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J Yanovski

Publications and source records attributed to J Yanovski.

4 recordsLinked to original sources

Lineage-specific telomere shortening and unaltered capacity for telomerase expression in human T and B lymphocytes with age.

Age effects on telomere length and telomerase expression in peripheral blood lymphocytes were analyzed from 121 normal individuals age newborn to 94 years and revealed several new findings. 1) Telomere shortening was observed in CD4+ and CD8+ T and B cells with age. However, the rate of telomere loss was significantly different in these populations, 35 +/- 8, 26 +/- 7, and 19 +/- 7 bp/year for CD4+ and CD8+ T and B cells, respectively. In addition, CD4+ T cells had the longest average telomeres at all ages, followed by B cells, with CD8+ T cell telomeres the shortest, suggesting that these lymphocyte populations may have different replicative histories in vivo. 2) Telomerase activity in freshly isolated T and B cells was indistinguishably low to undetectable at all ages but was markedly increased after Ag and costimulatory receptors mediated stimulation in vitro. Furthermore, age did not alter the magnitude of telomerase activity induced after stimulation of T or B lymphocytes through Ag and costimulatory receptors or in response to PMA plus ionomycin treatment. 3) The levels of telomerase activity induced by in vitro stimulation varied among individual donors but were highly correlated with the outcome of telomere length change in CD4+ T cells after Ag receptor-mediated activation. Together, these results indicate that rates of age-associated loss of telomere length in vivo in peripheral blood lymphocytes is specific to T and B cell subsets and that age does not significantly alter the capacity for telomerase induction in lymphocytes.

Adolescent↗

Suppression and recovery of GH secretion after GH injection in non-GH deficient short children.

OBJECTIVE: To identify the effect of exogenous GH on endogenous GH secretion in 48 non-GH deficient short children participating in a placebo-controlled trial of GH therapy on final adult height. DESIGN: Night GH secretion (mean of levels every 20 min from 20.00 to 08.00 h) was evaluated at baseline, 6 months before starting placebo or GH (somatotropin, 0.222 mg/kg/ week, divided into 3 doses each week). At 6 months after starting injections, blood samples for GH were obtained hourly for 24 h after an injection, and every 20 min on each of the next two nights (with no additional placebo or GH injection). RESULTS: IGF-I levels in the treatment group were elevated at 12 and 24 h but not at 36 h compared to the placebo group. Mean GH levels in the placebo group did not vary significantly among the four sampling periods. In the treatment group, the mean serum GH rose to a supraphysiological peak at an average time of 4 h after injection. Subsequently, mean GH level was significantly suppressed compared to placebo on the second night following GH injection, but returned to normal by the third night. CONCLUSION: After 6 months of a thrice weekly GH treatment regimen in non-GH deficient short children, endogenous GH secretion was reduced from 24 to 36 h after injection compared to placebo and returned to control levels by 48 to 60 h after injection.

Child↗

Selective venous sampling from the cavernous sinuses is not a more reliable technique than sampling from the inferior petrosal sinuses in Cushing's syndrome.

The purpose of this study was to compare ACTH levels in unstimulated samples obtained from the cavernous sinuses (CS) to unstimulated and CRH-stimulated samples obtained from the inferior petrosal sinuses (IPS) in 15 patients with surgically proven Cushing's disease. After unstimulated samples were obtained through 5-French catheters placed in both IPS, tracker catheters were introduced into both cavernous sinuses, and unstimulated samples were obtained within 5 min of the initial set. The Tracker catheters were removed, CRH was administered, and CRH-stimulated samples were obtained from the IPS. We compared the central to peripheral ACTH ratios in unstimulated samples from the cavernous sinuses to unstimulated and CRH-stimulated samples from the IPS as a basis for distinguishing pituitary from ectopic ACTH production. In addition, we compared the ability of the intercavernous and interpetrosal ACTH ratios to correctly predict the site of the microadenoma. Unstimulated levels of ACTH in the cavernous sinuses were generally higher than unstimulated levels of ACTH in the petrosal sinuses. However, 3 of 15 patients failed to show central to peripheral ACTH ratios greater than 2 in unstimulated samples from the cavernous sinuses and were thus falsely negative for the diagnosis of Cushing's disease (test sensitivity, 80%). By comparison, the test sensitivity for the petrosal sinus samples was 87% for the unstimulated samples and 100% for the CRH-stimulated samples. Lateralization was correct in 6 of 15 patients based on CS samples and in 9 of 15 patients based on IPS samples. Because of the 20% false negative rate, CS sampling without CRH stimulation is not recommended for the differential diagnosis of ACTH-dependent hypercortisolism.

Adenoma↗

Stimulation of the paraventricular nucleus area of the hypothalamus elevates urinary 6-hydroxymelatonin during daytime.

The paraventricular nucleus of the hypothalamus (PVN) is thought to be a part of the neural circuit comprising the melatonin rhythm generating system (MRGS). Electrical stimulation of the PVN during the early lights-on period significantly elevated urinary 6-hydroxymelatonin content to nearly 50% of night levels; stimulation during the lights-off period did not produce significant changes. In contrast to the effects of PVN stimulation, stimulation of surrounding brain areas was without effect at either time. This observation confirms the participation of the PVN in the MRGS.

Animals↗