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Biomedical subjects

J Jung

Publications and source records attributed to J Jung.

At least 73 records · Page 4Linked to original sources

Small terminal deletion of 1p and duplication of 1q: cytogenetics, FISH studies, and clinical observations at newborn and at age 16 years.

A small, extra chromosome segment added to 1p was found by Q-banding 16 years ago in a newborn baby with low birth weight, short stature, wide open fontanelle, small palpebral fissures, depressed nose bridge, and inguinal hernia. This chromosome abnormality has been characterized recently with G-banding and fluorescence in situ hybridization using multiple DNA probes. The karyotype is now described as 46,XY, der(1)(qter-->p36.13::q42.3-->qter), representing a small deletion of 1p36.13-pter and a small duplication of 1q42.3-qter. Re-examination of this patient at age 16 years showed marked psychomotor delay, severely accentuated dorsal kyphosis and scoliosis, pectus excavatum, and other anomalies but no clinical signs of neuroblastoma. Comparison of the clinical findings in this case with those described in the patients having either a deletion of 1p36-pter or a duplication of 1q42-qter further illustrated the complexity of the genotype-phenotype relationship.

Adolescent↗

Initiation of mammalian liver development from endoderm by fibroblast growth factors.

The signaling molecules that elicit embryonic induction of the liver from the mammalian gut endoderm or induction of other gut-derived organs are unknown. Close proximity of cardiac mesoderm, which expresses fibroblast growth factors (FGFs) 1, 2, and 8, causes the foregut endoderm to develop into the liver. Treatment of isolated foregut endoderm from mouse embryos with FGF1 or FGF2, but not FGF8, was sufficient to replace cardiac mesoderm as an inducer of the liver gene expression program, the latter being the first step of hepatogenesis. The hepatogenic response was restricted to endoderm tissue, which selectively coexpresses FGF receptors 1 and 4. Further studies with FGFs and their specific inhibitors showed that FGF8 contributes to the morphogenetic outgrowth of the hepatic endoderm. Thus, different FGF signals appear to initiate distinct phases of liver development during mammalian organogenesis.

Animals↗

The atrial defibrillator: a stand-alone device or part of a combined dual-chamber system?

Atrial fibrillation (AF) is an extremely common arrhythmia seen in clinical practice. Because of the limited efficacy of traditional therapeutic strategies to restore and maintain normal sinus rhythm, several nonpharmacologic options have evolved. The promising results achieved with internal atrial defibrillation have facilitated the development of an implantable atrial defibrilator. Preliminary results obtained from an initial study on a small number of highly selected patients with refractory AF suggest that atrial defibrillation can be performed effectively and safely with adequate patient tolerance by using a stand-alone device. The extension of this therapy will depend on the results of well-designed prospective studies comparing this new therapeutic option with traditional methods. Several acute studies have shown that internal conversion of AF is feasible at low energies with current endocardial transvenous lead configurations primarily designed for ventricular defibrillation, but long-term efficacy has, to date, only been demonstrated with atrial implantable defibrillator lead systems. As AF is a frequent arrhythmia in implantable cardioverter defibrillator (ICD) recipients, it would seem desirable to incorporate the capability for atrial defibrillation into an ICD. Clinical studies have shown that an atrial defibrillator, as part of a combined dual-chamber ICD system, may not require a potentially complicated switching network for establishing different electrode configurations for atrial and ventricular tachyarrhythmia. The efficacy in atrial cardioversion of such a combined, less complex device seems to be as high as reported for a pure atrial defibrillator, but generally at somewhat higher energy requirements. The results of further investigations will show whether a dual-chamber cardioverter defibrillator would be of clinical relevance in patients with ventricular and supraventricular tachyarrhythmia.

Atrial Fibrillation↗

Safety and efficacy of implantable defibrillator therapy with programmed shock energy at twice the augmented step-down defibrillation threshold: results of the prospective, randomized, multicenter Low-Energy Endotak Trial.

Whether the safety and efficacy of implantable cardioverter defibrillator (ICD) therapy can be assured with lower output devices is an important question. The purpose of this study was to evaluate whether programming the device output at twice the augmented defibrillation threshold was as safe and effective as using the maximum energy. Patients indicated for ICD therapy, but without slow monomorphic ventricular tachycardia (MVT), who achieved an augmented defibrillation threshold (DFT plus) < or = 15 joules (J) with a single endocardial lead system and a biphasic defibrillator were included in the study. Prior to ICD implantation, patients were randomized into 2 groups. The shock energies in test group patient were set as follows: first shock at twice DFT plus, the second to fifth shocks at maximum output (34 J). In control group patients, all shocks were programmed at 34 J. The study population consisted of 166 consecutive patients (mean age 57.4 +/- 12.1 years, mean left ventricular ejection fraction 36.8 +/- 13.8%). Mean DFT plus was 9.6 +/- 3.2 J in test group patients and 10.1 +/- 3.5 J in control group patients (p = 0.36). During a mean follow-up of 24.2 +/- 9.6 months, 736 arrhythmia episodes were analyzed. The first shock efficacy was 98.3% in the test group patients versus 97.4% in the control group (p = 0.45). Total mortality was 6%, equally distributed in both study groups. The results of this study prove that the method of doubling the defibrillation energy at the DFT plus level provides an adequate safety margin in defibrillator therapy.

Adult↗

Capsaicin binds to the intracellular domain of the capsaicin-activated ion channel.

Capsaicin (CAP) excites small sensory neurons, causing pain, neurogenic inflammation, and other visceral reflexes. These effects have been proposed to be the result of CAP activation of a nonselective cation current. It is generally assumed that CAP binds to an extracellular domain of the membrane receptor. However, the exact binding site is not known because of the lipophilic nature of CAP. To determine whether the binding domain is extracellular or intracellular, we tested the effect of a synthetic water-soluble CAP analog, DA-5018.HCl, on current activation. CAP activated the 45 pS (at -60 mV) nonselective cation channel from either side of the membrane. However, DA-5018.HCl, which had a greater potency and efficacy than CAP, activated the channels only from the cytosolic side of the patch membrane in a capsazepine, a CAP receptor antagonist, reversible manner. When applied extracellularly, DA-5018. HCl did not, but CAP did, activate whole-cell currents in sensory neurons, as well as in oocytes expressing vanilloid receptor 1, a recently cloned CAP receptor. Hydrogen ions, reported as a possible endogenous activator of cation current, failed to elicit any current when acidic medium (pH 5.0-6.0) was applied intracellularly, indicating that H+ does not mediate the CAP effect. These results indicate that CAP and its analog bind to the cytosolic domain of the CAP receptor and suggest that an endogenous CAP-like substance other than H+ may be present in the cell.

Animals↗

[Is ICD-programming for double intraoperative defibrillation threshold energy safe and effective during long-time follow-up? Results of a prospective randomized multicenter study (Low-Energy Endotak Trial--LEET)].

The aim of this prospective and randomized study was to evaluate the safety and efficacy of a reduced shock strength in transvenous implantable defibrillator therapy. So far clinical data concerning the safety margin of the shock energy in ICD therapy do not exist. The shock energy tested during long-term follow-up in this study was twice the intraoperatively measured defibrillation threshold (DFT). A total number of 176 consecutive patients representing a typical cohort of ICD patients were evaluated. All patients received a non-thoracotomy lead system (CPI, Endotak 0070, 0090) and a biphasic cardioverter-defibrillator with the ability to store episodes (Cardiac Pacemakers Inc., Ventac TM PRx II, PRx III). The intraoperative defibrillation threshold (DFT) was evaluated in a step-down protocol (15, 10, 8, 5 J) and had to be < or = 15 J for inclusion into the study. The lowest effective energy terminating induced ventricular fibrillation had to be confirmed and was defined as DFT+ augmented defibrillation threshold. The DFT+ value was tested immediately after successful implantation, at discharge, and after a follow-up period of one year. Prior to implantation the patients were randomized into two groups. The energy of the first shock in the study group was programmed at twice DFT+ and in the control group at the maximum energy output (34 J). The efficacy of the first shock and its reproducibility in DFT testings and in spontaneous episodes during long-term follow-up of the study group were compared to those in the control group. A DFT+ value was found to be < or = 15 J in 166 of 176 patients (94%). The DFT+ in the study group was 9.6 +/- 3.2; in control group 10.1 +/- 3.5 J. The prohability of successful defibrillation at DFT+ level after one year was 84%. The success rate of the first shock meant to terminate induced ventricular fibrillation (VF) was 99.5% in the study group (217 of 218 episodes) and 99% in the control group (201 of 203 episodes). During follow-up of 24 +/- 9 months spontaneous episodes in the study group, 83/86 (96.5%) monomorphic ventricular tachycardias (MVT) and 38/40 (95%) VF-episodes were converted successfully by the 2x DFT+ shock. In the control group the first shock was successful in 151/156 (96.8%) spontaneous MVTs and in 30/33 (91%) VF episodes. The efficacy of the first shock was not influenced by clinical data such as the underlying cardiac disease, left ventricular function, ongoing antiarrhythmic therapy with amiodarone, or the number of spontaneous episodes per day or by the DFT itself. At a mean follow-up of two years there was no significant difference between the two groups concerning the incidence of sudden cardiac death (2.4% in the study group vs. 3.8% in the control group). In conclusion programming the first shock with the ICD lead system used in this study at 2x DFT+ is as efficient as a shock energy of 34 J in order to terminate induced and spontaneous episodes of VT/VF. Thus, the safety of ICD-therapy is not impaired when programming the shock energy at the 2x DFT+ value.

Defibrillators, Implantable↗

Transvenous atrial cardioversion threshold in patients with implantable cardioverter defibrillator: influence of active pectoral can.

Recent studies have shown that transvenous atrial cardioversion is feasible with lead configurations primarily designed for implantable cardioverter defibrillators (ICD). The purpose of this study was to examine the influence of an active pectoral ICD can on the atrial cardioversion threshold (ADFT). Forty consecutive patients received a transvenous single lead system (Endotak DSP 0125, CPI, St. Paul, MN, USA) in combination with a left subpectoral ICD (Ventak Mini, CPI) for treatment of malignant ventricular tachyarrhythmias. Patients were randomized into two groups: 21 received a Hot Can 1743 and 19 patients a Cold Can 1741. Step-down testing of the ventricular defibrillation threshold (VDFT) was performed intraoperatively and evaluation of the ADFT for induced atrial fibrillation (AF) at predischarge. After testing, each patient received a 2-J shock and was asked to quantify discomfort on a numerical scale ranging from 0 to 10. Both groups were comparable with regard to all clinical parameters studied. The mean VDFT in patients with a Hot Can device was significantly lower than in patients with a Cold Can (7.5 +/- 2.3 J vs 9.8 +/- 3.8 J; P < 0.03). The mean ADFT in the Hot Can group tended to be lower than in the group with Cold Cans (3.4 +/- 1.4 J vs 4.5 +/- 2.4 J; P = 0.07), and the proportion of patients in whom atrial cardioversion was accomplished at low energies (< or = 3 J) was higher in patients with active compared with patients with inactive pulse generators (57% vs 26%; P < 0.04). The mean discomfort reported after delivery of a 2-J shock was comparable in both groups (Hot Can 5.2 +/- 1.9; Cold Can: 5.3 +/- 2.1; P = NS). We conclude that the inclusion of an active left subpectoral can in the defibrillation vector of a ventricular ICD seems to reduce the energy requirements for atrial cardioversion without increasing the discomfort caused by low energy shocks.

Atrial Fibrillation↗

Isolation of a novel auxin receptor from soluble fractions of rice (Oryza sativa L.) shoots.

An auxin binding protein (ABP) was isolated from the shoots of rice seedlings and characterized. The ABP was found to be a monomer with a molecular mass of 57 kDa and play a crucial role via auxin binding in regulating H+ translocation activity of the plasma membrane in a typical biphasic manner. The results of binding equilibrium experiments indicate that the ABP binds indole 3-acetic acid with a high affinity (Kd = 1.9 x 10(-8) M), having four primary binding sites for auxin and some secondary sites with low auxin affinities. The ABP appears to have an unambiguous auxin receptor function.

Binding Sites↗

Chromatin structure and functional analysis of the mouse HNF3alpha gene.

The transcription factor HNF3alpha is a member of the winged-helix family of regulatory proteins. It is expressed in the definitive endoderm, notochord, and neural tube in embryos, but in the adult is expressed primarily in endoderm-derived tissues such as liver, lung, and pancreas. We present here the cloning of the mouse HNF3alpha gene and a characterization of its chromatin structure and regulatory sequences. The HNF3alpha gene is encoded by two exons and its transcription initiates at multiple start sites at a TATA-less promoter that is highly conserved between mouse and rat. We found different patterns of DNaseI hypersensitive sites in HNF3alpha gene chromatin in different adult tissues in which HNF3alpha is expressed, suggesting distinct regulatory mechanisms occurring within different tissue derivatives of the endoderm germ layer. Cell transfection data indicate that sequences spanning certain upstream hypersensitive sites can enhance transcription from the HNF3alpha promoter, but only when stably integrated into chromatin and not when transiently transfected. The results suggest a complex regulatory interplay between distinct genetic regulatory sequences that function specifically in chromatin.

Animals↗

Stress-induced neuroendocrine modulation of viral pathogenesis and immunity.

Physical restraint (RST) was used to examine the interactions among the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system, and the immune response to infection. In these studies, mice were infected with either herpes simplex virus (HSV) or influenza A/PR8 virus so that the impact of neuroendocrine activation could be assessed on disease pathophysiology and anti-viral immunity. RST suppressed lymphadenopathy in draining lymph nodes, reduced mononuclear cellular infiltration in the lungs, and suppressed virus-specific cytokine and cytolytic T-cell responses. Blockade of type II glucocorticoid receptors (by RU486) restored cellularity and cytokine responses to both organs in restraint-stressed, infected mice. Thus, the HPA axis modulated cell trafficking and T-cell cytokine responses. However, RU486 treatment failed to restore cytolytic T-cell responses. Blockade of beta-adrenergic receptors (by nadolol), in combination with RU486 treatment, fully restored cytolytic T-cell responses, suggesting that catecholamines were involved in suppressing the virus-specific CD8+ cytolytic T-cell response. RST also modulated the local development or expression of antibody-secreting cells (ASC) in the lungs draining lymph nodes, and spleen following infection of restrained mice. RST significantly suppressed the number of virus-specific ASC (IgM, IgG and subclasses IgG1 and IgG2a) in the lungs, mediastinal (MLN) lymph nodes and spleen, while it enhanced the responses in the superficial cervical (SCV) lymph nodes. This observation of differential modulation of ASC responses in the MLN and SCV lymph nodes supports the concept of tissue-specific immunoregulation in response to stress.

Animals↗

Nucleotide and deduced amino acid sequences of rat myosin binding protein H (MyBP-H).

The complete nucleotide sequence of the cDNA clone encoding rat skeletal muscle myosin-binding protein H (MyBP-H) was determined and amino acid sequence was deduced from the nucleotide sequence (GenBank accession number AF077338). The full-length cDNA of 1782 base pairs(bp) contains a single open reading frame of 1454 bp encoding a rat MyBP-H protein of the predicted molecular mass 52.7 kDa and includes the common consensus 'CA__TG' protein binding motif. The cDNA sequence of rat MyBP-H show 92%, 84% and 41% homology with those of mouse, human and chicken, respectively. The protein contains tandem internal motifs array (-FN III-Ig C2-FN III-Ig C2-) in the C-terminal region which resembles to the immunoglobulin superfamily C2 and fibronectin type III motifs. The amino acid sequence of the C-terminal Ig C2 was highly conserved among MyBPs family and other thick filament binding proteins, suggesting that the C-terminal Ig C2 might play an important role in its function. All proteins belonging to MyBP-H member contains 'RKPS' sequence which is assumed to be cAMP- and cGMP-dependent protein kinase A phosphorylation site. Computer analysis of the primary sequence of rat MyBP-H predicted 11 protein kinase C (PKC) phosphorylation site, 7 casein kinase II (CK2) phosphorylation site and 4 N-myristoylation site.

Amino Acid Sequence↗

[Reproducibility of the effectiveness of defibrillation for terminating induced ventricular fibrillation using intraoperatively measured defibrillation threshold energy in patients with implanted cardioverter-defibrillator].

The aim of the present study was to assess the long-term reproducibility of the defibrillation efficacy of energies set at the intraoperatively measured defibrillation threshold using a modified testing protocol. Between December 1993 and January 1996, 83 patients receiving an implantable cardioverter-defibrillator (ICD) in combination with a non-thoracotomy lead system and having an intraoperatively measured defibrillation threshold (DFT) < or = 15 J were enrolled in a substudy of a prospective, randomized multicenter trial ("Low Energy Endotak Trial" (LEET)). Step-down DFT testing was performed intraoperatively (15, 10, 8, 5 J). It was mandatory to reproduce a successful conversion of ventricular fibrillation at the DFT energy during implantation (DFT+). At the end of implantation, at predischarge, and after one year, assessment of the defibrillation efficacy of DFT+ energy was repeated (first shock: DFT+, second shock: 2 x DFT+). Mean DFT+ at implant was 9.6 + 3.3 J. Immediately after implantation, successful conversion of induced ventricular fibrillation was achieved in 70/79 (89%) patients using DFT+ energies. In 7/8 (89%) patients only the second shock set at 2 x DFT+ and in one patient only the third shock set at maximum energy (34 J) was successful. At predischarge, defibrillation efficacy of DFT+ was reproducible in 61/77 (79%) patients. The remaining 16 patients were successfully converted using a second shock set at 2 x DFT+. One year after implantation, conversion of ventricular fibrillation was achieved at energies set at DFT+ in 52/62 (84%) patients and in the remaining 10 patients at energies set at 2 x DFT+. A total of 183/218 (84%) episodes of induced ventricular fibrillation were terminated successfully using DFT+ energies. There was no correlation between the intraoperatively determined DFT+ or the underlying cardiac disease and the defibrillation efficacy. These results demonstrate that the defibrillation efficacy for termination of induced ventricular fibrillation using DFT+ energies is reproducible at implantation, at predischarge, and one year after ICD insertion. Energies set at twice DFT+ seems to allow for reliable defibrillation within the first year after ICD implantation.

Adult↗

Inhibition of immediate type allergic reactions by the aqueous extract of Kum-Hwang-San.

We studied the effect of aqueous extract of Kum-Hwang-San (KHS) on mast cell-mediated immediate type allergic reactions. KHS (1-100 microg/site) inhibited concentration-dependently mast cell-dependent ear swelling response induced by compound 48/80 (200 microg/site) in mice by both topical and intradermal application. KHS (0.1-100 microg/site) inhibited concentration-dependently passive cutaneous anaphylaxis induced by anti-dinitrophenyl (DNP) IgE in rats by both topical and intradermal application. KHS also inhibited concentration-dependently the histamine release from the rat peritoneal mast cells (RPMC) by compound 48/80 and anti-DNP IgE. Moreover, KHS had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha (TNF-alpha) secretion from RPMC. These results indicate that KHS inhibits immediate type allergic reactions by inhibition of histamine release and TNF-alpha secretion from mast cells in vivo and in vitro.

Animals↗

Assessment of intersignal variability for discrimination of atrial fibrillation from atrial flutter.

The analysis of endocardial signals obtained from an electrode located in the right atrium enabled by new dual chamber implantable cardioverter defibrillators may be helpful to provide additional therapies such as overdrive pacing or low energy atrial cardioversion for the treatment of concomitant atrial flutter (AFL) or atrial fibrillation (AF). Algorithms for discrimination of atrial tachyarrhythmias based on rate counting are of limited efficacy. The aim of this study was to assess the intersignal variability by using fast discrete wavelet transforms (FDWT) as a new method of discrimination of AF from AFL. Patients with spontaneous episodes of AF/AFL or patients who developed AF/AFL during an electrophysiological study were studied. The endocardial signals were recorded from the high right atrium using a transvenous 5 Fr bipolar electrode catheter (interelectrode spacing: 1 cm). The signals were digitized (2 kHz, 12-bit resolution) after amplification and filtering (40-500 Hz). Within data segments of 10-second duration, 25 consecutive signals were selected and normalized and FDWT was applied. Standard deviations of the wavelet coefficients (SD) from coarse scales (scale 4-8) were calculated. A total of 94 data segments (AF: 52, AFL: 42) from 28 patients were analyzed. SD at each considered scale was higher for AF than for AFL (P < 0.001). SD at scale 8 discriminated between AF from AFL with 100% sensitivity and specificity. We conclude that assessment of intersignal variability of bipolar endocardial recordings using FDWT is an effective method for the discrimination of AF from AFL. The implementation of this tool in a discrimination algorithm of an implantable device may help provide the appropriate differential therapy for atrial tachyarrhythmias.

Algorithms↗

Discrimination of sinus rhythm, atrial flutter, and atrial fibrillation using bipolar endocardial signals.

INTRODUCTION: Analysis of endocardial signals obtained from an electrode located in the right atrium as realized in newly designed dual chamber, implantable cardioverter defibrillators might be used to provide additional therapeutic options, such as overdrive pacing or low-energy atrial cardioversion for the treatment of concomitant atrial flutter (AFL) or atrial fibrillation (AF). Therefore, we developed a computer algorithm for discrimination of normal sinus rhythm (NSR), AFL, and AF that may lead to adequate differential therapy of atrial tachyarrhythmias in an automated mode. METHODS AND RESULTS: During an electrophysiologic study, bipolar endocardial signals from the high right atrium were obtained in 28 patients during sustained AFL or AF and after restoration of NSR. A total of 286 data segments of 5-second duration were recorded (NSR: 96, AFL: 86, AF: 104). Mean atrial cycle length (MCL), standard deviation of mean atrial cycle length (SDCL), and index of irregularity (IR), defined as the ratio between MCL and SDCL, were calculated for each data segment. A cutoff of 315 msec for MCL allowed discrimination of NSR from atrial tachyarrhythmias with 100% sensitivity and specificity. For discrimination of AF from AFL by using SDCL, a cutoff value of 11.5 msec led to a sensitivity of 99% and a specificity of 90%. Best discrimination of AF from AFL was found for the criterion IR > or = 7.5%, resulting in a sensitivity of 100% with a specificity of 95% for AF detection. CONCLUSION: The investigated algorithm provides discrimination of NSR, AFL, and AF with high sensitivity and specificity. Incorporation of this algorithm in an implantable automated antitachycardia device may lead to adequate differential therapy in patients suffering from spontaneous episodes of AF and AFL.

Algorithms↗

Influence of thermal stress on the incidence of acute myocardial infarction in a temperate climate.

Using a Poisson regression model the relative incidence of acute myocardial infarctions (AMI) prospectively registered in 8 hospitals within a radius of 50 km during a 2-year period was correlated with the outside conditions characterized by a complete thermophysiological model (Klima-Michel Model) defining thermal stress. An increase in the incidence of AMI related to thermal stress could be demonstrated neither by splitting the study period into 12 equally sized 'felt-temperature' classes by months of the year nor by single days. This was confirmed by correlation of the AMI rate with the mean felt-temperature level during the preceding 14 days. Thermal stress caused by the atmospheric conditions in a temperate climate may be too weak to influence significantly the incidence of AMI.

Aged↗