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Biomedical subjects

S Stone

Publications and source records attributed to S Stone.

At least 145 records · Page 8Linked to original sources

Pregnancy in cyanotic congenital heart disease. Outcome of mother and fetus.

In a series of 416 women with congenital heart disease seen in the Royal Brompton National Heart and Lung Hospital, London, and the Hospital Giovanni Bosco, Torino, Italy, there were 822 pregnancies. The outcomes of 96 pregnancies in 44 patients with cyanotic congenital heart disease were studied. Patients with the Eisenmenger reaction were excluded. Patients were divided arbitrarily into groups according to the type of maternal congenital cardiac anomaly, and factors influencing maternal and fetal outcome were evaluated. The incidence of maternal cardiovascular complications was high (32%), with one death from endocarditis 2 months after delivery. Forty-one (43%) of 96 pregnancies resulted in a live birth; 15 (37%) were premature. Mean weight of full-term infants was 2575 g. Univariate analysis suggested that maternal disease, Ability Index, hemoglobin, and arterial oxygen saturation before the pregnancy were factors that discriminated between successful and unsuccessful fetal outcome, with hemoglobin and arterial oxygen saturation being the most important predictors. Women with cyanotic congenital heart disease can go through pregnancy with a low risk to themselves, with frequent treatable complications, but there is a high incidence of miscarriage, premature births, and low birth weights. An incidence of congenital heart disease in the fetus of 4.9% (2 of 41 live births) is higher than that found in the normal population.

Adolescent↗

A Caenorhabditis elegans act-4::lacZ fusion: use as a transformation marker and analysis of tissue-specific expression.

A plasmid vector that serves as a dominant marker for isolating transformed animals in Caenorhabditis elegans has been constructed as a translational fusion of the C. elegans act-4 gene (encoding actin) and the Escherichia coli lacZ gene. This gene fusion can be used as a marker in transformation rescue experiments in any fertile strain of C. elegans. Progeny of animals injected with the act-4::lacZ fusion vector are stained histochemically with XGal, and transformants turn blue. The internal eggs of stained animals remain viable, allowing recovery of the transformed strain. When the act-4::lacZ vector is co-injected with an unselected plasmid with which it shares some sequence homology, most transformants that are recovered by screening for expression of the act-4::lacZ fusion contain both plasmids. Production of active beta Gal in animals transformed with the act-4::lacZ gene fusions appears to be limited to certain tissues. A chimeric gene that contains the 5' and 3' regions of act-4 is expressed strongly in the body-wall muscles, vulval muscles, and spermathecae. Addition of the internal portion of act-4, including the protein-coding region and introns, to this chimeric gene leads to additional lacZ expression in the pharynx.

Actins↗

A comparison of total and free beta-HCG assays in Down syndrome screening.

Free beta-HCG is a new analyte that has been suggested to be superior to total HCG when used in combination with alpha-fetoprotein (AFP) for Down syndrome risk screening in early pregnancy. We have evaluated this claim on 21 samples collected from Down syndrome pregnancies and 180 samples from unaffected pregnancies. The detection rates for the combination of AFP with free beta-HCG or the combination of AFP with total HCG were identical (71 per cent) but the initial screen positive rate (equivalent to the false-positive rate) was 7.5 per cent for AFP + free beta-HCG screening compared with 3.5 per cent for AFP + total HCG screening. We conclude that the case for free beta-HCG is unproven and suggest that further data be collected before free beta-HCG becomes acceptable.

Biomarkers↗

Cumulative pregnancy rate from one gamete intra-fallopian transfer (GIFT) cycle with cryopreservation of embryos: a practical mathematical calculation.

We evaluated the cumulative pregnancy rate from one gamete intra-Fallopian transfer (GIFT) cycle plus subsequent cycles in which embryos cryopreserved at the time of the original GIFT cycle were transferred. All patients who had their first GIFT cycle in our centre between January, 1989 and March, 1991 were included. Ovarian stimulation was accomplished with leuprolide acetate (luteal phase protocol) and a combination of follicle stimulating hormone and human menopausal gonadotrophin. GIFT was performed with three to five oocytes. Excess oocytes were inseminated and good quality embryos were cryopreserved at the 2- to 4-cell stage with 1-2 propanediol. When the GIFT cycle did not result in a pregnancy, uterine transfer of cryopreserved embryos was carried out in subsequent unstimulated cycles. A total of 97 patients had GIFT and 46 pregnancies were achieved (47.4%). A total of 51 patients (52.5%) had embryos frozen; of these, 21 were from the non-pregnant group (41.1%) and 30 from the pregnant group (65.2%) (P < 0.05). Up to now, 22 of them have undergone a frozen-thawed embryo transfer cycle, and two of them achieved a pregnancy. Based on these data, patients having a GIFT could theoretically expect a cumulative pregnancy rate of 52.2%.

Cryopreservation↗

Prolactin-stimulated mitogenesis of cultured astrocytes is mediated by a protein kinase C-dependent mechanism.

Prolactin (PRL) has been reported to activate cellular proliferation in nonreproductive tissue, such as liver, spleen, and thymus. Recently, we have extended the possible role of PRL as a mammalian mitogen by demonstrating a mitogenic effect of PRL in cultured astrocytes. Although the cellular mechanisms by which PRL regulates cell growth are not fully understood, protein kinase C (PKC) has been implicated as one of the transmembrane signaling systems involved in the regulation of PRL-induced cell proliferation in Nb2 lymphoma cells and liver. In the present studies, we examined the possible role of PKC in PRL-induced proliferation of cultured astrocytes. Incubation of cultured astrocytes with 1 nM PRL resulted in a rapid translocation of PKC from the cytosol to the membrane, with maximal PKC activity in the membrane occurring 30 min after exposure to PRL. Translocation of PKC activity occurred over a physiological range of PRL, with maximal PKC activation occurring at 1 nM. At concentrations greater than 10 nM PRL, there was a decrease in the amount of PKC activity associated with the membrane fraction compared with that of cells stimulated with 1 nM PRL. Incubation of astrocytes with PRL in the presence of the PKC inhibitors staurosporine, 1-(-5-isoquinolinesulfonyl)-2-methylpiperazine, or polymyxin B blocked the PRL-induced increase in cell number with IC50 values of approximately 2 nM, 10 microM, and 6 microM, respectively. PKC is the only known cellular receptor for 12-O-tetradecanoylphorbol 13-acetate (TPA), which stimulates the translocation of PKC from the cytosol to the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Placental 5-deiodinase activity and fetal thyroid hormone economy are unaffected by selenium deficiency in the rat.

In adult male rats, selenium deficiency results in a near complete loss in the selenoprotein 5'-deiodinase in the liver, resulting in decreased peripheral deiodination of thyroxine (T4) and increased serum T4 concentrations. Serum 3,5,3'-triiodothyronine concentrations are normal or slightly decreased, and serum 3,3',5'-triiodothyronine concentrations are normal or slightly increased in selenium-deficient rats. We now report the effects of selenium deficiency on maternal and fetal thyroid hormone economy and on placental 5-deiodinase activity in the rat. Weanling female rats were fed either a selenium-deficient or selenium-supplemented diet for 4 wk before mating and then throughout gestation. Rats were killed at 21 d of gestation. Selenium deficiency was confirmed by a 95 and 94% decrease in glutathione peroxidase and a 84 and 56% decrease in liver type I outer ring 5' deiodinase activity in the mother and the fetus, respectively. In contrast to the increase in circulating T4 observed in selenium-deficient male and nonpregnant female adult rats, serum T4 was not affected by selenium deficiency in pregnant rats, but there was a 3-fold increase in serum 3,3',5'-triiodothyronine concentrations associated with a 70% decrease in maternal brain type II outer ring 5' deiodinase activity. Maternal serum 3,5,3'-triiodothyronine concentrations were decreased by 21%. Placental 5-deiodinase activity was unaffected by selenium deficiency. In the fetus, serum T4, 3,3',5'-triiodothyronine, and TSH concentrations were not affected by selenium deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The postnatal serum 3,5,3'-triiodothyronine (T3) surge in the rat is largely independent of extrathyroidal 5'-deiodination of thyroxine to T3.

In the rat, selenium deficiency causes a near-complete loss of the selenoenzyme type I 5'-deiodinase (5'D-I), resulting in a marked decrease in hepatic T4 to T3 conversion. In adult rats, serum T4 concentrations are consistently increased, whereas serum T3 and rT3 concentrations are unaffected or slightly decreased and increased, respectively. In rat fetuses near term, serum T4 and rT3 concentrations are not affected by selenium deficiency. We have now studied the effect of selenium deficiency on thyroid function in the neonatal rat. Weanling female rats were fed either a selenium-supplemented or a selenium-deficient diet for 4 weeks before mating and then throughout gestation and lactation. Neonatal rats were killed at 7, 14, 21, and 28 days. Selenium deficiency was confirmed by a more than 89% decrease in liver 5'D-I activity in mothers and pups. Selenium deficiency resulted in significant increases in serum T4 concentrations in 3- and 4-week-old pups. In contrast, selenium deficiency led to a striking increase in serum rT3 concentrations. The normal postnatal serum T3 surge was not affected by selenium deficiency at any age. In 2- and 4-week-old selenium-deficient pups obtained from a second litter from the same mothers, liver 5'D-I activity was markedly decreased, but thyroid 5'D-I activity was not affected. The increased serum rT3 and, less so, T4 concentrations observed in selenium-deficient pups were associated with a significant decrease in brain 5'D-II activity in 14- and 28-day-old pups and in brown adipose tissue 5'D-II activity in 14-day-old pups. In conclusion, the present study demonstrates that the increase in serum T4 concentrations consistently observed in selenium-deficient adult rats occurs only after the second week of life. The normal physiological postnatal 12-fold increase in serum T3 concentrations observed in selenium-deficient pups despite the marked decreases in liver 5'D-I and brain and brown adipose tissue 5'D-II activities suggests that T4 to T3 conversion by peripheral tissues may not be a major source of T3 in the neonate. In contrast, the thyroid gland, whose 5'D-I activity is not affected by selenium deficiency, is probably the principal source of circulating T3 in the neonate. Finally, the early and marked increase in serum rT3 concentrations observed in selenium-deficient pups suggests that liver 5'D-I is important in rT3 deiodination.

Adipose Tissue, Brown↗

Characteristics of epidemic hepatitis A in Baltimore City: implications for control measures.

In 1988, a hepatitis A epidemic began in Baltimore, Maryland. A total of 607 cases were reported to the Baltimore City Health Department between the period November 1, 1988, and December 31, 1989. The health department conducted case investigations to identify factors important to the development of control measures. Immunoglobulin was given to appropriate contacts, and an educational campaign was initiated. Of the 607 reported cases, 63% were white and 57% were male. Cases were geographically clustered within 5 of Baltimore's 23 zip codes. Among the 242 adults interviewed, 43% self-reported drug use and 44% were unemployed. Twenty-one percent of the adults and 56% of the children reported contact with either a suspected or confirmed case of hepatitis. Despite control efforts, the epidemic continued through 1990. Barriers to implementing traditional control measures resulted in continuing transmission of hepatitis A in the community.

Adolescent↗

Low ventricular performance and high resistance in established hypertension in adults.

OBJECTIVE: To investigate the relationship between left ventricular performance and sympathetic nervous activity. DESIGN: We studied the alpha- and beta-adrenergic responsiveness of the subjects and assessed their left ventricular performance. METHODS: Fifty-four adult established hypertensive patients, all with apparent left ventricular hypertrophy, and 36 age-matched normotensive controls were studied. Thirty-four of the hypertensive patients were within the +/- 2SD confidence area of fractional shortening/end-systolic stress relation of the normotensive controls and are denoted subgroup A; 19 patients were below the lower limit and are denoted subgroup B. Isoproterenol and neosynephrine injection tests were used to assess beta- and alpha-adrenergic responsiveness, respectively. Intravenous infusion tests using regitine and isoproterenol were performed in 16 patients to assess the effects of sympatho-adrenergic responsiveness on changes in left ventricular performance. RESULTS: Afterload and left ventricular mass were similar in the two subgroups. Left ventricular performance and beta-adrenergic responsiveness in subgroup A were comparable with the corresponding levels in the normotensives, whereas in subgroup B both were markedly decreased. The regitine infusion test induced a fall of 25% in peripheral resistance from baseline, but no significant improvement in left ventricular performance. In contrast, isoproterenol infusion test resulted in striking improvements: left ventricular performance increased by 60%, afterload decreased by 48% and peripheral resistance fell by 50% from baseline. CONCLUSION: The diminished ventricular performance and high resistance observed in adult established hypertension may be due to synergic effects of significantly reduced beta-adrenergic responsiveness coupled with enhanced alpha-adrenergic responsiveness.

Adult↗