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Biomedical subjects

L Beck

Publications and source records attributed to L Beck.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Role and significance of cytokines in the development of cardiac insufficiency].

The hypothesis of immune and inflammatory activation occurring during chronic cardiac failure, capable of maintaining the disease, is supported by many experimental and clinical trials. Plasma cytokines levels, particularly the tumour necrosis factor alpha (TNF alpha), are raised at advanced stages of the disease, especially in cachectic patients. The correlations with other, more traditional markers, especially neurohumoral, are not very close, probably suggesting different mechanisms. Cytokines are a group of very different molecules with multiple, non-specific, and even beneficial effects. However, the lack of regulation in severe cardiac failure may lead to deleterious effects on the heart. The experimental effects of TNF alpha (mini-pumps, transgenic animals) include features of myocarditis, chamber dilatation and contractile dysfunction. Large scale therapeutic trials of long acting TNF alpha antagonists could confirm the "inflammation hypothesis" of mutual interaction between cardiac failure and the production of cytokines.

Cardiac Output, Low↗
PubMed1997

Pex/PEX tissue distribution and evidence for a deletion in the 3' region of the Pex gene in X-linked hypophosphatemic mice.

PEX, a phosphate-regulating gene with homology to endopeptidases on the X chromosome, was recently identified as the candidate gene for X-linked hypophosphatemia. In the present study, we cloned mouse and human Pex/PEX cDNAs encoding part of the 5' untranslated region, the protein coding region, and the entire 3' untranslated region, determined the tissue distribution of Pex/PEX mRNA, and characterized the Pex mutation in the murine Hyp homologue of the human disease. Using the reverse transcriptase/polymerase chain reaction (RT/PCR) and ribonuclease protection assays, we found that Pex/PEX mRNA is expressed predominantly in human fetal and adult mouse calvaria and long bone. With RNA from Hyp mouse bone, an RT/PCR product was generated with 5' but not 3' Pex primer pairs and a protected Pex mRNA fragment was detected with 5' but not 3' Pex riboprobes by ribonuclease protection assay. Analysis of the RT/PCR product derived from Hyp bone RNA revealed an aberrant Pex transcript with retention of intron sequence downstream from nucleotide 1302 of the Pex cDNA. Pex mRNA was not detected on Northern blots of poly (A)+ RNA from Hyp bone, while a low-abundance Pex transcript of approximately 7 kb was apparent in normal bone. Southern analysis of genomic DNA from Hyp mice revealed the absence of hybridizing bands with cDNA probes from the 3' region of the Pex cDNA. We conclude that Pex/PEX is a low-abundance transcript that is expressed predominantly in bone of mice and humans and that a large deletion in the 3' region of the Pex gene is present in the murine Hyp homologue of X-linked hypophosphatemia.

Amino Acid Sequence↗
PubMed1997

PUVA-induced phototoxicity: incidence and causes.

BACKGROUND: Phototoxicity is the most significant short-term adverse effect of PUVA therapy. OBJECTIVE: We attempted to determine the incidence and possible causes of phototoxicity of sufficient degree to cause interruption of treatment. METHODS: A retrospective study was conducted of 16,506 PUVA treatments given to 414 patients in two treatment centers. RESULTS: Phototoxicity occurred in 10.9% of patients and was an adverse effect in 0.3% of treatments. Problems with the treatment protocol were the main cause. CONCLUSION: Phototoxicity is a common adverse effect, and patients should be warned of this potential occurrence. Awareness of the causes may help to reduce the incidence of this problem.

Clinical Protocols↗
PubMed1997

Chronic left main coronary artery occlusion: a complication of radiofrequency ablation of idiopathic left ventricular tachycardia.

We describe in this report the development of chronic left main coronary artery (LMCA) occlusion in a young patient 2 years after an uncomplicated, successful ablation of idiopathic left ventricular tachycardia. This complication appears to be a late consequence of trauma to the LMCA during the procedure rather than an acute or subacute embolic event.

Adult↗
PubMed1997

Cardiovascular regulation: a modelling approach.

A detailed analysis of autonomic cardiovascular control (ACVC) may provide a key to a better understanding of the mechanisms underlying postflight orthostatic hypotension. The central substrate of human ACVC is not directly accessible to measurements and observation in space research. Modelling--supporting inference and physiological reasoning--is a valuable tool to disclose its involvement We are currently determining the suitability of artificial neural networks (ANN's) as a model of the central substrate of ACVC. Having conducted a number of experiments with simulated tilt test data to clarify the choice of input coding and of architectural biases in network training we will now report on the approximation of data obtained from human subjects during preparation of the German MIR'97 and D-2 missions.

Adaptation, Physiological↗
PubMed1997

Vascular development: cellular and molecular regulation.

The vascular system forms through a combination of vasculogenesis and angiogenesis. In vasculogenesis, vessels form de novo via the assembly of endothelial precursors called angioblasts, whereas in angiogenesis new vessels arise by migration and proliferation of endothelial cells from preexisting vessels. Although the two processes are distinct in some respects, recent evidence suggests that they share a number of regulatory mechanisms. The identification of a number of defined growth factors, observations of genetically manipulated mice, and the recognition of the importance of cell-cell interactions have greatly expanded our understanding of the regulation of vascularization. The paracrine actions of a variety of polypeptide growth factors, including platelet-derived growth factor, vascular endothelial growth factor, transforming growth factor-beta, and the angiopoietins, appear to be orchestrated in a complex sequence of steps that lead to the development of the adult vascular system. Thus, communication between the forming vasculature and the tissue parenchyma, as well as interactions among cells of the vascular wall, all appear to influence vascular development and growth.

Animals↗
PubMed1997

[Classification of regular atrial tachycardia].

ECG criteria which for many years formed the basis of the classification of regular atrial tachycardias may now be completed by the results of endocavitary studies (stimulation and mapping). Flutter is a macroreentry phenomenon in the right atrium, anticlockwise in typical, common or classical forms, and more variable in atypical forms: sometimes antidromic and clockwise, sometimes functional more rapid without a gap of excitability, or in other cases, skirting around the sears of atriotomy, especially right-sided. Tachycardias are paroxysmal and often secondary to reentry; more rarely permanent, they are then often due to increased automaticity especially in young patients. The concordance with surface ECG changes is not perfect and the distinction between flutter and tachycardia often depends on the frequency of the tachycardia and the leads studied.

Anti-Arrhythmia Agents↗
PubMed1996

Comparison of monocytes and B cells for activation of human T helper cell subsets.

Human rye grass allergen Lol p I-specific T helper cell clones of Thp, Th0, Th1 and Th2 subtype were activated with Lol p I and monocytes or B cells as antigen-presenting cells, and cell proliferation, interleukin (IL)-2, interferon-gamma, and IL-4 secretion were measured. Monocytes induced activation of T cell clones of all four T helper cell subsets and were usually more potent antigen-presenting cells than B cells. B cells and monocytes similarly induced proliferation and IL-4 secretion by Th2 clones, whereas B cells, in contrast to monocytes, only weakly activated Th1 clones. However, exceptions to this rule existed within each T helper cell subset suggesting that individual T cell clones, regardless of the subset to which they belong, may have quantitatively and/or qualitatively different requirements for secondary activation signals which are provided by the antigen-presenting cells. The data demonstrate that, in general, monocytes are more effective than B cells in activating human T cell clones of all subtypes and that B cells were efficient antigen-presenting cells only for Th2 cells. However, individual T cell clones of any given T helper cell subset vary with respect to their activation by monocytes or B cells.

Allergens↗
PubMed1996

Regulation of leucine transport by intracellular pH in Bacillus pasteurii

The kinetics, specificity and mechanism of leucine uptake were studied in the alkaliphilic bacterium Bacillus pasteurii DSM 33 (ATCC 11859). Leucine was accumulated up to 200-fold by a sodium-dependent secondary transport system for branched-chain amino acids. Apparent Kt values of 9.6 μM for leucine, 8.9 μM for isoleucine, 9.3 μM for valine, and 0.71 mM for sodium were determined, and maximum uptake activity was observed at an external pH of 8.5 and at 35degreesC. The effect of several ionophores indicated that transport was energized by the membrane potential and a sodium gradient; each gradient alone was sufficient to drive the uptake of leucine. The activity of the leucine transport system was regulated by the intracellular pH and was inhibited at an internal pH below 7.0.

Journal Article↗
PubMed1996

Renal expression of Na+-phosphate cotransporter mRNA and protein: effect of the Gy mutation and low phosphate diet.

The X-linked Gy mutation is closely linked, but not allelic, to Hyp and is characterized by rickets, hypophosphatemia, decreased renal tubular maximum for phosphate (Pi) reabsorption (TmP) and a specific reduction in renal brush-border membrane (BBM) Na+-Pi cotransport. Gy mice, like their normal littermates, respond to a low-Pi diet with an increase in BBM Na+-Pi cotransport, but fail to show an adaptive increase in Tmp. Using an antibody raised against the NH2 terminal peptide of the rat renal-specific Na+-Pi cotransporter (NaPi-2) and a NaPi-2 cDNA probe, we examined the effect of the Gy mutation and low-Pi diet (0.03% Pi) on NaPi-2 protein and mRNA abundance. The reduction in BBM Na+-Pi cotransport in Gy mice (51 +/- 5% of normal, P < 0.05) was associated with a decrease in NaPi-2 protein (46 +/- 12% of normal, P < 0.05) and mRNA abundance (76 +/- 5%, P < 0.05). The low-Pi diet elicited a two- to three-fold increase in Na+-Pi cotransport in both normal and Gy mice that was accompanied by a large increase in NaPi-2 protein (10.2-fold in normal and 16.9-fold in Gy mice) and a modest increase in NaPi-2 mRNA (1.3-fold in both mouse strains, P < 0.05). The present data demonstrate that (1) the renal defect in BBM Pi transport in Gy mice can be ascribed to a deficit in NaPi-2 protein and mRNA abundance, (2) both normal and Gy mice respond to low Pi with an adaptive increase in NaPi-2 protein that exceeds the increase in Na+-Pi cotransport activity and NaPi-2 mRNA, (3) the adaptive increase in NaPi-2 protein and mRNA are not sufficient for the overall increase in TmP following Pi restriction.

Animals↗
PubMed1996

Release kinetics of serum cardiac troponin I in ischemic myocardial injury.

OBJECTIVES: The study was undertaken to evaluate the release kinetics of cardiac troponin I (cTn-I) in ischemic myocardial injury. DESIGN AND METHODS: The reference range for cTn-I was established by determination of cTn-I in sera and plasma obtained from 622 healthy volunteers (Group 1). cTn-I was compared to: (a) Creatine kinase (CK) MB mass and myoglobin in 12 patients with severe skeletal muscle damage (Group 2); (b) CK-MB activity in 48 patients with myocardial infarction (MI) receiving intravenous thrombolysis (Group 3) (in this group, an additional 43 patients with MI were analyzed separately to characterize cTn-I patterns in thrombolyzed and nonthrombolyzed populations): and in 44 patients with unstable angina (Group 4). RESULTS: In Groups 1 and 2, no positive results (> or = 0.1 microgram/L) were obtained. In Group 3, the time-courses of cTn-I were mostly monophasic in form. A pathologic increase occurred earlier in cTn-I than in CK-MB activity (p = 0.0002); the period with increased cTn-I was longer (p = 0.001), the overall sensitivity of cTn-I (93.9%) was higher than that of CK-MB activity (p = 0.00001). cTn-I was more sensitive at admission (p = 0.0004). In additional patients, the cTn-I peak occurred and cTn-I disappeared significantly later in nonthrombolyzed than in the thrombolyzed group. In Group 4, positive tests results were detected in 45% of patients for cTn-I, 16% for CK-MB activity, and 32% for CK-MB mass. CONCLUSIONS: The cTn-I assay appears to be ideally suited for the detection of ischemic myocardial injury in complex clinical situations because of its high specificity; cTn-I indicates myocardial tissue damage in patients with unstable angina and is superior to CK-MB activity and mass in this respect.

Adult↗
PubMed1996

Renal Na(+)-phosphate cotransporter gene expression in X-linked Hyp and Gy mice.

The X-linked Hyp and Gy mutations are murine homologues of X-linked hypophosphatemia (XLH), a dominant disorder of phosphate (Pi) homeostasis characterized by growth retardation, rickets, hypophosphatemia and decreased renal tubular maximum for Pi reabsorption relative to glomerular filtration rate (Tmp/GFR). In Hyp and Gy mice, the decrease in Tmp/GFR is associated with a reduction in renal brush-border membrane (BBM) Na(+)-Pi cotransport that can be ascribed to a decrease in renal-specific, Na(+)-Pi cotransporter (NPT2) mRNA and protein abundance. Although renal NPT2 gene expression is reduced in Hyp and Gy mice, the NPT2 gene does not map to the X chromosome. These findings exclude NPT2 as a candidate gene for murine and human X-linked hypophosphatemias and suggest that genes at the Hyp, Gy and XLH (HYP) loci are involved in regulation of NPT2 gene expression. Both Hyp and Gy mice respond to low Pi diet with an increase in BBM Na(+)-Pi cotransport, NPT2 mRNA and protein. The increase in NPT2 protein in Pi-depleted mice far exceeds the increase in NPT2 mRNA, suggesting that translational or post-translational mechanisms are involved in the adaptive process. NPT2 protein is localized to the apical surface of the proximal tubule, where immunostaining in both normal and Hyp mice is increased in response to low Pi diet. Pi-deprived Hyp and Gy mice fail to show an increase in Tmp/GFR, indicating that adaptation at the BBM is not sufficient for the overall increase in Tmp/GFR in response to low Pi diet.

Animals↗
PubMed1996

Professionalism behaviors of hospital nurse executives and middle managers in 10 western states.

What is the level of professionalism of nurse managers? These leaders of nurses are expected to establish a climate in which professional practice can flourish. In this study, the authors used the Professionalism Inventory to determine professional behaviors of 144 nurse executives and 135 middle managers. Nurse executives performed at consistently higher levels except for the categories concerning autonomy and knowledge of the Code for Nurses.

Adult↗
PubMed1996

[Value of human cardiac troponin I determination in the diagnosis of acute myocardial infarction].

Immunoenzymatic assay (IEMA) of human cardiac Troponin I (TnI c) was used in patients admitted to the coronary care unit with acute myocardial infarction (AMI). TnI c was detected in all patients with AMI. The detection of TnI c was earlier after the onset of pain (4.5 +/- 2.3 hours) than that of CKMB activity (6.3 +/- 3.6 hours), p = 0.003. The kinetics of TnI c are usually monophasic and parallel to that of CKMB activity. The peak value occurs 12.2 +/- 4.6 hours and 15.8 +/- 9.0 hours after the onset of pain in patients treated by thrombolysis. The TnI c disappears from the plasma between 5 and 9 days after the onset of pain, later than CKMB activity (p = 0.0001). In 49 patients admitted for AMI treated by thrombolysis, the comparative sensitivities of TnI c (threshold: 0.1 ng/ml) and of CKMB activity (threshold: 15 IU/l; CK > or = 100 Ul/l) were, at the first sampling on admission, 61% and 22% respectively (p = 0.0002) (average interval from onset of pain to first blood sampling: 3.4 +/- 1.3 hours). TnI c was not detected in the plasma of 145 normal subjects nor in any of the 6 patients with severe muscular trauma or rhabdomyolosis (specificity: 100%). This IEMA is a specific and a sensitive method of diagnosing acute and subacute myocardial infarction. It is ideal for the detection of myocardial necrosis in complex clinical situations when the usual enzymatic markers may be ineffective.

Adult↗
PubMed1995

Down-regulation by progesterone of CFTR expression in endometrial epithelial cells: a study by competitive RT-PCR.

To determine the effect of progesterone on the CFTR mRNA level in glandular epithelial cells of guinea-pig endometrium, a competitive RT-PCR was developed using an an internal standard a competitor with the same sequence as CFTR RNA except for a 20 nucleotide insertion. Using this method, the results showed that the CFTR mRNA level decreased in cells treated with estradiol plus progesterone compared to cells receiving estradiol alone. The decrease in CFTR mRNA level was maximal at 12 h incubation and was 27.3% of the CFTR mRNA level in estradiol-treated cells. The effect of progesterone was mimicked by the progestagen, R5020 and was inhibited by antiprogestins, RU 38,486 and ZK 98,299. Results are discussed in relation to the changes taking place in the endometrium in preparation for implantation of the embryo.

Animals↗
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↗