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Child↗
Biomedical subjects
M Haverkort
Publications and source records attributed to M Haverkort.
Detection of the t(14;18) translocation in frozen and formalin-fixed tissue.
As part of a retrospective study into the prevalence of the t(14;18) translocation in B-cell lymphomas, we assessed the suitability of the polymerase chain reaction (PCR) to amplify the t(14;18) major breakpoint region (MBR) in frozen and formalin-fixed tissue. Considering Southern blotting as a standard, the sensitivity of PCR was 81%. Of the various procedures used to extract DNA from paraffin-embedded tissue (PET), proteinase K digestion in the presence of nonionic detergents gave the highest yield and quality of DNA and the most efficient amplification rate. Using this method, excellent amplification rates (100%) were obtained for both the beta-globin control sequence and the MBR t(14;18) for fixed follicular lymphoma specimens collected in the previous 2 to 6 years (n = 27). Of nine older PETs, PCR on six gave inconsistent results, probably because of the poorer-quality substrate used for amplification. Specimens exposed to formol sublimate or formalin-acetic acid-alcohol were as suitable for amplification as tissues fixed in neutral-buffered formalin. The overall incidence of the MBR t(14;18) in all follicular lymphoma specimens as detected by both Southern blotting and PCR was 59% (23 of 39).
Base Sequence↗
Use of human keratinocyte and fibroblast cultures for toxicity studies of topically applied compounds.
Penetration enhancers are often used as additives in pharmaceutical and dermatological preparations. It should be expected that in many cases penetration enhancers not only enter the stratum corneum but also reach the viable cells of the epidermis and exert a toxic effect. This study focused on a series of well-known compounds that are often used as skin penetration enhancers; namely, ethanol, propylene glycol, dimethylsulfoxide, dimethylformamide, and Brij 96. In order to obtain more insight in the potential skin toxicity of these agents, they were administrated to cultured human keratinocytes and fibroblasts and the following cytotoxicity assays were performed: inhibition of the proliferation of fibroblasts and keratinocytes; inhibition of collagen contraction by fibroblasts; and cell morphology changes in confluent cultures of fibroblasts and keratinocytes. In all assays performed, the same trend was observed: ethanol was the least toxic, propylene glycol, dimethylsulfoxide, and dimethylformamide were moderately potent, and Brij 96 was the most toxic agent. An obvious advantage of the in vitro model presented here is its immediate availability and reproducibility, which allows for the comparison of a large series of topical agents (e.g., penetration enhancers) with respect to their cell toxicity under standardized conditions. However, this single-cell model lacks some of the properties found in intact skin, such as the stratum corneum barrier, and interactions between keratinocytes and other cells, such as Langerhans cells. Hence, extrapolation of these data to in vivo should be done with caution.
Adjuvants, Pharmaceutic↗
Toxicity screening of N-alkylazacycloheptan-2-one derivatives in cultured human skin cells: structure-toxicity relationships.
A number of N-alkylazacycloheptan-2-one derivatives, with the hydrocarbon chain lengths systematically varied from C2 to C16, were tested for their possible skin toxic effects. For this purpose, three in vitro cytotoxicity assays were used: (1) inhibition of proliferation of cultured human fibroblasts and keratinocytes; (2) inhibition of collagen contraction by human fibroblasts; and (3) cell morphology changes in confluent cultures of human fibroblasts and keratinocytes. With all assays used, the toxicity of N-alkylazacycloheptan-2-one derivatives increased from C2 to C8, remained constant at a hydrocarbon chain length between C8 and C14, and subsequently decreased with increasing alkyl chain length. A similar trend has been observed for flux enhancement of nitroglycerine in the presence of these N-alkylazacycloheptan-2-one derivatives, suggesting that with these compounds a parallelism exists between skin cell toxicity and penetration enhancing capacity. Since for practical use it is preferable to find a balance between skin toxicity and the penetration enhancement effect of a particular enhancer, it would be advisable to do QSAR studies of this kind with a number of congeners of a particular compound in order to optimize the choice. In this particular case, further modification of the N-alkylazacycloheptan-2-one structure might lead to an even better choice than the often propagated dodecyl derivative.
Cell Division↗