Interaction of tamoxifen with concurrent cytotoxic adjuvant treatment affects lymphocytes and lymphocyte subsets counts in breast cancer patients.

The effects and interaction of endocrine and cytotoxic adjuvant treatment on measures of cellular immunity were assessed in 41 stage I-II breast cancer patients from International Breast Cancer Study Group trials. Counts of lymphocytes and lymphocyte subsets [(T, T4, T8, B, natural killer (NK) and activated T (AT) cells] were assessed by flow cytometry immediately before adjuvant therapy at baseline and on day 1 of the 3rd cycle. Twenty-two patients received cyclophosphamide, methotrexate and 5-fluorouracil (CMF), 7 CMF and tamoxifen (TAM), and 12 TAM alone. On day 1 of the 3rd cycle the counts of total lymphocytes (P = 0.003) and all lymphocyte subsets (P<0.05) except AT cells were significantly lower than baseline in the CMF treatment group. There was no significant change in the CMF+TAM or in the TAM treatment group. The combination of CMF and TAM resulted in less pronounced decrease in lymphocyte and subset counts from baseline to day 1 of the 3rd cycle. It seems possible that there is an interaction between TAM with CMF that affects lymphocyte and lymphocyte subset counts during cytotoxic treatment.

Measurement of metastability, growth and aggregation of calcium oxalate in native urine. A new approach for clinical and experimental stone research.

Nucleation, growth and aggregation are thought to be the most important crystallization processes in stone formation. Since crystallization properties change with urinary dilution, centrifugation and filtration, crystallization should always be studied in freshly voided and not pretreated urine. Recently we developed an automated method where calcium oxalate crystallization is induced in native urine by an exogenous oxalate load and nucleation and growth are monitored by an ion-selective calcium electrode. The method has now been supplemented with the spectrophotometric measurement of crystal aggregation. Repeated experiments in the same urine with different oxalate loads enable the determination of the critical oxalate additionable to induce crystallization (metastable limit) and the calculation of an oxalate load-independent growth rate constant. Preliminary results obtained in the native urine of healthy controls showed an extremely high limit of metastability and a complete absence of crystal aggregation. These findings may explain why, despite frequent urinary calcium oxalate supersaturation, healthy people do not form stones.

Vesicular transport of sulfatide in the myelinating mouse brain. Functional association with lysosomes?

Sulfatide synthesis and its subcellular distribution kinetics was followed in the myelinating brain of 17-day-old mice. Pulse-labeling-chasing conditions were achieved by an intraperitoneal injection of (35S)sulfate followed 2 h later by a second injection of a high dose of unlabeled sulfate. At 1, 2, 3, 4, and 6 h after the (35S)sulfate injection, the brains were removed, homogenized, and subcellular fractions were obtained by differential and discontinuous sucrose gradient centrifugation (Eichberg, J., Whittaker, V. P., and Dawson, R. M. (1964) Biochem. J. 92, 91-100). The microsomal membranes were further subfractionated (Siegrist, H. P., Burkart, T., Wiesmann, U. N., Herschkowitz, N. N., and Spycher, M. A. (1979) J. Neurochem. 33, 497-504) into light myelin, plasma membranes, Golgi vesicles, endoplasmic reticulum membranes, and heavy vesicles associated with acid hydrolase activities. The [35S]sulfatide-labeling kinetics was measured in all subcellular fractions. The results indicate that sulfatides are synthesized in the Golgi-endoplasmic reticulum complex and transferred in vesicles at least partially associated with lysosomes to the myelin membranes. The association of sulfatides with lysosomes could explain the existence of the previously described labile pool of newly synthesized sulfatides (Burkart, T., Hofmann, K., Siegrist, H. P., Herschkowitz, N. N., and Wiesmann, U. N. (1981) Dev. Biol. 83, 42-48) and also could be a form of vesicular transport to the myelin.