Single-strand conformational polymorphism analysis of the M(r) 170,000 isozyme of DNA topoisomerase II in human tumor cells

Five cell lines selected for resistance to the cytotoxicity of inhibitors of DNA topoisomerase II have point mutations in the gene that codes for the M(r) 170,000 form of this enzyme. In each case, the mutation results in an amino acid change in or near an ATP binding sequence of the M(r) 170,000 isozyme of topoisomerase II. We used single-strand conformational polymorphism analysis to screen for similar mutations in other drug-resistant cell lines or in leukemic cells from patients previously treated with etoposide or teniposide. We also analyzed the region of the gene that codes for amino acids adjacent to the tyrosine at position 804 of topoisomerase II which binds covalently to DNA. CEM/VM-1, CEM/VM-1-5, and HL-60/AMSA human leukemic cell lines were used as controls; 3 of 3 known mutations were detected by migration differences of polymerase chain reaction products from the RNA extracted from these three lines. A previously unknown mutation was found in the tyrosine 804 region of the M(r) 170,000 topoisomerase II expressed by CEM/VM-1 and CEM/VM-1-5 cells. Sequence analysis showed that substitution of a T for a C at nucleotide 2404 resulted in an amino acid change of a serine for a proline at amino acid 802. No mutations in any of the ATP binding sequences or in the tyrosine 804 region were detected in polymerase chain reaction products from RNA extracted from human leukemia HL-60/MX2 or CEM/MX1 cells (both cell lines selected for resistance to mitoxantrone) or in human myeloma 8226/Dox1V cells (selected for resistance by simultaneous exposure to doxorubicin and verapamil). No mutations were detected in polymerase chain reaction products from RNA extracted from blasts of 15 patients with relapsed acute lymphocytic leukemia, previously treated with etoposide or teniposide. We conclude that: (a) single-strand conformational polymorphism analysis is useful for screening for mutations in topoisomerase II; (b) resistance to the cytotoxicity of inhibitors of DNA topoisomerase II is not always associated with mutations in ATP binding sequences or the active site tyrosine region of M(r) 170,000 topoisomerase II; and (c) mutations similar to those detected in drug resistant cells selected in culture have not been identified in blast cells from patients with relapsed acute lymphocytic leukemia, previously treated with etoposide or teniposide.     

Oncogene rearrangement in non-Hodgkin's lymphoma with a 14q+ chromosome of unknown origin

Southern blot analysis was performed with a panel of DNA probes to detect rearrangements of c-myc, bcl-1, bcl-2 and bcl-3 in 14 cases of B-cell non-Hodgkin's lymphoma (NHL) with a clonal cytogenetic rearrangement involving the chromosome 14q32 locus and no known donor chromosome [t(14;?)(q32;?)]. In our experience, 21% of all chromosomal abnormalities involving the 14q32 locus in B-cell NHL are of this type. We found oncogene rearrangements in five of the 14 cases: bcl-1 rearrangement on one mantle zone lymphoma, bcl-2 rearrangements in two follicular lymphomas, and c-myc rearrangements in two small noncleaved cell lymphomas. We conclude that a 14q32+ abnormality of unknown origin is a relatively frequent karyotypic finding in B-cell NHL. In one third of the cases, known oncogenes that have been previously described in reciprocal translocations involving the immunoglobulin heavy chain locus were shown to be involved in the 14q32+ abnormality. The translocations in the other cases are likely to have involved one of the above oncogenes with breakpoints not revealed by the probes employed, other known oncogenes, or oncogenes that have not yet been identified.     

Controlled oxygen incorporation in indium gallium arsenide and indium phosphide grown by metalorganic vapor phase epitaxy

The defect engineering in metalorganic vapor phase epitaxy In_xGa_1-xAs and InP by controlled oxygen doping using diethyl aluminum ethoxide (DEALO) was developed in this study. DEALO doping has led to the incorporation of Al and O, and the compensation of shallow Si donors in In_xGa_1−xAs: Si with 0 ≤ x ≤ 0.25. With the same DEALO mole fraction during growth, the incorporation of Al and O was found to be independent of x, but the compensation of Si donors decreases with increasing In content. Deep level transient spectroscopy analysis on a series of In_xGa_1-xAs: Si. samples with 0 ≤ x ≤ 0.18 revealed that oxygen incorporation led to a set of deep levels, similar to those found in DEALO doped GaAs. As the In composition was increased, one or more of these deep levels became resonant with the conduction band and led to a high electron concentration in oxygen doped In_0.53Ga_0.47As. Low temperature photoluminescence emission measurements at 12K on the same set of samples revealed the quenching of the near-band edge peak, and the appearance of new oxygen-induced emission features. DEALO doping in InP has also led to the incorporation of Al and O, and the compensation of Si donors due to oxygen-induced multiple deep levels.     

CAN IS AVOID MARGINALIZATION ?

Two major areas of concern for IS managers are the use of outsourcing and the often-expressed view that little competitive advantage has been gained from information processing. These developments have begun to mirror events in other professions from a bygone age. By looking outside the IS field for some perspective, we may avert a similar outcome and better define the role of IS in the organization.     

Accounting for case manager effects in the evaluation of mental health services.

Three methods of accounting for case manager effects in tests of the efficacy of mental health services are explored. These methods include (1) treating the case manager as a fixed factor, (2) treating the case manager as a random factor, and (3) examining service effects within the case manager. They are demonstrated with data from a nationally known case management program serving individuals with serious and persistent mental illness. Specifically, 3 conceptually distinct types of services provided or brokered by case managers are identified: habilitation-rehabilitation, community support, and traditional psychiatric services. The effectiveness of each in improving clients' adjustment is then examined with multiple regression adjustment strategies and each of the 3 methods to account for case manager effects. The results provide strong support for effects attributable to case managers and some support for the efficacy of habilitation-rehabilitation and community support services beyond the effects of traditional psychiatric services. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Methotrexate therapy in rheumatoid arthritis: a life table review of 587 patients treated in community practice

To determine whether methotrexate (MTX) maintains its effectiveness in rheumatoid arthritis (RA) in the setting of community based private rheumatology practice we used life table analysis to review the combined experience of a group of these practices. Of 587 patients with RA who started to take MTX, total termination rate at 70 months was 24.4% with most terminations prompted by drug toxicity. Older age (greater than 65 years) was associated with higher rates of toxicity. Treatment termination rates varied substantially between rheumatologists. We conclude that MTX therapy for RA is well tolerated and maintains effectiveness for at least 70 months.     

Ultrafast Spectroscopy of La2−x Sr x CuO4 Single Crystals

We present measurements of the ultrafast optical response of La_2–x Sr _x CuO₄ single crystals at two different doping levels (x=0.15, 0.07) as a function of temperature. Owing to the 40-fs time resolution of our experiment, we are able to measure both the build-up and the decay of the ultrafast signal. We show for the first time that the temperature dependence of the transient reflectance amplitude tracks the thermal depletion of the superfluid density. At low temperature we identify a new regime characterized by an extremely long, temperature-dependent rise-time (3 ps). The doping dependence of the relaxation rate suggests that this is sensitive to the scattering of quasiparticles by low-energy spin excitations.     

Enhancing the precision of the Mississippi Scale for Combat-Related Posttraumatic Stress Disorder: An application of item response theory.

Examined, using item response theory, the measurement qualities of the Mississippi Scale for Combat-Related Posttraumatic Stress Disorder, with data taken from the 2,348 veteran participants in the National Vietnam Veterans Readjustment Study. Using F. Samejima's (1969) graded response model, estimates of each item's discrimination and difficulty parameters were derived, and item and test information functions were then computed. Various item information patterns and sample items are discussed in terms of improved assessment of posttraumatic stress disorder (PTSD). (PsycINFO Database Record (c) 2010 APA, all rights reserved)