Biomedical subjects

S M Pincus

Publications and source records attributed to S M Pincus.

61 records · Page 4Linked to original sources

PubMed1991

A regularity statistic for medical data analysis.

A new statistic has been developed to quantify the amount of regularity in data. This statistic, ApEn (approximate entropy), appears to have potential application throughout medicine, notably in electrocardiogram and related heart rate data analyses and in the analysis of endocrine hormone release pulsatility. The focus of this article is ApEn. We commence with a simple example of what we are trying to discern. We then discuss exact regularity statistics and practical difficulties of using them in data analysis. The mathematic formula development for ApEn concludes the Solution section. We next discuss the two key input requirements, followed by an account of a pilot study successfully applying ApEn to neonatal heart rate analysis. We conclude with the important topic of ApEn as a relative (not absolute) measure, potential applications, and some caveats about appropriate usage of ApEn. Appendix A provides example ApEn and entropy computations to develop intuition about these measures. Appendix B contains a Fortran program for computing ApEn. This article can be read from at least three viewpoints. The practitioner who wishes to use a "black box" to measure regularity should concentrate on the exact formula, choices for the two input variables, potential applications, and caveats about appropriate usage. The physician who wishes to apply ApEn to heart rate analysis should particularly note the pilot study discussion. The more mathematically inclined reader will benefit from discussions of the relative (comparative) property of ApEn and from Appendix A.

Algorithms↗

PubMed1991

Aging and the complexity of cardiovascular dynamics.

Biomedical signals often vary in a complex and irregular manner. Analysis of variability in such signals generally does not address directly their complexity, and so may miss potentially useful information. We analyze the complexity of heart rate and beat-to-beat blood pressure using two methods motivated by nonlinear dynamics (chaos theory). A comparison of a group of healthy elderly subjects with healthy young adults indicates that the complexity of cardiovascular dynamics is reduced with aging. This suggests that complexity of variability may be a useful physiological marker.

Adult↗

PubMed1990

Early changes in phosphoprotein patterns of Friend erythroleukaemia cells induced by dimethylsulphoxide or phorbol esters.

Immediate changes in protein phosphorylation in Friend erythroleukaemia cells (FELC) were examined in response to stimulation with dimethylsulphoxide (DMSO), which triggers cell differentiation, 12-O-tetra-decanoyl-phorbol 13-acetate (TPA), a tumour promoter, and the Ca++ ionophore A23187. The effects of the cyclic nucleotides, cAMP and cGMP, on the patterns of phosphoproteins were also analysed. Autoradiographs of two-dimensional gels reveal that within 30 min of treatment by the various agents differences in the patterns of protein phosphorylation can be seen. Treatment with DMSO and TPA altered the phosphoprotein patterns in different ways. These patterns were distinct from those observed in untreated and cyclic nucleotide treated cells. Treatment with the calcium ionophore caused a unique phosphorylation pattern unlike any of the others. These data suggest that the very early changes seen in the patterns of protein phosphorylation in FELC may be related to the induction of differentiation.

Animals↗

PubMed1989

Interleukin-3 and bryostatin 1 mediate rapid nuclear envelope protein phosphorylation in growth factor-dependent FDC-P1 hematopoietic cells. A possible role for nuclear protein kinase C.

Interleukin-3 (IL-3) is a lymphokine which stimulates the proliferation of normal and transformed multilineage hematopoietic cells. Recently we reported that bryostatin 1, a macrocyclic lactone and potent activator of protein kinase C, could stimulate normal multipotential hematopoietic progenitor cells in vitro in the absence of added polypeptide growth factors. We have now used the murine IL-3-dependent cell line FDC-P1, derived from normal murine marrow cells, to examine the early biochemical events associated with stimulation of hematopoietic cells. We find that both IL-3 and bryostatin 1 are mitogenic and stimulate the growth of FDC-P1 cells. Cells grown for extended periods in the presence of bryostatin 1 (1 nM) alone retain IL-3 responsiveness, indicating that bryostatin 1 does not induce an IL-3-independent state. Protein phosphorylation studies in cells treated with either IL-3 or bryostatin 1 indicate that both stimulators can mediate the rapid (within 5 min) serine-specific phosphorylation of several nuclear envelope polypeptides, including lamin B. Both IL-3- and bryostatin 1-mediated nuclear envelope phosphorylation is dose-dependent, occurring at concentrations which are mitogenic to FDC-P1 cells. The extent of nuclear envelope phosphorylation mediated by IL-3 and bryostatin 1 correlates with the mitogenic response. Furthermore, both mitogens mediate the rapid immunologic translocation of protein kinase C to the nuclear envelope where phosphorylation occurs. These data indicate that the early mitogenic signal(s) generated by IL-3 and bryostatin 1 may converge at the level of the nuclear envelope, perhaps through a protein kinase C-like activity which mediates phosphorylation of specific nuclear envelope polypeptides such as lamin B.

Animals↗

PubMed1985

Effects of dibutyryl adenosine 3',5'-cyclic monophosphate on erythropoietin production in human renal carcinoma cell cultures.

A human renal carcinoma from a patient with erythrocytosis, serially transplanted into athymic nude mice, was grown in primary monolayer cell cultures. After reaching confluency, the cultured cells formed multicellular hemicysts (domes), which became more abundant as the cultures approached saturation density. Erythropoietin (Ep) production by this renal carcinoma in culture was only slightly increased at the time of semiconfluency but showed a marked increase after the cultures reached confluency, in parallel with dome formation. Dibutyryl adenosine 3',5'-cyclic monophosphate significantly (P less than .01) stimulated Ep production and dome formation in the semiconfluent and confluent cultures of the renal carcinoma.

Animals↗

PubMed1984

Inhibition of dimethylsulfoxide-induced differentiation in Friend erythroleukemic cells by diacylglycerols and phospholipase C.

The effects of diacylglycerols and phospholipase C on dimethylsulfoxide (DMSO)-induced differentiation were investigated in Friend erythroleukemic cells (FELC). Greater than 80% of cells become benzidine-positive when incubated with 1.5% DMSO. The tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), inhibits DMSO-induced differentiation in FELC. Diacylglycerols were found to inhibit DMSO-induced differentiation dose responsively with the order of potency being 1-oleoyl-2-acetylglycerol (OAG) greater than dicaprylin greater than dilaurin greater than diolein. Phospholipase C which releases endogenous diacylglycerols from membrane phospholipids also inhibited DMSO-induced differentiation dose responsively. These results support the hypothesis that diacylglycerols can have effects similar to tumor promoters and suggest that protein kinase C may be a common mechanism for tumor promotion.

Animals↗

PubMedDate not supplied

Sexual dimorphism in the synchrony of joint growth hormone and cortisol dynamics in children with classic 21-hydroxylase deficiency.

In humans, growth hormone (GH) and cortisol are secreted in a pulsatile fashion and a mutual bidirectional interaction between the GH/insulin-like growth factor (IGF)-I axis and hypothalamic-pituitary-adrenal (HPA) axis has been established. Classic congenital adrenal hyperplasia (CAH) is characterized by a defect in the synthesis of glucocorticoids and often mineralocorticoids, and adrenal hyperandrogenism. In view of the sexually dimorphic pattern in GH secretion, we investigated the GH-cortisol bihormonal secretory dynamics in male and female children with classic CAH. Thirty-eight children with classic 21-hydroxylase deficiency (M: 13, F: 25; age range: 6.1-18.8 yr) were studied prospectively. Serum GH and cortisol concentrations were determined at 20 min intervals for 24 hours. The irregularity of GH and cortisol pattern was assessed using approximate entropy (ApEn), a scale- and model-independent statistic. The synchrony of joint GH-cortisol dynamics was quantified using the cross-ApEn statistic. Cross-correlation analysis of GH and cortisol concentrations was computed at various time lags covering the 24-h period. There was no gender difference in mean 24-hour serum GH (males vs females: 5.25 +/- 4.72 vs 4.44 +/- 2.64 mIU/l) or cortisol (156.2 +/- 44.6 vs 172.0 +/- 58.5 nmol/l) concentrations. For GH, ApEn values were significantly higher in females (0.66 +/- 0.14) than in males (0.53 +/- 0.16) (p = 0.009). No difference in cortisol ApEn values was noted between sexes (0.53 +/- 0.21 vs 0.54 +/- 0.12). Cross-ApEn values of paired GH-cortisol, with cortisol leading GH, were significantly higher in females (0.94 +/- 0.14) than in males (0.83 +/- 0.20) (p = 0.03). These findings suggest that females with classic 21-hydroxylase deficiency have a more irregular pattern of GH secretion and a more asynchronous joint GH and cortisol dynamics than their male counterparts.

Activity Cycles↗