Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0729233 (Thoracic)
 6,478 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thoracic and abdominal aortas were obtained from rats after irradiation and used for the estimation of the synthesis of prostacyclin (PGI2) determined as 6-keto PGF1 alpha. Twenty four h after exposure to 7.0 Gy an increase was noted in the amount of PGI2 released, and 4 weeks later its level significantly decreased. The 24 h value did not increase with the further radiation dose increment (9, 12.5, 15 Gy). Cysteine or H2O2 intensified prostacyclin synthesis in control vessels but decreased it in vessels from the animals irradiated 24 h earlier. Later after the exposure cysteine or H2O2 were no longer effective.
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PMID:Irradiation of rats abolishes susceptibility of PGI2 synthesis in blood vessels to peroxidative agents. 211 Oct 36

The immediate effect of four different modes of treatment was assessed by lung function tests on 19 infants with cystic fibrosis (CF) during the first year of life. The regimens were applied in a randomized fashion and consisted of aerosol inhalation of salbutamol (n = 8; SAL), aerosol inhalation of N-acetyl cysteine (n = 5; AC), chest physiotherapy (n = 6; CPT), and combined treatment with aerosol inhalation of SAL and AC followed by CPT (n = 6; COMB). Pulmonary function was measured before and shortly after therapy with each mode of treatment. Thoracic gas volume (Vtg) and specific airway conductance (SGaw) were measured by an infant whole body plethysmograph, and forced expiratory flow at resting lung volume (VmaxFRC) was determined with a thoraco-abdominal squeeze jacket. There was no correlation between baseline lung function and changes in any parameter due to treatment. Overall group comparison showed that the combined therapy resulted in a significant improvement in lung function when compared to any of the three treatments applied separately. There was no significant change in lung volumes in any individual group, but SGaw and VmaxFRC showed a small but significant improvement following the COMB treatment when compared with AC or CPT.
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PMID:Immediate effect of various treatments on lung function in infants with cystic fibrosis. 268 64

Diabetes is known to cause impaired endothelium-dependent relaxation of blood vessels. The purpose of this study was to determine whether this endothelial dysfunction is a permanent defect or is reversible after acute arginine supplementation in vitro or by surgical intervention in vivo using syngeneic pancreatic islet transplantation. Lewis rats were injected with streptozotocin to induce diabetes and were studied either 8 or 12 weeks later. Another group received syngeneic islets via intraportal injection at 8 weeks of diabetes and were allowed to become euglycemic for 4 weeks before study. Thoracic aortic rings were tethered in isolated muscle baths, contracted with a submaximal concentration of norepinephrine, and challenged with either the endothelium-dependent vasodilator acetylcholine or the endothelium-independent vasodilator nitroglycerin. Relaxation to acetylcholine (but not nitroglycerin) was reduced in both 8- and 12-week diabetic rings compared with age-matched control rings. Preincubation of diabetic rings in vitro with L-arginine (but not D-arginine) restored relaxation to acetylcholine to normal to rings from 8-week but not 12-week diabetic animals. Plasma basic amino acids (arginine, lysine, and histidine) were reduced by diabetes, whereas other neutral or acidic amino acids were unchanged (phenylalanine, proline, and glutamate), reduced (serine, cysteine, threonine, tyrosine, tryptophan, and aspartate), or elevated (isoleucine, leucine, and valine). Islet transplantation restored to normal the changes in plasma amino acids. Elevation in blood glucose and total glycosylated hemoglobin in diabetic animals was normalized after islet transplantation. Furthermore, islet transplantation completely restored the defective endothelium-dependent relaxation to acetylcholine in diabetic rings.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Syngeneic pancreatic islet transplantation reverses endothelial dysfunction in experimental diabetes. 765 36

We tested the hypothesis as to whether elevated arterial pressure in hypertension alters cGMP, or cAMP, mediated vasorelaxation. Relaxation to nitroglycerin and isoproterenol was determined in isolated aortic rings from one-kidney, one clip hypertensive (1K1C), coarctation hypertensive (CH) and normotensive control (C) rats. Thoracic aortas from 1K1C and CH rats, as well as abdominal aortas from 1K1C rats, but not abdominal aortas from CH rats were exposed chronically (4-6 weeks) to elevated arterial pressure. Sensitivity of rings with and without endothelium to nitroglycerin was suppressed significantly only in vessels exposed chronically to high arterial pressure. Impaired sensitivity to nitroglycerin in abdominal rings from 1K1C rats could not be abolished by exposure to 100 uM L-arginine, the substrate for production of NO by endothelial nitric oxide synthase, or 100 uM L-cysteine, the source of thiol groups required for the production of nitric oxide from nitroglycerin. Maximum relaxation to isoproterenol was impaired significantly in thoracic and abdominal rings, with and without endothelium, from 1K1C and CH rats. Relaxation to 8-bromo-cGMP and dibutyryl cAMP was similar in abdominal rings from all groups. We conclude that impaired vasorelaxation to nitroglycerin and isoproterenol in hypertension involves mechanisms prior to activation of vascular smooth muscle cGMP-dependent and cAMP-dependent protein kinase, respectively. Impaired cGMP, but not cAMP, mediated relaxation of aortas appears to result from their exposure to high arterial pressure per se. This effect does not appear to involve the vascular endothelium or vascular sources of thiols, but rather may reflect an effect of high arterial pressure to impair the ability of the artery to respond to nitric oxide derived from nitroglycerin.
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PMID:Selective effect of high arterial pressure in hypertension upon inhibition of cGMP versus cAMP mediated vascular relaxation. 884 63

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic fibrosing interstitial pneumonia limited to the lung and associated with the histologic appearance of usual interstitial pneumonia (UIP) on lung biopsy. It is characterized by progresive dyspnea, worsening of pulmonary function and radiographically, by patchy subpleural interstitial infiltrates with minimal ground glass appearance predominantly affecting the lung bases. The etiology is unknown and no therapy has been clearly shown to prolong survival. The diagnosis, which earlier was difficult to establish, is now based on guidelines of American Thoracic Society. Newer insight into its etiopathogenesis, particularly the mechanisms involved including T helper 1 (Th1) and T helper 2 (Th2) types of responses occurring after the initial and repetitive lung insults and the ineffectiveness of conventional modes of therapy has prompted clinicians worldwide to look for alternative modes of therapy. Conventional therapy for this disorder has been steroids and immunosuppressives. Immunomodulators (Interferon gamma 1b) and antioxidants (Glutathione and its precursor N-acetyl cysteine) are promising results in this, otherwise, uniformly fatal condition.
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PMID:Idiopathic pulmonary fibrosis: newer concepts and management strategies. 1268 10

Thioredoxin 1 (Trx1) has redox-sensitive cysteine residues and acts as an antioxidant in cells. However, the extent of Trx1 contribution to overall antioxidant mechanisms is unknown in any organs. We generated transgenic mice with cardiac-specific overexpression of a dominant negative (DN) mutant (C32S/C35S) of Trx1 (Tg-DN-Trx1 mice), in which the activity of endogenous Trx was diminished. Markers of oxidative stress were significantly increased in hearts from Tg-DN-Trx1 mice compared with those from nontransgenic (NTg) mice. Tg-DN-Trx1 mice exhibited cardiac hypertrophy with maintained cardiac function at baseline. Intraperitoneal injection of N-2-mercaptopropionyl glycine, an antioxidant, normalized cardiac hypertrophy in Tg-DN-Trx1 mice. Thoracic aortic banding caused greater increases in myocardial oxidative stress and enhanced hypertrophy in Tg-DN-Trx1 compared with NTg mice. In contrast, transgenic mice with cardiac-specific overexpression of wild-type Trx1 did not show cardiac hypertrophy at baseline but exhibited reduced levels of hypertrophy and oxidative stress in response to pressure overload. These results demonstrate that endogenous Trx1 is an essential component of the cellular antioxidant mechanisms and plays a critical role in regulating oxidative stress in the heart in vivo. Furthermore, inhibition of endogenous Trx1 in the heart primarily stimulates hypertrophy, both under basal conditions and in response to pressure overload through redox-sensitive mechanisms.
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PMID:Inhibition of endogenous thioredoxin in the heart increases oxidative stress and cardiac hypertrophy. 1459 65

Non-small cell lung cancer (NSCLC) is the most commonly diagnosed cancer and the most frequent cause of cancer-associated mortality worldwide. Tesmin (MTL5) is a 60 kDa protein which has cysteine rich motifs, characteristic of metallothioneins. Tesmin expression was first observed in germ cells during spermatogenesis. Increased tesmin expression in NSCLC has been described previously. Minichromosome maintenance proteins (MCMs) serve a critical role in replication and cell cycle progression, i.e. in NSCLC. The aim of the present study was to evaluate the localization and intensity of tesmin, MCM5 and MCM7 protein expression in NSCLC and their association with the clinicopathological data of patients. Archival paraffin blocks of 243 cases of NSCLC and 104 non-cancerous tissue samples from the surgical margin (control) were obtained from patients treated at the Clinic of Thoracic Surgery of Wroclaw Medical University (Wroclaw, Poland) between 2010 and 2016, and were used for tissue microarrays and immunohistochemical (IHC) experiments. Laser capture microdissection was used for the isolation of cancer cells from 36 frozen samples of NSCLC and 8 control samples, and subsequently, MTL5, MCM5 and MCM7 mRNA expression was detected separately by reverse transcription-quantitative PCR. Positive cytoplasmic and nuclear tesmin, as well as nuclear MCM5 and MCM7 IHC expression were observed in 95.1, 83.67, 95.51 and 100% of the NSCLC cases, respectively. MTL5, MCM5 and MCM7 mRNA expression was observed in 91.66% of the cancer cases for all genes. The statistical analysis revealed increased tesmin IHC expression in cancer cells compared with the control. A positive correlation was observed between the IHC expression of nuclear tesmin and MCM5 proteins (r=0.33; P<0.0001) and nuclear tesmin and MCM7 proteins (r=0.315; P<0.0001). In addition, a positive correlation between the mRNA expression levels of MTL5 and MCM5 (r=0.421; P<0.05), MTL5 and MCM7 (r=0.557; P<0.01) was demonstrated. The survival analysis revealed that the presence of IHC cytoplasmic tesmin expression was a positive prognostic marker in NSCLC (P=0.0524). Furthermore, in vitro experiments performed on the NCI-H1703 cell line revealed that silencing of MTL5 mRNA and tesmin caused the downregulation of the expression levels of MCM5 and MCM7 and decreased the number of cells in the G2 phase. A positive association among tesmin, MCM5 and MCM7 could indicate a possible role of tesmin in the proliferation of NSCLC cancer cells.
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PMID:Role of tesmin expression in non-small cell lung cancer. 3328 59