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Summary: The lack of control of tumour behaviour is manifested in different ways, depending primarily on the type of tumour. This results in numerous problems of tumour diagnosis and therapy. In the case of "benign" tumours, like pituitary adenomas, in vitro studies are often used for evaluation of the tumour. The use of tissue explant cultures of human pituitary adenomas and the comparison of the feature of cultured tumours with their behaviour in vivo showed that corticotropin is released not only from the tumours associated with Gushing^ disease, but also from clinically non-functioning tumours. Hence, it was supposed that the release of corticotropin in vivo from non-secreting tumours is probably under the influence of certain neuroendocrine and/or systemic humoral factors. To test this possibility, samples of 22 tumours were cultured in plain culture medium or in the presence of the "human plasma ultrafiltrate bioactive fraction" (tentatively termed as TBP) prepared by anion-exchang e chromatography. In the presence of TBP the release of corticotropin was strongly inhibited in adenomas showing relatively high spontaneous secreting activity in vitro (> 200 ng/1 in 24 hours), while immunohistochemistry of these tumours indicated accumulation of corticotropin inside the cells. In contrast, TBP stimulated corticotropin release from tumours that showed relatively low basic corticotropin release (< 200 ng/1 in 24 hours), with no obvious change in cellular corticotropin immunoreactivity. Such a dual activity of TBP was not observed for 8 samples of adenomas cultured in the presence of surrounding pituitary tissue, probably because TBP did not affect corticotropin secretion by the normal pituitary cells (as indicated by immunohistochemistry). From these results, it appears that TBP could be one of the humoral factors involved in the regulation of corticotropin release from pituitary adenoma tissue. Its possible involvement in the regulation of corticotropin release from normal pituitary tissue, however, is uncertain.

The frequency of apolipoprotein E (apo E) phenotypes and genotypes due to allelic variation at amino acids 112 and 158 was analysed in 50 children with type I diabetes. Phenotypes were determined by isoelectric focusing and genotypes by the technique of polymerase chain reaction using allele-specific oligonucleotide probes (PCR/ASO) and the amplification refractory mutation system (ARMS). Discrepancies between phenotypes and genotypes as assigned by PCR/ASO were observed in 12 (24%) cases and by ARMS in eight (16%) cases. Results revealed the apo E3/3 genotype, as assigned by ARMS, to be the most frequent one (70%), followed by apo E3/4 in 16%, apo E2/2 in 2%, apo E2/3 in 8%, apo E2/4 in 2% and apo E4/4 in 2% of the cases. Apo E3/4 genotype and phenotype were more frequently present in the children with type I diabetes as compared with the diabetic adults previously reported on.

We assessed the effect of particular apolipoprotein (apo) E phenotypes, lipoprotein(a) [Lp(a)], and other lipoproteins on the development of dyslipoproteinemia in 450 patients with type I diabetes, ages 13-14 years. The control group consisted of 450 healthy school children of both sexes, ages 13-14 years. Both groups were found to be normolipidemic, but the concentration of Lp(a) was significantly (P < 0.05) higher in the diabetic children than in the control group. Apo E 3/2 and apo E 4/4 phenotypes were more frequent in the group of diabetics. Diabetics with the apo E 3/3 phenotype had higher concentrations of very-low-density lipoprotein (VLDL) and Lp(a), and lower concentrations of low-density lipoprotein (LDL) than the apo E 3/3 nondiabetics. For apo E 3/2 phenotypes, total cholesterol, LDL cholesterol, LDL, apo A-I, and Lp(a) concentrations were higher in the diabetic children than in the control group; for apo E 4/3 phenotypes, this was true for triglycerides and VLDL cholesterol. The distribution of Lp(a) lipoprotein concentrations between 0.01 and > 0.5 g/L indicated a more frequent occurrence of higher Lp(a) values in diabetic children than in the control group. Results of this study indicate that an increased concentration of Lp(a) lipoprotein and apo E 3/2 and apo E 4/3 phenotypes contribute to the expression of dyslipoproteinemia in type I diabetes in childhood.

We investigated deletion polymorphism in the gene for angiotensin-converting enzyme in patients with angiographically verified cerebral atherosclerosis. Genotypes were determined by the polymerase chain reaction with oligonucleotide flanking of the polymorphic region of intron 16 of the angiotensin- converting enzyme gene. Results of angiotensin- converting enzyme genotyping showed 46% of 50 studied patients to be homozygous for the DD allele, whose prevalence was significantly increased as compared with a group of controls without atherosclerotic changes. In this control group, the following genotypes were observed (%): II = 24, ID = 52 and DD = 24. The frequency of the I and D alleles in the group of patients with cerebral atherosclerosis was 0.28 and 0.72, respectively, whereas in the group without atherosclerosis it was 0.50 for both. Furthermore, in the present study, the DD genotype was associated with a high level of serum angiotensin- converting enzyme activity, total and LDL- cholesterol and triacylglycerol. A newly established association between DD genotype and cerebral atherosclerosis, detected even in our small group, supports the view that angiotensin- converting enzyme polymorphism might be indicative of the development of cerebral atherosclerosis.

The concentrations of total cholesterol, phospholipids, triacylglycerols and lipoproteins were measured in 87 follicular fluids obtained from 35 women undergoing in vitro fertilization and embryo transfer. The results were correlated with the levels of progesterone in follicular fluid. Two different types of ovarian stimulation were used. High density lipoproteins were the dominant lipoproteins found in the preovulatory follicular fluid. Low density lipoproteins were absent or appeared in trace amounts. Significantly higher triacylglycerol and high density lipoprotein levels were found when stimulation with human menopausal gonadotropins and chorionic gonadotropin was applied, as compared to the clomiphene citrate-menopausal gonadotropin- chorionic gonadotropin menstrual cycle. In both groups, extracorporal fertilization resulted in cleavage of oocytes and embryo transfer. No significant correlation between any follicular fluid lipid and progesterone concentration was found. The lipids estimated in the follicular fluid appeared to have no influence on the oocyte fertilizability. The presence of triacylglycerols and high density lipoproteins in the follicular fluid may indicate follicular wall permeability under the treatment with menopausal gonadotropins