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[Glycosaminoglycans in human normal lung tissues and lung cancer tissues].

The quantitative changes of glycosaminoglycans in tumor tissue of human lung cancers (6 squamous cell carcinomas, 7 small cell carcinomas and 10 adenocarcinomas) were studied. Normal lung tissues contained of 3.38 mumol uronic acid/g dry weight glycosaminoglycans which consisted of hyaluronic acid, chondroitin sulfates, dermatan sulfate and heparan sulfate. The total amount of glycosaminoglycans in human lung cancer tissues increased 1.7 to 3.5 times in comparison with that in normal lung tissues. The increase in tissue content of glycosaminoglycans was accompanied by an increase in the chondroitin sulfate level in every histologic type of lung cancer, as well as marked increase in hyaluronic acid level in squamous cell carcinomas, and a moderate increase in small cell carcinomas. The concentrations of dermatan sulfate and heparan sulfate in lung cancer tissues did not show any significant changes compared with those in normal lung tissues. The increase in total amount and changes in the composition of glycosaminoglycans in human lung cancer tissue were closely related to the histologic type of the tumor. In adenocarcinomas, some acid glycoprotein with sialic acid was simultaneously detected during the separating course of glycosaminoglycans, which was considered to be derived from mucinous substances related to adenocarcinoma cells.

Adenocarcinoma

Polycyclic aromatic hydrocarbon-DNA adducts in lung tissue from lung cancer patients.

In an attempt to probe for polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human subjects resulting from smoking (or other chronic environmental exposure), lung tissue and lung tumours were obtained from patients hospitalized for lung cancer. DNA was isolated from the tissue samples and examined both in an ELISA using a polyclonal antibody against (+/-)trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE)-DNA as well as by the nuclease P1-mediated modification of the 32P-post-labelling technique. The ELISA results showed BPDE-DNA antigenicity in lung DNA from 6 out of 21 patients, and adduct levels ranged from 2 to 134 adducts per 10(8) nucleotides. For all 21 patients, the autoradiographs of chromatograms of 32P-postlabelled digests of DNA from non-tumorous lung tissue showed a strong diagonal radioactive zone (DRZ). This DRZ was generally absent in tumorous tissue. DNA samples that were positive in the ELISA contained a dominant spot within the DRZ that co-chromatographed with the major BPDE-DNA adduct (BPDE-dG). The quantities of the BPDE-dG spots ranged from 2.1 to 42 adducts in 10(9) nucleotides. These values were lower than the levels found in the ELISA but correlated well with the ELISA results (Kendall W = 0.97; P = 0.00). The levels of the DRZ adducts ranged from 1.9 to 34 adducts in 10(8) nucleotides. Correlations between smoking and DNA adduct levels were poor because of the small number of current smokers (n = 13). However, smokers of filter cigarettes had significantly lower DNA adduct levels compared with smokers of cigarettes without a filter (P = 0.02 by Fischer's exact test).

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide

Large interindividual variations in metabolism of benzo(alpha)pyrene by peripheral lung tissue from lung cancer patients.

A very large variation (44-fold) was observed in the ability of short-term organ cultures of peripheral lung tissue from lung-cancer patients to metabolize the environmental carcinogen benzo(alpha)pyrene to organic solvent-soluble metabolites. The amounts of benzo(alpha)pyrene (2 microM) metabolized ranged from little (1%) to almost total (96.2%) metabolism within 24 h of culture. Previous work by Kellerman et al. (1973) has suggested a relationship between susceptibility to lung cancer and the indicibility of aryl hydrocarbon hydroxylase activity in cultured human lymphocytes. The metabolic fate of carcinogenic polycyclic aromatic hydrocarbons in the respiratory tract in vivo is undoubtedly more closely mimicked by short-term organ culture of human lung than by cultured lymphocytes. Thus the very wide interindividual variation observed in pulmonary metabolism of benzo(alpha)pyrene in this study and the large variations in covalent binding to human bronchial DNA observed by Harris et al. (1976) strongly suggest that there may be little basis for screening humans for variations in lymphocyte aryl hydrocarbon hydroxylase activity as a means of assessing their susceptibility to lung cancer.

Aged

Metal concentrations in human lung tissue, with special reference to age, sex, cause of death, emphysema and contamination of lung tissue.

Nine element concentrations in the lung tissues of 2,274 autopsies were determined in Japan by atomic absorption spectrometry. The metals determined were iron, calcium, magnesium, zinc, copper, cobalt, nickel, lead, and chromium. The range, mean, standard deviation, mode and median are described for each metal. Moreover, these data were analyzed statistically, based on their sex, age, degree of lung contamination (color and the amount of particle deposition), severity of pulmonary emphysema and cause of death. Iron, calcium, magnesium, zinc, copper and cobalt concentrations in the lung tissue seemed to be affected mostly by physiological variation and the levels in the blood. On the other hand, nickel, lead and chromium concentrations might reflect environmental exposure. Chromium concentration especially increased with age and showed a significantly positive correlation with the degree of contamination and severity of emphysema.

Age Factors

Metal concentrations in lung tissue of subjects suffering from lung cancer.

Concentrations of nine metals (Fe, Ca, Mg, Zn, Cu, Co, Ni, Pb and Cr) concentrations in lung tissues from 224 lung cancer cases were compared with those in other cases to achieve an understanding of their contribution to the development of lung cancer and the varieties after the development of cancer. Comparisons of metal concentrations in each cell type of lung cancer were also performed. All cases were collected from routine autopsies in Tokyo and Saitama, Japan. The copper concentration in tissue from lung cancers was significantly higher than that in other specimens, although calcium, magnesium, zinc and cobalt concentrations in lung cancers were significantly lower than those in other cases. There were no significant differences in the 99% intervals (excluding extremely high values for occupationally exposed cases) for chromium, nickel and lead concentrations between lung cancers and other cases, although these values were lower in lung cancers. However, in comparisons of men only, the chromium concentration, the degree of lung contamination and the severity of pulmonary emphysema in lung cancer cases were significantly higher than those in other specimens. Moreover, percentages of lung cancer in men at each degree of contamination and each severity of emphysema increased with increasing grades. Thus, this finding could be evidence that the exposure to contaminants other than chromium and nickel in the air had affected the development of lung cancer, except for occupationally exposed individuals. Therefore, almost all chromium and nickel in lung tissue might not deposit in carcinogenic forms such as hexavalent chromium or nickel subsulfide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Lung tissue resistance during contractile stimulation: structural damping decomposition.

Research in the mechanics of soft tissue, and lung tissue in particular, has emphasized that dissipative processes depend predominantly on the viscous stress. A corollary is that dissipative losses may be expressed as a tissue viscous resistance, (Rti). An alternative approach is offered by the structural damping hypothesis, which holds that dissipative processes within soft tissue depend directly more on the elastic stress than on the viscous stress. This implies that dissipative and elastic processes within lung tissues are coupled at a fundamental level. We induced alterations of Rti by exposing canines to aerosols of the constrictors prostaglandin F2 alpha, histamine, and methacholine and by changing volume history. Using the structural damping paradigm, we could separate those alterations in Rti into the product of two distinct contributions: change in the coefficient of coupling of dissipation to elastance (eta) and change in the elastance itself (Edyn). Response of Edyn accounted for most of the response of resistance associated with contractile stimulation; it accounted for almost all the response associated with differences in volume history. The eta changed appreciably with constriction but accounted for little of the response of Rti with volume history. According to the structural damping hypothesis, induced changes in eta with constriction must reflect changes in the kinetics of the stress-bearing process, i.e., differences in cross-bridge kinetics within the target contractile cell and/or differences in the influence of the target cell on other stress-bearing systems. We conclude that, regardless of underlying processes, the structural damping analysis demonstrates a fundamental phenomenological simplification: when Edyn responds, Rti is obligated to respond to a similar degree.

Airway Resistance

Amount and rates of CO2 storage in lung tissue.

The slope of the lung tissue CO2 dissociation curve and the rate of storage of CO2 in the lung tissue were studied at 22 degrees C and at 37 degrees C in 21 isolated, bloodless dog lungs with a total of 465 separate observations. Results at the two temperatures were similar. The slope of the tissue dissociation curve of lung tissue at a PCO2 of 40 torr was approximately 0.3 ml CO2 X 100 g wet tissue-1 X torr-1. Normally, this storage was 90% complete in about 5 seconds. After carbonic anhydrase inhibition by acetazolamide, the total storage capacity was unchanged, but the rate at which storage occurred decreased significantly, so that it took about 25 seconds for 90% of the storage to be completed.

Acetazolamide

Steroid metabolism by the lung: conversion of dihydrotestosterone to 5 alpha-androstan-3 alpha, 17 beta-diol by rat lung tissue in vitro.

The potential of lung tissue of adult male rats metabolize dihydrotestosterone (DHT) in vitro was examined. Within 3 min, a homogenate of 100 mg lung tissue, cleared of blood by perfusion before homogenization, metabolized 90% of the [3H]DHT substrate. Appoximately 80% of the DHT was converted to 5 alpha-androstan- alpha, 17 beta-diol. The amount of 5 alpha-androstan-3 alpha, 17 beta-diol formed during a 5-min incubation increased linearly, with substrate concentrations ranging from 3.3 x 10(-8) to 3 x 10(-6) M. Thus, the capacity of rat lung tissue to metabolize DHT in vitro and the rate of 3 alpha-reduction of DHT are sufficiently great to consider the possibility that lung may be responsible for the rapid clearance of DHT from the circulation in this species.

Androstane-3,17-diol

Concentrations of selected carotenoids and vitamin A in human liver, kidney and lung tissue.

Concentrations of preformed vitamin A and five individual carotenoids (alpha-carotene, beta-carotene, cryptoxanthin, lutein and lycopene) were determined in liver, kidney and lung tissue from 20 autopsies of subjects ranging in age from 4 mo to 86 y. Total carotenoid concentrations in liver tissue were always greater than in kidney or lung tissue within the same patient. Total carotenoid concentration in adult subjects was 2.5-77.1 nmol/g tissue (mean 21.0 nmol/g tissue) in liver tissue (n = 14), 0.2-12.7 nmol/g tissue (mean 3.1 nmol/g tissue) in kidney tissue (n = 13) and 0.1-8.4 nmol/g tissue (mean 1.9 nmol/g tissue) in lung tissue (n = 13). Carotenoid content in tissue samples from two infants was low, ranging from 0 to 1.0 nmol/g tissue. beta-Carotene and lycopene were almost always the predominant carotenoids found in liver, kidney and lung tissue. beta-Carotene was positively correlated (P less than 0.05) with alpha-carotene, lycopene and total carotenoids in all of the tissues examined. In addition, beta-carotene and total carotenoids from liver tissue were positively correlated with the same carotenoids in both kidney and lung tissue within each patient. Total vitamin A (free plus esterified) concentration was 8.7-1102.2 nmol/g tissue in liver (n = 17), 3.5-343.9 nmol/g tissue in kidney (n = 14) and 0.7-404.6 nmol/g tissue in lung (n = 14). Vitamin A concentrations were significantly correlated with both beta-carotene and total provitamin A carotenoid concentrations in liver tissue, but not in kidney or lung tissue.

Adult

[Chemical elements in the blood, bronchial lavage fluid and lung tissue of patients with pulmonary tuberculosis and lung cancer].

The examined groups included 58 patients with cancer, 61 subjects with pulmonary tuberculosis and 50 healthy persons as controls. The content of trace elements in blood, bronchial lavage fluid from the most affected portions of the lungs, and in pathologic and healthy lung tissues was determined by a C-115 atomic absorption spectrophotometer. The examination findings demonstrated that the content of blood serum ferric zinc and magnesium, and erythrocyte zinc, manganese, potassium and calcium was higher in patients with pulmonary tuberculosis than in those with lung cancer. At the same time the content of magnesium and calcium in bronchial lavage fluid was higher in persons with a malignant process than in those with pulmonary tuberculosis. As far as differential diagnosis of pulmonary tuberculosis and lung cancer is concerned, it is advisable to measure the levels of erythrocyte trace elements since the latter most precisely reflects their content in the lung pathologic tissue.

Bronchoalveolar Lavage Fluid

Measurement of lung tissue mass in interstitial lung disease.

A gamma camera and 99m Technetium were used to obtain transmission and emission scans of the thorax in order to estimate transthoracic tissue thickness, and volumes of blood and interstitial tissue in each pixel of the gamma camera image. This technique has been applied to six patients with stage 2/3 pulmonary sarcoidosis and eight with cryptogenic fibrosing alveolitis and age and sex-matched control groups without lung disease. In both conditions transthoracic tissue thickness was significantly increased: mean values (SD) were 14.6 (1.8) cm in cryptogenic fibrosing alveolitis and 12.3 (2.2) cm in stage 2/3 sarcoidosis. This was partially accounted for by an increase in the interstitial fluid compartment. Blood volume was unaffected. Measurement of transthoracic tissue thickness involves minimal radiation exposure and may be of value in monitoring these diseases; measurement of interstitial fluid volume may give information on disease activity.

Adult

Partial purification and characterization of adenosine- and guanosine-3',5'-monophosphate phosphodiesterases from human lung tissue.

Crude extracts of human lung tissue were examined for cyclic adenosine- and guanosine-3',5'-monophosphate (cAMP and cGMP) phosphodiesterase activities. Nonlinear reciprocal plots were observed for each substrate. DEAE-Sephadex chromatography of the extracts revealed four main fractions of activity, which were further purified by Sephadex gel filtration. The phosphodiesterase activity of the resulting individual fractions was partially characterized with respect to substrate specificity, kinetic parameters, apparent molecular weight (gel filtration), thermal stability at 30 and 37 degrees C, effect of the cyclic nucleotide not utilized as substrate, and the possible influence of Ca2+-dependent protein activator. The results indicate that the tissue contains phosphodiesterases with strict specificity and a high apparent affinity for each of the two cyclic nucleotides (the Km values determined were approximately 0.3-0.4 muM). The high affinity cAMP phosphodiesterase activity was enriched in two of the purified fractions; both activities probably represent fragments of the native high affinity cAMP specific enzyme. A third purified phosphodiesterase showed mixed substrate specificity. The Km value recorded for hydrolysis of either substrate with this enzyme was approximately 25 muM. A fourth, irregularly occurring, phosphodiesterase activity also showed mixed substrate specificity. The Km value registered for hydrolysis of either substrate with this fraction was approximately 0.4 muM. There was no evidence for a Ca2+-dependent specific activation by a boiled lung tissue supernatant of any of the purified enzymes.

3',5'-Cyclic-AMP Phosphodiesterases

Characterization of the forward and reverse reactions catalyzed by CDP-diacylglycerol:inositol transferase in rabbit lung tissue.

CDPdiacylglycerol:inositol transferase activity in rabbit lung tissue has been characterized and the optimum conditions for assaying this enzyme in vitro were determined. Rabbit lung tissue CDPdiacylglycerol:inositol transferase activity was found primarily in the microsomal fraction. The pH optimum of the enzyme activity was between 8.8 and 9.4, and the reaction was dependent on either Mn2+ or Mg2+. Detergents and Ca2+ inhibited the activity of the enzyme. The apparent Km values of the enzyme for CDPdioleoylglycerol and myoinositol were 0.18 mM and 0.10 mM, respectively. The reversibility of the reaction catalyzed by CDPdiacylglycerol:inositol transferase in microsomes prepared from rabbit lung tissue was demonstrated by the synthesis of [3H]CMPdiacylglycerol when [3H]CMP and phosphatidylinositol were present in the incubation mixture. The reverse reaction was characterized and its importance in the regulation of the acidic phospholipid composition of surfactant during lung development is discussed. The pH optimum for the reverse reaction was 6.2, and the reverse reaction was also dependent on Mn2+ or Mg2+. The apparent Km value of CDPdiacylglycerol:inositol transferase for CMP was found to be 2.8 mM.

Animals

[Scanning electron microscopy study of rat lung tissue].

Parts of rat lung tissue have been examined by means of a scanning electron microscope after either chemical or physical fixage. Chemical fixage produces retraction on the tissue structures and the alveoles appear of irregular shape. Physical fixage gives the possibility to observe lung morphology without distorsions; details reproduced are in this case very clear and in a shape which appears very close to the original conditions.

Animals

[Studies on the T-cell subset in lung tissue and BALF from patients with interstitial pneumonia].

The cellular components in bronchoalveolar lavage fluids (BALF) have been analyzed to obtain information on cellular kinetics in lung tissues of patients with diffuse pulmonary diseases. While various cells, alveolar macrophages, lymphocytes, and granulocytes appear in BALF, an increase in the percentage of lymphocytes has been noted in a variety of interstitial pneumonia. The T-cell subset of lymphocytes in BALF and biopsied lung tissues was, therefore, examined in patients with hypersensitivity pneumonitis (HP), sarcoidosis (Sar), idiopathic interstitial pneumonia (IIP) and rheumatoid arthritis with interstitial pneumonia (RA+IP) to compare the ratios of CD4/CD8 in BALF and lung tissues. The T-cell subset in BALF was analyzed by flow cytometry and the T-cell subset in lung tissues was detected with fresh frozen and thin-sliced specimens using an avidine-biotin complex (ABC) kit (Vecta Co. Ltd). The mean CD4/CD8 ratio in BALF was 0.36 in HP, 3.1 in Sar, 1.07 in IIP and 2.59 in RA+IP, while the mean CD4/CD8 ratio in lung tissues was 0.52 in HP, 2.59 in Sar, 1.11 in IIP and 2.25 in RA+IP, respectively. The ratios of CD4/CD8 in BALF and lung tissues from patients with these various interstitial pneumonia showed a positive correlation indicating that the changes of cellular components in BALF would reflect the changes in the lung tissues. Furthermore, CD4/CD8 ratios of lymphocytes infiltrating the alveolar portion and granuloma in lung tissues of HP were analyzed separately, because the CD4/CD8 ratios varied considerably from part to part of the lung tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic