Telomere length in the newborn.

Telomere length is similar in different organs of the human fetus but variable among fetuses. During extrauterine life telomere length is highly variable among individuals and longer in women than men. In the present work we addressed the following questions: 1) Are there sex-related differences in telomere length at birth? 2) Is there synchrony (i.

Decreased pituitary-gonadal secretion in men with obstructive sleep apnea.

Decreased libido is frequently reported in male patients with obstructive sleep apnea (OSA). The decline in morning serum testosterone levels previously reported in these patients was within the normal adult male range and does not explain the frequent association of OSA and sexual dysfunction. We determined serum LH and testosterone levels every 20 min between 2200-0700 h with simultaneous sleep recordings in 10 men with sleep apnea and in 5 normal men free of any breathing disorder in sleep.

Risk factors for cardiovascular disease in women with subclinical hypothyroidism.

Overt hypothyroidism may result in accelerated atherosclerosis and coronary heart disease (CHD) presumably because of the associated hypertension, hypercholesterolemia, and hyperhomocysteinemia. As many as 10%-15% of older women have subclinical hypothyroidism (SH) and thyroid autoimmunity. Whether SH is associated with risk for CHD is controversial.

Localization of heparanase in normal and pathological human placenta.

Degradation of extracellular matrix (ECM) components is critical for invasion. Heparan sulphate proteoglycans are abundant in the ECM of the placenta and the decidua, hence their degradation may disassemble the matrix and facilitate placentation and trophoblast invasion. This study investigates the expression of heparanase in normal and pathological placentation using RT-PCR, in-situ hybridization and immunohistochemistry analysis to detect heparanase in specific cells of the placenta and at the fetal-maternal interface throughout pregnancy.

Salt consumption, reactive oxygen species and cardiovascular ageing: a hypothetical link.

Opinions about the impact of dietary salt on blood pressure have dominated the debate regarding 'salt sensitivity', which can be broadly defined as the blood pressure response to changes in sodium intake among individuals in a population. However, the larger question is whether salt consumption exerts significant biological effects independent of changes in blood pressure. Provisional answers to this question are reviewed based on newly discovered links between sodium metabolism and the generation of reactive oxygen species.

Age dependent aneuploidy and telomere length of the human vascular endothelium.

Rationale: Aneuploidy and telomere length are two major parameters that have been associated with cellular senescence in vitro. In order to explore the role of aneuploidy and telomere length in aging of the human vasculature, we studied these two parameters in direct preparations of endothelial cells of the human abdominal aorta.

Methods: Using fluorescent in situ hybridization on 'touch prep' slides, we evaluated aneuploidy of two autosomes (chromosomes 6 and 16) and sex chromosomes in non cultured endothelial cells of the abdominal aorta as a function of the donor's age.

Molecular properties and involvement of heparanase in cancer progression and mammary gland morphogenesis.

Tumor spread involves degradation of various components of the extracellular matrix and blood vessel wall. Among these is heparan sulfate proteoglycan, which plays a key role in the self-assembly, insolubility and barrier properties of basement membranes and extracellular matrices. Expression of an endoglycosidase (heparanase) which degrades heparan sulfate correlates with the metastatic potential of tumor cells, and treatment with heparanase inhibitors markedly reduces the incidence of metastasis in experimental animals.

Expression of heparanase, Mdm2, and erbB2 in ovarian cancer.

Ovarian cancer is the most lethal of gynecological malignancies. Yet early diagnosis and prognosis are far from being satisfactory. Degradation of heparan sulfate proteoglycans by heparanase appears to play an important role in the invasiveness of tumor cells through the basement membrane and into the extracellular matrix.

Hypothesis: pulse pressure and human longevity.

In exploration of the association between pulse pressure and longevity in humans, 3 hypotheses are briefly discussed: the fetal origin hypothesis, antagonistic pleiotropy, and the telomere hypothesis of cellular aging. The implications of these hypotheses serve to draw a critical distinction between biologic age (aging) and chronological age and, thereby, offer an answer to a question that presently matters most in the field of hypertension: Why has it been so difficult to disentangle the genetic components of essential hypertension and to identify the variant genes responsible for elevated blood pressure in a large segment of the human population?

How long should telomeres be?

What began as a study of the "end-replication problem" took on a new dimension as it became clear that telomeres are a "molecular clock" of replication in human somatic cells. Here we review the biology of telomeres in vitro and in vivo, in mice and humans. We suggest that, in humans, telomeres are involved in the biology of aging and pathobiology of disorders of aging, including cancer and cardiovascular disease.

Telomere length as an indicator of biological aging: the gender effect and relation with pulse pressure and pulse wave velocity.

Chronological age is the primary determinant of stiffness of central arteries. Increased stiffness is an independent indicator of cardiovascular risk. The aim of this study was to determine whether telomere length, a possible index of biological aging, provides a better account than chronological age for variation in arterial stiffness, evaluated by measuring pulse pressure and aortic pulse wave velocity.

Telomeres: the time factor in essential hypertension.

Essential hypertension, particularly systolic hypertension, can be characterized as a disorder of aging. The diverse expressions of this disorder represent the interactions of a genetic script, the environment, chance, and a temporal factor. The temporal factor, namely the telomeres, is biological, intrinsic, and dynamic.

Loss of chromosome 13 in cultured human vascular endothelial cells.

In the vascular endothelium of human beings, telomere length is negatively related while the frequency of aneuploidy is positively related to donor age. Both in culture and in vivo the frequency of aneuploidy increases as telomere length is shortened. In this study we explored the relation between telomere length and aneuploidy in cultured human umbilical vein endothelial cells (HUVEC) by: (a) karyotype analysis and fluorescent in situ hybridization (FISH), (b) measurement of the terminal restriction fragments (TRF), and (c) assessment of replicative senescence by the expression of beta-galactosidase.

Expression of heparanase in normal, dysplastic, and neoplastic human colonic mucosa and stroma. Evidence for its role in colonic tumorigenesis.

The human heparanase gene, an endo-beta-glucuronidase that cleaves heparan sulfate at specific intrachain sites, has recently been cloned and shown to function in tumor progression and metastatic spread. Antisense digoxigenin-labeled heparanase RNA probe and monoclonal anti-human heparanase antibodies were used to examine the expression of the heparanase gene and protein in normal, dysplastic, and neoplastic human colonic mucosa. To our knowledge, this is the first systematic study of heparanase expression in human colon cancer.

Telomere attrition of the human abdominal aorta: relationships with age and atherosclerosis.

Little is known about the turnover rate (i.e. the rate of replication and death) of cells in the intima and media of human arteries as a function of age and atherosclerosis.

Telomere length inversely correlates with pulse pressure and is highly familial.

There is evidence that telomeres, the ends of chromosomes, serve as clocks that pace cellular aging in vitro and in vivo. In industrialized nations, pulse pressure rises with age, and it might serve as a phenotype of biological aging of the vasculature. We therefore conducted a twin study to investigate the relation between telomere length in white blood cells and pulse pressure while simultaneously assessing the role of genetic factors in determining telomere length.

Mammalian heparanase as mediator of tumor metastasis and angiogenesis.

Expression of heparan sulfate-degrading endoglycosidases, commonly referred to as heparanases, correlates with the metastatic potential of tumor cell lines, and treatment with heparanase inhibitors markedly reduces the incidence of metastasis in experimental animals. We purified a 50 kDa heparanase from human hepatoma and placenta and cloned a cDNA and gene encoding a protein of 543 amino acids. Only one heparanase sequence was identified, suggesting that this enzyme is the dominant endoglucuronidase in mammalian tissues.

Homocysteine thiolactone and protein homocysteinylation in human endothelial cells: implications for atherosclerosis.

Editing of the nonprotein amino acid homocysteine by certain aminoacyl-tRNA synthetases results in the formation of the thioester homocysteine thiolactone. Here we show that in the presence of physiological concentrations of homocysteine, methionine, and folic acid, human umbilical vein endothelial cells efficiently convert homocysteine to thiolactone. The extent of this conversion is directly proportional to homocysteine concentration and inversely proportional to methionine concentration, suggesting involvement of methionyl-tRNA synthetase.

Cellular proliferation and telomerase activity in CHRF-288-11 cells.

Telomerase activity is detected in many immortalized cell lines. Recent studies suggest that terminal differentiation of some of these cell lines is associated with a reduction in telomerase activity. However, the question remains whether the reduction in telomerase activity results from terminal differentiation or from cessation of cellular proliferation.

Physiological and molecular characterization of the Na+/Ca2+ exchanger in human platelets.

In this report, we have demonstrated that Na+/Ca2+ exchanger activity in a human megakaryocytic cell line (CHRF-288 cells) is K+ dependent, similar to the properties previously described for Na+/Ca2+ exchange activity in human platelets. With the use of RT-PCR techniques and mRNA, the exchanger expressed in CHRF-288 cells was found to be identical to that expressed in human retinal rods. Northern blot analysis of the mRNA for the human retinal rod exchanger in CHRF-288 cells revealed a major transcript at 5.

Telomeres and essential hypertension.

The dynamics of telomere attrition in human beings might shape the course of age-dependent, complex genetic traits. One of these traits is essential hypertension. Age-dependent telomere attrition could lead to critically shortened telomeres and aneuploidy (ie, the loss or gain of chromosomes) with a resultant mosaicism that will be variably expressed in different cells and tissues.

The relationship between Ca2+-ATPase and freely exchangeable Ca2+ in the dense tubules: a study in platelets from women.

The main aims of this work were to examine in women: the relationship between the freely exchangeable Ca2+ (FECa2+) in the dense tubules and the activity of the sarco(endo)plasmic reticulum (SER) Ca2+-ATPase (SERCA) in platelets, and the relationship of these parameters with blood pressure and serum lipoproteins. Platelets from 14 white and 13 black women in good health were studied. The FECa2+ was measured as the ionomycin-evoked Ca2+ release (in the presence of thapsigargin) in Ca2+-free medium.

Life after infertility treatment: a long-term investigation of marital and sexual function.

After leaving in-vitro fertilization (IVF) treatment, both successful and unsuccessful women are generally lost to follow-up. In order to assess overall life satisfaction as well as marital and sexual adjustment after the completion of infertility treatment, three groups of women were studied: group 1 (n = 41), successful IVF women; group 2 (n = 16), unsuccessful IVF women who adopted; and group 3 (n = 18), unsuccessful IVF women who remained childless. All women who had completed a minimum of three IVF cycles between the years 1982 and 1993 were invited to participate in a 'life after infertility' follow-up study.

Parameters of lymphocyte Na+-Ca2+ regulation and blood pressure: the gender effect.

Alterations in cellular Ca2+ and Na+ regulation play a role in the pathogenesis of essential hypertension. Using peripheral lymphocytes from 68 normal persons, we observed the following relationships for major cellular Ca2+ regulatory parameters. Among men and women, Na+-Ca2+ exchanger activity was positively correlated with the resting cytosolic free Ca2+ ([Ca2+]c) (r=0.