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.     

The idiographic nature of human personality: examples of the idiographic self-concept

Arguments are made for the practical and theoretical merits of idiographic approaches to personality. In addition, it is argued that idiographic approaches to personality afford levels of prediction that cannot be provided by nomothetic analyses, and 2 studies of the role of self-investment in interpersonal perception are presented in support of this position. Finally, in contrast to previous arguments for idiographic approaches, it is suggested that idiographic approaches to personality can provide special insight into universal patterns of human personality.     

Synteny mapping of four genes from the short arm of human chromosome 19 to bovine chromosome 7

Four genes on the short arm of human chromosome 19 (HSA 19p) were assigned to bovine chromosome 7 (BTA 7) using a bovine x rodent somatic hybrid cell panel. These four genes were cartilage oligomeric matrix protein (COMP), lymphoblastic leukemia derived sequence 1 (LYL1), lysosomal alpha-mannosidase (MANB), and RAS oncogene family member RAB3A. Bovine sequence tagged sites were developed for the four genes and used for screening a bovine x rodent somatic cell panel. All four genes were mapped to bovine synteny group U22 (BTA 7) with a correlation coefficient of 0.901-1.000. This study confirms that the centromeric region of BTA 7 is conserved with HSA 19p.     

Ductile-phase toughening and Fatigue-Crack Growth in Nb-Reinforced Molybdenum Disilicide Intermetallic Composites

A study has been made of the role of ductile-phase toughening on the ambient temperature fracture toughness and fatigue-crack propagation behavior of a molybdenum disilicide intermetallicmatrix composite reinforced with 20 vol pct niobium spheres. Using disk-shaped compact DC(T) samples, only moderate improvements (∼24 pct) in fracture toughnessK _lcvalues were found for the composite compared to the unreinforced MoSi₂ matrix material. Moreover, (cyclic) fatigue- crack propagation was seen at stress intensities as low as 75 to 90 pct ofK _Ic, with growth rates displaying a high dependency (∼14) on the applied stress-intensity range. The lack of significant toughening due to the incorporation of ductile Nb particles is associated with an absence of crack/particle interactions. This is attributed to the formation of a weak reaction-layer interface and elastic mismatch stresses at the crack tip between the Nb and MoSi₂, both factors which favor interfacial debonding; moreover, the spherical morphology of Nb phase stabilizes cracking around the particle. Results suggest that increasing the aspect ratio of the distributed Nb rein- forcement phase with attendant interfacial debonding and eliminating possible Nb-phase em- brittlement due to interstitial impurity contamination are critical factors for the successful development of tougher Nb/MoSi₂ structural composites. Formerly with McDonnell Formerly with McDonnell     

Glucose-dependent uptake of chromium in human and rat insulin-sensitive tissues

Su Vida, Su Salud/Your Life, Your Health is a community program to increase participation in breast and cervical cancer screening. This program illustrates the diffusion of an innovative outreach strategy from a research environment to two local health departments. The program uses A Su Salud, the communication model in which positive role models are featured in the media, and community volunteers who give positive social reinforcement. Local health departments in Galveston and Corpus Christi, TX, were selected to implement the model because of excessive mortality rates in the region and the departments' adequate level of resources and commitment. Over an 18-month period, 54 stories of role models appeared in the media in Corpus Christi, and 60 appeared in Galveston. There were 490 volunteers active in Corpus Christi and 279 in Galveston. Of 365 inquiries to the Corpus Christi program, 35 percent were from the Mexican American target group of women ages 40-70. Of 1,457 women who contacted the Galveston program, 9 percent were from the African American target group ages 40-70. Local health departments are well-suited to participation in cancer control research applications because they have direct access to high-risk populations and have the authority to institutionalize effective interventions.     

Gene amplification as a prognostic factor in primary and secondary high-grade malignant gliomas

ND10 are recently characterized nuclear domains that are composed of 0.5 microm sized, precisely circumscribed dots in cultured human cell lines. To investigate the distribution and number of ND10 on various types of normal and neoplastic human tissues, we carried out immunostaining and immunoprecipitation analyses with monoclonal antibodies 138 and 1150. The number of ND10 varied from 1 to 10 or more in various tissues as did their size. ND10 were diffusely located in early embryonic and normal tissues, except for the exocrine and endocrine cells of the pancreas and for hepatocytes. In normal squamous mucosa, basal cells had more ND10 than did differentiated superficial squamous cells. The number and size of ND10 were markedly increased in malignant neoplasms but were similar in benign tumors and corresponding normal tissues. Sex hormone-related normal tissues, such as the endometrium or myometrium, and neoplasms strongly stained for ND10. The distribution pattern of ND10 in human tissues indicates that they are conserved nuclear substructures that are closely associated with cellular differentiation, hormonal stimulation, and oncogenesis.     

Activities of novel aryloxyalkylimidazolines on rat 5-HT2A and 5-HT2C receptors

One impact of socioeconomic progress on populations has been to reduce the number of cases due to diseases of undernutrition and microbial contamination of food, which affected mostly infants and young children, and to increase those due to diseases of excessive food consumption, which are affecting adults and a growing number of children. This article reviews the main dietary factors which have an influence on cardiovascular disease and cancer, and discusses the link between economic development and increased rates of chronic diseases. There is evidence that the noncommunicable diseases and their risk factors have risen rapidly in countries of the WHO Western Pacific Region. Data from 29 countries and areas in the region indicate that 70% of them show lifestyle diseases in three or more of the top five causes of death. While public health measures have been implemented by some countries to prevent and control nutrition-related chronic diseases, further action is needed.