RESUMEN
Pulse transit time (PTT) is defined as the time it takes the blood pressure (BP) wave to propagate from the heart to a specified point on the body. After an initial BP measurement, PTT can track BP over short periods of time. This paper evaluates two PTT algorithms: Chen's and Poon's algorithm; two of the most cited works in the area. The criteria for evaluating them were: which was capable of best tracking changes in BP and which provided the longest time between subsequent BP measurements. These establish the suitability of the PTT method for practical applications, which has not been examined previously. Accuracy was evaluated using the Association of Advancement of Medical Instrumentation (AAMI) and the British Hypertension Society's (BHS) standards. Results show that Chen's algorithm is dependent on its lookup table at short intervals but remains accurate using a 6-min calibration interval, with r=0.96 and r(2)=0.98. Poon's algorithm fails when using a 2-min calibration interval, but is more capable of reflecting changes in BP. The short calibration interval and accuracy limit the usefulness of calculating BP using PTT. Therefore, neither of the algorithms can be recommended because of their shortcomings when estimating BP.
Asunto(s)
Análisis de la Onda del Pulso/métodos , Algoritmos , Calibración , HumanosRESUMEN
Monocytes (MO) influenced phosphoinositide metabolism when human T lymphocytes, isolated from peripheral blood, were activated by polyclonal mitogens. In the 3 hr immediately following mitogenic challenge, the synthesis of phosphatidylinositol (PI) was augmented and the synthesis of PI-4-phosphate (PIP) and PI-4,5-bisphosphate (PIP2) was induced in cultures of T lymphocytes and MO. In addition, MO induced a rapid and transient degradation of PIP and PIP2 in T cells prelabeled with [32P]PL and subsequently activated by mitogen. Induction of a PIP/PIP2 response correlated well with induction of DNA replication by MO when T cells were activated by phytohemagglutinin or by neuraminidase plus galactose oxidase. MO did not influence polyphosphoinositide metabolism when T cells were stimulated by the nonmitogenic lectin wheat germ agglutinin. Interleukin 1 could not substitute for monocytes in inducing a polyphosphoinositide response. By causing a rapid and transient release of the second messengers diacylglycerol and inositol phosphates and by subsequently increasing their cellular precursors, MO may induce the interleukin 2 responsive state in T lymphocytes.
Asunto(s)
Células Presentadoras de Antígenos/fisiología , Macrófagos/fisiología , Mitógenos/farmacología , Monocitos/fisiología , Fosfatidilinositoles/biosíntesis , Linfocitos T/metabolismo , Galactosa Oxidasa/farmacología , Humanos , Técnicas In Vitro , Activación de Linfocitos/efectos de los fármacos , Neuraminidasa/farmacología , Fosfolípidos/metabolismo , Fitohemaglutininas/farmacología , Linfocitos T/efectos de los fármacos , Aglutininas del Germen de Trigo/farmacologíaRESUMEN
The role of the CD4 molecule in the transmission and regulation of the biochemical signals involved in T cell activation was investigated using an anti-CD4 monoclonal antibody termed 6B10. 6B10 immunoprecipitated the 55-kDa CD4 molecule and detected an epitope of CD4 that overlapped with that detected by OKT4A, B, and D. 6B10, 6B10 Fab fragments and recombinant HIV envelope glycoprotein (gp120) induced calcium mobilization in PBMC. 6B10 stimulation also resulted in calcium mobilization in murine L cells expressing transfected CD4 gene products, indicating that CD4-mediated calcium mobilization occurred independently of the CD3/T cell receptor (TCR) complex. 6B10 induced a phosphatidylinositol response, but the response resulted in reduced inositol phosphate production compared to levels obtained using OKT3. Though 6B10 caused calcium mobilization and a phosphatidylinositol response, 6B10 did not induce DNA synthesis. The amount of inositol phosphates produced by 6B10 may be below the threshold necessary for cell cycle progression. We hypothesized that 6B10-mediated calcium mobilization is important in the regulation of T cell proliferation. 6B10, but not 6B10 Fab fragments, inhibited OKT3-induced DNA synthesis. Furthermore, 6B10 but not 6B10 Fab fragments inhibited OKT3-induced calcium mobilization, suggesting that crosslinking of CD4 may be an important factor determining whether signals result in both the up- and down-regulation of CD3/TCR complex function. The implication of this work is that signals generated via the CD4 molecule are important in the regulation of T cell function and that the signals generated as a result of HIV gp120 binding to CD4 can contribute to the mechanism by which HIV inhibits T cell function.
Asunto(s)
Antígenos CD4/fisiología , Transducción de Señal , Linfocitos T/fisiología , Animales , Anticuerpos Monoclonales/inmunología , Antígenos de Diferenciación de Linfocitos T/fisiología , Complejo CD3 , Antígenos CD4/genética , Antígenos CD4/inmunología , Calcio/metabolismo , Proteína gp120 de Envoltorio del VIH/farmacología , Fosfatos de Inositol/metabolismo , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB C , Receptores de Antígenos de Linfocitos T/fisiología , TransfecciónRESUMEN
Lipoproteins of hydrated densities less than 1.063 g/ml, very low density (VLDL) and low density (LDL) lipoproteins, could both enhance and suppress the proliferation of T lymphocyte cell lines. Enhancement and suppression were dependent on lipoprotein and transferrin concentrations. Enhancement occurred at low lipoprotein and high transferrin; suppression, at high lipoprotein and low transferrin. Lipoprotein suppression required a constituent of cell-conditioned medium as evidenced by the fact that lipoproteins did not suppress the replicative response of the IL-2-dependent murine cell line CTLL-2 to purified IL-2 but could suppress the response to cell-conditioned medium IL-2. For lipoprotein suppression and its relief by transferrin, both growth-regulating factors were required early in the cell cycle, suggesting that events important to progression through G1 are influenced. The data establish that the interplay between plasma lipoproteins, transferrin, and an unknown constituent of cell-conditioned medium can regulate the proliferation of T lymphocytes.
Asunto(s)
Lipoproteínas/farmacología , Activación de Linfocitos/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Transferrina/farmacología , Animales , Ciclo Celular/efectos de los fármacos , Línea Celular , ADN/biosíntesis , Interleucina-2/farmacología , Lipoproteínas VLDL/farmacología , RatonesRESUMEN
The activation of T lymphocytes was regulated in vitro by low-density lipoproteins (LDL). Not all prereplicative events induced by the oxidative enzymatic mitogens neuraminidase and galactose oxidase (NAGO) were susceptible to inhibition by LDL. The accessory cell-independent early blastogenic response was not suppressed. LDL suppressed accessory cell-dependent responses, and the extent of LDL suppression, depended on the concentration of transferrin. A gradient of transferrin determined the point in the cell cycle at which NAGO-primed lymphocytes were suppressed by LDL. When transferrin was low (0-10 micrograms/ml) and in serum-free medium (SFM), LDL suppressed the expression of cell surface receptors for interleukin-2 (IL-2R) and transferrin (TfR), the late blastogenic response prior to DNA replication (72 hr), and DNA replication. At higher levels of transferrin, about 100 micrograms/ml, the LDL-suppressed cells were IL-2R+, TfR+ and responsive to IL-2, but did not enter S phase. LDL suppression could be ablated by IL-2 and by high levels of transferrin (250-1000 micrograms/ml). In RPMI medium containing serum (FBS), the pattern of LDL suppression was different from that in SFM: fully activated IL-2R+, TfR+ lymphocytes were unresponsive to exogenous IL-2, suggesting that they were blocked at the G1/S boundary. This block was also relieved by transferrin (greater than 100 micrograms/ml). The data suggest that the interplay between transferrin and LDL is a critical factor in the NAGO-induced stimulation of T lymphocytes. LDL and transferrin exert negative and positive control of lymphocyte activation, respectively. In SFM, LDL appear to alter transferrin utilization by accessory cells; in RPMI-FBS, by fully activated T lymphocytes.
Asunto(s)
Lipoproteínas LDL/fisiología , Activación de Linfocitos , Linfocitos/fisiología , Transferrina/fisiología , Células Presentadoras de Antígenos/fisiología , Células Cultivadas , Replicación del ADN , Galactosa Oxidasa/farmacología , Humanos , Técnicas In Vitro , Interleucina-2/farmacología , Neuraminidasa/farmacología , Fitohemaglutininas/farmacología , Factores de TiempoRESUMEN
The low density classes of plasma lipoproteins (d less than or equal to 1.063 g/ml) suppress mitogenic activation and proliferation of peripheral blood T lymphocytes. Here we demonstrate that lipoprotein suppression can be directed against the accessory cells (greater than 85% monocytes) required for optimal activation of lymphocytes by polyclonal mitogens. Preincubation of accessory cells for 24 h with very low (VLDL) and low (LDL) density lipoproteins suppressed their ability to enhance lymphocyte activation, whereas preincubation of T lymphocytes with lipoproteins did not alter their responsiveness to mitogens. The phenotypic distribution of the accessory cell population was not specifically altered by the lipoproteins, nor did loss of viability account for the suppressive effect of the lipoproteins. Furthermore, the lipoprotein-preincubated accessory cells did not secrete stable inhibitory substances, nor was their ability to produce interleukin 1 diminished. The results of mixing experiments indicate that VLDL-incubated accessory cells had not differentiated into suppressor cells. The lipoprotein-incubated accessory cells appeared to induce the interleukin 2-responsive state in the mitogen-activated lymphocytes, but could not deliver a signal or signals required for the further progression of the activated lymphocytes through the cell cycle. These important findings define at least two types of accessory cell function in the in vitro activation of T lymphocytes.