Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A naturally occurring cardiomyopathy (round heart disease) which is potentiated by inbreeding and a cardiomyopathy produced by furazolidone, a nitrofuran derivative, were studied for an associated alpha1-antitrypsin deficiency in two flocks of turkeys (one inbred for round heart disease and a commercial flock). At 4 weeks of age, the furazolidone-fed birds of both flocks demonstrated a marked increase in mortality and cardiac dilatation associated with disordered hepatic metabolism when compared with controls. Although PAS-positive, diastase-resistant globules were observed in the livers of both strains of turkeys fed furazolidone, these globules were present in lysosomes and not in the rough endoplasmic reticulum as in alpha1-antitrypsin deficiency. The control inbred birds with round heart disease did not demonstrate histologic or biochemical evidence of an alpha1-antitrypsin deficiency. It is proposed that furazolidone in the turkey produces primary hepatic damage that is reflected in lowered total serum proteins, including trypsin inhibitory capacity, and that the alterations produced by furazolidone are superimposed on round heart disease in the inbred flock.
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PMID:Furazolidone-induced cardiomyopathy in turkeys. Association with a relative alpha1-antitrypsin deficiency. 14 46

Twenty-five large broad-breasted white turkeys were fed a 22% protein diet supplemented with 500 ppm furazolidone from day 1 to 3.5 weeks of age and the same diet supplemented with 700 ppm furazolidone until 9.5 weeks of age. Following the development of round heart disease as indicated by altered electrocardiograms the 25 turkeys were sacrificed. In the livers of turkeys with biventricular dilatation (72% of cases) there was bile duct hyperlasia, portal fibrosis and intracytoplasmic globules in the hepatocytes. Globules stained pink with hematoxylin-eosin, deep red with PAS and variable with Massons trichrome stains in paraffin-embedded liver sections. Clear intracytoplasmic vacuoles demonstrable in hepatocytes of PAS stained liver sections embedded in paraffin did not stain as lipid in frozen sections but did contain sparse flocculent material in 1 micrometer sections of liver embedded in epoxy resin and stained with toluidine blue. At the subcellular level, the intracytoplasmic globules in hepatocytes were surrounded by a single membrane, contained flocculent material and had enzymatic properties characteristic of lysosomes. Blood pressure, heart rate, dp/dt max, total plasma proteins and plasma trypsin inhibitory capacity of turkeys with round heart disease were lower than corresponding values for control turkeys. Control turkeys did not exhibit the characteristic gross or microscopic lesions of round heart disease.
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PMID:Hepatitis, cardiomyopathy and hemodynamics in furazolidone-induced round heart disease of turkeys. 23 51

It is described the occurrence of dextrocardia together with the congenital cyanotic heart disease in 20 year old man included in the fruste forme of the Marfan's syndrome. The diagnosis was made by the physical examination with the evidence of the arachnodactyly by the metacarpal indices and confirmed by autopsy with the following results: dextrocardia, large atrial septal defect, common ventricle, atresia of the pulmonary artery with the collateral lung perfusion from the descending aorta. There were found neither ocular manifestations, nor unambiguous manifestations of the aortic lesions. The ultrastructural examinations showed only greater accumulation of the PAS positive substances. Dextrocardia as the cardiovascular manifestation of the Marfan's syndrome has not yet been reported in the available literature.
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PMID:Dextrocardia and Marfan's syndrome. 134 97

A newborn with severely shortened ribs, short limbs, and postaxial polydactyly died shortly after birth. Postmortem roentgenograms established the diagnosis of type 3 short rib-polydactyly (SRP) syndrome as described by Naumoff and associates. Histopathologic study showed the chondrocytes to contain previously undescribed cytoplasmic inclusion bodies that were PAS-positive and diastase-resistant. The material appeared by staining reactions to be a glycoprotein that was seen electron microscopically to accumulate within dilated cisterns of rough endoplasmic reticulum. Similar cytoplasmic inclusions have not been seen in other short rib-polydactyly syndromes, including SRP types 1 and 2, Jeune syndrome, and Ellis-van Creveld syndrome. It is often difficult to differentiate cases of type 3 and type 1 (Saldino-Noonan) syndrome, and in the past the diagnosis has sometimes been confused. A review of previously reported cases showed that type 3 syndrome rarely (1 in 13) had cloacal developmental abnormalities, which are invariably present in patients with type 1 syndrome. Type 3 is also associated with a lower incidence of congenital heart disease, and cardiac malformations, when present, differ from those associated with type 1 syndrome. Both type 3 and type type 1 SRP syndromes are transmitted in autosomal recessive fashion. Type 3 SRP syndrome has had an equal sex distribution, although type 1 has so far been reported to occur only in girls. Further investigation with additional patients is necessary to verify the above preliminary findings.
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PMID:Short rib-polydactyly syndrome, type 3 with chondrocytic inclusions: report of a case and review of the literature. 746 48

Contractile failure of myocardial cells is a common cause of mortality in ischemic heart disease. In response to hypoxic conditions, cells upregulate the activity of hypoxia-inducible factor 1 (HIF-1) and express a number of genes encoding proteins that either enhance O (2)delivery or increase cellular ATP levels. HIF-1 is a heterodimer of bHLH-PAS proteins, HIF-1 alpha and HIF-1 beta. Both subunits are constitutively expressed under normoxic conditions, but HIF-1 alpha levels are kept low by proteolytic degradation, then stabilized under conditions of low O (2)by a mechanism that is poorly understood. Here we tested the hypothesis that expression of HIF-1 alpha in cardiac cells may be affected by two known cardioprotective agents. We tested l-carnosine, a naturally occurring dipeptide which has been shown to improve myocardial contractility during hypoxia, and verapamil, a calcium channel blocker frequently prescribed for the treatment of heart disease. The levels of HIF-1 alphamRNA remained relatively stable during time course hypoxia (1% O (2)) in H9c2 cardiomyoblasts, then increased slightly after 24 h. In cells pretreated with 1 microM carnosine, the levels of mRNA were transiently reduced, but then increased after 24 h similar to the controls. The levels of HIF-1 alpha protein increased rapidly in H9c2 cells within 30 min of hypoxia, but this induction was significantly reduced in cells treated with either carnosine or verapamil. In addition, treatment of cells with these agents further reduced the low levels of HIF-1 under normoxic conditions. These results suggest that l-carnosine and verapamil may affect the regulated proteolytic degradation of HIF-1 alpha in heart cells during hypoxia.
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PMID:l-carnosine and verapamil inhibit hypoxia-induced expression of hypoxia inducible factor (HIF-1 alpha) in H9c2 cardiomyoblasts. 1188 12

Three white men, who died of a condition clinically diagnosed as alcoholic heart disease, showed virtually identical autopsy findings. These consisted of global cardiomegaly and absence of stigmata of arteriosclerotic, hypertensive, rheumatic or congenital heart disease. Histological examination revealed degenerative and occlusive changes in small branches of coronary arteries, associated with microscopic foci of heart muscle necrosis and scarring. In two of the cases the degenerative changes were severe and extensive in the atria. Edema of the arterioles in the early stages was followed by disorganization of the vessel wall and subintimal accumulation of homogeneous, smudgy, PAS (periodic acid-Schiff)-positive material. This sequence of events, which suggests increased vascular permeability, is believed to be related directly or indirectly to chronic alcohol intake.
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PMID:ALCOHOLIC CARDIOMYOPATHY. 1431 52

In human Chagas'disease previous work has shown the occurrence of a T-lymphocyte CD4-positive population (a high producer of PAS-positive glycoproteins) with evidence suggesting a role in the formation of damages to the myocardium and neural structures in chagasic heart disease (ChHD). Other workers have taken such facts into consideration and have employed gangliosides (biological substances with neurotrophic and immunomodulatory properties) in chagasics with chronic cardiomyopathy and disautonomic signs, obtaining an Improvement in functional signs and a decrease in the number of PAS+ lymphocytes. In the present work we have studied the effect of mixed gangliosides (Cronassial on cell cultures of total leukocytes, or on mononuclear cells prepared through Ficoll-Hypaque. Blood was obtained from 14 patients with ChHD. Experiments were undertaken to assess the effect of policlonal mitogens Phytohaemagglutinin (Phy) and Concanavalin A (Con A) on blastic transformation, estimated by cell size and cytologic study. In addition, the production of PAS+ substances by the lymphocytes and blast were assessed. Gangliosides were added at final concentrations of 100 mg/ml or 200 mg/ ml. Cell viability was assessed by means of the Trypan blue test. With respect to blastic transformation, results showed a significant decrease in the cultures that received gangliosides 24 hours before mltogen administration, as compared with controls (p<0.001) (both for Phy and Con A). On the other hand, the production of lymphocytic PAS+ substances decreased in the cultures of chagasics in which gangliosides were added. Some of these results confirmed previous findings on the matter. The facts suggest that gangliosides can modulate some lymphocytic activities in chagasics.
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PMID:[Gangliosides in vitro effects on lymphocytes from patients with chronic Chagas disease stimulated with mitogens or heart or brain antigens]. 1672 38

The function of the retina is sensitive to oxygen tension. Any change in the perfusion pressure of the eye affects the retina although the eye is able to autoregulate its hemodynamics. Systemic hypoxemia (lung or heart disease) or a vascular disease in the retina can cause retinal hypoxia. All the hypoxia-dependent events in cells appear to share a common denominator: hypoxia-inducible factor (HIF), which is a heterodimeric transcription factor, a protein. HIF comprises a labile alpha subunit (1-3), which is regulated, and a stable beta subunit, which is constitutively expressed. Both are helix-loop-helix factors and belong to the PAS-domain family of transcription factors. Oxygen plays the key role in stabilizing HIF-1alpha and its function. When the oxygen tension is normal, HIF-1alpha is rapidly oxidized by hydroxylase enzymes, but when cells become hypoxic, HIF-1alpha escapes the degradation and starts to accumulate, triggering the activation of a large number of genes, like vascular endothelial growth factor (VEGF) and erythropoietin. HIF-1alpha has been shown to have, either clinically or experimentally, a mediating or contributing role in several oxygen-dependent retinal diseases such as von Hippel-Lindau, proliferative diabetic retinopathy, retinopathy of prematurity and glaucoma. In retinitis pigmentosa and high-altitude retinopathy, however, the evidence is still indirect. There are three different strategies available for treating retinal diseases, which have all shown promising results: retinal cell transplantation or replacement, gene replacement, and pharmacological intervention. Specifically, recent results show that the HIF pathway can be used as a therapeutic target, although there is still a long way to go from bench to clinic. HIF can be stabilized by inhibiting prolyl hydroxylase or by blocking the VHL:HIF-alpha complex if angiogenesis is the goal, as in retinitis pigmentosa. On the other hand, the downregulation of HIF has a pivotal role if we are to inhibit neovascularization, as in proliferative diabetic retinopathy. To date, several small-molecule inhibitors of HIF have been developed and are entering clinical trials. HIF is a remarkable example of a single transcription factor that can be regarded as a "master switch" regulating all the oxygen-dependent retinal diseases.
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PMID:Oxygen-dependent diseases in the retina: role of hypoxia-inducible factors. 1675 May 26

This article reviews the changes in bronchoalveolar lavage (BAL) cytology and cell differentials in some of the rarer interstitial lung diseases. In a few of these diseases BAL has a diagnostic value and can replace lung biopsy. In pulmonary Langerhans cell histiocytosis the characteristic diagnostic finding is an increase in CD1 + Langerhans cells greater than 4% of total cells. The sensitivity of this cutoff value is low because only approximately 50% of patients show this elevation. In pulmonary alveolar proteinosis, the sensitivity of a diagnostic BAL is almost 100%, and the characteristic finding of milky and turbid fluid on gross examination and the characteristic findings with acellular globules that stain pink with PAS (periodic-acid-Schiff), along with abnormal foamy macrophages and a characteristic dirty background obviates the need for lung biopsy. In diffuse alveolar hemorrhage, BAL is the method of choice to diagnose the alveolar bleeding by showing free red blood cells and hemosiderin-laden, iron-positive macrophages. The underlying disorder has to be identified by history and clinical and laboratory tests. In eosinophilic lung disease, the diagnosis can be made if the BAL cell differentials show 25% or more eosinophils. In collagen vascular disease-associated lung fibrosis, the precise role of BAL in assessment and monitoring disease remains unclear. In drug-induced interstitial lung disease BAL may support a certain clinical/pathological pattern of lung involvement and is helpful for exclusion of other diseases, such as malignancies with pulmonary metastasis, heart disease with pulmonary congestion, or infections. The same is true for radiation-induced lung injury.
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PMID:Bronchoalveolar lavage in other interstitial lung diseases. 1797 79

Doxorubicin is employed alone or in combination for the treatment of several hematological and solid malignancies; despite its efficacy, there are associated cardiotoxicity limits both in its application in patients with heart disease risk factors and also in its long-term use. HFt-MP-PAS40 is a genetically engineered human ferritin heavy chain (HFt)-based construct able to efficiently entrap and deliver doxorubicin to cancer cells. HF-MP-PAS contains a short motif sequence (defined as MP) responsive to proteolytic cleavage by tumor matrix metalloproteases (MMPs), located between each HFt subunit and a masking polypeptide sequence rich in proline (P), alanine (A), and serine (S) residues (PAS). This carrier displayed excellent therapeutic efficacy in a xenogenic pancreatic cancer model in vivo, leading to a significant increase in overall animal survival in treated mice. Herein, we describe the HFt-MP-PAS40-Dox efficacy against squamous cell carcinomas of the head and neck (HNSCC) with the goal of validating the application of our nano-drug for the treatment of different solid tumors. In addition, a tolerability study in healthy mice was also performed. The results indicate that HFt-MP-PAS40-Dox produced increased anti-tumor effects both in vitro and in vivo in comparison to the free drug in several HNSCC cell lines. In the acute toxicity studies, the maximum tolerated dose (MTD) of HFt-MP-PAS40-Dox was about 3.5 higher than the free drug: 25 mg/kg versus 7 mg/kg doxorubicin equivalents. Importantly, evaluation of heart tissues provided evidence that doxorubicin is less cardio-toxic when encapsulated inside the ferritin carrier. In conclusion, HFt-MP-PAS40-Dox may be administered safely at higher doses compared with the free drug, resulting in superior efficacy to control HNSCC malignancies.
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PMID:Therapeutic Efficacy of the Novel Stimuli-Sensitive Nano-Ferritins Containing Doxorubicin in a Head and Neck Cancer Model. 2871 12


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