2-(4-Aminophenyl)benzothiazoles: novel agents with selective profiles of in vitro anti-tumour activity

OBJECTIVE: To evaluate the results of cervical cytology screening in the National Breast and Cervical Cancer Early Detection Program and to compare the findings with results from other screening programs. METHODS: We analyzed data on 312,858 women aged 18 years and older who received one or more Papanicolaou smears, and follow-up if indicated, from October 1991 through June 1995 at screening sites across the United States providing comprehensive National Breast and Cervical Cancer Early Detection Program services. RESULTS: Of the women screened, more than half were 40 years or older; slightly less than half (44%) were of racial and ethnic minorities. During the first screening cycle, 3.8% of Papanicolaou tests were reported as abnormal (squamous intraepithelial lesion [SIL] or squamous cell cancer); proportions of abnormals decreased with increasing age. The age-adjusted rate of biopsy-confirmed cervical intraepithelial neoplasia (CIN) II or worse among women screened was 7.4 per 1000 Papanicolaou tests; rates of CIN were highest among young women, but cancer rates peaked among women in their 50s and 60s. The percentages of first screening cycle-Papanicolaou tests interpreted as high-grade SIL and squamous cell carcinoma associated with biopsy-confirmed CIN II or worse (the positive predictive value) were 56.0% for CIN II/III and 3.7% for invasive cancer. Of the 150 invasive cancers diagnosed, 54.0% were classified as local disease. CONCLUSION: Observed results emphasize the duality of cervical neoplasia-CIN in younger women and invasive cancer in older women. This finding points to the importance of reaching both younger and older women for cervical cancer screening.     

Korrosionsschäden am Förderband eines Ofens zur Reinigung von mit organischen Chlorverbindungen kontaminiertem Erdboden

Corrosion damage to the conveyor belt of a furnace for the removal of soil from organic chlorine compounds This paper reports the corrosion behaviour of metallic materials which were used in components of a conveyor belt of a decontamination furnace or of which specimens were attached to the belt for testing purposes. The furnace was used for decontaminating soil containing organic chlorine compounds. A total of 1 ferritic and 8 austenitic steels, 9 nickel base alloys, 2 east steels with 15 % Si and 15 % Si + 5 % Cr respectively, and 3 aluminised steels were tested and afterwards investigated by metallographic and micro-analytical methods. Most of the materials failed due to external and/or internal corrosion, preferentially along grain boundaries. The 2 cast steels revealed fairly good corrosion resistance. The material 2.4061 (LC-Ni 99.6) displayed surprisingly good behaviour, however it remains to be seen whether the inward migration of O and C along grain boundaries causes embrittlement. The materials 2.4610 and 2.4831, containing 14-17 % Mo and 8.5-9,5 % Mo respectively, showed good resistance. The reason for this good corrosion resistance could not be clarified. One reason may be the relatively high Mo content but other materials with a comparable Mo content, like materials 2.4856 and 2.4663, were significantly attacked. It appears necessary to check the long-term behaviour of these two materials.     

CVT-313, a specific and potent inhibitor of CDK2 that prevents neointimal proliferation

The activity of cyclin-dependent kinase 2 (CDK2) is essential for progression of cells from G1 to the S phase of the mammalian cell cycle. CVT-313 is a potent CDK2 inhibitor, which was identified from a purine analog library with an IC50 of 0.5 microM in vitro. Inhibition was competitive with respect to ATP (Ki = 95 nM), and selective CVT-313 had no effect on other, nonrelated ATP-dependent serine/threonine kinases. When added to CDK1 or CDK4, a 8.5- and 430-fold higher concentration of CVT-313 was required for half-maximal inhibition of the enzyme activity. In cells exposed to CVT-313, hyperphosphorylation of the retinoblastoma gene product was inhibited, and progression through the cell cycle was arrested at the G1/S boundary. The growth of mouse, rat, and human cells in culture was also inhibited by CVT-313 with the IC50 for growth arrest ranging from 1.25 to 20 microM. To evaluate the effects of CVT-313 in vivo, we tested this agent in a rat carotid artery model of restenosis. A brief intraluminal exposure of CVT-313 to a denuded rat carotid artery resulted in more than 80% inhibition of neointima formation. These observations suggest that CVT-313 is a promising candidate for evaluation in other disease models related to aberrant cell proliferation.     

Age-related differences in the temporal and spatial regulation of matrix metalloproteinases (MMPs) in normal skin and acute cutaneous wounds of healthy humans

Despite the association of increasing age with chronic wound-healing disorders and an impaired rate of healing of acute cutaneous wounds, the role of matrix metalloproteinases (MMPs) is unknown. To determine the spatial and temporal patterns and activities of MMP-1, -2, -3 and -9, 132 healthy humans aged between 19 and 96 years underwent 4-mm punch biopsies followed by wound excision between day 1 and day 180 post-wounding. Wounds showed an age-related increase in MMP-2 and MMP-9 immunostaining from day 3; this was associated with degradation of gelatin as shown by zymograms and with increased proteinase activity as shown by azocoll assays. Distinct spatial localisations for each MMP were observed: MMP-2 was found in epidermal structures; MMP-9 was observed in inflammatory cells up to day 21; MMP-1 was localised to keratinocytes at the wound margin. Normal old skin showed pro-MMP-2 bands on zymography and increased MMP-2 immunostaining. These results indicate that: (1) intrinsic ageing is associated with the up-regulation of MMPs previously associated with chronic wound healing; (2) wound-tissue proteinases are essentially active up to day 21 postwounding; and (3) intrinsic ageing may predispose to tissue breakdown disorders because of MMP-2 up-regulation in normal skin.     

Theory of crystallization in high-speed spinning

Removal of the heat of fusion during steady-state crystallization in a high-speed spinline places restrictions on the morphology of the crystallites. An appropriate model is that of a thermal dendrite. It is shown that for this case there exists at each temperature along the threadline a limiting growth velocity, beyond which heat cannot be conducted away fast enough to permit growth. It is suggested that crystallization occurs when a fluid element reaches a temperature at which heat can just be conducted away rapidly enough. Comparison of dendrite theory predictions with experimental values of crystallite diameter and crystallization temperature shows satisfactory agreement. Poly(ethylene terephthalate) has been taken as the example.     

The influence of microstructure on the failure behaviour of PEEK

In this study, different molecular weight PEEK materials were used to determine the effect of spherulite size on fracture. Melt processing of the PEEK at different temperatures produced samples of different average spherulite size. A permanganic etching technique was used to reveal the spherulites. It was found that for low molecular weight 150P PEEK, the spherulite size increased with melt processing temperature; but, for the higher molecular weight 450G PEEK, the spherulite size remained approximately constant. Also, the average spherulite size was markedly lower for the material of higher molecular weight. The failure behaviour of these samples was studied using a compact tension test. It was found that the fracture toughness of PEEK varied with processing temperature. Also, the average spherulite size of this material had a profound influence on the fracture mechanism.     

Amorphization reaction during mechanical alloying: influence of the milling conditions

Amorphous Ni-Zr powders have been prepared by mechanical alloying of elemental crystalline powders. The glass-forming range has been determined in detail at different milling intensities. Depending on the milling conditions, at least partial crystallization of the formerly amorphous material can occur from 66 to 75 at% Ni, due to a temperature rise during milling at high intensity. In comparison with isothermal annealing experiments at various temperatures on completely amorphous powder, a relation between milling temperature and milling time is shown. This confirms the similarity of the amorphization process during mechanical alloying with the solid-state interdiffusion reaction in alternating crystalline multilayers.