Benzyl alcohol poisoning.
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Ceramides are intermediates in the biosynthesis of membrane sphingolipids. These biomolecules are also important as second messengers in signal transduction pathways controlling cell growth. We have developed two reversed-phase high pressure liquid chromatography (RPHPLC) techniques for identification and quantification of ceramides from mammalian cells. One method was based on atmospheric pressure chemical ionization-mass spectrometry (APCI-MS) detection of ceramides and had the advantage of requiring minimal sample preparation, yielding significant structural information, and affording high sensitivity. The second method relied on perbenzoylation of the ceramides and detection at 230 nm. The predominant ceramides detected in the human leukemic HL-60 cell were N-(palmitoyl)-sphingosine, N-(nervonyl)-sphingosine, and N-(lignoceroyl)-sphingosine. When selected ion monitoring was used with RPHPLC/APCI-MS, approximately 2.2 pmol N-(palmitoyl)-sphingosine and 1.7 pmol N-(nervonyl)-sphingosine were observed in an extract from 40,000 HL-60 cells. Perbenzoylation with benzoyl chloride permitted RPHPLC separation and 230 nm UV absorbance detection of the trisbenzoyl derivatives of sphingosine, N-(palmitoyl)-sphingosine, N-(nervonyl)-sphingosine, and N-(lignoceroyl)-sphingosine in the HL-60 cells. These results demonstrate the utility of utilizing two different methods coupled with APCI-MS for the quantification and identification of ceramides in biological samples.
Capillary electrophoresis has been applied to monitor model reactions in solution-phase combinatorial chemistry. In particular, the simultaneous alkylation reactions of secondary amines with a series of benzyl halides has been investigated. Reactant and product concentrations were monitored using capillary electrophoresis in a non-aqueous buffer system. The simplified sample preparation was a key feature making this an attractive method of analysis. The results demonstrate that capillary electrophoresis is a useful tool for monitoring reactions to determine initial rates, rate constants, and extinction correlation coefficients for quantitative analysis in combinatorial chemistry, and is a broadly applicable technique for the analysis of a variety of organic and bioorganic transformations.
An efficient procedure is described for the synthesis of N(alpha)-Fmoc-O-monobenzyl phosphonotyrosine from the corresponding dibenzyl derivative by monodebenzylation in the presence of sodium iodide. A simple work up procedure removes the by-products and the monobenzylated phosphono product is obtained in high yield.
The collagen cross-link (+)-deoxypyrrololine (Dpl, 1), a potential biochemical marker for diagnosis of osteoporosis, has been obtained by a general and convergent total synthesis. The key synthetic features involve utilization of a L-glutamic acid derivative as a source for all three chiral centers in (+)-1, and construction of the pyrrole ring by condensation of an alpha-acetoxynitro compound with benzyl isocyanoacetate.
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MUC1 mucin expression has been shown to be associated clinicopathologically with metastasis and poor clinical outcome in a variety of tumors. To further investigate this finding experimentally, human pancreatic cancer S2-013 cells overexpressing MUC1 were used for spontaneous metastatic potential in nude mice. It was found that the number of lung metastases of MUC1 transfectants was significantly higher than that of control cells. To analyze the molecular mechanisms that underlie the increased metastatic activity, in vitro adhesion assays were performed. MUC1 mucin expression enhancedin vitro invasiveness and motility of S2-013 cells, and decreased the binding of S2-013 cells to type I collagen, Type IV collagen and laminin. Similar effects were not observed for cells expressing tandem repeat-deleted MUC1 cDNA. Adhesion properties were abolished by benzyl-alpha-GalNAc treatment, indicating that glycosylation of the extracellular domain of MUC1 was essential for these biological adhesive functions. Our data support the hypothesis that MUC1 expression contributes to the metastatic ability of pancreatic cancer cells.
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The cohort of this historical prospective mortality study consisted of 697 male employees at a chlorination plant. A majority of the cohort was potentially exposed to benzotrichloride, benzyl chloride, benzoyl chloride, and other related chemicals. The mortality experience of the cohort was observed from 1943 through 1982. For the cohort as a whole, no statistically significant mortality excess was detected. The overall Standardized Mortality Ratio (SMR) was 100, and the SMR for all cancers combined was 122 (not significant). The respiratory cancer SMR for the cohort as a whole was 246 (7 observed vs. 2.8 expected). The excess was of borderline statistical significance, the lower 95% confidence limit being 99. Analysis by race showed that all 7 respiratory cancer deaths came from the white male employees, with an SMR of 265 (p less than 0.05). The respiratory cancer mortality excess was higher among employees in maintenance (SMR = 229) than among those in operations or production (SMR = 178). The lung cancer mortality excess among the laboratory employees was statistically significant (SMR = 1292). However, this observation should be viewed with caution, since it was based on only 2 deaths. Further analysis indicated that the respiratory cancer mortality excess was limited to the male employees with 15 or more years of employment (SMR = 379, p less than 0.05). Based on animal data as well as other epidemiologic studies, together with the internal consistency of analysis by length of employment, the data suggest an association between the chlorination process of toluene at the plant and an increased risk of respiratory cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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