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Biomedical subjects

R Stone

Publications and source records attributed to R Stone.

At least 55 records · Page 3Linked to original sources

U.K. funding. New program supports facilities, stipends.

British scientists are celebrating a $1.7 billion windfall, announced last week by the U.K. government, to shore up deteriorating facilities and raise stipends for Ph.D. students. The 2-year spending boost is intended to keep the pool of British science well stocked, both by attracting more talented students into the field and stemming the flow of scientists out of the country. But the benefits are not spread evenly across the research spectrum.

Academies and Institutes↗

Social science. Stress: the invisible hand in Eastern Europe's death rates.

The end of communism opened up a life of economic uncertainty in the Eastern Bloc. And that, say some social scientists, may be exerting a deadly effect on residents, whose high expectations that their lives would improve were quickly dashed by the bumpy transition to a market economy. Disillusionment led to stress and depression, and depression was a harbinger of death.

Communism↗

Isolation of thirty-one new porcine microsatellites from a microsatellite enriched microdissected chromosome 8 library.

Chromosome 8 (SSC8) is an important one in the swine genome because it has been shown to harbor several economically important quantitative trait loci (QTL). The entire porcine chromosome 8 was microdissected and amplified by degenerate oligonucleotide primer (DOP) PCR. The PCR product was then enriched for (CA)n microsatellites by hybridization to a biotinylated CA repeat oligonucleotide and captured by streptavidin-coated magnetic beads. The captured DNA was cloned into a TA cloning vector. Screening with an isotopically labeled CA oligonucleotide probe resulted in the isolation of 31 informative and polymorphic microsatellite clones. Seventeen of those were mapped to chromosome 8, 12 to chromosome 15, 1 to chromosome 10 and 1 to chromosome X. The markers were all placed on the USDA-MARC porcine genetic linkage map.

Animals↗

Effect of roost size on the emergence behaviour of pipistrelle bats.

We refined established methods for examining the temporal organization of behavioural events and applied them to the study of bats emerging from roost sites. Previous studies have shown that as roosting numbers of bats increase, temporal patterning (clustering) in their emergence behaviour, as measured by chi(2)or G statistics, also increases. Expressing the extent of temporal clustering using chi(2)or G, however, confounds two effects. The statistic may increase because clustering increases. However, an increase will occur, even if the amount of clustering stays constant, if the sample size of observations increases. A positive relation between emergence size and chi(2)or G may not necessarily reflect increased clustering. We developed a method to separate these effects using computer-modelled event streams. Using this method, we examined intra- and inter-roost variation in the temporal patterning of emergences of the pipistrelle bat, Pipistrellus pipistrellus, from four roosts in northeast Scotland. The 'corrected' expression of clustering decreased as roost size increased, which was opposite to the effect found with the uncorrected expression and also opposite that predicted a priori from the bottleneck hypothesis. This novel result suggests bottlenecks may disrupt clustering rather than promote it. This latter interpretation was supported by observations that clustering was significantly reduced in the middle of large emergences. Variation in clustering between roosts was significant, suggesting exit topology may have an important influence on clustering behaviour. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗

Bartter's syndrome and pregnancy.

Bartter's syndrome is a rare renal tubular disorder and few cases are reported associated with pregnancy. We describe a case of long standing disease with a good obstetric outcome in which the main concern was to maintain normal potassium serum levels.

Adult↗

Interstitial pneumonitis following mitozantrone, chlorambucil and prednisolone (MCP) chemotherapy.

We describe two cases of interstitial lung disease in patients with non-Hodgkin's lymphoma who were treated with combination chemotherapy including mitozantrone. In both we had radiological and histological evidence of interstitial lung disease, with patterns of organizing pneumonia and hypersensitivity without a clear aetiological agent. Clinical resolution occurred on withdrawal of chemotherapy. One patient required a course of corticosteroid treatment. To date, both patients are well and in remission, and there has been no recurrence of their respiratory disease. We postulate that these observations are hitherto undescribed pulmonary abnormalities secondary to mitozantrone therapy.

Aged↗

Functional role for protein kinase Cbeta as a regulator of stress-activated protein kinase activation and monocytic differentiation of myeloid leukemia cells.

Human myeloid leukemia cells respond to 12-O-tetradecanoylphorbol-13-acetate (TPA) and other activators of protein kinase C (PKC) with induction of monocytic differentiation. The present studies demonstrated that treatment of U-937 and HL-60 myeloid leukemia cells with TPA, phorbol-12,13-dibutyrate, or bryostatin 1 was associated with the induction of stress-activated protein kinase (SAPK). In contrast, TPA-resistant TUR and HL-525 cell variants deficient in PKCbeta failed to respond to activators of PKC with the induction of SAPK. A direct role for PKCbeta in TPA-induced SAPK activity in TUR and HL-525 cells that stably express PKCbeta was confirmed. We showed that TPA induced the association of PKCbeta with MEK kinase 1 (MEKK-1), an upstream effector of the SAPK/ERK kinase 1 (SEK1)-->SAPK cascade. The results also demonstrated that PKCbeta phosphorylated and activated MEKK-1 in vitro. The functional role of MEKK-1 in TPA-induced SAPK activity was further supported by the demonstration that the expression of a dominant negative MEKK-1 mutant abrogated this response. These findings indicate that PKCbeta activation is necessary for activation of the MEKK-1-->SEK1-->SAPK cascade in the TPA response of myeloid leukemia cells.

Calcium-Calmodulin-Dependent Protein Kinases↗

Learning rate for laparoscopic surgical skills on MIST VR, a virtual reality simulator: quality of human-computer interface.

Acquiring laparoscopic surgical skills involves initial learning of cognitive and motor skills followed by refinement of those skills. The successful use of a virtual reality simulator depends on the quality of the interface for the human-computer interaction and this can be determined by the initial learning rate. MIST VR, a part-task virtual reality laparoscopic simulator, provides objective assessment of psychomotor skills and can generate an overall score for performance, based upon errors made and time taken for six different tasks. This study analysed the rate of early task/instrument/computer familiarization on consecutive scores achieved by surgically experienced and naive individuals. Eleven surgeons, 18 medical students and seven non-medical personnel were tested on the simulator up to ten consecutive times, within a 2-week period. Performance data from every task and repetition were analysed to obtain individual scores of task performance. The calculation of overall score penalized errors far more heavily than total time taken, with high scores indicating poor performance. The surgeon-computer interface generated a rapid and significant early familiarization curve up to the third session on the simulator, with significant reductions in both time taken and total contact errors made. These results suggest that MIST VR represents a high quality interface. Surgeons scored consistently and significantly better than other subjects on all tasks. For surgically naive individuals, it was possible to predict the level of laparoscopic skills performance that would be attained after overcoming initial simulator learning curve, by studying their initial score. Overall scores reflected surgical experience and suggest that the simulator is measuring surgically relevant parameters. MIST VR provides a validated and much needed method for objective assessment of laparoscopic skills, for a variety of surgical disciplines.

Adult↗

Blood product requirements in patients undergoing elective endovascular abdominal aortic aneurysm repair.

OBJECTIVE: Endovascular repair (EVR) of abdominal aortic aneurysm (AAA) has many potential advantages, one of which may be reduced blood product requirements. The aim of this study was to compare the current blood product usage in our unit for three types of elective operation: EVR of AAA, open AAA repair and femorofemoral crossover grafts. DESIGN: Prospective data analysis with historical controls. MATERIALS: One-hundred and thirty-two patients undergoing elective EVR of AAA, 35 patients undergoing elective open repair of AAA and 37 patients having femorofemoral crossover grafts. METHODS: Data was collected on the blood product requirements of patients having EVR of AAA, with open AAA repair and femorofemoral crossover graft providing historical controls. RESULTS: There was no difference in the haematological parameters preoperatively between the three groups but postoperatively patients having EVR had a slightly lower haemoglobin than the open group (10.6 g/dl vs. 10.85 g/dl, p = 0.015). The number of patients who received blood transfusion in the EVR group was 82/132 (62%) and the open group 27/35 (77%), p = 0.4. CONCLUSION: Patients undergoing EVR of AAA require blood transfusion in the same numbers when compared to those undergoing open repair.

Aortic Aneurysm, Abdominal↗

FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome.

Various histological subtypes of leukaemia and lymphoma are associated with diagnostic chromosome translocations, and substantial strides have been made in determining the specific oncogenes targetted by those translocations. We report the cloning of a novel fusion oncogene associated with a unique leukaemia/lymphoma syndrome. Patients afflicted with this syndrome present with lymphoblastic lymphoma and a myeloproliferative disorder, often accompanied by pronounced peripheral eosinophilia and/or prominent eosinophilic infiltrates in the affected bone marrow, which generally progress to full-blown acute myelogenous leukaemia within a year of diagnosis. A specific chromosome translocation, t(8;13)(p11;q11-12), is found in both lymphoma and myeloid leukaemia cells from these patients, supporting bi-lineage differentiation from a transformed stem cell. We find that the 8p11 translocation breakpoints, in each of four patients, interrupt intron 8 of the fibroblast growth factor receptor 1 gene (FGFR1). These translocations are associated with aberrant transcripts in which four predicted zinc-finger domains, contributed by a novel and widely expressed chromosome-13 gene (ZNF198), are fused to the FGFR1 tyrosine-kinase domain. Transient expression studies show that the ZNF198-FGFR1 fusion transcript directs the synthesis of an approximately 87-kD polypeptide, localizing predominantly to the cytoplasm. Our studies demonstrate an FGFR1 oncogenic role and suggest a tumorigenic mechanism in which ZNF198-FGFR1 activation results from ZNF198 zinc-finger-mediated homodimerization.

Amino Acid Sequence↗

[Diurnal axial eye growth rhythm in chicks is modified by diurnal light-dark cycle].

BACKGROUND: In chicks, the distance from the cornea to the posterior sclera (defined as axial eye length) grows in a diurnal rhythm: growth during the day is greater than during the night. The purpose of this study was to investigate whether this diurnal, axial eye growth rhythm is influenced by the diurnal light/dark illumination cycle. METHODS: One day after hatching, 18 White Leghorn chicks were reared under a 12 hour light/dark illumination cycle. After seven days, 12 chicks were switched to continuous light; the other 6 chicks remained under the 12 hour light/dark cycle and served as controls. Every 12 hours, at times corresponding to the onset of former light and dark phases over a period of 2 days, axial eye length was measured in the right eyes by laser Doppler interferometry with a precision of 20 microns. RESULTS: In group 1, axial eye growth during time intervals corresponding to former light phases (0.063 +/- 0.024 mm; mean +/- 95% confidence limit) and dark phases (0.040 +/- 0.017 mm) were not significantly different (one-factor ANOVA). In group 2, axial eye growth during light phases (0.065 +/- 0.028 mm) was significantly greater than during dark phases (0.015 +/- 0.023 mm; p = 0.015). Significantly, total axial eye growth during the two-day period was greater in group 1 (0.206 +/- 0.015 mm) than in group 2 (0.160 +/- 0.021 mm; p = 0.02; unpaired, two-tailed Student's t-test). CONCLUSION: The diurnal, axial eye growth rhythm is strongly attenuated following an acute switch from a 12 hour light/dark cycle to continuous light. Control chicks exhibit the normal rhythm. This observation demonstrates that the diurnal, axial eye growth rhythm is influenced by the light/dark illumination cycle. Whether the alteration of the rhythm and the increased axial growth during continuous light is caused by the increased amount of light alone or by increased light-induced form vision remains to be investigated.

Age Factors↗

First International Pharmacoeconomic Conference on Alzheimer's Disease: report and summary.

The First International Pharmacoeconomic Conference on Alzheimer's Disease (AD) was held in Amsterdam in July 1998. The meeting was held under the auspices of the International Working Group for Harmonization of Dementia Drug Guidelines (http://dementia.ion.ucl.ac.uk/harmon), bringing together academics, clinicians, purchasers, and representatives from industry. Presentations were given on the methodology of pharmacoeconomic studies in AD, particularly focusing on caregiver burden, quality of life (QOL), and resource utilization. Three economic models of AD were presented based on data from the United States, Canada, and the United Kingdom. In two studies, these data were then used to model the cost-effectiveness and effect on cost of treatment with donepezil. Both studies suggested a possible cost advantage for the use of donepezil, when compared with no placebo or treatment, particularly when donepezil is used appropriately in mild-to-moderate AD. These data need to be interpreted with care, as none of the cost or utility information were collected during the clinical trials. Additional data from a 2-year clinical trial of selegiline and vitamin E suggest that cognitive measures may be poor predictors of economic outcome, which is better measured directly. Both economic models of donepezil rely on short-term cognitive data to predict long-term outcome, a methodf that may not be useful in predicting economic savings. The issues facing pharmacoeconomists, researchers, clinicians, and families in the future were addressed in a series of workshops using a method of strategic futuring. The workshops attempted to see 7 years into the future for a range of areas, including consumer and caregiver use of pharmacoeconomic data; early detection and prevention; Japanese perspectives; activities of daily life and what will be daily life activities; caregiver burden; QOL at the end of life; new uses for new information and communication technology in clinical research; and physicians' use of pharmacoeconomic data. A range of exciting futures were predicted, although common themes that arose when considering barriers to achieving these futures included cost, education, political will, confidentiality, privacy, and ethics. The first conference was deemed to have been a success, having attracted more than 160 delegates and many distinguished speaker. A second conference is planned for the year 2000. Over the next 2 years, research needs to be broadened particularly in the methodological areas of resource utilization, QOL, and caregiver burden. Data from clinical trials with relevant economic and QOL outcomes will be needed by purchasers if drug treatments for dementia are to gain widespread use. It is also hoped that the models described at the meeting may become more freely available to politicians, purchasers, clinicians, and caregivers to help them make better decisions about treatment.

Aged↗