The participation of (6R) 5,6,7,8-tetrahydrobiopterin (6-BH4) in regulating the tyrosine supply for melanin biosynthesis was investigated by the examination of human keratinocytes, melanocytes, and epidermal suction blisters from normal human skin and from patients with the depigmentation disorder vitiligo. Cells, as well as total epidermis, contained high phenylalanine hydroxylase activities and also displayed the capacity to synthesize and recycle 6-BH4, the essential cofactor for this enzyme. In vitiligo, 4a-hydroxy-BH4 dehydratase activity was extremely low or absent, yielding an accumulation of the nonenzymatic by-product 7-tetrahydrobiopterin (7-BH4) at concentrations up to 8 x 10(-6) M in the epidermis. This by-product is a potent competitive inhibitor in the phenylalanine hydroxylase reaction with an inhibition constant of 10(-6) M. Thus, 6-BH4 seems to control melanin biosynthesis in the human epidermis, whereas 7-BH4 may initiate depigmentation in patients with vitiligo.

Bispecific antibodies (bsAb) are considered as promising tools for the elimination of disseminated tumour cells in a minimal residual disease situation. The bsAb-mediated recruitment of an immune effector cell in close vicinity of a tumour cell is thought to induce an antitumoural immune response. However, classical bispecific molecules activate only a single class of immune effector cell that may not yield optimal immune responses. We therefore constructed an intact bispecific antibody, BiUII (anti-CD3 × anti-EpCAM), that not only recognizes tumour cells and T lymphocytes with its two binding arms, but also binds and activates Fcγ-receptor positive accessory cells through its Fc-region. We have demonstrated recently that activated accessory cells contribute to the bsAb-induced antitumoural activity. We now analyse this stimulation in more detail and demonstrate here the BiUll-induced upregulation of activation markers like CD83 and CD95 on accessory cells and the induction of neopterin and biopterin synthesis. Experiments with pure cell subpopulations revealed binding of BiUll to CD64+ accessory cells and CD16+ NK cells, but not to CD32+ B lymphocytes. We provide further evidence for the importance of the Fc-region in that this bispecific molecule stimulates Fcγ-R-positive accessory cells to eliminate tumour cells in vitro by direct phagocytosis. © 2000 Cancer Research Campaign

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This review describes pteridine biosynthesis and its relation to the differentiation of neural crest derivatives in zebrafish. During the embryonic development of these fish, neural crest precursor cells segregate into neural elements, ectomesenchymal cells and pigment cells; the latter then diversifying into melanophores, iridophores and xanthophores. The differentiation of neural cells, melanophores, and xanthophores is coupled closely with the onset of pteridine synthesis which starts from GTP and is regulated through the control of GTP cyclohydrolase I activity. De novo pteridine synthesis in embryos of this species increases during the first 72-h postfertilization, producing H 4 biopterin, which serves as a cofactor for neurotransmitter synthesis in neural cells and for tyrosine production in melanophores. Thereafter, sepiapterin (6-lactoyl-7,8-dihydropterin) accumulates as yellow pigment in xanthophores, together with 7-oxobiopterin, isoxanthopterin and 2,4,7-trioxopteridine.Sepiapterin is the key intermediate in the formation of 7-oxopteridines, which depends on the availability of enzymes belonging to the xanthine oxidoreductase family. Expression of the GTP cyclohydrolase I gene (gch) is found in neural cells, in melanoblasts and in early xanthophores (xanthoblasts) of early zebrafish embryos but steeply declines in xanthophores by 42-h postfertilization. The mechanism(s) whereby sepiapterin branches off from the GTP-H 4 biopterin pathway is currently unknown and will require further study. The surge of interest in zebrafish as a model for vertebrate development and its amenability to genetic manipulation provide powerful tools for analysing the functional commitment of neural crest-derived cells and the regulation of pteridine synthesis in mammals.

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Contents I. Introduction _____________________________________________________ 79 II. Fate of SO. in the plant __________________________________________ 81 a) llptake of SO. ________________________________________________ 81 b) Dissolution of SO. ____________________________________________ 83 c) Sulfite metabolism and transport ________________________________ 84 d) Distribution of the incorporated sulfur in the plant ________________ 86 e) Accumulation of sulfur compounds ______________________________ 86 f) Nutritive effect of low doses of SO. ____________________________ 87 III. Damaging effect on plant metabolism ______________________________ 87 a) Effect on transpiration, respiration, and photosynthesis ____________ 87 b) Effect on enzymes and coenzymes ______________________________ 89 IV. Damaging effect on plant composition and plant structure ____________ 93 a) Changes in the amount of plant constituents ______________________ 93 h) Effect on submicroscopic and microscopic structure _______________ 94 c) Visible damage _______________________________________________ 95 V. ModiJication of the damaging effect ________________________________ 95 a) Species and race differences ____________________________________ 95 b) Influence of external factors ____________________________________ 97 c) Effect of internal factors _______________________________________ 97 d) Synergistic effect of air polluting gases __________________________ 98 VI. Conclusions ______________________________________________________ 98 Summary _____________________________________________________________ 99 References ____________________________________________________________ 99

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SO 3 (--) inhibits the activity of ribulose-1,5-diphosphate carboxylase in isolated spinach chloroplasts. It shows a non-competitive inhibition pattern with respect to ribulose-1,5-diphosphate and Mg(++) but a competitive one with respect to HCO 3 (-) . The K i -values are 14 mM SO 3 (--) and 9.5 mM SO 3 (-) respectively for the non-competitive inhibition but only 3.0 mM SO 3 (--) in the case of competitive inhibition with HCO 3 (--) as a substrate. Thus it is concluded that the competitive inhibition type will predominate at low SO 3 (--) and low internal CO2 concentrations.