Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone diseases such as osteoporosis and osteoarthritis are regarded as age-associated diseases, and occur in a significantly increasing number of patients, but the underlying mechanisms of these age-associated bone diseases are not yet clear. We have established a transgenic mouse line by an insertion mutation. These mice exhibit many features related to precocious aging. Homozygote mutant mice, which lack expression of the newly identified targeted gene,klotho (kl), exhibit atherosclerosis, emphysema, hypogonadism and calcification of soft tissues, and die within 3-4 months. We describe here the radiological and histological characteristics of the skeletal abnormalities in the bones of the mice with a mutation in the kl gene locus. In heterozygous mice (+/kl), the skeletal patterns and structures remain normal and most features are similar to those in the wild-type, whereas histological examinations of homozygous mice (kl/kl) show abnormal elongation of the trabecular bone(s) in the epiphyses of long bones. As with their long bones, on radiographic examination the mid parts of the vertebral bones of these mice show less radiopacity compared with the wild-type, again resembling human vertebrae of osteoporotic patients. The elongation of the trabecular bones results in high radiopacity on both ends of each of the vertebrae, and in the epiphyses of the long bones. Cancellous bone volume in the epiphyses of the homozygote mice is three times that of the wild-type mice. The kl/kl mice are smaller than the wild-type litter mates and hence the size of their long bones is less than that of the wild-type litter mates. These observations, and the osteopenia in the vertebrae and long bones in these mice, suggest the presence of abnormality in bone metabolism, the elongation of the trabecular bone apparently resulting from the relatively low levels of bone resorption. Therefore, thekl/kl mutant mice could serve as an interesting tool to study the effects of the lack of the product of the new gene,klotho, on bone metabolism.
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PMID:Elongation of the epiphyseal trabecular bone in transgenic mice carrying a klotho gene locus mutation that leads to a syndrome resembling aging. 979 35

Common complications of cardiac transplantation include infection, rejection, accelerated coronary artery atherosclerosis, and lymphoproliferative disease. The authors reviewed radiographic and computed tomographic (CT) features of cardiac transplantation and its complications in a series of 232 patients (with 89 complications and 49 deaths). Normal postoperative findings in the first few weeks after surgery included enlarged cardiac silhouette, pneumomediastinum, pneumothorax, pneumopericardium, subcutaneous emphysema, and mediastinal widening. Infection was the most common complication, with pneumonia being the leading infectious condition (28 cases, with Aspergillus [n = 11] and cytomegalovirus [n = 10] being the most common pathogens) and the cause of death in seven cases. Although many cases of pulmonary infections occur in the first 3-4 months after surgery, in this series several cases developed up to 3 years afterward. Radiographic signs of acute rejection were nonspecific in the eight patients affected who died, and endomyocardial biopsy was used to confirm the suspected diagnosis. Accelerated atherosclerosis occurred in 13 patients between 10 months and 6.5 years after transplantation and led to death in eight. Lymphoproliferative disorders, which range from benign lymphoid hyperplasia to malignant lymphoma and which are the third leading cause of death beyond the immediate perioperative period in heart transplant recipients, developed in four patients who later died. Other complications related to endomyocardial biopsy and cardiothoracic surgery (i.e., pneumothorax, hemothorax, pneumomediastinum, mediastinitis, aortic dissection, aortic pseudoaneurysm, and pulmonary embolism) occurred in 31 cases and were diagnosed with radiography and CT.
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PMID:Imaging of cardiac transplantation complications. 1019 82

Gene therapy, the science of altering cellular function or structure at a molecular level, is currently one of the most exciting fields of research across medical specialties. By replacing lost or defective genes or adding genes known to produce proteins with beneficial effects, investigators hope to treat and possibly cure everything from inborn errors of metabolism to acquired diseases, such as emphysema and atherosclerosis. Genetic modification of engineered tissue, the offspring of these two fields, offers the promise of not simply replacing tissue, but improving on the restoration. The studies presented in this article demonstrate many of the principles that form the basis of gene therapy and provide insight into the potential of this emerging technology.
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PMID:Gene therapy and tissue engineering. 1055 21

Inactivation mutation of the recently discovered klotho gene in mice causes a syndrome resembling aging. Manifestations include short life span, atherosclerosis, gonadal atropy, skin atropy, emphysema, ataxia and ectopic calcification. These mice also exhibit abnormally high bone density in the epiphyses of their tibiae based on X-ray and histological analyses. However, micro-structures of the trabecular bones in arbitrary two-dimensional planes or three-dimensional regions are difficult to analyze by these techniques. Therefore, we applied high resolution micro-computed tomography (microCT) to characterize the micro-structural abnormality in the trabecular bone in long bones as well as in vertebrae of four- to six-week-old klotho mutant mice. Two-dimensional microCT analyses in the mid-sagittal plane as well as three-dimensional microCT analyses indicated that the trabecular bone volume fraction measured in the proximal metaphyses of the tibiae was increased more than twofold in klotho mutant mice compared with the wild-type mice. Similarly, the trabecular bone area fraction in the mid-sagittal plane of the lumbar vertebral bodies was also increased by about 80% at the proximal and distal ends. No significant difference was observed with regard to the cortical thickness in the mid-shaft of femora between klotho mutant and wild-type mice. Three-dimensional microCT analyses also indicated that the trabecular number and thickness of the proximal metaphyses of the tibiae were increased by about 80% and 300% respectively in the klotho mutant mice, while trabecular separation was 60% less in klotho mutant mice compared with the wild-type mice. These quantitative microCT analyses indicate that the inactivation of klotho gene expression results in an increase in three-dimensional bone volume fraction, number and thickness of the trabecular bones in these mice.
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PMID:High-resolution micro-computed tomography analyses of the abnormal trabecular bone structures in klotho gene mutant mice. 1065 59

Neutrophils and other phagocytes manufacture O(2)(-) (superoxide) by the one-electron reduction of oxygen at the expense of NADPH. Most of the O(2)(-) reacts with itself to form H(2)O(2) (hydrogen peroxide). From these agents a large number of highly reactive microbicidal oxidants are formed, including HOCl (hypochlorous acid), which is produced by the myeloperoxidase-catalyzed oxidation of Cl(-) by H(2)O(2); OH(*) (hydroxyl radical), produced by the reduction of H(2)O(2) by Fe(++) or Cu(+); ONOO(-) (peroxynitrite), formed by the reaction between O(2)(-) and NO(*); and many others. These reactive oxidants are manufactured for the purpose of killing invading microorganisms, but they also inflict damage on nearby tissues, and are thought to be of pathogenic significance in a large number of diseases. Included among these are emphysema, acute respiratory distress syndrome, atherosclerosis, reperfusion injury, malignancy and rheumatoid arthritis.
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PMID:Phagocytes and oxidative stress. 1093 76

Chlamydia pneumoniae has been detected in atherosclerotic plaques by various means. Chlamydiae are able to cause persistent infections. Serologically elevated antibody titers are found in severe chronic obstructive pulmonary disease. In atherosclerosis and pulmonary emphysema, inflammatory reactions can be seen by means of light microscopy. Specimens from patients with obliterative arteriosclerosis undergoing thrombendarteriectomy and with advanced emphysema undergoing lung volume reduction surgery were examined using scanning (SEM) and transmission (TEM) electron microscopy, and using immunofluorescence with monoclonal antibodies and antiserum against chlamydiae. SEM shows spherical bodies (SBs) with a diameter from 0.3 microm to 0.6 microm on the surface of the alveoli and bronchioles, as well as in atherosclerotic plaques. In atherosclerosis and emphysema, SBs reveal a double membrane, adherence to collagen fibers, tissue destruction, as well as intracellular and interstitial localization in TEM. They show in parts a densely packed central structure. SBs are seen both in alpha-1-antitrypsin deficiency emphysema and smoker's emphysema. Using immunofluorescence microscopy, spots are seen in corresponding distributions to the SBs. Morphological findings are typical for aberrant chlamydiae seen in persistent infections. Chronic infection and bacterial colonization associated with progressive disease seems to be relevant not only in atherosclerosis but also in pulmonary emphysema.
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PMID:The role of chlamydia in the pathogenesis of pulmonary emphysema. Electron microscopy and immunofluorescence reveal corresponding findings as in atherosclerosis. 1099 81

Cigarette smoking is the primary preventable cause of various diseases and death. Smoking has been causally related to lung cancer, other malignancies, atherosclerosis, coronary heart disease, and chronic obstructive pulmonary disease. There have been few studies, however, of whether the ordinary citizen in Japan understand the risks of serious diseases caused by smoking. Four hundred and thirty six people attended a seminar of respiratory diseases entitled "Cigarette smoking and lung cancer; prevention and treatment of asthma; senile care and prevention of pneumonia". After the seminar, unsigned questionnaires were filled out by 403 of those in attendance. Three hundred eighty nine (165 males and 224 females) respondents correctly answered the questionnaires, and these were analyzed in the study. Attendants comprised 243 who had never smoked (63%), 99 former smokers (25%), and 39 current smokers (10%). Three hundred forty seven attendants (89%) answered that smoking is harmful to the health, and 371 (95%) that it is causally related to lung cancer. In contrast, lower numbers of attendants answered that smoking is causally related to other diseases: pulmonary emphysema, 65% of the responses; chronic bronchitis, 68%; laryngeal cancer, 77%; myocardial infarction, 53%; and atherosclerosis, 49%. Of the 39 current smokers, 27 answered that they would stop smoking after the seminar. Although many people partly understand the risks of smoking, they do not have a clear knowledge of the risks of diseases besides lung cancer. Education about the risks of smoking and about smoking cessation is required.
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PMID:[Lack of knowledge about smoking-related risks for diseases in the general public in Japan]. 1153 Mar 85

Elastases are proteinases capable of solubilizing fibrous elastin. They may belong to the class of serine proteinases, cysteine proteinases and metalloproteinases. Mammalian elastases occur mainly in the pancreas and the phagocytes. Among non-mammalian elastases there is a great variety of bacterial metallo and serine elastases. The elastolytic activity varies from one elastase to another and is usually not correlated with the catalytic efficiency of these proteinases. One may measure this activity using native or labelled elastins. With pure elastases one may use synthetic substrates. There is a large number of natural (proteins) and synthetic elastase inhibitors. Elastases play a pathologic role in pulmonary emphysema, cystic fibrosis, infections, inflammation and atherosclerosis.
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PMID:[The elastases]. 1172 30

The pathogenesis of primary pulmonary hypertension is still unclear. The case of a 68-yr-old female patient who complained of recurrent dizzy spells and collapses over a period of 6 weeks and died of global cardiac failure is presented. Autopsy revealed severe pulmonary hypertension, slight chronic bronchitis, and bronchiolitis as well as intra-alveolar accumulation of macrophages. Chlamydiae were detected within the pulmonary arteries and in intramural and intra-alveolar macrophages by immunofluorescence, confocal laser scanning microscopy, scanning and transmission electron microscopy. Nested-polymerase chain reaction (PCR) and nonradioactive deoxyribonucleic acid (DNA) hybridization of PCR products from pulmonary arteries revealed Chlamydia pneumoniae DNA. Chlamydia pneumoniae has already been detected in atherosclerosis and in pulmonary emphysema. It can induce proliferation of smooth muscle cells. Chlamydia pneumoniae might be relevant in aggravation of primary pulmonary hypertension and might perhaps be a trigger factor in some cases.
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PMID:Detection of Chlamydia pneumoniae in unexplained pulmonary hypertension. 1184 18

Cathepsin S is a cysteine protease with potent endoproteolytic activity and a broad pH profile. Cathepsin S activity is essential for complete processing of the MHC class II-associated invariant chain within B cells and dendritic cells, and may also be important in extracellular matrix degradation in atherosclerosis and emphysema. Unique among cysteine proteases, cathepsin S activity is up-regulated by IFN-gamma. Given its importance, we sought to elucidate the pathway by which IFN-gamma increases cathepsin S expression. Our data demonstrate that the cathepsin S promoter contains an IFN-stimulated response element (ISRE) that is critical for IFN-gamma-induced gene transcription in a cell line derived from type II alveolar epithelial (A549) cells. IFN response factor (IRF)-2 derived from A549 nuclear extracts associates with the ISRE oligonucleotide in gel shift assays, but is quickly replaced by IRF-1 following stimulation with IFN-gamma. The time course of IRF-1/ISRE complex formation correlates with increased levels of IRF-1 protein and cathepsin S mRNA. Overexpression of IRF-1, but not IRF-2, markedly augments cathepsin S promoter activity in A549 cells. Furthermore, overexpression of IRF-1 increases endogenous cathepsin S mRNA levels in 293T epithelial cells. Finally, freshly isolated bone marrow cells from IRF-1(-/-) mice fail to up-regulate cathepsin S activity in response to IFN-gamma. Thus, IRF-1 is the critical transcriptional mediator of IFN-gamma-dependent cathepsin S activation. These data elucidate a new pathway by which IRF-1 may affect MHC class II processing and presentation.
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PMID:IFN regulatory factor-1 regulates IFN-gamma-dependent cathepsin S expression. 1197 Sep 93


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