mL$; 3 [60%] below); para-aminosalicylic acid in five (mean $C_{6hr}$, $65.0{\pm}29.1{\mu}g/mL$; all within or above); linezolid in three (mean $C_{2hr}$, $11.4{\pm}4.1{\mu}g/mL$, 1 [33%] below); amikacin in two (mean $C_{2hr}$, $35.3{\pm}3.7{\mu}g/mL$; 1 [50%] below); ethionamide in one ($C_{2hr}$, $1.49{\mu}g/mL$, within expected). Two patients died: a 38-year-old woman with human immunodeficiency virus/acquired immune deficiency syndrome and TB meningitis without TDM, and a 76-year-old man with fluoroquinolone-resistant (pre-extensively drug-resistant) pulmonary TB and low linezolid and capreomycin concentrations. Conclusion: Individual pharmacokinetic variability was common. A more standardized approach to TDM for MDR-TB may limit over-testing and maximize therapeutic gain.

JCMT-CHIMPS2 Survey

Kee-Tae Kim,Toby Moore,Tetsuhiro Minamidani,OscarMorata,Erik Rosolowski,Yang Su,David Eden,CHIMPS2 Team 한국천문학회 2019 天文學會報 Vol.44 No.1

Asia Pacific Journal of Cancer Prevention MEDLINE/PubMed Listing and Solution to the PRESERVATION Issue

Jarrahi, Alireza Mosavi,Moore, Malcolm Antony,Huang, Xinen,Roder, David Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.10

Manganese sulfide formation via concomitant microbial manganese oxide and thiosulfate reduction

Lee, Ji‐,Hoon,Kennedy, David W.,Dohnalkova, Alice,Moore, Dean A.,Nachimuthu, Ponnusamy,Reed, Samantha B.,Fredrickson, James K. Blackwell Publishing Ltd 2011 Environmental microbiology Vol.13 No.12

<P><B>Summary</B></P><P>The dissimilatory metal‐reducing bacterium, <I>Shewanella oneidensis</I> MR‐1 produced γ‐MnS (rambergite) nanoparticles during the concurrent reduction of MnO<SUB>2</SUB> and thiosulfate coupled to H<SUB>2</SUB> oxidation. To investigate effect of direct microbial reduction of MnO<SUB>2</SUB> on MnS formation, two MR‐1 mutants defective in outer membrane <I>c</I>‐type cytochromes (Δ<I>mtrC</I>/Δ<I>omcA</I> and Δ<I>mtrC</I>/Δ<I>omcA</I>/Δ<I>mtrF</I>) were also used and it was determined that direct reduction of MnO<SUB>2</SUB> was dominant relative to chemical reduction by biogenic sulfide generated from thiosulfate reduction. Although bicarbonate was excluded from the medium, incubations of strain MR‐1 with lactate as the electron donor produced MnCO<SUB>3</SUB> (rhodochrosite) as well as MnS in nearly equivalent amounts as estimated by micro X‐ray diffraction (micro‐XRD) analysis. It was concluded that carbonate released from lactate metabolism promoted MnCO<SUB>3</SUB> formation and that Mn(II) mineralogy was strongly affected by carbonate ions even in the presence of abundant sulfide and weakly alkaline conditions expected to favour the precipitation of MnS. Formation of MnS, as determined by a combination of micro‐XRD, transmission electron microscopy, energy dispersive X‐ray spectroscopy, and selected area electron diffraction analyses was consistent with equilibrium speciation modelling predictions. Biogenic manganese sulfide may be a manganese sink in the Mn biogeochemical cycle in select environments such as deep anoxic marine basins within the Baltic Sea.</P>