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Biomedical subjects

G E Hook

Publications and source records attributed to G E Hook.

At least 73 records · Page 4Linked to original sources

Plasma proteins of the bronchoalveolar surface of the lungs of smokers and nonsmokers.

Plasma proteins were measured in bronchoalveolar lavage effluents and serums from normal healthy nonsmokers and smokers, and their concentrations in the 2 fluids were compared. Two-dimensional polyacrylamide gel electropherograms suggested, and radial immunodiffusion assays confirmed, that the soluble proteins of the bronchoalveolar surface resemble serum in kind and amount with the following significant exceptions. Two immunoglobulins, IgG and IgA, were present in amounts that exceeded their concentrations in serum; of the 2, IgG was more abundant. Large nonimmunoglobulin proteins (greater than 300,000 daltons) were absent or present at very low concentrations compared with the amounts found in serum. Transferrin was the only nonimmunoglobulin with a concentration significantly higher at the bronchoalveolar surface than in serum. Smoking did not cause a significant change in the concentration of any protein in serum, but did cause an increase in IgG, C4, and C3 and a decrease in alpha 2-thioglycoprotein, alpha 1-acid glycoprotein, and Gc-globulin in lavage effluents from females.

Adult↗

Phospholipid exchange between subcellular organelles of rabbit lung.

A soluble protein fraction (PLEP) prepared from rabbit lung can catalyze the exchange of phospholipids between subcellular organelles of the lung and between these subcellular organelles and synthetic liposomes. Phospholipid exchange between microsomes and synthetic liposomes and between mitochondria and synthetic liposomes was stimulated 8-fold and 2.5-fold, respectively, in the presence of the protein fraction. Lung exchange protein could also catalyzed phospholipid exchange between subcellular organelles of the liver and synthetic liposomes. Phospholipid transfer between microsomes and lamellar bodies of the lung was stimulated 2-fold by the exchange protein. Both radiolabeled phosphatidylcholine (PC) and phosphatidylinositol (PI) were transferred from 32P-labeled microsomes to lamellar bodies, but the exchange protein exhibited no transfer activity for phosphatidylglycerol (PG) and that for phosphatidylethanolamine (PE) was insignificant compared to the transfer activity for phosphatidylcholine and phosphatidylinositol. While the physiological role of the phospholipid exchange proteins in the lung is unknown, it is possible that they participate in the distribution of the newly synthesized phospholipids from the site of synthesis to lamellar bodies and other membrane compartments of cells.

Animals↗

Pulmonary alveolar proteinosis: analysis of airway and alveolar proteins.

Lavage effluents from the lungs of patients with pulmonary alveolar proteinosis were analyzed for soluble constitutents. Antiserums monospecific for normal plasma components, C-reactive protein, and secretory piece were used to investigate the presence of these proteins in lavage effluent, wheras 2-dimensional polyacrylamide gel electrophoresis provided a comprehensive map of the major proteins that were present. The proteins of lung washing obtained from normal subjects and of patient and normal serums were similarly analyzed. Most of the soluble-phase proteins from lavage of patients with pulmonary alveolar proteinosis were also found in patient serum, and were present in amounts consistent with a theory that they originate from the plasma by passage through channels of approximately normal size and selectivity. This findings suggests that the abundant soluble protein found in the alveoli of the lungs of these patients does not arise by leakage through a serverly damaged blood-air barrier. Patients had in their lung lavage effluents 2 soluble proteins of molecular weights 47,000 and 52,000 daltons not found in their serum and not present in lung washings from normal subjects. Uniformly increased concentrations of immunoglobulins in patient lavage effluent, abnormal immunoglobulin concentrations in patient serum, and the presence of C-reactive protein in the serum from 4 of 5 patients indicate a response of the immune system to the disease process and suggest that an atypical hypersensitivity reaction may be involved.

Adolescent↗

Extracellular hydrolases of the lung.

A pool of acid hydrolases exists within the acellular lining material of the alveoli and distal airways of the lungs. These extracellular hydrolases, obtained using pulmonary lavage procedures, appear to be of a selected variety insofar as some hydrolases (beta-N-acetylglucosaminidase and alpha-mannosidase) are highly active while others (beta-glucuronidase and arylsulfatase) are barely detectable. The origins of these hydrolases were investigated. Neither leakage of serum nor cell damage can account for the presence of the extracellular hydrolases in lavage effluents. Electrophoretic mobilities on acrylamide gels indicate that the extracellular hydrolases generally differ from those found in serum. Cytoplasmic soluble enzymes such as lactate dehydrogenase were used to monitor cell damage and show that the extracellular hydrolases did not originate from cell leakage during the lavage procedure. Hydrolases similar to those found extracellularly are associated with highly purified lysosome-free lamellar bodies isolated from homogenates of lung. The extracellular hydrolases are probably selected by the type 2 cells of the pulmonary alveolar epithelium during their selection of lamellar bodies.

Animals↗

Composition of bronchoalveolar lavage effluents from patients with pulmonary alveolar proteinosis.

The lungs of patients with pulmonary alveolar proteinosis were lavaged with saline. The lavage effluents were examined for the presence of unusual components which might be considered characteristic of the disease. Soluble proteins were resolved by electrophoresis on polyacrylamide linear gradient (2.5 to 27 per cent acrylamide) gel slabs and compared with proteins found in the patients' sera and lavage effluents from nondiseased human lungs. Many proteins in lavage effluents from both diseased and nondiseased lungs appeared similar to those found in serum. Several proteins from diseased lungs were not present in serum nor lavage effluents from nondiseased lungs. A number of proteins present in lavage effluents from nondiseased lungs appeared to be absent from lungs with alveolar proteinosis. Particulate components of lavage effluents from diseased and normal lungs were examined and compared using the electron microscope. Many particulate components including degenerate and disintegrating cells, ultrastructurally abnormal alveolar macrophages, and myelin-like structures were present in lavage effluents from diseased lungs but absent from normal lungs. Much of the particulate material resembled cell debris. The insoluble accumulations present in the pulmonary alveoli and airways of patients with alveolar proteinosis do not come from serum leakage nor from hypersecretion of materials normally found in these regions of the lungs. The major insoluble components appear to arise from cellular disintegration and the extracellular formation of myelin-like structures.

Blood Proteins↗

Tetrachlorodibenzo-p-dioxin induction of renal microsomal enzyme systems: ultrastructural effects on pars recta (S3) proximal tubule cells on the rat kidney.

A single oral administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin to rats at a dose level of 25 microgram/kg produced marked proliferation of smooth endoplasmic reticulum in renal proximal tubule cells of the straight (S3) segments. This ultrastructural effect was associated with a pronounced induction of the microsomal enzymes glucuronyl transferase and benzopyrene hydroxylase which persisted for at least 16 days after treatment. Renal dissection studies disclosed that the activities of these enzymes in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated animals were not uniformly distributed within the kidney but followed the general known distribution of S3 cells. Enzyme activities were highest in the outer stripe of the medulla and cortex and lowest in the medulla. These studies demonstrate that the kidney does possess inducible microsomal enzyme systems, capabilities of which have not been appreciated previously due to the lack of a suitable inducing agent and their apparent concentration in a relatively small population of proximal tubule cells.

Animals↗

Secretory cells of the peripheral pulmonary epithelium as targets for toxic agents.

The extracellular lining of the pulmonary peripheral airways is of vital importance to the lung. In this report, some aspects of the pulmonary extracellular lining and the epithelial cells believed to be responsible for its formation and secretion have been briefly reviewed. The influence of a number of toxic agents on the extracellular lining either directly or via those cells involved in its formation indicates that the extracellular lining may be important in understanding numerous toxic agent interactions with the lung.

Albumins↗

Postnatal stimulation of hepatic microsomal enzymes following administration of TCDD to pregnant rats.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) administered to pregnant rats at 3 mu-g/kg as a single oral dose during early, middle, or late gestation caused marked elevations of some maternal hepatic microsomal enzymes for at least 10 weeks after treatment. This dose was not teratogenic and fetal rates of glucuronidation of testosterone and p-nitrophenol (PNP) were unaffected. Increases in fetal liver benzpyrene hydroxylase (BPH) activities were evident during late gestation although cytochrome P-450 and cytochrome b-5 contents were unchanged. The offspring of pregnant rats administered TCDD had markedly elevated hepatic PNP UDP-glucuronyltransferase (UDPGT) BPH, and microsomal cytochrome contents whereas the perinatal development of testosterone UDPGT was unchanged. PNP glucuronidation attained a maximal 8-fold increase above controls by 3 weeks after birth and activities were twice that of controls 8 weeks after birth (adults). Maximal increases in benzpyrene hydroxylation rates occurred one day after birth when in the prenatally exposed group activities were approximately 20 times higher than controls. Foster mother experiments demonstrated that the postnatal inductive effect resulted both from exposure of newborns to TCDD via maternal milk and the activation of an inducing mechanism occurring after birth. Tese data demonstrate that multiple factors are responsible for the induction of hepatic microsomal enzymes in the newborn following administration of TCDD to pregnant rats.

Animals↗

Induction and suppression of hepatic and extrahepatic microsomal foreign-compound-metabolizing enzyme systems by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on a number of hepatic and extrahepatic foreign-compound-metabolizing enzyme systems in microsomes from rats, rabbits and guinea pigs were investigated. Following TCDD treatment, the N-demethylation of benzphetamine, aminopyrine and ethylmorphine was suppressed in hepatic microsomes from male but not from female rats. However, both cytochrome P-450 and benzpyrene hydroxylase were significantly stimulated in hepatic microsomes from both male and female rats at doses as small as 1 mug TCDD/kg body weight. The inductive effect on rat hepatic microsomal enzymes was considerably more persistent than the suppressive effect. Following a single oral dose of 25 mug TCDD/kg weight, benzpyrene hydroxylase of male rat liver microsomes remained significantly elevated for 73 days but the suppression of benzphetamine N-demethylase had gone after 35 days. The induction of benzpyrene hydroxylase in male rat liver microsomes by TCDD was independent of the age of the rat and the levels to which this enzyme was increased was similar in male rats of all ages. However, the suppression of benzphetamine N-demethylase in male rat liver microsomes was age related: the suppression was seen only in adult animals and in the very young (10 days old) the enzyme was actually induced by TCDD. Inductive effects appeared in both smooth and rough-surfaced hepatic microsomes from male rats but the suppression of N-demethylation occurred only in the smooth-surfaced microsomes (SER). In microsomes from extrahepatic tissues of the rat, induction of mixed-function oxidases (MFOs) by TCDD occurred only in the kidney. However, UDPglucuronyltransferase was induced in microsomes from lung, kidney, intestine and brain but not testes. The response in the rabbit and guinea pig to TCDD differed considerably from that in the rat. Benzpyrene hydroxylase was unaffected in hepatic microsomes from the guinea pig and actually suppressed in microsomes from rabbit liver. Benzphetamine N-demethylase was also suppressed in rabbit liver microsomes. Glucuronyl-transferase was unaffected by TCDD in microsomes from liver, lung or kidney of the rabbit and guinea pig. The only lung enzyme responsive to TCDD was biphenyl 4-hydroxylase of the rabbit and guinea pig. Suppression was not observed in any of the extraheptic tissues studied and may be confined to only certain hepatic systems.

Animals↗

The liver parenchyma and foreign compound metabolism in red-winged blackbird compared with rat.

1. Aniline p-hydroxylase, aminopyrine N-demethylase, and p-nitroanisole O-demethylase activities were measured in liver microsomes prepared from the red-winged blackbird (Agelaius phoeniceus) and compared with analogous preparations from rat. All had lower activities in birds than in rats, when expressed in terms of microsomal protein. 2. Hepatic parenchyma of the bird was observed by electron microscopy to contain less endoplasmic reticulum than that of rat. This morphological difference may partially explain the species difference in enzyme activities. 3. Cytochrome P-450 levels were not sex-dependent in the red-winged blackbird, unlike rat, but the opposite was true for the rate of hydroxylation of aniline. 4. There was no species difference in the activity of aniline p-hydroxylase when expressed in terms of activities per unit of cytochrome P-450, but the activity of p-nitroanisole O-demethylase was higher in red-winged blackbird than in rat; the reverse may be true for the activity of aminopyrin N-demethylase.

Aminopyrine N-Demethylase↗

Problems associated with the assay of arylsulphatases A and B of rat tissues.

A method for the separation and purification of rat liver arylsulphatases A and B by gel filtration on Sephadex G-200 is described. The properties of the A enzyme and its molecular weight are similar to those of the corresponding ox liver enzyme. The B enzymes were found to be dissimilar. The method already developed for the assay of the corresponding enzymes from human tissues was shown to be unsuitable for the assay of the enzymes of rat tissues. A method of assay was developed which permits an approximate determination of the individual rat liver enzymes in a mixture of the two, but precise determination requires prior separation of the enzymes by gel-filtration chromatography.

Animals↗