Overweight: costs and management.
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Body Mass Index↗
Biomedical subjects
David Roberts
Publications and source records attributed to David Roberts.
LOT1 (PLAGL1/ZAC1), the candidate tumor suppressor gene at chromosome 6q24-25, is epigenetically regulated in cancer.
LOT1 is a zinc-finger nuclear transcription factor, which possesses anti-proliferative effects and is frequently silenced in ovarian and breast cancer cells. The LOT1 gene is localized at chromosome 6q24-25, a chromosomal region maternally imprinted and linked to growth retardation in several organs and progression of disease states such as transient neonatal diabetes mellitus. Toward understanding the molecular mechanism underlying the loss of LOT1 expression in cancer, we have characterized the genomic structure and analyzed its epigenetic regulation. Genome mapping of LOT1 in comparison with the other splice variants, namely ZAC1 and PLAGL1, revealed that its mRNA ( approximately 4.7 kb; GenBank accession number U76261) is potentially spliced using six exons spanning at least 70 kb of the human genome. 5'-RACE (rapid amplification of cDNA ends) data indicate the presence of at least two transcription start sites. We found that in vitro methylation of the LOT1 promoter causes a significant loss in its ability to drive luciferase transcription. To determine the nature of in vivo methylation of LOT1, we used bisulfite-sequencing strategies on genomic DNA. We show that in the ovarian and breast cancer cell lines and/or tumors the 5'-CpG island of LOT1 is a differentially methylated region. In these cell lines the ratio of methylated to unmethylated CpG dinucleotides in this region ranged from 31 to 99% and the ovarian tumors have relatively higher cytosine methylation than normal tissues. Furthermore, we show that trichostatin A, a specific inhibitor of histone deacetylase, relieves transcriptional silencing of LOT1 mRNA in malignantly transformed cells. It appears that, unlike DNA methylation, histone deacetylation does not target the promoter, and rather it is indirect and may be elicited by a mechanism upstream of the LOT1 regulatory pathway. Taken together, the data suggest that expression of LOT1 is under the control of two epigenetic modifications and that, in the absence of loss of heterozygosity, the biallelic (two-hit) or maximal silencing of LOT1 requires both processes.
Alternative Splicing↗
Communication problems between dementia carers and general practitioners: effect on access to community support services.
OBJECTIVES: To investigate the circumstances that led general practitioners to refer dementia sufferers and their carers to community support services. DESIGN: Qualitative study using semi-structured interviews, carried out between 1 September 1999 and 30 April 2000. SETTING AND PARTICIPANTS: 21 live-in carers of patients with dementia referred for the first time to a Western Australian metropolitan Aged Care Assessment Team, and 19 of their referring general practitioners. RESULTS: Most referrals occurred after the carers had been experiencing carer stress, and were precipitated by crisis situations. Carers failed to discuss their difficulties with the referring GP for a variety of reasons, including the belief that they should cope because it was their duty. The doctors found it difficult to know how the carers were coping or when to intervene, and some carers tended to resist their attempts to help. Time constraints were a significant problem for both groups. CONCLUSION: Attitudinal barriers in both carers of patients with dementia and GPs, combined with time constraints, often lead to inadequate assessment of carer problems. While it is important that strategies to improve communication between carers and GPs are developed, it would be sensible for GPs to assume that dementia carers are at risk of carer stress and should be encouraged to use community care services.
Aged↗
Bell-type inequalities to detect true n-body nonseparability.
We analyze the structure of correlations among more than two quantum systems. We introduce a classification of correlations based on the concept of nonseparability, which is different a priori from the concept of entanglement. Generalizing a result of Svetlichny [Phys. Rev. D 35, 3066 (1987)] on three-particle correlations, we find an inequality for n-particle correlations that holds under the most general separability condition and that is violated by some quantum-mechanical states.
Journal Article↗
Citation for the Down Surgical Prize 2002, Michael Corrigan.
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Awards and Prizes↗
Decreased expression of retinol-binding proteins is associated with malignant transformation of the ovarian surface epithelium.
We have developed a modified form of suppression subtractive hybridization (SSH) that allows multiple specimens of distinct phenotypic groups to be compared for consistent differences in gene expression. We applied this system to identify genes that were expressed in normal rat ovarian surface epithelial (ROSE) cells but whose expression was lost/downregulated in four independently transformed rat ovarian cancer cell lines. Northern blot analysis using 14 of 28 nonredundant cDNA fragments from this difference library showed that the mRNA transcripts were present in normal ROSE cells but lost or markedly downregulated in four related transformed cell lines. Of particular interest, cellular retinol-binding protein 1 (CRBP1) and retinol-binding protein (RBP), two genes whose products are involved in retinol transport and metabolism, were found to be downregulated in this ovarian cancer model system. To determine if this change had relevance to human ovarian cancer, we evaluated a series of human ovarian cancer cell lines and a limited number of frozen human ovarian tumors and found lost or decreased expression of CRBP1 and RBP relative to expression in human ovarian surface epithelial (HOSE) cells. We hypothesize that the loss of CRBP1 and RBP expression disrupts retinol metabolism and retinoic acid production, which may facilitate the occurrence of genetic damage leading to the malignant transformation of the ovarian surface epithelium, the cells from which ovarian cancer arises.
Blotting, Northern↗
Representative payee programs for persons with mental illness in Illinois.
OBJECTIVE: Representative payee programs can improve the community tenure of persons with mental illness by ensuring that their basic needs, such as housing, are met. The authors conducted a survey to assess the extent to which representative payee programs are provided by community mental health centers and the criteria used in enrolling clients in these services. METHODS: Community mental health centers under contract to the Illinois Department of Human Services participated in a census survey. Survey questions concerned provision of representative payee programs, service characteristics, and criteria for enrollment in the programs. RESULTS: Representative payee programs were directly provided by 59 percent of the 95 community mental health centers in the sample. More than a third of clients who were receiving intensive services had a representative payee. More than three times as many such clients had a representative payee when agencies provided representative payee programs directly rather than through referrals of family members. Frequently cited criteria for enrollment in a representative payee program included a lack of financial skills (89 percent), a lack of rent money (52 percent), substance abuse (50 percent), homelessness (33 percent), and frequent (37 percent) or long-term (30 percent) hospitalization. The majority of the representative payee programs (76 percent) provided this service to clients who received representative payee services under the mandate of the Social Security Administration. CONCLUSIONS: Given the high proportion of clients of agencies that directly provided representative payee services who were assigned to a representative payee, all community mental health centers that provide intensive services should also directly provide representative payee services in order to improve access to representative payee services.
Community Mental Health Centers↗
Synthesis of Pyrrolo[4,3,2-de]quinolines from 6,7-Dimethoxy-4-methylquinoline. Formal Total Syntheses of Damirones A and B, Batzelline C, Isobatzelline C, Discorhabdin C, and Makaluvamines A-D.
2-Amino-4-nitrophenol and 2-methoxy-5-nitroaniline were converted into the 5-nitroquinolines 6b and 6d, respectively, and then the latter into nitro-acetal 6f. 6,7-Dimethoxy-4-methylquinoline (6g) was nitrated at C-5 and then the methyl substituent converted into aldehyde 6j and then protected giving acetal 6l. Various means, notably a large excess of NiCl(2)/NaBH(4), were used to reduce both nitro group and pyridine ring, forming 1,2,3,4-tetrahydroquinolines such as 7b, 7c, 7d, which under acidic conditions closed to give 1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolines 9a, 9d, 9c, respectively. In some cases it was unnecessary to protect the aldehyde function, for example quinolinium salt 12c gave 9j and nitro-aldehyde 6j gave 9e (after BOC protection) directly by reaction with NiCl(2)/NaBH(4). Substitution of the indole and aniline nitrogens in the 1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolines was based on a combination of protection, selective deprotection, and the exploitation of the greater acidity of the indole N-hydrogen. 8-Chlorination of 6h and then conversions, as above, gave chloro-diamine-acetal 7e which on acid treatment produced iminoquinone 11b; formylation of the nitrogens in 7e and then acidic treatment allowed formation of the chlorine-substituted 1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinoline 9m which was then converted into 9p. De-O-methylation and then oxidation of 9b and 9c gave o-quinones 10b and 10a, respectively.
Journal Article↗
Patents, ethics and improving healthcare.
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Biomedical Research↗
Effectiveness of a medical priority dispatch protocol for abdominal pain.
OBJECTIVE: Medical Priority Dispatch System (MPDS) protocols are used to determine the appropriate level of emergency medical services (EMS) response that is sent to care for patients in the prehospital setting. The objective of this study was to determine the proportion of patients with abdominal pain who would benefit from advanced life support (ALS) when called for by these protocols. METHODS: All 9-1-1 calls were processed using MPDS protocols to determine whether the patient required ALS or basic life support (BLS) services. Consecutive patients having an ALS response for a chief complaint of abdominal pain were included. Dispatch decisions that did not follow the MPDS protocols, and cases taken to facilities other than the primary study hospitals, were excluded. EMS run sheets and hospital records were reviewed to determine: 1) whether prehospital ALS interventions were required, 2) emergency department (ED) disposition, 3) hospital course, and 4) final diagnosis. Calls were classified according to the need for ALS and the seriousness of the subsequent diagnosis. Data analysis was performed by determining 95%, confidence intervals (CIs). RESULTS: Of the 343 patients classified as 1C1 or 1C2 who were transported by ALS during the time period, 227 (67%) were transported to the study hospitals. Nine (4%) were excluded because of inappropriate dispatch, leaving 218 for analysis. Hospital records were available for 186 (86%) cases, of which 12 (6%; CI 3%, 9%) were potentially life-threatening, requiring ALS intervention. Seventeen (9%; CI 5%, 1%) were non-life-threatening, but potentially benefited from ALS intervention. The remaining 157 (84%; CI 79%, 89%) were classified as not requiring ALS. CONCLUSIONS: Use of age- and gender-specific MPDS protocols for patients with a chief complaint of abdominal pain results in significant overtriage and overuse of ALS. Steps should be taken to develop key questions that provide more accurate classification of these patients that goes beyond age and gender classification alone.
Abdominal Pain↗
Vagus nerve stimulation for refractory epilepsy: a transatlantic experience.
Vagus nerve stimulation (VNS) is an alternative treatment for medically or surgically refractory epilepsy. The long-term efficacy and safety of VNS were evaluated in a large patient series at Ghent University Hospital and Dartmouth-Hitchcock Medical Center. Between March 1995 and February 2003, seizure frequency and type as well as prescribed antiepileptic drugs and side effects were prospectively assessed in 131 patients treated with VNS in either center. Patients with a minimum follow-up duration of 6 months were included in the efficacy and safety analysis. A total of 118 of 131 implanted patients had a minimum postimplantation follow-up period of 6 months (mean, 33 months). The mean age of these patients was 32 years and the mean duration of refractory epilepsy was 22 years. The mean reduction in monthly seizure frequency in all patients was 55% (range, 0-100; SD = 31.6). Seven percent of patients were free of seizures with impaired consciousness, 50% of patients had a seizure frequency reduction of more than 50%, and 21% of patients were nonresponders. Fifteen patients reported stimulation-related side effects such as hoarseness or gagging. In a large patient series from two geographically distinct epilepsy centers located in two different continents, VNS proved to be efficacious and safe during long-term follow-up.
Adolescent↗
Effects of short-term cycling on knee joint proprioception in healthy young persons.
BACKGROUND: Criteria are needed for measuring the effects of exercise and fatigue on proprioception. PURPOSE: To measure knee joint proprioception in healthy subjects before and after exercise and to establish a reference for further comparisons of patients with knee injuries. STUDY DESIGN: Controlled laboratory study. METHODS: We tested proprioception in the knees of 24 healthy subjects with a mean age of 24 years and median Tegner score of 5. Subjects were tested to estimate their thresholds for detecting slow passive motion, from starting positions of 20 degrees and 40 degrees before and after cycling on an ergometer bicycle until the pulse rate reached a steady state level and they reached a score of 14 to 17 on Borg's Ratio of Perceived Exertion scale. RESULTS: After cycling, significantly higher threshold values were found for perception of movement toward flexion from both 20 degrees and 40 degrees. No significant differences were seen in measurements of movement toward extension. CONCLUSIONS: Knee joint proprioception seems to be impaired by exercise or training. CLINICAL RELEVANCE: This impairment may lead to defective dynamic stabilization of the joint, leading to an increased risk of injuries.
Adult↗