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At least 577 records · Page 32Linked to original sources
PubMed1999

An EGS4 Monte Carlo examination of the response of a PTW-diamond radiation detector in megavoltage electron beams.

The EGS4 Monte Carlo code has been used to investigate the response of a PTW/diamond detector irradiated in both clinical and monoenergetic megavoltage electron beams ranging in energy from 5 to 20 MeV. The sensitive volume of the PTW/diamond detector simulated has a thickness of 0.4 mm and a diameter of 4.4 mm. Irradiation was simulated at various depths in a water phantom. The results show that the PTW/diamond detector has a constant response (within 1.0%) in electron beams if irradiated at depths closed to dmax, and its response is almost independent of irradiation depth or incident electron energy (within 3%). A detailed examination of the average detector dose shows that the sensitive volume of the PTW/diamond detector acts as a Spencer-Attix cavity within 1%. The encapsulation of the bare diamond detector with low-Z epoxy and polystyrene wall material does not affect its response in electron beams. The difference in response between the unencapsulated (TLD) and the encapsulated form of the detector is less than 0.5% for all depths over electron energy range investigated.

Diamond↗
PubMed1986

A comparative study of corneal incisions induced by diamond and steel knives and two ultraviolet radiations from an excimer laser.

This paper reviews the potential role of excimer lasers in corneal surgery. The morphology of incisions induced by two wavelengths of excimer laser radiation, 193 nm and 248 nm, are compared with the morphology of incisions produced by diamond and steel knives. Analysis suggests that ablation induced by excimer laser results from highly localised photochemical reactions and that 193 nm is the optimal wavelength for surgery. The only significant complication of laser surgery is loss of endothelial cells when incisions are within 40 micron of Descemet's membrane.

Animals↗
PubMed1990

Rapidly fatal progression of cobalt lung in a diamond polisher.

Interstitial lung disease was diagnosed in a 52-yr-old male diamond polisher, who worked with polishing disks containing cobalt. After a further 7 months of probably high occupational exposure without any specific treatment, he had to quit work because of dyspnea. Despite treatment with systemic corticosteroids and continuous oxygen administration, he died 3 months later in respiratory distress. Postmortem examination of the lung tissue showed a typical giant-cell interstitial fibrosis, with active inflammatory cell infiltration superimposed on an established centrilobular fibrosis. The lung tissue contained 2.1 micrograms cobalt/g wet weight (more than 100-fold the normal concentration); cobalt particles, mainly localized in macrophages, were identified by transmission electron microscopy and energy-dispersive X-ray analysis. We speculate that the rapid deterioration and fatal outcome resulted from the continued exposure to cobalt, leading to a high pulmonary concentration of cobalt, and from the oxygen treatment because cobalt promotes the formation of hydroxyl free radicals.

Air Pollutants, Occupational↗
PubMed2001

Single-wall carbon nanotubes under high pressures to 62 GPa studied using designer diamond anvils.

Single-wall carbon nanotube samples were studied under high pressures to 62 GPa using designer diamond anvils with buried electrical microprobes that allowed for monitoring of the four-probe electrical resistance at elevated pressure. After initial densification, the electrical resistance shows a steady increase from 3 to 42 GPa, followed by a sharp rise above 42 GPa. This sharp rise in electrical resistance at high pressures is attributed to opening of an energy band gap with compression. Nanoindentation hardness measurements on the pressure-treated carbon nanotube samples gave a hardness value of 0.50 +/- 0.03 GPa. This hardness value is approximately 2 orders of magnitude lower than the amorphous carbon phase produced in fullerenes under similar conditions. Therefore, the pressure treatment of single-wall carbon nanotubes to 62 GPa did not produce a superhard carbon phase.

Crystallization↗
PubMed2001

Thermal stability of nanocrystalline diamond films grown by biased enhanced microwave plasma chemical vapor deposition.

The thermal stability of nanocrystalline diamond (NCD) films grown on mirror-polished silicon substrates by biased enhanced microwave plasma chemical vapor deposition was investigated. Different pieces of a NCD sample were annealed for 1 h in an ambient argon atmosphere at 200, 400, 600, and 800 degrees C. The structural and mechanical properties of as-grown and annealed samples were assessed. The surface roughness and high hardness of the samples remained fairly constant with annealing temperature.

Argon↗
PubMed2006

Ordered, self-organized cobalt nanodots in Co-diamond-like carbon thin films.

A formation process for ordered, self-organized cobalt (Co) nanodots in diamond-like carbon (DLC) thin films deposited by magnetron sputtering in a plasma-assisted Ar/CH4 discharge is presented. episilon-Co dots -5 nm in diameter, separated by 1-2 nm DLC boundaries and arranged in hexagonal arrays were produced on Si substrates. The formation mechanism relies on a self-organization process which is based on surface energy minimization and local magnetic field interaction. The proposed plasma-assisted process presents a controlled and cost-effective bottom-up nanofabrication approach for the production of well-ordered magnetic nanodots based on self-organization.

Carbon↗
PubMed2001

Measurements of drill-induced temperature change in the facial nerve during mastoid surgery: a cadaveric model using diamond burs.

The purpose of this study was to investigate the changes in temperature in the facial nerve that occur during mastoid drilling by the facial recess approach and to confirm the beneficial effects of constant irrigation while drilling. Mastoid drilling was performed on human cadaveric temporal bones by means of 4-mm diamond burs with and without irrigation. There were 6 subjects in each group. Changes in facial nerve temperature were recorded on a continuous-output monitor. Significant changes were found in temperature for both the irrigation and non-irrigation groups (p < .0001). Constant irrigation minimized the rise in temperature. Facial recess drilling poses a potential threat to cranial nerve VII via thermal injury. The temperature elevation in the non-irrigation group was significantly greater than that in the irrigation group and was greater than the tolerable limits of peripheral nervous tissue. This finding supports the need for constant irrigation during the approach to the facial recess in mastoid surgery.

Body Temperature↗
PubMed2003

Nucleolar localization of RPS19 protein in normal cells and mislocalization due to mutations in the nucleolar localization signals in 2 Diamond-Blackfan anemia patients: potential insights into pathophysiology.

Ribosomal protein S19 (RPS19) is frequently mutated in Diamond-Blackfan anemia (DBA), a rare congenital hypoplastic anemia. Recent studies have shown that RPS19 expression decreases during terminal erythroid differentiation. Currently no information is available on the subcellular localization of normal RPS19 and the potential effects of various RPS19 mutations on cellular localization. In the present study, using wild-type and mutant RPS19 cDNA, we explored the subcellular distribution of normal and mutant proteins in a fibroblast cell line (Cos-7 cells). RPS19 was detected primarily in the nucleus, and more specifically in the nucleoli, where RPS19 colocalized with the nucleolar protein nucleolin. Using various N-terminal and C-terminal deletion constructs, we identified 2 nucleolar localization signals (NoSs) in RPS19: the first comprising amino acids Met1 to Arg16 in the NH2-terminus and the second comprising Gly120 to Asn142 in the COOH-terminus. Importantly, 2 mutations identified in DBA patients, Val15Phe and Gly127Gln, each of which localized to 1 of the 2 NoS, failed to localize RPS19 to the nucleolus. In addition to their mislocalization, there was a dramatic decrease in the expression of the 2 mutant proteins compared to the wild type. This decrease in protein expression was specific for the mutant RPS19, since expression of other proteins was normal. The present findings enable us to document the nucleolar localization signals in RPS19 and help define the phenotypic consequences of some mutations in RPS19 in DBA.

Anemia, Diamond-Blackfan↗
PubMed2004

Two-phase culture in Diamond Blackfan anemia: localization of erythroid defect.

The erythroid defect in Diamond Blackfan anemia (DBA) is known to be intrinsic to the stem cell, but its molecular pathophysiology remains obscure. Using a 2-phase liquid erythroid culture system, we have demonstrated a consistent defect in DBA, regardless of clinical severity, including 3 first-degree relatives with normal hemoglobin levels but increased erythrocyte adenosine deaminase activity. DBA cultures were indistinguishable from controls until the end of erythropoietin (Epo)-free phase 1, but failed to demonstrate the normal synchronized wave of erythroid expansion and terminal differentiation on exposure to Epo. Dexamethasone increased Epo sensitivity of erythroid progenitor cells, and enhanced erythroid expansion in phase 2 in both normal and DBA cultures. In DBA cultures treated with dexamethasone, Epo sensitivity was comparable to normal, but erythroid expansion remained subnormal. In clonogenic phase 2 cultures, the number of colonies did not significantly differ between normal cultures and DBA, in the presence or absence of dexamethasone, and at both low and high Epo concentrations. However, colonies were markedly smaller in DBA under all conditions. This suggests that the Epo-triggered onset of terminal maturation is intact in DBA, and the defect lies down-stream of the Epo receptor, influencing survival and/or proliferation of erythroid progenitors.

Adolescent↗
PubMed2004

Deficiency of ribosomal protein S19 in CD34+ cells generated by siRNA blocks erythroid development and mimics defects seen in Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a congenital red cell aplasia in which 25% of the patients have a mutation in the ribosomal protein S19 (RPS19) gene. To study effects of RPS19 deficiency in hematopoiesis we transduced CD34(+) umbilical cord blood (CB) and bone marrow (BM) cells with 3 lentiviral vectors expressing small interfering RNA (siRNA) against RPS19 and 1 scrambled control vector. All vectors also express green fluorescent protein (GFP). Transduction with the siRNA vectors reduced RPS19 mRNA levels to various degrees, which resulted in erythroid defects, correlating to the degree of RPS19 down-regulation, and was rescued by expression of an siRNA-resistant RPS19 transcript. Erythroid colony formation capacity conjointly decreased with RPS19 levels in CD34(+) CB and BM cells. In liquid culture supporting erythroid differentiation, RPS19-silenced as well as DBA patient CD34(+) cells exhibited reduced proliferative capacity and impaired erythroid differentiation resulting in fewer erythroid colony-forming units (CFU-Es). When assaying myeloid development, a less pronounced influence on proliferation was seen. This study shows for the first time that RPS19 silencing decreases the proliferative capacity of hematopoietic progenitors and leads to a defect in erythroid development.

Anemia, Diamond-Blackfan↗
PubMed2005

An RNA interference model of RPS19 deficiency in Diamond-Blackfan anemia recapitulates defective hematopoiesis and rescue by dexamethasone: identification of dexamethasone-responsive genes by microarray.

Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia, is a model disease for the study of erythroid differentiation but is poorly understood. RPS19 is the only gene yet to have been associated with DBA, but its relevance to erythroid differentiation is unclear. The molecular basis for the stimulation of erythropoiesis by glucocorticoids in patients with DBA has not been identified. We demonstrate that targeted degradation of the RPS19 transcript, through retroviral expression of short hairpin RNAs (shRNAs), blocks the proliferation and differentiation of erythroid progenitor cells in cultured human CD34(+) cells. Treatment of RPS19-deficient cells with dexamethasone restores erythroid differentiation to normal levels. We investigated the molecular basis of pharmacologic therapies for DBA using oligonucleotide microarrays to survey gene expression in CD34(+) cells treated with combinations of dexamethasone, erythropoietin, stem cell factor, and interleukin-3. Dexamethasone did not alter expression of RPS19 but activated a genetic program that includes a set of key hematopoietic regulatory genes. Genes specific to erythroid progenitor cells were up-regulated by dexamethasone, while genes specific to nonerythroid lineages were down-regulated. Deficiency of RPS19 therefore blocks proliferation of immature erythroid progenitor cells, and dexamethasone activates proliferation of the same cell population through mechanisms independent of RPS19.

Anemia, Diamond-Blackfan↗
PubMed2006

Human RPS19, the gene mutated in Diamond-Blackfan anemia, encodes a ribosomal protein required for the maturation of 40S ribosomal subunits.

Diamond-Blackfan anemia (DBA) typically presents with red blood cell aplasia that usually manifests in the first year of life. The only gene currently known to be mutated in DBA encodes ribosomal protein S19 (RPS19). Previous studies have shown that the yeast RPS19 protein is required for a specific step in the maturation of 40S ribosomal subunits. Our objective here was to determine whether the human RPS19 protein functions at a similar step in 40S subunit maturation. Studies where RPS19 expression is reduced by siRNA in the hematopoietic cell line, TF-1, show that human RPS19 is also required for a specific step in the maturation of 40S ribosomal subunits. This maturation defect can be monitored by studying rRNA-processing intermediates along the ribosome synthesis pathway. Analysis of these intermediates in CD34- cells from the bone marrow of patients with DBA harboring mutations in RPS19 revealed a pre-rRNA-processing defect similar to that observed in TF-1 cells where RPS19 expression was reduced. This defect was observed to a lesser extent in CD34+ cells from patients with DBA who have mutations in RPS19.

Anemia, Diamond-Blackfan↗
PubMed2006

Impaired ribosome biogenesis in Diamond-Blackfan anemia.

The gene encoding the ribosomal protein S19 (RPS19) is frequently mutated in Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia. The consequence of these mutations on the onset of the disease remains obscure. Here, we show that RPS19 plays an essential role in biogenesis of the 40S small ribosomal subunit in human cells. Knockdown of RPS19 expression by siRNAs impairs 18S rRNA synthesis and formation of 40S subunits and induces apoptosis in HeLa cells. Pre-rRNA processing is altered, which leads to an arrest in the maturation of precursors to the 18S rRNA. Under these conditions, pre-40S particles are not exported to the cytoplasm and accumulate in the nucleoplasm of the cells in perinuclear dots. Consistently, we find that ribosome biogenesis and nucleolar organization is altered in skin fibroblasts from DBA patients bearing mutations in the RPS19 gene. In addition, maturation of the 18S rRNA is also perturbed in cells from a patient bearing no RPS19-related mutation. These results support the hypothesis that DBA is directly related to a defect in ribosome biogenesis and indicate that yet to be discovered DBA-related genes may be involved in the synthesis of the ribosomal subunits.

Anemia, Diamond-Blackfan↗
PubMed2006

Diamond-Blackfan anemia: erythropoiesis lost in translation.

Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia that usually presents as macrocytic anemia during infancy. Linkage analysis suggests that at least 4 genes are associated with DBA of which 2 have been identified so far. The known DBA genes encode the ribosomal proteins S19 and S24 accounting for 25% and 2% of the patients, respectively. Herein, we review possible links between ribosomal proteins and erythropoiesis that might explain DBA pathogenesis. Recent studies and emerging findings suggest that a malfunctioning translational machinery may be a cause of anemia in patients with DBA.

Anemia, Diamond-Blackfan↗
PubMed2002

Response of Diamond-Blackfan anemia to metoclopramide: evidence for a role for prolactin in erythropoiesis.

A 47-year-old woman with severe macrocytic anemia markedly improved during the second and third trimesters of 3 pregnancies and when breast-feeding her 2 children. Because the serum prolactin level is elevated at these times, we later treated her with metoclopramide (10 mg orally 3 times daily), a medication known to induce prolactin release. Her serum prolactin levels increased from 7 to 133 ng/mL (normal < 20 ng/mL) and hematocrit from 17% to 22% to 35%. With continued therapy (now 10 mg orally daily), her hematocrit has ranged from 30% to 40% for 6 years, although the macrocytosis persists (mean corpuscular volume, 100-112 fL). On the basis of this observation, a pilot study was undertaken of metoclopramide therapy in patients with Diamond-Blackfan anemia who were refractory to low doses of corticosteroids. Fifteen patients were enrolled and 9 completed the planned 16 weeks of therapy. Three individuals responded, suggesting that this therapeutic approach may benefit others. As with the index case, the anemia did not improve until 12 to 15 weeks of therapy had been completed.

Anemia, Diamond-Blackfan↗
PubMed2002

Gene transfer improves erythroid development in ribosomal protein S19-deficient Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by a specific deficiency in erythroid progenitors. Forty percent of the patients are blood transfusion-dependent. Recent reports show that the ribosomal protein S19 (RPS19) gene is mutated in 25% of all patients with DBA. We constructed oncoretroviral vectors containing the RPS19 gene to develop gene therapy for RPS19-deficient DBA. These vectors were used to introduce the RPS19 gene into CD34(+) bone marrow (BM) cells from 4 patients with DBA with RPS19 gene mutations. Overexpression of the RPS19 transgene increased the number of erythroid colonies by almost 3-fold. High expression levels of the RPS19 transgene improved erythroid colony-forming ability substantially whereas low expression levels had no effect. Overexpression of RPS19 had no detrimental effect on granulocyte-macrophage colony formation. Therefore, these findings suggest that gene therapy for RPS19-deficient patients with DBA using viral vectors that express the RPS19 gene is feasible.

Adult↗
PubMed2004

The DiAMOND trial protocol: a randomised controlled trial of two decision aids for mode of delivery among women with a previous caesarean section [ISRCTN84367722].

BACKGROUND: Caesarean section (CS) has become an increasingly common method of delivery worldwide, rising in the UK from 9% of deliveries in 1980 to over 21% 2001. This increase, and the question of whether CS should be available to women on request, has been the subject of considerable debate, and national reports and guidelines have specifically highlighted the importance of patient choice in the decision making process. For women who have already experienced CS, the UK National Institute of Clinical Excellence recommends that the decision should consider maternal preferences and priorities in addition to general discussion of the overall risks and benefits of CS. Decision aids for many different medical treatment and screening decisions have been developed and evaluated, but there is relatively little evidence for the use of decision aids for choice of mode of delivery among women with a previous CS. The aim of the study is to evaluate two interventions to assist decision making about mode of delivery among pregnant women with one previous CS. METHODS/DESIGN: Women with one previous CS are recruited to the trial during their booking visit at approximately 12-20 weeks' gestation in participating maternity units in Bristol, Weston and Dundee. Using central randomisation, women are allocated to one of three arms: information programme and website; decision analysis; usual care. Both interventions are computer-based, and are designed to provide women with detailed information about the potential outcomes for both mother and baby of planned vaginal delivery, planned CS and emergency CS. The decision analysis intervention additionally provides a recommended 'preferred option' based on maximised expected utility. There are two primary outcomes (decisional conflict and actual mode of delivery), and five secondary outcomes (anxiety, knowledge, perceptions of shared decision making; satisfaction with decision making process, proportion of women attempting vaginal delivery). Primary follow up for the questionnaire measures is at 36-37 weeks' gestation, and a total of 660 women will be recruited to the study. The primary intention-to-treat analyses will comprise three pair-wise comparisons between decision analysis, information and usual care groups, for each of the two primary outcomes. A qualitative study will investigate women's experiences of the decision making in more depth, and an economic evaluation from the perspective of the NHS will be conducted. DISCUSSION: Provision of information to women facing this decision appears variable. The DiAMOND study aims to inform best practice in this area by evaluating the effectiveness of two interventions designed to aid decision making.

Journal Article↗
PubMed2001

Occupational asthma with paroxysmal atrial fibrillation in a diamond polisher.

We present a case of a diamond polisher who developed occupational asthma as a result of prolonged exposure to various potent and well-recognized asthma-inducing agents, including cobalt dust. Although the patient was seen by various medical professionals during the initial course of his illness and given an early diagnosis of a respiratory condition, there were no attempts to evaluate the nature of his work, and therefore to establish a possible causal relationship with his exposures. This case clearly illustrates the importance of such an assessment. The ultimate fate of this patient (he had to retire from his job with a chronic and permanent illness) could have been avoided by early environmental intervention. In addition, this case illustrates a possible complication of asthma, that is, a severe cardiac arrhythmia. In this case, both the patient's symptoms and the prescribed medications contributed to worsening of the patient's underlying condition. Early diagnosis and intervention of this patient's work practices could have avoided this complication.

Asthma↗