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S Rath

Publications and source records attributed to S Rath.

At least 37 records · Page 2Linked to original sources
PubMed1999

Acute myocardial infarction with isolated ST-segment elevation in posterior chest leads V7-9: "hidden" ST-segment elevations revealing acute posterior infarction.

OBJECTIVES: This study was done to determine whether electrocardiographic (ECG) isolated ST-segment elevation (ST) in posterior chest leads can establish the diagnosis of acute posterior infarction in patients with ischemic chest pain and to describe the clinical and echocardiographic characteristics of these patients. BACKGROUND: The absence of ST on the standard 12-lead ECG in many patients with acute posterior infarction hampers the early diagnosis of these infarcts and thus may result in inadequate triage and treatment. Although 4% of all acute myocardial infarction (AMI) patients reveal the presence of isolated ST in posterior chest leads, the significance of this finding has not yet been determined. METHODS: We studied 33 consecutive patients with ischemic chest pain suggestive of AMI without ST in the standard ECG who had isolated ST in posterior chest leads V7 through V9. All patients had echocardiographic imaging within 48 h of admission, and 20 patients underwent coronary angiography. RESULTS: Acute myocardial infarction was confirmed enzymatically in all patients and on discharge ECG pathologic Q-waves appeared in leads V7 through V9 in 75% of the patients. On echocardiography, posterior wall-motion abnormality was visible in 97% of the patients, and 69% had evidence of mitral regurgitation (MR), which was moderate or severe in one-third of the patients. Four patients (12%), all with significant MR, had heart failure, and one died from free-wall rupture. The circumflex coronary artery was the infarct related artery in all catheterized patients. CONCLUSIONS: Isolated ST in leads V7 through V9 identify patients with acute posterior wall myocardial infarction. Early identification of those patients is important for adequate triage and treatment of patients with ischemic chest pain without ST on standard 12-lead ECG.

Adult↗
PubMed1999

Integration of generic indicators for quality management in hospital information systems.

Hospital information systems may contribute in different ways to quality management activities such as monitoring of quality indicators. Most existing quality management activities in hospitals are adjusted to a special medical field or particular disease. These activities often run simultaneously with other procedures and the documentation of patient care. To determine an interdisciplinary integrated quality management procedure, a pilot study was carried out at the Neurosurgery Department and Neonatology Division of the Medical Center of the University of Heidelberg. Predefined generic indicators that may be integrated in an existing information system and used in hospital routine were the basis of this project. The aim of the study was to support the quality management with periodic reports of these indicators. The pilot study showed that there were barriers along the path to an integrated generic quality management. To meet the requirements of routine monitoring, using predefined generic indicators of hospital care, much integration effort, directed at organizational aspects of information processing and information systems architecture, is still needed.

Germany↗
PubMed1999

Th1 dominance in the immune response to live Salmonella typhimurium requires bacterial invasiveness but not persistence.

Factors responsible for the predictable generation of Th1 or Th2 immune responses to microorganisms in vivo are not well characterized, although the ability of antigen presenting cells (APC) to provide co-stimulation, the kinetics of MHC-peptide ligand generation as well as the cytokine environment are all considered important factors for the differential Th1/Th2 priming of T cells. Our earlier findings of an IFN-gamma-dominant, Th1-type response to live Salmonella typhimurium (Stm) and a Th2-type response to killed Stm suggested that persistence of viable bacteria might be an important factor in the generation of IFN-gamma-dominant responses. Using genetically susceptible and resistant strains of mice to limit bacterial replication and persistence in vivo, we show that mice of the lty(r) genotype, capable of a 10-fold better clearance of Stm, mount an IFN-gamma-dominant immune response following immunization with live Stm similar to that in the lty(s) strain. Further, metabolically defective mutants of Stm, aroA and purA, when used in the live form, also elicit IFN-gamma-dominant immune responses similar to the wild-type Stm strain despite their inability to proliferate in vivo. While a laboratory strain of Escherichia coli, which is antigenically cross-reactive but non-invasive, elicits hardly any IFN-gamma in immune responses, an invasive strain of E. coil induces an IFN-gamma-dominant response. These data together indicate that, while entry of bacteria into macrophages is likely to be critical for the generation of IFN-gamma-dominant immune responses, their persistence is not.

Animals↗
PubMed1999

Effect of multiple antigenic exposures in the gut on oral tolerance and induction of antibacterial systemic immunity.

We have analyzed oral tolerance of microbial antigens in an experimental model in which mice are treated orally with a single small dose of soluble antigen and challenged systemically with the antigen in complete Freund's adjuvant. We found that, while oral administration of sonicated extracts of either Leishmania major, Leishmania donovani, or Staphylococcus aureus was tolerogenic, as was administration of the nominal antigen ovalbumin or conalbumin, oral administration of Escherichia coli or Salmonella typhimurium sonicated extract was not. Since E. coli is an enteric commensal that colonizes the intestine soon after birth, these data suggested that lack of demonstrable oral tolerance may be related to the frequency of oral exposure to an antigen. In support of this, we found that multiple oral doses of ovalbumin or S. aureus or L. donovani antigens did not increase systemic hyporesponsiveness beyond that achieved with a single oral dose. We have also tested the ability of mice fed with sonicates of the tolerogenic S. aureus or the nontolerogenic S. typhimurium to clear a subsequent systemic infection with the homologous bacteria and found that, while clearance of S. aureus was unaffected by prior feeding, clearance of S. typhimurium was actually enhanced. The data suggest that frequent oral antigenic exposure may eventually lead to induction of systemic immunity in tolerant mice.

Administration, Oral↗
PubMed1998

Deletion of a recombined Ig heavy chain transgene in B-lineage cells of transgenic mice.

Fully recombined transgenes are stable in their transmission in the germline of transgenic mice, in common with the endogenous genetic complement of most mammalian somatic tissues, including the genes for lymphoid Ag receptors somatically generated from germline minigenes. There have, however, been isolated reports of unusual low frequency transgene losses in various transgenic mice. Here we show, using Southern blots and PCR-based assays, that plasmablast hybridomas and B cells from three independently derived founder lines of transgenic mice bearing a recombined heavy chain Ig transgene we have been studying show a significant net loss of transgene copies. This loss is more marked in the B cells expressing endogenous heavy chains than in those expressing transgenic heavy chains. We have also examined cells of the B lineage in the bone marrow, and a small degree of deletion is also evident in CD19+ CD23- IgM- immature B-lineage cells. As greater deletion is observed in mature B cells, it is possible that the deletion process either continues into B cell maturity and/or provides a selective advantage. We have investigated the relationship between transgene expression and deletion, and we find that while thymocytes in these mice express the transgene well, T cell hybridomas derived from transgenic thymus do not show any loss of the transgene. Thus, a recombined Ig heavy chain transgene prominently undergoes somatic deletion in B-lineage cells independent of its insertion site or expression. This transgenic instability is significant to the analysis of genomic stability as well as to the design of gene therapy strategies.

Animals↗
PubMed1998

Modulation of T cell cytokine profiles and peptide-MHC complex availability in vivo by delivery to scavenger receptors via antigen maleylation.

We have previously shown that conversion of proteins to scavenger receptor (SR) ligands by maleylation increases their immunogenicity. We now show that maleyl-Ag-immune spleen cells make relatively more IFN-gamma and less IL-4 or IL-10 than native Ag-immune cells. This is also reflected in the IgG1:IgG2a ratios in Abs generated in vivo. SR engagement on macrophages does not alter their surface levels of the adhesive/costimulatory molecules CD11a/CD18, CD11b/CD18, CD24, CD54, or CD40, nor does it enhance their ability to support anti-CD3-driven proliferation of naive T cells in vitro. Costimulatory molecules implicated in differential Th1/Th2 commitment--CD80, CD86, and IL-12--are not inducible by SR ligation. In addition to macrophages and dendritic cells, B cells also show receptor-mediated uptake and enhanced presentation of maleyl-Ags. Using a monoclonal T cell line to detect peptide-MHC complexes expressed on spleen cells in Ag-injected mice, we find that higher levels of these complexes are generated in vivo from maleyl-proteins and they persist longer than those generated from the native protein. Together, these data suggest that in certain situations, the levels of cognate ligand available and/or the time course of their availability may play a major role in determining the cytokine profiles of the responding T cells in addition to the costimulatory signals implicated so far.

Animals↗
PubMed1998

Significance of ST segment elevations in posterior chest leads (V7 to V9) in patients with acute inferior myocardial infarction: application for thrombolytic therapy.

OBJECTIVES: This study was designed to examine whether ST segment elevation in posterior chest leads (V7 to V9) during acute inferior myocardial infarction (MI) identifies patients with a concomitant posterior infarction and whether these patients might benefit more from thrombolysis. BACKGROUND: Because the posterior wall is faced by none of the 12 standard electrocardiographic (ECG) leads, the ECG diagnosis of posterior infarction is problematic and has often remained undiagnosed, especially in the acute phase. METHODS: Eighty-seven patients with a first inferior infarction who were treated with recombinant tissue-type plasminogen activator were stratified according to the presence (Group A [46 patients]) or absence (Group B [41 patients]) of concomitant ST segment elevation in posterior chest leads V7 to V9. RESULTS: Patients in Group A had a higher incidence of posterolateral wall motion abnormalities (p < 0.001) on radionuclide ventriculography, a larger infarct area (as evidenced by higher peak creatine kinase levels) (p < 0.02) and a lower left ventricular ejection fraction (LVEF) at hospital discharge (p < 0.008) than those in Group B. ST segment elevation in leads V7 to V9 was associated with a higher incidence of at least one of the following adverse clinical events: reinfarction, heart failure or death (p = 0.05). Although patency of the infarct-related artery (IRA) in Group A resulted in an improved LVEF at discharge (p < 0.012), LVEF was unchanged in Group B, regardless of the patency status of the IRA. CONCLUSIONS: ST segment elevation in leads V7 to V9 identifies patients with a larger inferior MI because of concomitant posterolateral involvement. Such patients might benefit more from thrombolytic therapy.

Adult↗
PubMed1998

Pentoxifylline inhibits Ig kappa gene transcription and rearrangements in pre-B cells.

Pentoxifylline (PF) has been used in a wide variety of clinical situations; however, the molecular consequences of this drug are not well characterized. In this paper we assayed the effects of PF in two models of pre-B differentiation. In 70Z pre-B cells, transcriptional induction of rearranged Ig kappa-chain gene in response to LPS was suppressed by PF, without affecting the induction of Rel family proteins. In contrast, kappa induction by IFN-gamma was not suppressed by PF, indicating that the drug inhibited certain activation pathways. We also found that LPS-induced activation of germline kappa transcription and V kappa to J kappa recombination were inhibited by PF in the pre-B cell line 38B9. These observations suggest that PF may adversely affect B lymphopoiesis during chronic administration.

Animals↗
PubMed1998

Presence of activated antigen-binding B cells during immunization enhances relative levels of IFN-gamma in T cell responses.

To examine the influence of Ag presentation by B cells on immune responses, we have used mice transgenic for an Ig heavy chain from a monoclonal anti-azobenzenearsonate (Ars) Ab to deliver Ag to B cells during immunization. A large proportion of transgene-expressing B cells in these mice binds Ars, while transgenic serum Ig shows poor Ars binding. Transgenic B cells present Ars proteins better than their nonhaptenated counterparts. This is associated with an increase in the proliferative responses of transgenic T cells to Ars protein immunization. Although B cell numbers in the transgenic mice are lower, many B cells in them show an activated phenotype, as identified by altered surface levels of peanut agglutinin reactivity, CD23, CD24, CD44, CD62L, and CD86. Even against nonhaptenated immunogens, transgenic responses show significant enhancement in the relative proportions of the Th1 cytokine IFN-gamma over the Th2 cytokines IL-4 and IL-10. Haptenated immunogens further enhance the predilection of transgenic mice to produce relatively more IFN-gamma. Consistent with this, there is an increase in IgG2a/IgG1 ratios in serum Abs in response to haptenated immunogens in transgenic mice. Adoptive transfer of primed hapten-specific secondary B cells into nontransgenic mice also induces an increase in relative levels of IFN-gamma in response to haptenated immunogens. Thus, presentation of immunogen in vivo by activated Ag-binding B cells contributes to enhanced immunogenicity and a Th1 cytokine bias.

Animals↗
PubMed1998

Coronary arterioluminal communications in routine angiography.

Visualization of the left ventricular cavity from coronary arterioventricular communications is rarely encountered in routine coronary angiography. We report 14 patients, of 5,500 consecutive cardiac catheterizations, in whom these communications were evident during coronary angiography. All 14 patients had angina pectoris; in each the arterioluminal communication originated from the left anterior descending coronary artery. Two patients had evidence of anterior wall ischemia despite a normal left anterior descending coronary artery, suggesting that a possible steal phenomenon is responsible for the myocardial ischemia.

Aged↗
PubMed1997

Disruption of T cell tolerance by directing a self antigen to macrophage-specific scavenger receptors.

Breakdown of immune self tolerance is speculated to cause autoimmune diseases, but most studies on tolerance use foreign molecules as targets. In this study, we show another approach using delivery of a maleylated self protein to macrophage-specific scavenger receptors. Mice generate Abs against the maleylated form of a ubiquitous self Ag, mouse serum albumin (MSA), although native MSA is nonimmunogenic. This generation of anti-maleyl MSA Abs depends on binding of maleyl MSA to scavenger receptors in vivo, since coinjection of a serologically unrelated scavenger receptor ligand inhibits it, suggesting that the Ab response is T cell dependent. Spleen cells as well as nylon adherence-purified splenic T cells from maleyl MSA-immune mice proliferate in response to both maleyl MSA and MSA; this response is blocked by anti-MHC class II mAbs, and the autoimmune cells can recognize at least five 15-mer peptides from the MSA sequence, establishing that T cell tolerance to MSA has been broken in these mice. Maleyl MSA and MSA are recognized equally well, provided the scavenger receptor-specific delivery of maleyl MSA is blocked during stimulation in vitro, indicating that maleyl MSA-specific non-self peptides are unlikely to play a major role in the observed disruption of T cell tolerance. Thus, delivery of some self molecules to scavenger receptors may lead to disruption of immune tolerance. These results are relevant to mechanisms of immune tolerance and the etiopathogenesis of autoimmunity.

Animals↗
PubMed1997

Differential regulation of T cell activation for primary versus secondary proliferative responses.

T cell activation in vivo results in proliferation and generation of effector cytokine-secreting cells, as also in development of memory cells that mount enhanced responses upon restimulation. However, differences in the signals promoting generation of effector vs memory T cells are not yet characterized. In this study, using various strategies to modulate an allorecognition system for priming human T cells in vitro, we show that there are indeed differences between the signaling requirements for a first proliferative response and those for priming T cells for enhanced recall proliferative responses. Using APCs fixed with varying concentrations of paraformaldehyde, we show that the loss of ability of these APCs to generate a first response is not matched by a similar loss in their ability to prime responder T cells for recall responses. Prevention of DNA replication during T cell priming with aphidicolin, a DNA polymerase inhibitor, is not inimical to successful T cell priming. Thus, clonal expansion during priming is less crucial than the primed activation status of T cells for the enhanced recall response. We also show that pentoxifylline, a phosphodiesterase inhibitor, inhibits the primary proliferative response, but its presence during priming enhances the recall response capabilities of T cells. On the other hand, the presence of the calcineurin inhibitor cyclosporin A during priming reduces the efficiency of priming, but at low concentrations it induces, like pentoxifylline, enhancement in recall response capability. These findings have significant implications in designing immunosuppressive therapy and in the analysis of signals for T cell memory commitment.

Aphidicolin↗
PubMed1997

c-Rel is a target of pentoxifylline-mediated inhibition of T lymphocyte activation.

The possible clinical use of the methyl xanthine derivative, pentoxifylline (PF), for the treatment of T cell-dependent diseases is being noted with increasing interest. In this paper, we studied the molecular consequences of PF treatment during lymphocyte activation. We found that in T cells, anti-CD3-induced c-Rel expression was blocked by PF, whereas the induction of other NF-kappaB family members was not significantly affected. However, induction of NF-AT, which has the same signaling requirements as c-Rel induction, was not inhibited by PF. Among genes that respond to these transcription factors, IL-2 mRNA induction was suppressed by PF, whereas IL-2R(alpha) chain mRNA induction was not affected. These observations implicated c-Rel as an IL-2 promoter factor, for which experimental support was obtained from transient transfection experiments. In contrast with the observation in T cells, c-Rel induction was not blocked by PF in B cells. The greater selectivity of PF, compared with FK506, at both the molecular and cellular levels may prove advantageous in manipulating T cell responses in vivo.

Animals↗
PubMed1997

Coronary artery calcification in women with syndrome X: usefulness of double-helical CT for detection.

PURPOSE: To determine the usefulness of double-helical computed tomography (CT) for detection of diseased coronary arteries in women with anginal pain, positive exercise stress test results, and angiographically normal coronary arteries (syndrome X). MATERIALS AND METHODS: Double-helical CT of the coronary arteries was performed in 81 consecutive women who were referred for coronary angiography for evaluation of chest pain. Patients were classified into three groups according to stress test and angiographic results: normal (normal exercise test results and angiographically normal coronary arteries), syndrome X (abnormal exercise test results and angiographically normal coronary arteries), and coronary artery disease (at least one diseased vessel seen at angiography). RESULTS: The prevalence of coronary calcification in the syndrome X group was 63% (10 of 16 patients) compared with 96% (45 of 47 patients) in the coronary artery disease group (P = .002) and 22% (four of 18 patients) in the normal group (P = .02). The lowest total coronary calcification score and logarithmic transformed data were found in the normal group (2.9 +/- 0.7), statistically significantly higher values were found in the syndrome X group (4.3 +/- 1.5), and the highest values were found in the coronary artery disease group (5.1 +/- 2.0; for trend, P = .03). CONCLUSION: Double-helical CT may be useful in detection of atherosclerosis in women with syndrome X who demonstrate normal coronary arteries at angiography.

Calcinosis↗