Whereas the chemotactic peptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (Met-Leu-Phe), induced NADPH-oxidase-catalyzed superoxide (0;) formation in human neutrophils, purine and pyrimidine nucleotides per se did not stimulate NADPH oxidase but enhanced 0; formation induced by submaximally and maximally stimulatory concentrations of Met-Leu-Phe up to fivefold. On the other hand, Met-Leu-Phe primed neutrophils to generate 0; upon exposure to nucleotides. At a concentration of 100 pM, purine nucleotides enhanced 0; formation in the effectiveness order adenosine 5'-0-[3-thio]triphosphate (ATP[yS]nucleotides were similarly effective potentiators of 0; formation as the corresponding adenine nucleotides. GDP[PS] and UDP[PS] synergistically enhanced the stimulatory effects of ATP[yS], GTP[yS] and UTP[yS]. Purine and pyrimidine nucleotides did not induce degranulation in neutrophils but potentiated Met-Leu-Phe-induced release of P-glucuronidase with similar nucleotide specificities as for 0; formation. In contrast, nucleotides per se induced aggregation of neutrophils. Treatment with pertussis toxin prevented aggregation induced by both nucleotides and Met-Leu-Phe. Our results suggest that purine and pyrimidine nucleotides act via nucleotide receptors, the nucleotide specificity of which is different from nucleotide receptors in other cell types. Neutrophil nucleotide receptors are coupled to guanine-nucleotide-binding proteins. As nucleotides are released from cells under physiological and pathological conditions, they may play roles as intercellular signal molecules in neutrophil activation Human neutrophils play a major role in host defense reactions against bacterial infections and in the pathogenesis of various diseases such as rheumatoid arthritis, glomeruloncphritis, dermatoses, myocardial infarction and asthma [l]. The intercellular signal molecules, PAF, LTB4 and the cheinotactic peptide, Met-Leu-Phe, stimulate NADPHoxidase-catalyzed 0; formation [2 -51. Combinations of Met-Leu-Phe plus PAF or LTB4 synergistically induce 0 : formation [2]. In addition to 0; formation, these agents induce degranulation and aggregation [2 -51. Receptors for Met-Leu-Phe, PAF and LTB4 interact with G proteins lead-
Although thyroglobulin is generally recognized as a useful marker for metastases in cases of differentiated thyroid carcinoma, there have been few reports of the use of thyroglobulin determination for long‐term follow‐up. This report presents the results of long‐term follow‐up studies carried out for periods of up to 4 years in 18 patients, including 4 patients with local and 14 with distant metastases. After successful treatment, thyroglobulin fell to unmeasurable levels in the four patients with local metastases and in four of six patients with distant metastases. In some patients treated successfully with 131I, the thyroglobulin level remained elevated for several months before falling to within the normal range. Thyroglobulin levels correlated with tumor growth in six of eight patients with tumor progression, remained high with a slight downward trend in one patient, and declined to unmeasurable levels in another case. Only one patient in this group showed radioiodine uptake in the metastases at the end of the observation period. The lack of 131I uptake in the other patients probably reflects the low degree of differentiation of the metastases. The following conclusions regarding the use of thyroglobulin measurement for the long‐term follow‐up of thyroid carcinoma can be made: (1) Following 131I therapy for metastatic thyroid carcinoma, return of thyroglobulin levels to within the normal range may take several months. The trend observed in serial thyroglobulin determinations is more meaningful than the absolute values for evaluating the success of therapy. (2) Thyroglobulin levels correlate with tumor growth in most cases of tumor progression, even when changes in differentiation may have led to a loss of radioiodine uptake by the metastases. It may be concluded that serial thyroglobulin determinations are therefore useful for the detection of metastases that do not accumulate radioiodine.
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