Adjuvant chemotherapy for breast cancer: side effects and quality of life.

In a trial of postoperative adjuvant chemotherapy women with primary breast cancer and spread to one or more axillary nodes were randomised to receive a six-month course of either the single agent chlorambucil or the five-drug combination of chlorambucil, methotrexate, fluorouracil, vincristine, and adriamycin. On completing the treatment 47 patients were asked to fill in questionnaires at home on the side effects of treatment and its influence on the quality of their life. Side effects including nausea, vomiting, malaise, and alopecia had been severe enough to interfere with their lifestyle in 9 (42%) of the patients who had received the single agent and 19 (79%) of those who had received multiple-drug treatment. Various other side effects were reported by a few patients. Seven (29%) of the patients who had received the multiple-drug schedule voluntarily added that the treatment had been "unbearable" or "could never be gone though again." The proportion of patients who had experienced severe side effects while receiving the treatment was considerable; hence such adjuvant chemotherapy is justifiable only if it will substantially improve a patient''s prognosis.     

Effets des fluctuations rapides de la lumiere sur la photosynthese du phytoplancton

[¹⁴C]-assimilation rates were measured on cultures of two unicellulargreen algae (Chlamydomonas sp. and Oocystis sp.) as a functionof light intensities (saturation curves), under steady lightand also under rapidly alternating high and low light intensities.Assimilation rates vary according to the frequency of the intermittentlight regime and it falls under two categories: (1) at 0.1 and0.2 Hz, the assimilation rate is equal to the average of therates observed at high and low light intensities under steadylight, and (2) under 1.0, 1.6 and 10 Hz the assimilation rateis equal to the rate observed under a mean steady irradiance.Moreover, the range of assimilation rates at a given frequencydepends on the difference between the high and the low intensities.Batch cultures of Oocystis sp. have been grown under intermittentlight of 0.1, 1.0 and 10.0 Hz (same mean intensity). Growthrate under intermittent light of 0.1 Hz is –40% lowerthan the control under steady light. Photosynthetic potential(P^B_max)and efficiency () change with the growth stages of thecultures. At the end of the logarithmic growth phase, both photosyntheticparameters are maximum at 1.0 Hz and minimum at 0.1 Hz. Averagecell concentrations of chlorophyll a increase as the frequencyof the light regime decreases. During the log phase, concentrationof carotenoids relative to chlorophyll a increases at 1.0 Hz,decreases at 0.1 Hz, and remains constant at 10.0 Hz. Underclear sky conditions, wave-induced light fluctuations in thephotic layer may therefore enhance primary production, especially(1) in the lower part of the photic layer, where low frequencylight changes might cause cell chlorophyll a to increase, and(2) at a depth of 1–4 m, where the main frequencies (ofthe order of 1.0 Hz), might cause a significant increase ofboth the photosynthetic potential (P^B_max)and efficiency (). ¹Contribution au programme du GIROQ (Groupe interuniversitairede recherches océanographiques du Québec) ²Adresse actuelle: Centre de recherches en nutrition, UniversitéLaval, Québec, Qué. G1K 7P4, Canada     

Oxygen reactivity of p-hydroxybenzoate hydroxylase containing 1-deaza-FAD

The flavin prosthetic group (FAD) of p-hydroxybenzoate hydroxylase (EC 1.14.13.2) was replaced by 1-deaza-FAD (carbon substituted for nitrogen at position 1). An improved method for production of apoenzyme by precipitation with acidic ammonium sulfate was developed. The modified enzyme, in the presence of p-hydroxybenzoate, catalyzed the oxidation of NADPH by oxygen, yielding NADP+ and H2O2, but the ability to hydroxylate p-hydroxybenzoate and other substrates was lost. An analysis of the mechanism of NADPH-oxidase catalysis showed a close analogy between the reaction pathways for native and modified enzymes. In the presence of p-hydroxybenzoate, the rate of NADPH consumption catalyzed by the 1-deaza-FAD form was about 11% that of the native enzyme. Both formed a stabilized flavin-C (4a)-OOH intermediate upon reaction of reduced enzyme with oxygen, but the 1-deaza-FAD enzyme could not utilize this peroxide to hydroxylate substrates, and the peroxide decomposed to oxidized enzyme and H2O2.     

Displacements of Simulium damnosum and strategy of control against onchocerciasis.

Regular aerial treatment of 14 000 km of watercourses has achieved and maintained, over an area of 700 000 km2 of West African savannah, a very high degree of control of the larvae of Simulium damnosum sensu stricto and S. sirbanum, the vectors of onchocerciasis in this area. However, particular and relatively restricted parts of this area, mainly in northern Ivory Coast and neighbouring parts of Upper Volta, experience regular and prolonged reinvasions by parous female vectors, which have already taken bloodmeals (and many of them carrying the parasites) and arrive from unknown sources probably hundreds of kilometres away, from directions probably between southwest and north. This reinvasion, now experienced in three successive years, represents the outstanding scientific, epidemiological and logistic problem still facing the WHO Onchocerciasis Control Programme. An outline is presented of the multidisciplinary investigations being undertaken to find a solution.     

Identification of the protein kinase C phosphorylation site in neuromodulin

Neuromodulin (P-57, GAP-43, B-50, F-1) is a neurospecific calmodulin binding protein that is phosphorylated by protein kinase C. Phosphorylation by protein kinase C has been shown to abolish the affinity of neuromodulin for calmodulin [Alexander, K. A., Cimler, B. M., Meier, K. E., & Storm, D. R. (1987) J. Biol. Chem. 262, 6108-6113], and we have proposed that the concentration of free CaM in neurons may be regulated by phosphorylation and dephosphorylation of neuromodulin. The purpose of this study was to identify the protein kinase C phosphorylation site(s) in neuromodulin using recombinant neuromodulin as a substrate. Toward this end, it was demonstrated that recombinant neuromodulin purified from Escherichia coli and bovine neuromodulin were phosphorylated with similar Km values and stoichiometries and that protein kinase C mediated phosphorylation of both proteins abolished binding to calmodulin-Sepharose. Recombinant neuromodulin was phosphorylated by using protein kinase C and [gamma-32P]ATP and digested with trypsin, and the resulting peptides were separated by HPLC. Only one 32P-labeled tryptic peptide was generated from phosphorylated neuromodulin. The sequence of this peptide was IQASFR. The serine in this peptide corresponds to position 41 of the entire protein, which is adjacent to or contained within the calmodulin binding domain of neuromodulin. A synthetic peptide, QASFRGHITRKKLKGEK, corresponding to the calmodulin binding domain with a few flanking residues, including serine-41, was also phosphorylated by protein kinase C. We conclude that serine-41 is the protein kinase C phosphorylation site of neuromodulin and that phosphorylation of this amino acid residue blocks binding of calmodulin to neuromodulin.(ABSTRACT TRUNCATED AT 250 WORDS)