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PubMed1978

Valve replacement in patients with active infective endocarditis.

Eleven of 138 patients with infective endocarditis (IE) who underwent cardiac valve replacement for IE during a 12 1/2-year period had active IE. Eight of the 11 (all with aortic IE) had positive blood cultures within 48 hours preoperatively; six of the eight had positive Gram stains and cultures of the excised cardiac tissue. All 11 patients had Class IV cardiac functional disability (New York Heart Association classification) at the time of surgery. Staphylococci (three patients with Staphylococcus aureus and one with S. epidermidis) were the most frequent isolates. Three patients died; two of these three deaths occurred in patients who had a sudden onset preoperatively of severe aortic regurgitation and heart failure. In one patient (S. epidermidis infection) prosthetic valve endocarditis developed. Cardiac valve replacement may be performed successfully in patients with active IE even when blood cultures are positive in the immediate perioperative period. The hemodynamic status of patients with IE should be the determining factor in the timing of cardiac valve replacement, rather than the activity of the infection or the length of preoperative antimicrobial therapy. A radical surgical procedure may be necessary in patients with myocardial or aortic abscesses in whom conventional aortic valve replacement is not possible.

Adolescent↗
PubMed2000

Up-regulation of natriuretic peptides in the ventricle of Csx/Nkx2-5 transgenic mice.

A cardiac homeobox-containing gene Csx/Nkx2-5, which is essential for cardiac development, is abundantly expressed in the adult heart as well as in the heart primordia. Targeted disruption of this gene results in embryonic lethality due to abnormal heart morphogenesis. To elucidate the role of Csx/Nkx2-5 in the adult heart, we generated transgenic mice which overexpress human Csx/Nkx2-5. The transgene was expressed abundantly in the heart and the skeletal muscle. mRNA levels of several cardiac genes including natriuretic peptides, CARP, MLC2v, and endogenous Csx/Nkx2-5 were increased in the ventricle of the transgenic mice. Electron microscopic analysis revealed that the ventricular myocardium of the transgenic mice had many secretory granules, which disappeared after administration of vasopressin. These results suggest that Csx/Nkx2-5 regulates many cardiac genes and induces formation of secretory granules in the adult ventricle.

Animals↗
PubMed1995

Protective influence of zinc against the deleterious effects of ethanol in postimplantation rat embryos in vivo.

Zinc is a cofactor for alcohol dehydrogenase, the ethanol metabolizing enzyme. Ethanol-induced zinc deficiency could decrease ethanol metabolism, resulting in an increase in circulating and tissue ethanol levels. This may cause retardation in embryonic growth and development. The influence of zinc supplementation on ethanol-induced embryopathy was studied by the simultaneous administration of ethanol and zinc to pregnant SD rats from gestational day 6 through 12. Ethanol was given in the form of a liquid diet and zinc was administered intraperitoneally. The ethanol group received the liquid ethanol diet, the ethanol+zinc group received the ethanol diet and zinc and the pair-fed control group was given an isocaloric control diet. Embryos were explanted from all groups on day 12 of gestation. Embryos of animals treated with ethanol alone exhibited a significantly higher rate of resorption and retarded embryonic growth and development compared to the pair-fed control group. The embryonic protein content, crown-rump length, the number of somites and embryonic morphological score were significantly reduced in the ethanol-treated group. In addition, serum zinc concentration also was lower. Compared to embryos from ethanol-treated animals, embryos from ethanol+zinc treated animals showed a significantly higher number of somites; cardiac development was more advanced and embryonic protein content was higher. These observations suggest that zinc supplementation of ethanol-treated pregnant rats may have some protective influence against the embryopathic effects of ethanol.

Animals↗
PubMed2004

Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outflow tract during heart development.

Tbx2 is a member of the T-box transcription factor gene family, and is expressed in a variety of tissues and organs during embryogenesis. In the developing heart, Tbx2 is expressed in the outflow tract, inner curvature, atrioventricular canal and inflow tract, corresponding to a myocardial zone that is excluded from chamber differentiation at 9.5 days post coitus (dpc). We have used targeted mutagenesis in mice to investigate Tbx2 function. Mice heterozygous for a Tbx2 null mutation appear normal but homozygous embryos reveal a crucial role for Tbx2 during cardiac development. Morphological defects are observed in development of the atrioventricular canal and septation of the outflow tract. Molecular analysis reveals that Tbx2 is required to repress chamber differentiation in the atrioventricular canal at 9.5 dpc. Analysis of homozygous mutants also highlights a role for Tbx2 during hindlimb digit development. Despite evidence that TBX2 negatively regulates the cell cycle control genes Cdkn2a, Cdkn2b and Cdkn1a in cultured cells, there is no evidence that loss of Tbx2 function during mouse development results in increased levels of p19(ARF), p16(INK4a), p15(INK4b) or p21 expression in vivo, nor is there evidence for a genetic interaction between Tbx2 and p53.

Animals↗
PubMed2004

The transcriptional repressor Tbx3 delineates the developing central conduction system of the heart.

OBJECTIVE: The molecular mechanisms that regulate the formation of the conduction system are poorly understood. We studied the developmental expression pattern and functional aspects of the T-box transcription factor Tbx3, a novel marker for the murine central conduction system (CCS). METHODS: The patterns of expression of Tbx3, and of Cx40, Cx43, and Nppa, which are markers for atrial and ventricular chamber-type myocardium in the developing heart, were analyzed in mice by in situ hybridization and three-dimensional reconstruction analysis. The function of Tbx3 in regulating Nppa and Cx40 promoter activity was studied in vitro. RESULTS: In the formed heart, Tbx3 is expressed in the sinoatrial node (SAN), atrioventricular node (AVN), bundle and proximal bundle branches (BBs), as well as the internodal regions and the atrioventricular region. Throughout cardiac development, Tbx3 is expressed in an uninterrupted myocardial domain that extends from the sinoatrial node to the atrioventricular region. This expression domain is present in the looping heart tube from E8.5 onwards. Expression of the chamber-type myocardial markers is specifically absent from the Tbx3 expression domain. Tbx3 is able to repress Nppa and Cx40 promoter activity and abolish the synergistic activation of the Nppa promoter by Tbx5 and Nkx2.5. CONCLUSION: We identified the T-box transcription factor Tbx3 as a novel and accurate marker for the central conduction system. Our analysis implicates a role for Tbx3 in repressing a chamber-specific program of gene expression in regions from which the components of the central conduction system are subsequently formed.

Animals↗
PubMed1994

Activation of the renin-angiotensin system in heart failure and hypertrophy--studies in human hearts and transgenic rats.

Numerous in vitro studies have demonstrated that angiotensin II has distinctive cellular effects in the cardiovascular system, independent from its effects on blood pressure. These have led to the hypothesis that activation of the angiotensin system in the heart could be of functional relevance for the adaptive processes in several cardiovascular disorders, such as cardiac hypertrophy and heart failure. This concept has been supported by clinical studies showing the beneficial effects of blockers of the system such as angiotensin converting enzyme (ACE) inhibitors in these circumstances. In order to study the regulation of gene expression of renin angiotensin system components in cardiac disorders we have performed two studies. First, we investigated the gene expression of ACE in human heart failure. Results showed that the enzyme is activated locally in this condition, supporting previous studies in animals. Second, in a different approach, we asked whether the selective activation of the renin angiotensin system in the hearts of transgenic rats expressing an additional renin gene leads to the development of pathological changes in the cardiovascular system. The results of this study demonstrated that the transgenic animals developed cardiac hypertrophy and heart failure independent of the increase in blood pressure seen in these rats. Taken together, these studies provide further evidence for the functional role of local angiotensin systems in the heart.

Animals↗
PubMed1999

Inactivation of erythropoietin leads to defects in cardiac morphogenesis.

Erythropoietin is an essential growth factor that promotes survival, proliferation, and differentiation of mammalian erythroid progenitor cells. Erythropoietin(-/-) and erythropoietin receptor(-/-) mouse embryos die around embryonic day 13.5 due, in part, to failure of erythropoiesis in the fetal liver. In this study, we demonstrated a novel role of erythropoietin and erythropoietin receptor in cardiac development in vivo. We found that erythropoietin receptor is expressed in the developing murine heart in a temporal and cell type-specific manner: it is initially detected by embryonic day 10.5 and persists until day 14.5. Both erythropoietin(-/-) and erythropoietin receptor(-/-) embryos suffered from ventricular hypoplasia at day 12-13 of gestation. This defect appears to be independent from the general state of hypoxia and is likely due to a reduction in the number of proliferating cardiac myocytes in the ventricular myocardium. Cell proliferation assays revealed that erythropoietin acts as a mitogen in cells isolated from erythropoietin(-/-) mice, while it has no effect in hearts from erythropoietin receptor(-/-) animals. Erythropoietin(-/-) and erythropoietin receptor(-/-) embryos also suffered from epicardium detachment and abnormalities in the vascular network. Finally, through a series of chimeric analysis, we provided evidence that erythropoietin acts in a manner which is non-cell-autonomous. Our results elucidate a novel role of erythropoietin in cardiac morphogenesis and suggest a combination of anemia and cardiac failure as the cause of embryonic lethality in the erythropoietin(-/-) and erythropoietin receptor(-/-) animals.

Animals↗
PubMed2005

[Critical incidents during regional anesthesia in Japanese Society of Anesthesiologists-Certified Training Hospitals: an analysis of responses to the annual survey conducted between 1999 and 2002 by the Japanese Society of Anesthesiologists].

BACKGROUND: Recently, a national survey in France including 35,439 patients who had received spinal anesthesia showed that the incidences of cardiac arrest and mortality associated with spinal anesthesia were 2.5 and 0.8 per 10,000 anesthetics, respectively. In this study, we investigated these values using data obtained from annual surveys conducted by the Japanese Society of Anesthesiologist (JSA). METHODS: Since 1994, JSA has conducted annual surveys concerning critical incidents in the operating theater by sending confidential questionnaires to JSA-certified training hospitals, then collecting and analyzing the responses. We investigated critical incidents associated with regional anesthesia using data from annual surveys between 1999 and 2002. The questionnaire was identical in each survey conducted during these years. The total number of anesthetics available for this analysis was 3,855,384, of which spinal anesthesia, combined spinal-epidural anesthesia and epidural anesthesia were performed in 409,338, 146,282, and 69,001 patients, respectively. In patients receiving regional anesthesia, 628 critical incidents including 108 cardiac arrests, and 45 subsequent deaths were reported. The causes of critical incidents were classified as follows: totally attributable to anesthetic management, due mainly to intraoperative pathological events, preoperative complications, and surgical management. IP consists of coronary ischemia including coronary vasospasm not suspected preoperatively, arrhythmias including severe bradycardia, pulmonary thromboembolism, and other conditions. Mortality was determined by postoperative day 7. Statistical analysis was performed by chi-square test and Mann-Whitney test. A p value less than 0.05 was considered significant. RESULTS: The incidences of cardiac arrest and mortality due to all etiologies were 1.69 and 0.76 with spinal anesthesia, 1.78 and 0.68 with combined spinal-epidural anesthesia, and 1.88 and 0.58/10,000 anesthetics with epidural anesthesia, respectively. The incidences of cardiac arrest and mortality due to anesthetic management were 0.54 and 0.02 with spinal anesthesia, 0.55 and 0.00 with combined spinal-epidural anesthesia, and 0.72 and 0.14/10,000 anesthetics with epidural anesthesia, respectively. These values did not significantly differ among regional anesthesia. Death attributable to anesthetic management was reported in 2 patients: both patients were classified as ASA-PS 3 E, and developed cardiac arrest; one due to inadvertent high spinal anesthesia with spinal anesthesia, and the other due to local anesthetic intoxication with epidural anesthesia. Anesthetic management and intraoperative pathological events comprised 33 and 43% of cardiac arrests, respectively. The distribution of causes of death was as follows: anesthetic management, 5%; intraoperative pathological events, 34%; preoperative complications, 35%; surgical management, 26%. Among the causes of anesthetic management-induced critical incidents, inadvertent high spinal anesthesia was the leading cause of cardiac arrest in spinal and combined spinalepidural anesthesia: 90% of arrests occurred in patients with ASA-PS 1+2; 88% in patients below 65 years of age; 45 and 25% in patients undergoing hip or lower extremities surgery, and cesarean section, respectively. Among the causes of intraoperative pathological event-induced critical incidents, pulmonary thromboembolism was the leading cause of cardiac arrest in spinal and combined spinal-epidural anesthesia: 59% of arrests occurred in patients with ASA-PS 1+2; 81% in patients above 66 years of age; 91% in patients undergoing hip or lower extremity surgery. CONCLUSIONS: The incidence of cardiac arrest and mortality associated with spinal anesthesia in Japan was shown to be in the same order as in France by analyzing a larger population. In patients with good ASA-PS, critical incidents occurred more often under regional anesthesia than under general anesthesia. Inadvertent high spinal anesthesia should be carefully avoided. We should also pay much attention to subclinical deep vein thrombosis in patients who were scheduled for hip or lower extremity surgery, and tourniquet- or bone cement-associated pulmonary embolism in these patients.

Anesthesia↗
PubMed1982

Abnormal cardiac enzyme responses after strenuous exercise: alternative diagnostic aids.

Serial estimations of activities of creatine kinase and its MB isoenzyme, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase and of concentrations of alpha(1)-acid glycoprotein were performed in 15 healthy well-trained male marathon runners. Estimations were made initially within three days before a race and then one, 24, and 96 hours after the race. Technetium-99m pyrophosphate myocardial scintigraphy was carried out at the initial prerace assessment and repeated 48 to 96 hours after the race. None of the subjects developed cardiac symptoms during or after the race.Activities of creatine kinase and creatine kinase MB became maximal 24 hours after the race. One and 96 hours after the race two and five subjects, respectively, showed amounts of creatine kinase MB totalling 5% or more of total creatine kinase. Lactate dehydrogenase activity peaked at one hour after the race, and activities of aspartate and alanine aminotransferases peaked at 24 and 96 hours after the race, respectively. Activities of all these enzymes showed a significant increase from prerace values during the rest of the study. Electrocardiographic features noted were similar to those reported elsewhere in athletes under similar conditions. They included first-degree heart block, incomplete right bundle-branch block, left ventricular hypertrophy, pseudoischaemic T-wave changes, and early repolarisation of variant ST-segment elevations in precordial leads. Technetium-99m pyrophosphate myocardial scintigraphy did not show evidence of myocardial damage before or after the race. Alpha(1)-acid glycoprotein concentrations were normal throughout.These data suggest that reliance on standard enzyme estimations and electrocardiographic criteria may yield false-positive indicators of myocardial injury during prolonged strenuous exercise. Technetium-99m pyrophosphate scintigraphy and alpha(1)-acid glycoprotein measurements offer additional information and may usefully be employed in evaluating circulatory collapse associated with such exercise.

Adult↗
PubMed1997

Automated external defibrillators: design considerations.

Biphasic defibrillation waveforms are now the standard of care in clinical use for defibrillation with implantable cardioverter-defibrillators (ICDs), due to the superior performance demonstrated over that of comparable monophasic waveforms. To better understand these significantly different outcomes, ICD research has developed cardiac cell response models to defibrillation. Waveform design criteria have been derived from these first principles and have been applied to monophasic and biphasic waveforms to optimize their parameters. These principles-based design criteria have produced significant improvements over the current art of waveforms. Monophasic defibrillation waveforms remain the standard of care in clinical use for transthoracic defibrillation. Waveform design has not yet been influenced by the important gains made in ICD research. The limitations of present transthoracic waveforms may be due in part to a lack of application of these design principles to determine optimal waveform characteristics. To overcome these limitations, design principles based on cell response have recently been developed for external defibrillation waveforms. The transthoracic model incorporates elements into a cell response model that extends it to external defibrillation. External waveform design principles demonstrate reductions in capacitance, voltage, duration, and delivered energy. Therefore, design principles based on cardiac electrophysiology may provide a means to significantly reduce the energy required for safe and efficacious external defibrillation. Footnotes, formulae, and figures augment this presentation in order to clarify the defibrillation waveform theory.

Animals↗
PubMed1991

[Hospital spread of scabies from an immunocompromised patient with Norwegian scabies].

Scabies was first found in a 71-year-old female who had been diagnosed as having leukemic transformation of primary myelofibrosis and had undergone treatment for the disease. She was admitted to the hospital in December 1986, because of abdominal fullness and a generalized subcutaneous tumor that proved to be myeloblastoma. For treatment of the underlying disease, the regimen of the combination of vindesine, cyclophosphamide, 6-mercaptopurine, and prednisolone was selected. She developed cardiac failure and fell into a coma one month after starting the anticancer therapy. She was put on artificial respiration and on additional steroid therapy as well. Dexamethasone was administrated at 16 mg/day. Since the myeloblastomas found on admission regressed, the steroid therapy was continued. She was in coma for a few days before her skin lesions turned red and formed a grayish crust in the lower abdominal region. Several days later, the doctor responsible for the treatment of this patient developed pruritus and exanthema on both arms, and soon many nurses in the same hospital-ward developed similar symptoms. At approximately the same time, the patient with myelofibrosis was diagnosed as having Norwegian scabies: the crusted skin lesions revealing many Sarcoptes scabiei mites. Two doctors (2/18), 17 nurses (17/19) and 3 other patients (3/51) were found to have contracted scabies, and we recognized the hospital spread of the infection. The first patient was isolated in a private room, and we avoided direct contact with her. The persons with scabies were treated with crotamiton liniment. The first scabies patient died of cardiac failure 1 month after falling into a coma.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Organization and fine structure of a pacemaker derived from fetal rat myocardium.

At an unknown point in mammalian development, cardiac precursor cells become committed to the cardiocyte phenotype. Certain of these are believed to specialize further into pacemaker cardiocytes. By culturing explanted embryonic ventricles into in vivo organ culture (Tucker DC, Snider C, Woods WT Jr: Pediatr Res 23:637-642, 1988), we observed pacemaker cells arising apparently from cardiocytes. We hypothesized that this event can be triggered by intercellular attachments, innervation, vascularization, or other factors. The present study was designed to test the hypothesis that primitive ventricular cells in the tubular heart can organize into an anatomically and electrophysiologically distinct pacemaker structure in the absence of innervation or vascularization from extrinsic sources. Developing ventricles of tubular hearts from 10-d-old rat embryos (n = 22) were excised and incubated in culture dishes. Within each explant, a group of cells organized into a uniform cluster (diameter, 150 +/- 50 microns) after 8 +/- 2 d in culture. These cells resembled immature conduction system cells and had electrophysiologic features similar to those of mature pacemaker cells. Single-cell action potentials and impulse conduction patterns proved that the pacemaker cluster was the dominant pacemaker for the entire explant. These results confirm that, in the absence of extrinsic nerves and blood vessels, culture of the tubular ventricle elicits formation of an organized pacemaker, resembling the mature cardiac pacemaker and suggesting that contact with the culture dish surface or some other factor triggers conversion of cardiocytes to the pacemaker phenotype.

Action Potentials↗
PubMed2006

Heart muscle engineering: an update on cardiac muscle replacement therapy.

Cardiac muscle engineering aims at providing functional myocardium to repair diseased hearts and model cardiac development, physiology, and disease in vitro. Several enabling technologies have been established over the past 10 years to create functional myocardium. Although none of the presently employed technologies yields a perfect match of natural heart muscle, it can be anticipated that human heart muscle equivalents will become available after fine tuning of currently established tissue engineering concepts. This review provides an update on the state of cardiac muscle engineering and its utilization in cardiac regeneration. We discuss the application of stem cells including the allocation of autologous cell material, transgenic technologies that may improve tissue structure as well as in vivo engraftment, and vascularization concepts. We also touch on legal and economic aspects that have to be considered before engineered myocardium may eventually be applied in patients and discuss who may be a potential recipient.

Animals↗
PubMed1997

iNOS expression and nitrotyrosine formation in the myocardium in response to inflammation is controlled by the interferon regulatory transcription factor 1.

BACKGROUND: Production of NO by inducible NO synthase (iNOS) has been implicated in the pathology of spontaneous and antigen-induced autoimmune diseases, and iNOS is expressed in the myocardium of patients with heart failure. It is not clear whether inflammatory murine autoimmune heart disease, an experimental model for human postviral heart disease, is characterized by increased iNOS expression within the heart and whether iNOS and NO are essential in the pathogenesis of autoimmune myocarditis. METHODS AND RESULTS: In the murine model of cardiac myosin-induced myocarditis, we demonstrate that iNOS expression was elicited in inflammatory macrophages and in distinct cardiomyocytes. Autoimmune heart disease was accompanied by formation of the NO reaction product nitrotyrosine in inflammatory macrophages as well as in cardiomyocytes. iNOS expression and nitrotyrosine formation were strictly dependent on myocardial inflammation. Focal myocarditis was sufficient to induce nitrotyrosine formation throughout the whole heart muscle. Mice defective for the interferon regulatory transcription factor-1 (IRF-1(-/-)) after gene targeting failed to induce iNOS expression and nitrotyrosine formation in the heart but developed cardiac myosin-induced myocarditis at prevalence and severity similar to those of heterozygous littermates (IRF-1(+/-)). CONCLUSIONS: These data provide the first in vivo evidence that iNOS expression and NO synthesis in macrophages and distinct cardiomyocytes are elicited in experimental murine inflammatory heart disease. The transcription factor IRF-1 controls iNOS expression and NO synthesis in disease. Because autoimmune myocarditis can develop in animals lacking IRF-1, these mice will be useful to elucidate the link between iNOS expression in inflammatory heart disease and the development of dilated cardiomyopathy and heart failure.

Animals↗
PubMed1993

Hemodynamic monitoring during CPR.

Real-time hemodynamic monitoring provides useful information that can be used to assess and optimize mechanical and pharmacological interventions during CPR. The standard algorithms should always be the initial approach to resuscitation, because they offer a rapid, logical, coordinated series of treatments with proven success. Pressure and flow measurements during conventional, closed-chest CPR in humans indicate that the technique typically produces a hemodynamic state resembling profound cardiogenic shock, with a low systemic arterial pressure, markedly reduced cardiac output, and high intravascular filling pressures. End-tidal carbon dioxide monitoring provides useful, noninvasive information during clinical resuscitation. A low end-tidal carbon dioxide value during resuscitation should alert the rescuers that something is wrong with ventilation, perfusion, and/or carbon dioxide production and should prompt a search for correctable causes. If one or more hemodynamic parameters are being monitored at the time the patient develops cardiac arrest (eg, an intensive care unit patient who has an arterial line and a pulmonary artery catheter in place), it is appropriate for the resuscitation team to pay attention to the data that are generated during the resuscitation, particularly if the initial algorithm approach is not successful. For patients who are not being monitored at the time of their arrest, end-tidal carbon dioxide measurements provide noninvasive, semiquantitative information that can help the team detect and troubleshoot problems during resuscitation. Further research and better, more affordable technologies are needed to provide in- and out-of-hospital resuscitation teams feedback on the hemodynamic effectiveness of their resuscitative efforts.

Animals↗
PubMed1993

ANG II receptors, c-myc, and c-jun in myocytes after myocardial infarction and ventricular failure.

To determine the relationship between reactive cardiac hypertrophy and the expression of angiotensin II (ANG II) receptors in surviving myocytes after infarction, large infarcts were produced in rats that were killed 2-3 days later. Measurements of global ventricular dynamics indicated that left ventricular failure and right ventricular dysfunction occurred in experimental animals. These alterations in ventricular pump function were associated with increases in ventricular weight-to-body weight ratio, indicative of developing cardiac hypertrophy. Such a response was coupled with a 6.6-fold increase in ANG II receptor mRNA in myocytes from the left ventricle. A 2.3-fold increase in the expression of ANG II receptor in myocytes from the right ventricle was also found. Radioligand binding assay documented a 44% increase in the density of ANG II receptors on left ventricular myocytes of infarcted hearts. To establish whether the induction of genes commonly associated with myocyte hypertrophy was present, the message for c-myc and c-jun was biventricularly assessed. Myocardial infarction was accompanied by overexpressions of c-myc and c-jun that were more prominent in left than in right ventricular myocytes. In conclusion, the enhanced expression of ANG II receptor and its receptor protein and c-myc and c-jun in myocytes may participate in the reactive growth processes of these cells after infarction.

Animals↗
PubMed2006

The role of basic leucine zipper protein-mediated transcription in physiological and pathological myocardial hypertrophy.

Accumulating evidence suggests that nuclear transcription factors from the basic leucine zipper (bZIP) family play an important role in cardiac development and function. This class includes the CREB/ATF family of transcription factors, namely CREB, cAMP response element modulator (CREM), ATF, and the related AP-1 and C/EBP families. An effort has been made to elucidate the role of specific bZIP members in the heart. Unfortunately, little insight could be gained from knockout experiments, either due to embryonic lethal phenotypes or functional compensation by other bZIP family members. Surprisingly, cardiac overexpression of several inhibitory transcription factors from the bZIP family, such as a nonphosphorylatable form of CREB (CREB(ser133)), a nonfunctional isoform of CREM, or ATF3 resulted in massive atrial dilatation. In order to try and characterize this pathway we have expressed the potent bZIP inhibitory protein, Jun dimerization protein 2 (JDP2), specifically in the mouse heart in a temporally controlled manner. Expression of JDP2 resulted in massive biatrial dilatation; loss of connexin 40 (Cx40), connexin43 (Cx43), and myosin light chain 2 (MLC2a) expression; atrioventricular defects in conduction; and a lethal phenotype. All these effects were independent of any developmental events acquired during adulthood, and were totally reversible upon abolishing the bZIP inhibition. The results of this article suggest that bZIP inhibition is sufficient to cause atrial dilation, that this dilatation is acquired postnatally, and that it is reversible upon the relief of inhibition. Thus, bZIP repressors may serve as novel drug targets for the prevention of atrial dilatation a major risk of atrial fibrillation (AF).

Animals↗
PubMed2000

[Study on the epidemiological features of Kawasaki disease in Jiangsu].

OBJECTIVE: To investigate the incidence of Kawasaki disease and epidemiological characteristics in Jiangsu province. METHODS: Questionnaire and diagnostic guidelines for Kawasaki disease with color - printed photographs of typical clinical symptoms were sent to all county hospitals with pediatric beds. All the in - patients with Kawasaki disease hospitalized from January, 1993 to December, 1997 were studied regarding age, sex, season of illness, cardiac sequelae, outcome etc. RESULTS: There were 509 cases (329 males and 180 females) diagnosed with 489 cases (96%) clinically typical. The incidence of the 5 - year period was averaged 2.53 per 100,000 children under 5. The number of male patients with Kawasaki disease was higher than that in female. The age peak of incidence was between 6 month and 2 - year olds. 13.6% of all cases developed cardiac sequelae which mostly occurred in males and in those younger than 2 years of age. There was one patient recurred among total patients reported (recurrence rate 0.2%) and 2 patients died (fatality rate 0.4%). CONCLUSION: The epidemiological characteristics of Kawasaki disease in Jiangsu province were similar to those in Japan in sex, season distribution and cardiac sequelae. The number of patients in male was higher than in female. Patients were more commonly seen in spring than in winter. However, the incidence rate in Jiangsu was significantly lower than that in Japan and the age peak was between 6 month and 2 years old.

Adolescent↗