Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 44-year-old woman with AML, while receiving a conditioning treatment with BU-CY for an allogeneic sibling transplant, developed septic shock with pulmonary embolism and heart failure. Conditioning was stopped at the end of the busulfan course and cyclophosphamide omitted. After antibiotics, dopamine and steroids the patient was allografted, using the donor's G-CSF-primed PBSC. She recovered her peripheral blood counts promptly and developed an acute GVHD grade II that responded to steroids. The DNA microsatellite analysis showed full donor engraftment up to a year from transplantation. This case suggests that the use of PBSC may facilitate engraftment in the absence of an effective immunosuppression during conditioning.
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PMID:Successful engraftment of allogeneic PBSC after conditioning with busulfan alone. 908 42

1. We evaluated responses of peripheral resistance arterial smooth muscle to alpha 1-adrenoceptor stimulation in a rat model of heart failure in relation to neurohumoral changes, wall structure, receptor density and cellular calcium handling. 2. Plasma samples and third order mesenteric artery side-branches were obtained from Wistar rats after induction of left ventricular infarction (M1) or sham surgery. Vessels were denuded of endothelium, sympathectomized, depleted of neuropeptides, and mounted in a myograph for recording of isometric force development in response to calcium, agonist and high potassium. Also, the morphology of these preparations was determined. Separate vessel segments were used in radioligand binding assays with [1H]-prazosin. 3. At 1 week after MI, circulating plasma levels of adrenaline, angiotensin II, atrial natriuretic factor (ANF) and vasopressin were significantly elevated. At 5 weeks only a significant elevation of ANF persisted. 4. At 5 weeks after MI, the structure of the vessels and responsiveness to high potassium or Bay K 8466 (10(6) mol l-1) were not modified. Yet, at this stage, sensitivity to phenylephrine was increased (pD2: 6.24 +/- 0.04 vs 5.98 +/- 0.04 for controls) while maximal contractile responses to phenylephrine in the presence of 2.5 mmol l-1 calcium (2.26 +/- 0.28 vs 3.53 +/- 0.34 N m-1) and the sensitivity to calcium in the presence of phenylephrine (pD2: 2.81 +/- 0.22 vs 3.74 +/- 0.16) were reduced. Responses to the agonist in calcium-free solution and the calcium sensitivity in the presence of 125 mmol l-1 potassium or of phorbol myristate acetate (PMA, 10(-6) mol l-1) were not altered. 5. At 5 weeks after MI, the density of prazosin binding sites was not reduced (4.04 +/- 1.40 vs 2.29 +/- 0.21 fmol microgram-1 DNA in controls). 6. In conclusion, myocardial infarction leads in the rat to a reduction of contractile responses of mesenteric resistance arterial smooth muscle to alpha 1-adrenoceptor stimulation. This seems to involve impaired agonist-stimulated calcium influx.
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PMID:Reduced responsiveness of rat mesenteric resistance artery smooth muscle to phenylephrine and calcium following myocardial infarction. 911 72

Two families of nuclear receptors for retinoic acid (RA) have been characterized. Members of the RAR family (types alpha, beta and gamma and their isoforms alpha 1, alpha 2, beta 1 to beta 4, and gamma 1 and gamma 2) are activated by most physiologically occurring retinoids (all-trans RA, 9-cis RA, 4oxo RA and 3,4 dihyroRA). In contrast, members of the RXR family (types alpha, beta and gamma and their isoforms) are activated by 9cis-RA only. In addition to the multiplicity of receptors, the complexity of retinoid signalling is further increased by the fact that, at least in vitro, RARs bind to their cognate response elements as heterodimers with RXRs. Moreover, RXRs can also bind, in vitro, to some DNA elements as homodimers, and are heterodimeric partners for other nuclear receptors, including TRs, VDR, PPARs and a number of orphan nuclear receptors. To evaluate the functions of the different RARs and RXRs types and isoforms, we have generated null mutant mice by targeted gene disruption in ES cells. As to the functions of RARs, we found that RAR alpha 1 and RAR gamma 2 null mutant mice are apparently normal. Mice deficient in RAR alpha or RAR gamma (i.e., all alpha or gamma isoforms disrupted) show aspects of the post-natal vitamin A deficiency (VAD) syndrome which can be cured or prevented by RA, including post-natal lethality, poor weight gain and male sterility. RAR beta 2 (and RAR beta) null mutants display a retrolenticular membrane which represents the most frequent defect of the fetal VAD syndrome. That these abnormalities were restricted to a small subset of the tissues normally expressing these receptors suggested that some degree of functional redundancy should exist in the RAR family. To test this hypothesis we then generated RAR double null mutants. RAR alpha beta, RAR alpha gamma and RAR beta gamma compound mutants exhibit all the malformations of the fetal VAD syndrome, thus demonstrating that RA is the vitamin A derivative which plays a crucial role at many different stages and in different structures during organogenesis. Interestingly, almost all the structures derived from mesenchymal neural crests cells (NCC) are affected in RAR compound mutants. As to the functions of RXRs, RXR gamma null mutants are viable, fertile and morphologically normal. In contrast, RXR alpha null fetuses display a thin ventricular wall and die in utero from cardiac failure. A myocardial hypoplasia has also been observed in some RAR compound mutants as well as in VAD fetuses. Thus, RXR alpha seems to act as an inhibitor of ventricular cardiocyte differentiation and/or as a positive regulator of their proliferation, and these functions might involve heterodimerization with RARs and activation by RA. RXR beta null mutants are viable but the males are sterile, most probably because of an abnormal lipid metabolism in the Sertoli cells. New abnormalities, absent in RXR alpha mutants, are generated in RXR alpha/RAR (alpha, beta or gamma) compound mutants. All these abnormalities are also seen in RAR double mutants as well as in VAD fetuses. In contrast, such manifestations of synergism are not observed between the RXR beta or RXR gamma and the RAR (alpha, beta or gamma) null mutations. These data strongly support the conclusion that RXR alpha/RAR heterodimers represent the main functional units of the RA signalling pathway during embryonic development. Moreover, since RXR gamma-/-/RXR beta-/-/RXR alpha +/-mutants are viable, a single allele of RXR alpha can perform most of the developmental RXR functions.
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PMID:[Genetic control of the development by retinoic acid]. 918 Nov 29

A 46-year-old man was admitted to our clinic because of acute heart failure. Six years before admission he was pointed out cardiomegary and hematuria. One year later, he was diagnosed as having jugular foramen syndrome. On admission, he had a fever and dyspnea. Pansystolic blowing murmur was audible at the apex. The chest ratio on his chest X-ray was 52.5%. An electrocardiogram showed left ventricular hypertrophy. An echocardiogram showed marked dilatation and severe dysfunction of left ventricle. Radionuclide scanning with technetium 99 m pyrophosphate identified inflammatory change in the apex. Myocardial biopsy showed fibrotic degeneration and IgG deposits in myocardium. Blood examination showed anemia, lymphopenia. positive anti-nuclear antibody (1000 times, shaggy pattern), positive anti ds-DNA antibody and hypocomplementemia. Furthermore, proteinuria was pointed out. Renal biopsy showed focal segmental glomerulonephritis with active necrotizing lesion (type III nephritis). Lupus myocarditis and nephritis was diagnosed. After prednisolone (80 mg/day) was administered. left ventricular function and hypocomplementemia improved. The ACE inhibitor was also used for proteinuria. In spite of a little amount of blood transfusion, he showed hepatic hemosiderosis. We suspect that the cause of hemosiderosis was related chronic inflammation of active lupus. It was treated with Erythropoietin.
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PMID:[A case of lupus myocarditis and nephritis with transient foramen jugular syndrome]. 939 74

Although relatively uncommon among cardiac diseases, myocarditis may often have significant sequelea, including heart failure and death. The development of a murine model and the use of myocardial biopsy and Dallas criteria have broadened our understanding of myocarditis and its manifestations. Regrettably, little can still be done to alter the natural course of the disease. The results of the Myocarditis Treatment Trial do not support routine treatment with immunosuppressive drugs for all patients with myocarditis, however the study did not incorporate methods of viral (DNA or RNA) identification or immunohistochemical techniques. Specific viral myocarditis diagnosis, by polymerase chain reaction or in situ hybridization, together with immunohistochemical markers, may help classify patients according to acute or chronic myocarditis and by etiology, and possibly identify subgroups of patients who would be most likely to benefit from immunosuppression. Some important questions regarding therapy for myocarditis may be answered by the ongoing European Study of the Epidemiology and Treatment of Cardiac Inflammatory Disease, while others still await double-blind controlled confirmation. In the interim, therapy is being directed towards the management of symptoms and complications, using conventional medical regimens for heart failure.
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PMID:Is immunosuppressive treatment an option for myocarditis? 943 18

Mitochondrial disorders are a group of diseases that can affect virtually all organ systems. A 19 year old man was seen in 1993 with neurologic abnormalities consisting of impaired function of muscles, diplopia, progressive loss of vision, impaired phonation and swallowing, during the last 10 years. Physical examination disclosed moderate wasting of the four limb muscles, mild motor weakness of neck muscles, symmetrical hyporeflexia, cerebellar dysfunction, severe external ophtalmoplegia and ptosis. Fundii oculi examination showed retinitis pigmentosa. The electromyogram demonstrated myopathic changes with normal nerve conduction velocities. The cerebrospinal fluid was normal, except for a mild increase in lactic acid. Histochemical study of a muscle biopsy specimen demonstrated ragged red fibers and increase of the subsarcolemal oxidative activity of mitochondriae. The diagnosis of Kearns-Sayre disease was confirmed and he was discharged advising physical therapy. On February 1995, he was again admitted, this time with right cardiac failure and worsening of all his previous symptoms and signs. He complained of myalgias and his muscle weakness was more striking on clinical examination. Echocardiography showed biventricular dilatation and left ventricular hypertrophy with preserved systolic function. A new muscle biopsy revealed an heteroplasmic deletion of 5 Kb with 80% of mutant mitochondrial DNA. In brief, we report a patient with the clinical phenotype of Kearns-Sayre syndrome who presented an acute congestive cardiac failure due to cardiomyopathy, an association which has seldom been, reported in the literature.
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PMID:[Severe cardiac failure in Kearns-Sayre syndrome]. 943 73

Duchenne and Becker muscular dystrophies (DMD and BMD, respectively) are the most common inherited muscular diseases and caused by mutations in the dystrophin gene. Half to two-thirds of DMD and BMD patients carry deletions (usually of several kilobases of genomic DNA). The clinical progression in DMD and BMD patients with deletions can be predicted in 92% of cases based on whether the deletion maintains or disrupts the translational reading frame (frame-shift hypothesis). However, some exceptional cases have been reported; BMD cases whose dystrophin gene exons 3 to 7 were deleted (out-of-frame), more severe case whose dystrophin gene deletion maintains reading frame but includes N-terminal region, and so on. Splicing mutation is one kind of mutations of dystrophin gene, and usually induced by small mutation of exon-intron boundary sequence. However, intraexonal small mutation also induces exon skipping, due to disruption of exon recognition sequence, which is intraexonal sequence and necessary for splicing of the upstream intron. For molecular diagnosis of DMD/BMD it is important to analyze not only in genomic DNA level, but also in mRNA, protein, and clinical levels. And the relationship between molecular abnormality and clinical phenotype should be examined, especially when extramuscular symptoms (heart failure and mental retardation) are prominent.
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PMID:[Molecular genetics and problems found in genetic diagnosis of Duchenne Becker muscular dystrophy]. 943 21

Carvedilol, a new vasodilating beta-adrenoceptor antagonist and a potent antioxidant, produces a high degree of cardioprotection in a variety of experimental models of ischemic cardiac injury. Recent clinical studies in patients with heart failure have demonstrated that carvedilol reduces morbidity and mortality and inhibits cardiac remodeling. The present study was designed to explore whether the protective effects of carvedilol on the ischemic myocardium include inhibition of apoptosis of cardiomyocytes and, if so, to determine its mechanism of action. Anesthetized rabbits were subjected to 30 minutes of coronary artery occlusion followed by 4 hours of reperfusion. Detection of apoptosis of cardiomyocytes was based on the presence of nucleosomal DNA fragments on agarose gels (DNA ladder) and in situ nick end labeling. Carvedilol (1 mg/kg IV), administered 5 minutes before reperfusion, reduced the number of apoptotic myocytes in the ischemic area from 14.7 +/- 0.4% to 3.4 +/- 1.8% (77% reduction, P<.001). Propranolol, administered at equipotent beta-blocking dosage, reduced the number of apoptotic myocytes to 8.9 +/- 2.1% (39% reduction, P<.05). DNA ladders were observed in the hearts of all six vehicle-treated rabbits but only one of six carvedilol-treated rabbits (P<.01). Immunocytochemical analysis of rabbit hearts demonstrated an upregulation of Fas protein in ischemic cardiomyocytes, and treatment with carvedilol reduced both the intensity of staining as well as the area stained. Myocardial ischemia/reperfusion led to a rapid activation of stress-activated protein kinase (SAPK) in the ischemic area but not in nonischemic regions. SAPK activity was increased from 2.1 +/- 0.3 mU/mg (basal) to 8.9 +/- 0.8 mU/mg after 30 minutes of ischemia followed by 20 minutes of reperfusion. Carvedilol inhibited the activation of SAPK by 53.4 +/- 6.5% (P<.05). Under the same conditions, propranolol (1 mg/kg) had no effect on SAPK activation. Taken together, these results suggest that carvedilol prevents myocardial ischemia/reperfusion-induced apoptosis in cardiomyocytes possibly by downregulation of the SAPK signaling pathway, by inhibition of Fas receptor expression, and by beta-adrenergic blockade. The former two actions represent novel and important mechanisms that may contribute to the cardioprotective effects of carvedilol.
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PMID:Possible involvement of stress-activated protein kinase signaling pathway and Fas receptor expression in prevention of ischemia/reperfusion-induced cardiomyocyte apoptosis by carvedilol. 946 87

Duchenne/Becker muscular dystrophies (DMD/BMD) are the most common inherited muscular disease and caused by mutations in the dystrophin gene. A half to two-thirds of DMD and BMD patients carry deletions (usually of several kilobases of genomic DNA). The clinical progression in DMD and BMD patients with deletions can be predicted in 92% of cases based on whether the deletion maintains or disrupts the translational reading frame (frame-shift hypothesis). However, some exceptional cases have been reported in which some posttranscriptional modifications were suggested, such as alternative splicing and reinitiation of translation. Splicing mutation is one kind of mutations of dystrophin gene, and usually induced by a small mutation of exon-intron boundary sequence. However, intraexonal small mutation also induces exon skipping, due to disruption of an exon recognition sequence, which is an intraexonal sequence and necessary for splicing of the upstream intron. Carrier diagnosis is one of the important clinical application of genetic diagnosis. In the case of DMD/BMD with deletions of the dystrophin gene, carrier diagnosis is difficult because of the existence of normal X chromosome. In these cases a linkage analysis is useful, and in some cases non-carriers can be directly diagnosed on the basis of microsattelite polymorphism detected in deleted region of patient. For the molecular diagnosis of DMD/BMD it is important to analyze not only at the genomic DNA level, but also at the mRNA, protein, and clinical levels. And the relationship between the molecular abnormality and clinical phenotype should be examined, especially extramuscular symptoms such as heart failure and mental retardation.
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PMID:[Genetic diagnosis of Duchenne/Becker muscular dystrophy; clinical application and problems]. 954 79

Endothelin-1 (ET-1) is a peptide hormone with potent vasoconstrictor properties that is synthesized and secreted predominantly by vascular endothelial cells. Its production is regulated by numerous stimuli including ischemia and hypoxia, and the enhanced levels that occur during myocardial ischemia may contribute to the progression of heart failure. We previously reported that ET-1 expression was induced by both hypoxia and transition metals in endothelial cells (ECs). Here we define an element in the proximal promoter of the ET-1 gene that is responsible for this induction. By using deletions and site directed mutagenesis of the human ET-1 promoter, in combination with electrophoretic gel mobility shifts and transient expression assays in human ECs, we identified an active hypoxia-inducible factor 1 (HIF-1) binding site starting at position -118 upstream of the transcription start site on the non-coding DNA strand. Mutation of this site eliminated induction by hypoxia without affecting basal (aerobic) expression, and the mutated sequence did not display hypoxia-specific binding of HIF-1.
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PMID:Hypoxia regulates expression of the endothelin-1 gene through a proximal hypoxia-inducible factor-1 binding site on the antisense strand. 958 11


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