1,435 research outputs found
P53 mutations in human adrenocortical neoplasms
The mechanisms of tumorigenesis of adrenocortical neoplasms have not been elucidated as yet. However, loss of heterozygosity at chromosomal locus 17p has been consistently observed in adrenocortical cancer. p53 is a recessive tumor suppressor gene located on chromosome 17p. Mutations in the p53 gene play an important role in the tumorigenesis of diverse types of human neoplasms including breast and colon cancers. More than 90% of all mutations discovered in such tumors have been detected in 4 hot spot areas that lie between exons 5 and 8. In contrast to wild-type p53, mutant p53 accumulates intracellularly and can be easily detected by immunohistochemistry. We therefore investigated the frequency of p53 mutations in human adrenocortical neoplasms using molecular biology and immunohistochemistry techniques. Five patients with adrenocortical adenomas (5 female; ages 39-72 yr), 11 patients with adrenocortical carcinomas (8 female, 3 male; ages 15- 50 yr), and two adrenocortical tumor cell lines were studied. After DNA extraction from frozen tumor tissue or paraffin-embedded material, exons 5 through 8 were amplified using the polymerase chain reaction and directly sequenced by the dideoxy termination method. Immunohistochemistry was performed on paraffin-embedded tumor specimens obtained during adrenalectomy using a monoclonal antibody reacting with both wild-type and mutant p53. Prevalence of mutations was adenomas, 0/5, carcinomas, 3/11, and adrenocortical cell lines, 2/2. Single point mutations were detected in 3 cases (exons 5, 6, and 7, respectively), and rearrangements of exon 7/8 and 8 were found in 2 cases. Immunohistochemistry detected strong nuclear and/or cytoplasmic p53 immunoreactivity in all adrenocortical carcinomas with point mutations of the p53 gene but not in adenomas and carcinomas with the wild-type sequence or with deletion/rearrangement of the p53 gene. We conclude that p53 plays a role in the tumorigenesis of adrenocortical carcinomas but is of less importance to benign adenomas
Bench-scale synthesis of nanoscale materials
A novel flow-through hydrothermal method used to synthesize nanoscale powders is introduced by Pacific Northwest Laboratory. The process, Rapid Thermal Decomposition of precursors in Solution (RTDS), uniquely combines high-pressure and high-temperature conditions to rapidly form nanoscale particles. The RTDS process was initially demonstrated on a laboratory scale and was subsequently scaled up to accommodate production rates attractive to industry. The process is able to produce a wide variety of metal oxides and oxyhydroxides. The powders are characterized by scanning and transmission electron microscopic methods, surface-area measurements, and x-ray diffraction. Typical crystallite sizes are less than 20 nanometers, with BET surface areas ranging from 100 to 400 sq m/g. A description of the RTDS process is presented along with powder characterization results. In addition, data on the sintering of nanoscale ZrO2 produced by RTDS are included
Early stages of ramified growth in quasi-two-dimensional electrochemical deposition
I have measured the early stages of the growth of branched metal aggregates
formed by electrochemical deposition in very thin layers. The growth rate of
spatial Fourier modes is described qualitatively by the results of a linear
stability analysis [D.P. Barkey, R.H. Muller, and C.W. Tobias, J. Electrochem.
Soc. {\bf 136}, 2207 (1989)]. The maximum growth rate is proportional to
where is the current through the electrochemical cell,
the electrolyte concentration, and . Differences
between my results and the theoretical predictions suggest that
electroconvection in the electrolyte has a large influence on the instability
leading to ramified growth.Comment: REVTeX, four ps figure
Outcomes for 18 to 25-year-olds with borderline personality disorder in a dedicated young adult only DBT programme compared to a general adult DBT programme for all ages 18
Aim
Targeting young adults with borderline personality disorder (BPD) for treatment may carry significant social and clinical benefits. We aimed to evaluate a communityâbased Dialectical Behaviour Therapy (DBT) programme delivered exclusively to young adults with BPD.
Methods
We describe a naturally occurring nonâequivalent, quasiâexperimental comparison of outcomes for young adults (18â25âyears) with BPD following 1 year of treatment in either a young adult only DBT programme or a general adult DBT programme (18+ years). Twentyâfour young adults enrolled in a communityâbased young adult DBT programme open only to 18â to 25âyearâolds with BPD. Another 13 young adults, also 18â25âyears, enrolled in a general adult DBT programme open to all ages above 18âyears. Both treatment conditions offered all modes of standard DBT for 1 year. Participants completed a battery of selfâreport measures on mental health symptoms at baseline and again at treatment completion after 1 year. Discharge rates at 2 years postâtreatment completion were also recorded.
Results
Better outcomes were found on borderline symptom severity and general psychopathology among completers of young adult DBT, with a large effect size for treatment condition as well as greater clinically significant change. Discharge rates from mental health services 24âmonths later were also higher for completers of young adult DBT.
Conclusions
There may be advantages in delivering DBT to young adults in an ageâspecific programme, possibly due to group cohesion. Methodological limitations apply, such as small sample size and nonârandomization. Further controlled research is needed
The violent accounts of men diagnosed with co-morbid antisocial and borderline personality disorders
Acute Loss of Iron-Sulfur Clusters Results in Metabolic Reprogramming and Generation of Lipid Droplets in Mammalian Cells
Ironâsulfur (Fe-S) clusters are ancient cofactors in cells and participate in diverse biochemical functions, including electron transfer and enzymatic catalysis. Although cell lines derived from individuals carrying mutations in the Fe-S cluster biogenesis pathway or siRNA-mediated knockdown of the Fe-S assembly components provide excellent models for investigating Fe-S cluster formation in mammalian cells, these experimental strategies focus on the consequences of prolonged impairment of Fe-S assembly. Here, we constructed and expressed dominantânegative variants of the primary Fe-S biogenesis scaffold protein ironâsulfur cluster assembly enzyme 2 (ISCU2) in human HEK293 cells. This approach enabled us to study the early metabolic reprogramming associated with loss of Fe-Sâcontaining proteins in several major cellular compartments. Using multiple metabolomics platforms, we observed a âŒ12-fold increase in intracellular citrate content in Fe-Sâdeficient cells, a surge that was due to loss of aconitase activity. The excess citrate was generated from glucose-derived acetyl-CoA, and global analysis of cellular lipids revealed that fatty acid biosynthesis increased markedly relative to cellular proliferation rates in Fe-Sâdeficient cells. We also observed intracellular lipid droplet accumulation in both acutely Fe-Sâdeficient cells and iron-starved cells. We conclude that deficient Fe-S biogenesis and acute iron deficiency rapidly increase cellular citrate concentrations, leading to fatty acid synthesis and cytosolic lipid droplet formation. Our findings uncover a potential cause of cellular steatosis in nonadipose tissues
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