Deconstructing PML-induced premature senescence

In this study, we investigated the subcellular and molecular mechanisms underlying promyelocytic leukemia (PML)-induced premature senescence. We demonstrate that intact PML nuclear bodies are not required for the induction of senescence. We have determined further that of seven known PML isoforms, only PML IV is capable of causing premature senescence, providing the first evidence for functional differences among these isoforms. Of interest is the fact that in contrast to PML(+/+) fibroblasts, PML(-/-) cells are resistant to PML IV-induced senescence. This suggests that although PML IV is necessary for this process to occur, it is not sufficient and requires other components for activity. Finally, we provide evidence that PML IV-induced senescence involves stabilization and activation of p53 through phosphorylation at Ser46 and acetylation at Lys382, and that it occurs independently of telomerase and differs from that elicited by oncogenic Ras. Taken together, our data assign a specific pro-senescent activity to an individual PML isoform that involves p53 activation and is independent from PML nuclear bodies.     

Beta-adrenergic sensitivity--imminent premature delivery

In order to determine individual sensitivity, 0.4 microgram/kg/min of fenoterol was in fused to 95 pregnant women prior to institution of tocolytic treatment against premature delivery. Changes of maternal heart rate during this test was recorded and analysed retrospectively. The following conclusions were drawn: Even in a carefully prescreened pregnant population, 4.2% of gravidas proved to be hypersensitive to fenoterol: the irreversible commencement of premature delivery was accompanied by a significant decrease of beta sensitivity: to avoid complications due to tocolytic therapy, it is necessary to stop sympathomimetic medication in a stepwise manner: there was no pathologic consequences of fenoterol treatment to the newborn babies.     

Genetic aspects of premature ovarian failure

Among the causes of premature ovarian failure (POF) two groups of factors are reported: factors which lead to decrease of follicular number and factors which stimulate follicular atresia. In the first group genetic factors are the most important whereas in the second: enzymatic autoimmunological, iatrogenic, toxins and infections are reported. In 1986 familiar POF on the background of long arm of chromosome X deletion was reported. Other chromosomes which are important for normal ovarian function are: chromosome 21 (AIRE gene), chromosome 11 (gene of beta FSH, ATM gene), chromosome 3 (gene responsible for BEPS syndrome) and chromosome 2 (genes of FSH and LH receptors). In this review the role of these genes and results of several epidemiological studies are reported.     

Detection and prevention of premature labour

Preterm birth is a major public health problem, affecting up to 10% of pregnancies. The cause of premature labour in humans is not known, although some risk factors have been identified. Currently it is not possible to predict which women will go into labour prematurely or deliver preterm. New possible methods for the detection of premature labour are the measurement of biochemical markers in cervical or vaginal secretions, the measurement of collagen in cervical tissue and the recording of electrical properties of contractions of the uterus. Agents used to prevent premature labour include beta-agonist drugs, magnesium sulphate, calcium channel blockers, nitric oxide donors and prostaglandin synthesis inhibitors. A new approach is the use of oxytocin antagonists. Premature labour is still not completely understood, but some advances are being made, arising from basic research.     

Familial premature ovarian failure.

Premature menopause, ovarian failure younger than 40 years of age, is relatively rare but may preclude childbearing for some women who delay attempts at fertility. We present five kindreds in which a genetic association for premature ovarian failure is strongly suggested. Transmission is either autosomal or (less likely) X-linked dominant in these examples. Chromosomal abnormalities, history of diseases, and toxic chemical or viral exposures previously associated with premature ovarian failure could not be demonstrated in these women. This suggests that these kindreds all represent familial idiopathic premature ovarian failure. These data support the need for menopausal histories on both sides of the family for women seeking to postpone reproduction, as well as for patients with ovarian failure.