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Biomedical subjects

L Stern

Publications and source records attributed to L Stern.

At least 19 recordsLinked to original sources

Expression of the tumor-associated mucin MUC1 in an ovarian tumor cell line.

Epithelial sialomucins constitute a family of high-molecular-weight glycoproteins associated with epithelial cell surfaces. Aberrant expression of these molecules has been observed in certain types of human epithelial tumors. Members of the MUC1 family of mucins isolated from different tissue types have been shown to differ in biochemical properties and in immunological reactivity. The polymerase chain reaction (PCR) has been used in a study of the MUC1 mRNA expressed in ovarian tumor cells. The intron/exon structure of the ovarian mucin gene has been examined, the nucleotide sequence of regions of the cDNA 5' and 3' to a central highly repetitive region of the molecule determined and genomic clones for this mucin from the ovarian tumor cell line COLO316 have been isolated and analyzed. The results are compared with the nucleotide sequence data obtained by others for MUC1 cDNA in breast and pancreatic cell lines. With a single nucleotide exception, the splicing pattern and nucleotide sequence obtained from MUC1 mRNA in the ovarian cell line is the same as that of the mRNA found in breast and pancreatic cell lines. However, it appears that the use of alternate splice acceptors for intron I in the ovarian cell line studied here is independent of the specific sequence variation thought to determine splicing of MUC1 in breast tumor cells.

Base Sequence

Controlled clinical trial of cannabidiol in Huntington's disease.

Based on encouraging preliminary findings, cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, was evaluated for symptomatic efficacy and safety in 15 neuroleptic-free patients with Huntington's Disease (HD). The effects of oral CBD (10 mg/kg/day for 6 weeks) and placebo (sesame oil for 6 weeks) were ascertained weekly under a double-blind, randomized cross-over design. A comparison of the effects of CBD and placebo on chorea severity and other therapeutic outcome variables, and on a Cannabis side effect inventory, clinical lab tests and other safety outcome variables, indicated no significant (p greater than 0.05) or clinically important differences. Correspondingly, plasma levels of CBD were assayed by GC/MS, and the weekly levels (mean range of 5.9 to 11.2 ng/ml) did not differ significantly over the 6 weeks of CBD administration. In summary, CBD, at an average daily dose of about 700 mg/day for 6 weeks, was neither symptomatically effective nor toxic, relative to placebo, in neuroleptic-free patients with HD.

Adolescent

Effects of IL-1 and cortisol on beta-adrenergic receptors, cell proliferation, and differentiation in cultured human A549 lung tumor cells.

The effects of IL-1 and cortisol, and their interactions on the density of beta-adrenergic receptors (beta AR), cell proliferation, and the adherence of cells to plastic were studied in cultured human A549 lung tumor cells. The density of beta AR, assayed by 125I-pindolol binding, was increased two- to threefold by a 24-h incubation of the cells with IL-1 alpha, IL-1 beta, and TNF-alpha (EC50: 2.7, 8.2, and 24 pM, respectively), although a series of other cytokines and growth factors did not have this effect. Cortisol also increased beta AR density (EC50: 30 nM) and markedly potentiated the effects of IL-1 alpha, IL-1 beta, and TNF-alpha. Neither IL-1 nor cortisol influenced the proportion of cell surface vs internalized beta AR. The IL-1-induced increase in beta AR density was half-maximal after 6 h, was reversible at a similar rate, and was blocked by 1 microM of cycloheximide. The effect of IL-1 on beta AR was specific, as the density of glucocorticoid receptors, measured by 3H-dexamethasone binding, was reduced by IL-1. Both cortisol and IL-1 potentiated the isoproterenol-induced increase in cAMP accumulation. IL-1 inhibited cell proliferation and thymidine uptake, and increased the adherence of A549 cells to the plastic culture flask, as quantified by a cell detachment assay. The effect of IL-1 on cell adherence was not inhibited by cycloheximide. Cortisol decreased cell adherence and prevented the IL-1-induced increase in adherence. The results indicate that multiple effects of IL-1 in a cultured tumor cell line involve different mechanisms, suggesting heterogeneity of IL-1R and/or coupling of IL-1R to distinct, nuclear, and nonnuclear, effector pathways.

Cell Adhesion

Deposition of bilirubin acid in the central nervous system--a hypothesis for the development of kernicterus.

On the basis of the concentration of unconjugated bilirubin and available albumin for the binding of bilirubin it is possible to calculate the level of unbound bilirubin in a serum sample. The solubility of bilirubin can further be calculated when the pH is known. In cases of threatened kernicterus the free bilirubin concentration in serum samples from newborn infants surpasses the solubility by a factor close to one hundred. It is hypothesized that deposition of bilirubin in tissues takes place as an ongoing event, the deposited pigment being eliminated by bilirubin oxidase in healthy infants. Kernicterus results when the rate of deposition becomes overwhelming as a result of high bilirubin concentration, low albumin reserve, low pH, after administration of a displacing drug, or if the bilirubin oxidase system has been compromised by preceding birth asphyxia or other forms of central nervous system injury.

Adolescent

Effect of ethane-1-hydroxy-1,1-diphosphonate and vitamin D on bone mineralization.

Administration of large quantities of ethane-1-hydroxy-1,1-diphosphonate to growing chicks resulted in a decrease in percent bone ash and an increase in percent osteoid. The degree of inhibition of bone mineral accumulation was a function of both duration and quantity of ethane-1-hydroxy-1,1-diphosphonic acid administration. The inhibition of bone mineral accumulation could be partially corrected with administration of 1,25-dihydroxyvitamin D3. Administration of high levels of ethane-1-hydroxy-1,1-diphosphonate also resulted in inhibition of intestinal calcium absorption. This could be reversed or prevented by the administration of 1,25-dihydroxyvitamin D3.

Animals

Assessment of ventilation-perfusion inequality by aADN2 in newborn infants.

The contribution (Qo/Qt) of gas-filled air spaces with reduced ventilation-perfusion ratio (VA/Qc) to the production of total venous admixture in nondistressed premature infant and newborn infants with transient tachypnea was assessed by the aADN2 and AaDo2. The mean value for Qo/Qt in both nondistressed prematures and infants with transient tachypnea was 0.08. In both groups this represented about 30% of total venous admixutre.

Carbon Dioxide

Current advances in perinatal medicine.

The enhancement of pulmonary maturation with the resultant ability to prevent hyaline membrane disease has given rise to the use of a number of drugs experimentally including corticosteroids, thyroxine, aminophylline, heroin, and several suggested others for this purpose. In clinical use to date only the corticosteroids have been widely utilized in man but it is clear that these agents are capable of effecting an advancement in the maturation of the surfactant system of the lung and a subsequent reduction in the incidence of severity of hyaline membrane disease. However, all agents which act by the enhancement of maturation also carry with them a resultant arrest to replication of tissues and there have been demonstrable effects on both the lung and possibly the brain of the organisms to whom these agents have been administreted. In this connection it is, therefore, important to realize that the advantages gained from these agents may be counterbalanced by disadvantages from their usage and that a reasoned and careful approach in each individual case is mandatory when use of such agents is considered. Experimental and clinical studies suggest the possibility that Vitamin E acting as a free radical scavenger may be important in the prevention of oxygen toxicity both to the eye (retrolental fibroplasia) as well as ameliorating the oxygen component of the destructive effects of respirator lung disease (bronchopulmonary dysplasia). The action of Vitamin E under these circumstances is not dependent upon its actual quantitative level in the plasma of premature infants but in utilization to its excess. Although phototherapy has been universally and widely used since 1958, precise studies of its mechanism of action have not been revealing. Recent work has suggested that following exposure to photoirradiation, bilirubin in its unconjugated form can be seen to appear in the excretory bile ducts suggesting the transport of unconjugated bilirubin through the liver. More recent evidence has also suggested that this occurrence is the result of internal rotation following light exposure of one of the double bonded rings which effectively converts the molecule from a lipid soluble to a water soluble and thereby excretable form. These studies would not only account for an appropriate explanation of the quantitative reduction in bilirubin observed but carry with them the other important consideration that the amount of light exposure necessary to accomplish this is strikingly less than the previously considered photooxidation reaction. The clinical implications of these findings may suggest a reevaluation of the quanta of light which has been used for purposes of phototherapy to date.

Adrenal Cortex Hormones