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Biomedical subjects

L Beck

Publications and source records attributed to L Beck.

At least 37 records · Page 2Linked to original sources
PubMed1995

Anti-CD3-induced anergy in cloned human Th0, Th1, and Th2 cells.

In the mouse, activation of T cells by T cell receptor (TCR) crosslinking with anti-CD3 antibodies in the absence of a costimulatory signal induces Th1 but not Th2 cell anergy. Furthermore, anti-CD3 induces anergy of Th1- but not Th2-type lymphokine secretion in Th0 cells. This study was designed to determine whether this is also the case in man. Human rye grass allergen Lol p I-specific cloned CD4+ T helper cells of subtypes Th0, Th1, and Th2 were treated with immobilized anti-CD3. The cells were rested for 4 days and then activated under optimal conditions with antigen and antigen-presenting cells (APCs). Cell proliferation and IL-2, IFN-gamma, and IL-4 secretion was determined to test for the anergic state. The initial anti-CD3 treatment induced cell proliferation, IL-2, IFN-gamma, and/or IL-4 secretion by T cells of all three subsets which was followed by an anergic state in Th0, Th1, and Th2 cells as shown by a 51 to > 94% decrease in cell proliferation and IFN-gamma and/or IL-4 secretion after subsequent APC and Lol p I activation. Addition of IL-2 or IL-4 during anti-CD3 treatment of the cells did not prevent unresponsiveness. However, the addition of IL-2 but not IL-4 during APC and Lol p I stimulation partially reversed the anergic state. These data demonstrate that, contrary to the mouse, cloned T cells of all three human T helper cell subtypes are anergized by anti-CD3 TCR activation in the absence of costimulatory signals. The fact that human Th2 cells can be anergized may be important for the development of new treatments in Th2-mediated allergic disorders.

Allergens↗
PubMed1995

Immunosuppressive actions of 1,25-dihydroxyvitamin D3: preferential inhibition of Th1 functions.

1,25-Dihydroxyvitamin D3 [1,25-(OH)2-D3] is known to be an immunosuppressive hormone. This review primarily deals with in vitro and in vivo effects of 1,25-(OH)2-D3 and analogue, 1,25-dihydroxy-16ene-vitamin D3 [1,25-(OH)2-16ene-D3], on T helper subsets type 1 (Th1) or type 2 (Th2) that have distinctive functional characteristics in humans. Th1 secrete interferon (IFN-gamma), interleukin (IL-2) and induce B cells to produce immunoglobulin IgG2a while Th2 secrete IL-4, IL-10 and induce the production of IgG1 and IgE by B cells. The sterol inhibits the secretion of IL-12, a cytokine produced by monocytes and B cells, which leads to the activation and differentiation of Th1. In addition, 1,25-(OH)2-D3 directly inhibits IFN-gamma secretion by Th1 clones while it has little effect on IL-4 secretion by Th2 clones. The analogue, 1,25-(OH)2-16ene-D3, is 100-fold more potent than 1,25-(OH)2-D3 in inhibiting IFN-gamma secretion but also has little effect on IL-4 secretion. In mice, when given in vivo, the sterol prevents the induction of spontaneous and induced autoimmune diseases and inhibits Th1 induce IgG2a responses. These actions of the vitamin D3 compounds suggest that it may have potential therapeutic applications in Th1-mediated clinical situations such as autoimmunity and transplantation.

Animals↗
PubMed1995

Adenosine 3',5'-monophosphate mediates progesterone effect on sulfate uptake in endometrial epithelial cells.

We have previously shown that progesterone increased sulfate uptake in glandular epithelial cells of guinea pig endometrium. To investigate whether cAMP might be the cause of the progesterone effect on sulfate uptake, cAMP accumulation and the effect of cAMP on sulfate uptake were evaluated in cells treated with 17 beta-estradiol alone or with progesterone. Progesterone provoked an increase in the intracellular cAMP accumulation in cells treated with 17 beta-estradiol. Moreover, cAMP or forskolin elicited the same marked increase in sulfate uptake as that observed with progesterone. The effect of progesterone on sulfate uptake was abolished by blocking either the cAMP pathway or the genomic action of progesterone and was independent of the cAMP-activatable apical chloride channel. This study is the first evidence of cAMP activation of sulfate uptake and suggests a genomic effect of progesterone on the production of cAMP which activates the sulfate transport system in a short term activation and a long term activation independent of transcriptional or translational events. The endometrium is a unique tissue that undergoes profound highly regulated modifications during the secretory phase in providing a suitable environment for embryo implantation. The regulation of sulfate uptake could participate in this process.

Animals↗
PubMed1995

[Ventricular fibrillation and defibrillation; electrophysiological bases and clinical applications].

During sinus rhythm, the successive responses to the application of electrical stimuli of increasing intensity during the vulnerable period are cardiac stimulations followed by repetitive ventricular responses and then ventricular fibrillation. An impulse of even greater intensity is not followed by ventricular fibrillation (shock at the upper limit of vulnerability) suggesting that defibrillatory shock is effective only when it does not reinduce fibrillation. Two other hypotheses are also proposed in fibrillation, that of critical mass and that of extension of the refractory periods, in particular after biphasic shocks. Clinically, the measurement of the threshold of defibrillation is difficult as it is a random process which does not obey the all or nothing principle. Ideally, a graph of efficacy versus energy should be constructed but this is only possible under experimental conditions. The effects of different antiarrhythmic drugs have been studied in this manner; in general, the sodium channel blockers improve the energies of defibrillation.

Animals↗
PubMed1995

[New indications for cardiac pacing].

New indications have recently appeared for cardiac pacing with haemodynamic and antiarrhythmic objectives without any symptomatic bradycardia. The best documented indication, though relatively rare, is stimulation of obstructive hypertrophic cardiomyopathy; initially reserved for cases with favorable results of an acute haemodynamic test, it is now used in other cases without this criterion; hypertrophic cardiomyopathy without permanent obstruction, atrial fibrillation or left bundle branch block. The improvement observed during follow-up is always greater as a real remodeling of the myocardium seems to occur with ventricular dilatation and/or septal thinning. However, the position of the atrial, and above all, of the ventricular pacing catheters is critical as is regulation of the pacemaker which should allow complete ventricular capture with an AV delay allowing good filling. The follow-up of these patients must therefore be regular and the effects on longevity are unknown. DDD pacing has also been proposed in dilated cardiomyopathy. The results are contradictory and only very selected cases with left bundle branch block and long PR interval seem justified with, again, optimisation of the pacing sites with high septal or biventricular stimulation. Recurrent atrial tachycardia, special algorithms preventing extrasystoles have been tried with variable results. In cases with inter-atrial block, atrial resynchronisation by bi-atrial stimulation has been assessed with promising results but many technical problems remain unsolved.

Adolescent↗
PubMed1994

Recognition of T cell epitopes and lymphokine secretion by rye grass allergen Lolium perenne I-specific human T cell clones.

T cell lines (TCL) and CD4+ T cell clones (TCC) with specificity for the rye grass allergen Lolium perenne (Lol p) I were isolated from the blood of nine donors, six having active atopic disease, two being in remission, and one having IgE anti-Lol pI Abs but not atopic disease. The T cell epitopes of Lol pI were determined by TCLs and TCCs reactivity with 23 overlapping, 20 amino acid-long peptides spanning the entire length of the 230 amino acid-long allergen. In addition, the Th subsets (Th1, Th2, Th0, Thp) were determined by measuring IL-2, IFN-gamma, and IL-4 in the supernatants of TCC activated with Lol pI and irradiated APC. TCC from individuals from which a large panel of clones were obtained from 10(5) PBMC initial cultures recognized multiple peptides (5-9) and 23 overlapping peptides a total of 16 were recognized by at least one TCC from one of the patients. These 16 peptides were derived from all areas of the Lol pI molecule, indicating the ability of human Th cells to recognize many peptide epitopes on Lol pI. Although no clear cut immunodominant peptides were detected, T cell clones of 50% of the patients reacted with peptide 191-210. There was no correlation between peptide epitope reactivity and lymphokine secretion pattern of the TCC. Of 12 TCC obtained from six patients with active atopic disease, four (33%) were of Th1, five (42%) of Th2, one (8%) of Thp, and two (17%) of Th0 type. Of 14 TCCs isolated from three atopic donors in remission, five (36%) were of Th1, three (21%) of Th2, four (29%) of Thp, and two (14%) of Th0 type. The data demonstrate that T cells from rye grass pollen allergic patients can recognize multiple peptide epitopes on Lol pI scattered over the entire molecule. No correlation existed between epitope reactivity and lymphokine secretion pattern of the TCC.

Adolescent↗
PubMed1994

Effect of progesterone on hydrophobic cell-associated proteoglycans bound to cholesterol sulfate in glandular epithelial cells of guinea-pig endometrium.

Sulfate incorporation was studied in subcultured glandular epithelial cells of guinea-pig endometrium untreated or treated with 10(-8) M 17 beta-estradiol alone or associated with various concentrations of progesterone. In the cells treated with progesterone in association with 17 beta-estradiol, the maximum of the 35S-labelled cell-associated macromolecules failed to bind with an anion-exchange resin (53% of total radioactivity) and had a hydrophobic character. This fraction was separated as an aggregate when the cells were extracted with 4 M guanidine-HCl, and separated as a single component in the presence of Triton X-100, suggesting that it aggregates with cellular lipid. The guanidine-extracted material contained 23.5% proteoglycans. However, the bulk of the radioactivity was in the sulfated lipids (68-75%), essentially represented by cholesterol sulfate. In the progesterone-treated cells, the amount of cholesterol sulfate was significantly higher than in 17 beta-estradiol-treated or untreated cells (1.35-1.5-fold). Thus, the effect of progesterone is located on a lipophilic proteoglycan associated with cholesterol sulfate. These results are discussed in relation to the preparation of the endometrium for embryo implantation.

Animals↗
PubMed1994

Comparison of interferon-gamma and interleukin-4 production by peripheral blood mononuclear cells and isolated T cells after activation with polyclonal T cell activators.

Controversial data have been reported regarding the ability of peripheral blood T cells to secrete interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) from atopic patients as compared to nonatopic healthy controls. In most of these studies, T cells in peripheral blood mononuclear cell preparations (PBMC) were stimulated with polyclonal T cell activators. Some of these activators are able to activate cells other than T cells in the PBMC preparations which may influence the lymphokine levels in supernatants of PBMC. To evaluate this, we compared the IFN-gamma and IL-4 levels in PBMC and isolated T cell preparations after activation with phytohemagglutinin (PHA), Concanavalin A (ConA), anti-CD3 plus phorbol myristate acetate (PMA), or ionomycin plus PMA. The IFN-gamma and IL-4 levels in the supernatants were calculated based on the percent T cells in the preparations. Whereas all activators induced significant IFN-gamma secretion, only ionomycin plus PMA stimulation induced large IL-4 secretion. In virtually all cases, the IFN-gamma levels calculated on a per T cell basis differed for PBMC versus isolated T cells. Whereas in some donors the IFN-gamma levels were higher in PBMC preparations than in T cells, in others it was the opposite. Similarly, in about one half of both normal and atopic donors tested, the IL-4 levels of activated PBMC were 2- to 7-fold lower than levels in isolated T cells. The data suggest that non-T cells have a significant effect on the IFN-gamma and IL-4 levels in supernatants of polyclonally activated PBMC.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1994

Sympathetic activation decreases medium-sized arterial compliance in humans.

This study used a precise noninvasive method in normotensive humans to determine the effects of sympathetic activation on arterial compliance. A recently developed, high-resolution echo-tracking system capable of measuring systolic/diastolic variations of arterial diameter was coupled to a Finapres system and used to calculate instantaneous systolic/diastolic pressure-diameter and compliance-pressure curves for a muscular medium-sized artery, the radial artery. Two standardized tests of sympathetic system activation, a cold pressor test (2 min) and a mental stress test (2 min of mental arithmetic), were performed at an interval of 8 days in random order in nine healthy volunteers [30 +/- 9 (SD) yr]. Radial arterial parameters were recorded every 30 s for 9 min, which included 2 min of cold pressor test or mental stress test. During both tests, radial arterial mean diameter did not change despite t he increase in mean arterial pressure (P < 0.001); stroke change in diameter decreased (P < 0.01), whereas pulse pressure increased (P < 0.01). Arterial compliance, calculated for the instantaneous level of mean arterial pressure, decreased significantly (P < 0.01). Compliance (C) calculated at 100 mmHg (C100) was arbitrarily chosen as a reference point for comparing compliance among the different periods of the test. C100 decreased significant (P < 0.05) during both tests (from 2.93 +/- 1.27 to 2.04 +/- 0.94 and from 3.29 +/- 1.73 to 2.63 +/- 1.55 mm2.mmHg-1.10(-3) during mental stress and the cold pressor test, respectively). These results indicate that sympathetic activation is able to decrease radial arterial compliance in healthy subjects. The reduction in arterial compliance probably resulted from complex interactions between changes in distending blood pressure and changes in radial arterial smooth muscle tone.

Adult↗
PubMed1994

Elastic modulus of the radial artery wall material is not increased in patients with essential hypertension.

Hypertension is known to decrease arterial distensibility and systemic compliance. However, the arterial tree is not homogeneous, and it has been shown that the medium-size radial artery does not behave like the proximal, elastic, large, common carotid artery. Indeed, radial artery compliance in hypertensive patients (HTs) has been shown to be paradoxically increased when compared with that in normotensive control subjects (NTs) at the same blood pressure level. To determine whether this increase was due to hypertension-related hypertrophy of the arterial wall, radial artery functional and geometric parameters from 22 NTs (mean +/- SD, 44 +/- 11 years) were compared with those from 25 age- and sex-matched never-treated essential HTs (48 +/- 12 years) by using a high-precision ultrasonic, echo-tracking system coupled to a photoplethysmograph (Finapres system), which allows simultaneous arterial internal diameter, intima-media thickness, and finger blood pressure measurements. When the values for HTs were compared with those of NTs at their respective mean arterial pressures, HTs had similar internal diameter (2.50 +/- 0.56 versus 2.53 +/- 0.32 mm, mean +/- SD) and greater intima-media thickness (0.40 +/- 0.06 versus 0.28 +/- 0.05 mm, P < .001) measurements and increased arterial wall cross-sectional areas (3.79 +/- 1.14 versus 2.45 +/- 0.57 mm2, P < .001). Circumferential wall stress was not significantly different between the two groups. Compliance calculated for a given blood pressure, ie, 100 mm Hg (C100), was greater in HTs than NTs (3.46 +/- 2.41 versus 2.10 +/- 1.55 m2.kPa-1 x 10(-8), P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Carotid artery distensibility and distending pressure in hypertensive humans.

Whether the decrease in large-artery distensibility observed in hypertensive patients is due primarily to an increase in distending pressure or to hypertension-induced changes in structural properties has been much debated. We determined noninvasively the diameter-pressure curve of the common carotid artery over the systolic-diastolic range by continuously recording both the pulsatile changes in internal diameter (high-resolution echo-tracking system) and, simultaneously on the contralateral artery, the pressure waveform (high-fidelity applanation tonometry). We then derived the distensibility/pressure curve and compared arterial distensibility in 14 normotensive subjects and 15 age- and sex-matched hypertensive subjects at their respective mean arterial pressures (MAP) and at a common distending pressure: 100 mm Hg. Distensibility decreased as blood pressure increased, and distensibility at MAP was significantly lower in hypertensive than in normotensive subjects (7.8 +/- 0.7 versus 11.7 +/- 1.7 kPa-1.10(-3), mean +/- SEM; P < .05). In hypertensive subjects, the distensibility-pressure curve was shifted toward higher levels of blood pressure, and a large part of the curve overlapped that of normotensive subjects. No significant downward shift of the distensibility-pressure curve was observed in hypertensive subjects, and distensibility at 100 mm Hg was not significantly different from that of normotensive subjects (10.0 +/- 1.0 versus 9.0 +/- 1.1 kPa-1.10(-3)). Distensibility at 100 mm Hg decreased with aging (P < .05) and was not reduced in hypertensive subjects compared with normotensive subjects after adjustment for age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Role of interleukin-4 in human immunoglobulin E formation in hu-PBL-SCID mice.

We studied the role of IL-4 in human IgE formation in severe combined immunodeficient mice engrafted with peripheral blood mononuclear leukocytes (hu-PBL-SCID). PBL from four nonatopic donors produced only small (< 20 ng/ml) or undetectable amounts of IgE in SCID mice whereas engrafted PBL from seven atopic donors secreted IgE with IgE serum levels reaching a mean +/- SE of 184 +/- 37 ng/ml (n = 20). Serum IgE levels peaked 2-3 wk after PBL transfer and declined thereafter with a half-life of 1-2 wk. In contrast, IgG of all subclasses reached maximum serum levels 5-7 wk after PBL transfer and declined little thereafter. Injection of a neutralizing monoclonal antibody to the human IL-4 receptor (IL-4R) on day 0 inhibited completely the IgE formation and caused an approximate twofold reduction of IgG production of all subclasses. The anti-IL-4 R antibody had no effect on IgE secretion when administered 4 wk after PBL engraftment. Incubation of PBL with IL-4 before engraftment resulted in a 10-fold increase in IgE production and could be further enhanced by 100 fold if, in addition to preincubation with IL-4, IL-4 was injected daily for 5 d after PBL transfer. This treatment with IL-4 also induced two- to threefold increase in IgG levels. IFN-gamma had no effect on either IgE or IgG subclass production. In approximately 50% of the mice, one or more IgG subclasses increased disproportionally 5 wk after PBL injection as a result of monoclonal IgG formation. These data demonstrate that PBL from atopic donors secrete IgE in SCID mice in an IL-4-dependent manner, and that IgE production can be enhanced 10- to 100-fold with exogenous human IL-4 in these mice. This mouse model is amenable for the in vivo study of immunomodulators on human IgE formation.

Animals↗
PubMed1994

Effect of progesterone on proteins vectorially secreted by glandular epithelial cells of guinea-pig endometrium: modulation by homologous stroma.

Endometrial glandular epithelial cells were subcultured on matrix-coated filters in bicameral chambers in a serum-free chemically defined medium. The cells were untreated or treated with 50 nmol progesterone l-1 or 10 nmol oestradiol l-1 or 10 nmol oestradiol l-1 plus 50 nmol progesterone l-1 and the proteins secreted into the basal or apical compartment were analysed after [35S]methionine labelling. Compared with the untreated cells, oestradiol treatment did not affect the electrophoretic profiles of proteins secreted by the glandular epithelial cells in either compartment. Progesterone treatment induced a decrease in the labelling of 88 and 53 kDa proteins secreted in the apical and basal compartments and an increase in the labelling of a 28 kDa protein. Moreover, progesterone specifically induced the apical secretion of a 137 kDa protein. Interaction between the epithelial and stromal cells was also investigated. When stromal cells were cultured in the basal compartment under the epithelial monolayer, the progesterone effect on the apical secretion of the 137 kDa protein and basal secretion of the 88 and 28 kDa proteins were altered, whereas this progesterone effect was not altered when the epithelial cells were cultured alone in media conditioned with stromal cells. Interactions between epithelial and stromal cells modified the effect of progesterone on protein secretion by the epithelial cells.

Animals↗
PubMed1994

[Arterial compliance is not diminished in hypertensive patients when compared at the same level of blood pressure].

Whether the decrease in large artery compliance, observed in hypertensive patients (HT), is due to an increase in distending pressure or to intrinsic alterations of the vascular wall remains much debated. We determined the diameter-pressure curve of the common carotid artery over the systolic-diastolic range, then derived the compliance-pressure curve, in order to compare arterial compliance in normotensive subject (NT) and in HT, for a common level of distending blood pressure: 100 mmHg (isobaric compliance). Fourteen NT and 15 never treated essential HT were included in the study. The diameter-pressure curve of the common carotid artery was determined non-invasively by simultaneously and continuously recording the systolic-diastolic changes in internal diameter (using a high resolution echotracking system) and pressure waveform (using high fidelity applanation tonometry on the contralateral artery) over 4-6 cardiac cycles. The level of MAP of the carotid pressure waveform was determined electronically and set equal to mean brachial pressure. Compliance-pressure curve was then derived from the pressure-diameter curve in order to determine compliance (C) for any given level of blood pressure, particularly MAP (CMAP) and 100 mmHg (C100). Despite the considerable differences in blood pressure, the compliance-pressure curve of HT was not different from that of NT. CMAP decreased with aging (p < 0.001) and MAP (p < 0.001). According to age, CMAP was reduced in HT as compared to NT (84 +/- 49 vs 116 +/- 52 mm2.mmHg.10(-3) p < 0.01). C100 decreased with aging (p < 0.05) but not with MAP. According to age, C100 was not reduced in hypertensives.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗