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Biomedical subjects

M Moser

Publications and source records attributed to M Moser.

At least 127 records · Page 7Linked to original sources
PubMed1998

Increased heart rate in depressed subjects in spite of unchanged autonomic balance?

A clinical study was conducted to examine the effects of depression on cardiac autonomic control. Cardiac autonomic control was measured in 26 nonmedicated patients (19 females) suffering from Major Depression, melancholic type, and in 26 age- and sex-matched normal controls. We measured heart rate and high frequency heart rate variability (respiratory sinus arrhythmia), pulsewave velocity and blood pressure, during 10 min of supine rest under controlled conditions. Using a log transformed time domain measure of respiratory sinus arrhythmia (logRSA), we found an inverse linear dependence between cardiac vagal tone and age in the healthy subjects as well as the depressed patients. logRSA was 0.22+/-0.25 in the patients and 0.25+/-0.16 in the control group. While this difference was not significant (P > 0.1), the deviations from the regression line were significantly (P < 0.0005) greater in the patients (0.21+/-0.12) than in the control group (0.09+/-0.07), indicating a more heterogeneous vagal tone in the depressed patients. Heart rate was also significantly (P < 0.03) greater in the depressed patients (76.6+/-12.4) than in the control group (69.5+/-6.9). No between-group differences were found in pulsewave velocity or systolic blood pressure, but diastolic blood pressure was lower in depressed patients (73.5+/-8.7 vs. 80.8+/-9.1). We discuss the possibility that the increased heart rate seen in the absence of vagal tone changes may not be due to altered vagal or sympathetic tone, as measured in this study. Other factors, including altered autonomous heart rate, may be responsible for the higher heart rate in the depressed group.

Adolescent↗
PubMed1998

Results of therapy with carvedilol, a beta-blocker vasodilator with antioxidant properties, in hypertensive patients.

Carvedilol is a new beta-blocker antihypertensive agent with vasodilating properties secondary to alpha 1-blocking activity. Peripheral vascular resistance is reduced and cardiac output and renal function are not altered with carvedilol. The antihypertensive effects of this agent are equivalent to those of other beta-blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, and diuretics. Carvedilol has a neutral effect on lipids and glucose metabolism. The percentage of responders is increased when carvedilol is combined with a diuretic. This agent has several unique properties. In addition to its antihypertensive effects, carvedilol in vitro and in vivo has been shown to have antiproliferative effects on smooth muscle cells and to inhibit the action of oxygen-free radicals. The antioxidant properties of this compound are significantly greater than those of vitamin E. In animal models, carvedilol may slow the process of atherogenesis, reduce infarct size, and improve postinfarction survival to a greater degree than other beta-blockers. Recent studies have demonstrated that carvedilol reduces morbidity and mortality in patients with congestive heart failure who are already receiving angiotensin converting enzyme inhibitors, diuretics, and digitalis. The antioxidant and antiproliferative activities of carvedilol may present an advantage over other available antihypertensive medications.

Adrenergic beta-Antagonists↗
PubMed1998

Current recommendations for initial therapy in hypertension: are they still valid? Introduction.

This symposium will address questions regarding current recommendations for initial therapy in the management of hypertension: Are we treating too many hypertensive patients or too few? When do we start treatment with medications and what medications should we use? Professor Lawrence Ramsay from England will discuss the concept of absolute versus relative risk and review the long-term hypertension treatment trials and what they have and have not told us. Dr. Michael Weber of New York will discuss some newer data on angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, and calcium channel blockers and attempt to answer the question: are these data sufficient to warrant recommending these agents as initial therapy? Finally, Dr. Henry Black of Chicago and I will update a new-old concept: is it time to consider low-dose fixed combination therapy as initial treatment in hypertension?

Angiotensin II↗
PubMed1998

The role of combination therapy in the treatment of hypertension.

Only approximately 40% to 50% of hypertensive patients will achieve goal blood pressures of <140/ 90 mm Hg with monotherapy, regardless of the medication used. Fixed-dose combination therapy with two different classes of antihypertensive agents will achieve goal pressures in more than 70%. The sixth Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure has suggested that the use of combination therapy is appropriate as initial treatment. The advantages of combinations include: 1) greater blood pressure decrease and response rates than monotherapy; 2) fewer side effects with small doses of two drugs than with large doses of one agent; 3) improved adherence to treatment; and 4) possibly lower cost of therapy. Many different combinations of diuretics and beta-blockers, angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists, as well as ACE inhibitors and calcium antagonists are available. Two of these, Ziac and Capozide, have been approved as initial therapy. It is possible that the number of hypertensive individuals controlled at goal blood pressure levels will be increased if combination therapy is used as initial treatment.

Adrenergic beta-Antagonists↗
PubMed1998

The cost of treating hypertension: can we keep it under control without compromising the level of care?

The cost of hypertension treatment can be contained without compromising outcome. National recommendations for the routine diagnostic evaluation of hypertensive subjects do not include echocardiograms or ambulatory monitoring. These are expensive procedures, which, if performed in only a fraction of the total hypertensive population, would add several billion dollars to the cost of care. At present there are no data indicating that outcome of treatment would be improved. Costs of labeling before a definitive diagnosis is made, continuing lifestyle modification too long, medication switching, and not treating to goal blood pressures also increase cost without increased benefit. Although there are special indications for the more expensive newer medications, the majority of patients can be managed, at least initially, with less expensive therapies. Cost should not be a consideration, however, if one therapy has been shown to be more beneficial than another. Finally, the benefits of antihypertensive drug therapy have been underestimated because of the lack of consideration of prevention of left ventricular hypertrophy or progression to more severe disease by early treatment. On the other hand, the cost per quality of life-years saved has been overestimated. Pharmacoeconomic models may serve to mislead practitioners regarding treatment decisions.

Antihypertensive Agents↗
PubMed1998

[Auditory speech-evoked cerebral cortex potentials in patients with stuttering syndromes].

BACKGROUND: The cause of stuttering is unknown. For clinical purposes it proved to be useful to assume a multifactorial genesis with organic psychological and social aspects. A longstanding organic theory focussed on the failure to develop left-hemispheric dominance for speech, whereas others favoured deficits of the speech motor system. Positron emission tomography (PET) studies support organic theories for the development of stuttering. The purpose of this study was to find out whether in stutterers auditory cortical potentials evoked by pure tones, noise and words are different to those of healthy controls. PATIENTS AND METHODS: 10 young adults having suffered from stuttering since infancy were examined. The potentials were measured and analysed as previously described. RESULTS: No correlation of clinical and electrophysiological findings were found. In one case the evoked potentials were normal, in all other patients heterogeneous results were obtained in respect of tone-evoked and both noise- and speech-evoked potentials. Cortical hemispheric differences could be detected. CONCLUSIONS: In agreement with PET findings reported in the literature the data obtained in this study indicate an organic, central nervous cause of stuttering. Obviously both speech motoric components and perception elements are affected. These facts have to be taken into account whenever a psychological cause of stuttering is suspected. Nevertheless, psychosomatic aspects of the disturbances must be considered since they influence the patients' ability to cope with their symptom.

Adolescent↗
PubMed1998

The immune response induced in vivo by dendritic cells is dependent on B7-1 or B7-2, but the inhibition of both signals does not lead to tolerance.

Dendritic cells (DC) can be used as physiological adjuvant in vivo. Indeed, a single injection of DC, pulsed in vitro with antigen, induces activation of specific T and B lymphocytes in syngeneic mice. The unique capacity of DC to sensitize naive T lymphocytes correlates with elevated expression of MHC antigens as well as co-stimulatory molecules. The aim of this work was to evaluate the functional role of the individual CD28 ligands in the induction of primary humoral and cellular responses, and to characterize the nature of the immune response induced in the presence of selected co-stimulatory molecules. Our data show that the primary response is strictly B7 dependent, and that B7-1 and B7-2 mediate overlapping co-stimulatory functions, as either molecule alone is sufficient to initiate an immune reaction. Inhibition of B7-1 and B7-2, however, does not lead to tolerance as predicted by the two-signal hypothesis. Rather, recognition of antigen in the absence of B7 appears as a null event, since subsequent immunogenic stimulation results in a primary response. Blockade of B7-2 co-stimulatory molecules significantly inhibits antigen-specific IgG1 but not IgG2a production, suggesting that B7-2 may direct the development of Th2 cells. These data emphasize the critical role of the CD28/B7 pathway in the induction of the immune response by DC, which appear to be the initiating antigen-presenting cells in situ.

Abatacept↗
PubMed1998

Circadian rhythm of the soluble p75 tumor necrosis factor (sTNF-R75) receptor in humans--a possible explanation for the circadian kinetics of TNR-alpha effects.

Circadian alterations of several immune functions in vivo are well established, and may have important physiological and clinical implications. In line with this, tumor necrosis factor (TNF)-alpha has been implicated in the circadian regulation of body temperature. As soluble TNF receptors (TNF-R) act as naturally occurring competitive inhibitors of this cytokine, we investigated plasma levels of the soluble sTNF-R55 and sTNF-R75 in comparison with plasma cortisol and body temperature in nine healthy male volunteers during a defined 16 h light/8 h dark cycle. It was found that sTNF-R75, but not sTNF-R55, exhibited a clear-cut circadian rhythm with a significant (P < 0.01) peak at 7:51 a.m. +/- 58 min. The phase of the sTNF-R75 rhythm preceded that of cortisol by approximately 1 h and inversely corresponded to the circadian rhythm of body temperature. Moreover, the individual amplitudes of sTNF-R75 and body temperature exhibited a significant (P < 0.01) positive correlation. These results suggest that (i) the two sTNF-R are regulated independently, (ii) the sTNF-R75 rhythm is not primarily due to the cortisol rhythm and (iii) the fluctuation of the sTNF-R may contribute to the regulation of body temperature by modulating the availability of free TNF.

Adult↗
PubMed1998

Murine dendritic cells pulsed in vitro with Toxoplasma gondii antigens induce protective immunity in vivo.

The activation of a predominant T-helper-cell subset plays a critical role in disease resolution. In the case of Toxoplasma gondii, the available evidence indicates that CD4(+) protective cells belong to the Th1 subset. The aim of this study was to determine whether T. gondii antigens (in T. gondii sonicate [TSo]) presented by splenic dendritic cells (DC) were able to induce a specific immune response in vivo and to protect CBA/J mice orally challenged with T. gondii cysts. CBA/J mice immunized with TSo-pulsed DC exhibited significantly fewer cysts in their brains after oral infection with T. gondii 76K than control mice did. Protected mice developed a strong humoral response in vivo, with especially high levels of anti-TSo immunoglobulin G2a antibodies in serum. T. gondii antigens such as SAG1 (surface protein), SAG2 (surface protein), MIC1 (microneme protein), ROP2 through ROP4 (rhoptry proteins), and MIC2 (microneme protein) were recognized predominantly. Furthermore, DC loaded with TSo, which synthesized high levels of interleukin-12 (IL-12), triggered a strong cellular response in vivo, as assessed by the proliferation of lymph node cells in response to TSo restimulation in vitro. Cellular proliferation was associated with gamma interferon and IL-2 production. Taken together, these results indicate that immunization of CBA/J mice with TSo-pulsed DC can induce both humoral and Th1-like cellular immune responses and affords partial resistance against the establishment of chronic toxoplasmosis.

Adoptive Transfer↗
PubMed1998

Augmented platelet aggregation as predictor of reocclusion after thrombolysis in acute myocardial infarction.

RATIONALE: Reocclusion after thrombolysis diminishes the benefits of early reperfusion after acute myocardial infarction (AMI). No clinical or laboratory variables have been identified as predictors for reocclusion yet. METHODS AND RESULTS: To evaluate hemostatic variables as potential risk determinants platelet aggregation (PA, representing platelet activity), thrombin/antithrombin complexes (TAT, representing thrombin generation), and plasminogen activator inhibitor type 1 (PAI-1, representing endogenous fibrinolysis) were determined in 31 patients with AMI at 0, 1, 2. and 12 h after the start of thrombolysis as well as at hospital discharge. Reocclusion (defined as reinfarction or angiographically confirmed, clinically silent coronary reocclusion) occurred in 5 patients within 5-14 days and in 8 patients within 1 year. TAT plasma concentrations were lower in patients with reocclusion than in those without (9.9+/-5.7 vs. 22.9+/-22.2 ng/ml at 2 h, 6.5+/-3.1 vs. 1 1.2+/-6.4 ng/ml at 12 h, means+/-SD, p <0.05 each). Neither concentration nor activity of PAI-1 in plasma differed between both patient groups. However, both slope and maximum of PA (induced by 2 micromol/l ADP) were augmented in patients with reocclusion (slope: 39.4+/-1.7 vs. 32.5+/-7.4 at 2 h, p <0.001; 42.6+/-2.6 vs. 36.6+/-8.9 at 12 h, p <0.01). Results were independent of the thrombolytic agent used (alteplase or reteplase). A PA slope at 2 h higher than the average slope before thrombolysis (37.2+/-5.7) could be identified as best predictor for early (within 5-14 d, p=0.017, sensitivity 1.00, specificity 0.69) and late reocclusion (within 1 y, p=0.009, 0.88 and 0.74, respectively). CONCLUSIONS: Increased PA following coronary thrombolysis appears to be associated with early and late reocclusion. This marker could be useful in identifying patients who may benefit from more aggressive antiplatelet (such as GP IIb/IIIa receptor antagonists), interventional, or both strategies.

Adenosine Diphosphate↗
PubMed1997

Purification and characterization of bovine dendritic cells from peripheral blood.

Optimal activation of T lymphocytes depends on TCR interaction with peptide/MHC complexes in conjunction with costimulatory signals, which are delivered by specialized cells called antigen-presenting-cells (APC). The population of APC is heterogeneous and includes dendritic cells, B cells and macrophages. The family of dendritic cells (DC) is widely distributed in tissues and plays a major role in the induction of primary T-dependent immune responses. The aim of this paper was to isolate and characterize dendritic cells from cattle. Two methods are described that have been used to isolate dendritic cells from bovine peripheral blood. One method involves sequential depletion of other cells, adherence and isolation of low buoyant density cells on Metrizamide column. The second involves enrichment of cells displaying receptors for plasma fibronectin, followed by adherence and separation on Metrizamide. Both preparations were characterized morphologically by flow cytometry and functionally. Both procedures produced enriched populations that did not express molecules typical of T cells (CD3, CD4, CD8, WC1), B cells (sIg, CD21) and monocytes (CD14, Fc gamma 2R). Procedure 2 yielded cells with a typical veiled DC morphology that were highly effective at stimulating allogeneic T cells. Procedure 1 yielded cells that did not have the veiled morphology and were less effective in the MLR which may represent a more immature stage.

Animals↗
PubMed1997

Major depression and cardiac autonomic control.

We investigated autonomic control of heart rate in patients with major depression, melancholic type. Twenty-three depressed inpatients who were being treated with tricyclic antidepressants and 23 depressed patients who were taking no medications were compared with age- and sex-matched control groups on resting cardiac vagal tone and heart rate. In unmedicated depressed patients, cardiac vagal tone was comparable to that of control subjects, but heart rate was significantly higher. This increase in heart rate may have been due to sympathetic activation caused by anxiety, since the depressed patients were significantly more anxious than the control subjects. Medicated patients exhibited diminished cardiac vagal tone and higher heart rate than unmedicated patients and controls. This was probably due to the anticholinergic effects of the antidepressants. Our findings suggest that cardiac vagal tone is not lower than normal in patients with depression, melancholic type.

Adult↗
PubMed1997

Prion (PrPSc)-specific epitope defined by a monoclonal antibody.

Prions are infectious particles causing transmissible spongiform encephalopathies (TSEs). They consist, at least in part, of an isoform (PrPSc) of the ubiquitous cellular prion protein (PrPC). Conformational differences between PrPC and PrPSc are evident from increased beta-sheet content and protease resistance in PrPSc. Here we describe a monoclonal antibody, 15B3, that can discriminate between the normal and disease-specific forms of PrP. Such an antibody has been long sought as it should be invaluable for characterizing the infectious particle as well as for diagnosis of TSEs such as bovine spongiform encephalopathy (BSE) or Creutzfeldt-Jakob disease (CJD) in humans. 15B3 specifically precipitates bovine, murine or human PrPSc, but not PrPC, suggesting that it recognizes an epitope common to prions from different species. Using immobilized synthetic peptides, we mapped three polypeptide segments in PrP as the 15B3 epitope. In the NMR structure of recombinant mouse PrP, segments 2 and 3 of the 15B3 epitope are near neighbours in space, and segment 1 is located in a different part of the molecule. We discuss models for the PrPSc-specific epitope that ensure close spatial proximity of all three 15B3 segments, either by intermolecular contacts in oligomeric forms of the prion protein or by intramolecular rearrangement.

Amino Acid Sequence↗
PubMed1997

Enhanced apoptotic cell death of renal epithelial cells in mice lacking transcription factor AP-2beta.

Expression of AP-2 transcription factors has been detected previously in embryonic renal tissues. We show here that AP-2beta -/- mice complete embryonic development and die at postnatal days 1 and 2 because of polycystic kidney disease. Analyses of kidney development revealed that induction of epithelial conversion, mesenchyme condensation, and further glomerular and tubular differentiation occur normally in AP-2beta-deficient mice. At the end of embryonic development expression of bcl-X(L), bcl-w, and bcl-2 is down-regulated in parallel to massive apoptotic death of collecting duct and distal tubular epithelia. Addressing the molecular mechanism we show that transfection of AP-2 into cell lines in vitro strongly suppresses c-myc-induced apoptosis pointing to a function of AP-2 in programming cell survival during embryogenesis. The position of the human AP-2beta gene was identified at chromosome 6p12-p21.1, within a region that has been mapped for autosomal recessive polycystic kidney disease (ARPKD). Sequence analyses of ARPKD patients and linkage analyses using intragenic polymorphic markers indicate that the AP-2beta gene is located in close proximity to but distinct from the ARPKD gene.

Animals↗
PubMed1997

Staphylococcal enterotoxin B induces an early and transient state of immunosuppression characterized by V beta-unrestricted T cell unresponsiveness and defective antigen-presenting cell functions.

Staphylococcal enterotoxin B (SEB) is a bacterial enterotoxin able to simultaneously bind to class II molecules on APCs and to selected V beta regions (including V beta 8) of the TCR complex. Administration of SEB to adult BALB/c mice results in clonal activation of T cells bearing V beta 8 receptors, leading to an excessive release of proinflammatory cytokines. This initial immune response is followed by a long-lasting state of V beta 8-specific unresponsiveness, thought to benefit both the host (as it contributes to the down-regulation of the inflammatory response) and the bacterium (through ligand-specific T cell anergy). However, it is not clear how this type of restricted unresponsiveness can effectively impair the generation of an antibacterial response. To gain insight into the mechanism by which Gram-positive bacteria subvert the host immune response, we have investigated the immune competence of SEB-treated mice 48 h following SEB administration. We demonstrate in this report that in vivo, SEB induces a transient but profound state of unresponsiveness affecting both T and Ag-presenting cell functions. Although in vivo activation by SEB appears to be V beta-restricted under our experimental conditions, SEB-treated mice displayed an early (lasting 48 to 72 h postinjection) and V beta-unrestricted unresponsive state characterized by the inability to produce IL-2 in response to polyclonal TCR mitogens including third party bacterial superantigens (staphylococcal enterotoxin A and toxic shock syndrome toxin 1, SEA and TSST-1, respectively), Abs to non-SEB reactive V beta regions (V beta 6), anti-CD3 epsilon Abs, and a lectin (Con A). Spleen cell populations from SEB-treated mice also displayed defective APC functions, possibly related to a selective decrease in splenic dendritic cells numbers. Taken together, these observations indicate that SEB induces an early and transient state of immunodeficiency in vivo, representing a potential mechanism for escaping host immune surveillance.

Animals↗