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L A Russo

Publications and source records attributed to L A Russo.

7 recordsLinked to original sources

ADP ribosylation of type II pulmonary epithelial cell G proteins.

Secretion of pulmonary surfactant by type II pulmonary epithelial cells (T2P) is regulated by receptor-mediated mechanisms. In other systems, coupling of receptor-linked signals to intracellular events involves guanine nucleotide-binding proteins (G proteins), but the specific role of G proteins in T2P signaling pathways is poorly defined. The present studies begin to address the role of G proteins in transmembrane signaling in these pneumocytes. Membrane preparations from purified T2Ps demonstrated ADP ribosylation of specific substrates by pertussis, cholera, and botulinum toxins (PT, CT, and BT, respectively). Toxin-dependent T2P substrate labeling from 32P-labeled NAD was dependent on time and membrane protein concentration. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography showed ADP ribosylation of membrane substrates of the following molecular masses: PT, 40/41 kDa; CT, 47/51 kDa; BT, 22 kDa. BT-dependent ADP ribosylation of a 22-kDa cytosolic substrate was also observed. Pretreatment of cultured T2P with the individual toxins led to ADP ribosylation of their respective specific substrates in a time-dependent fashion. In cells pretreated with PT or CT, substrates for the complimentary toxins remained available for subsequent ADP ribosylation in vitro. This result supports the specificity of the toxin effects. Basal secretion of the major phospholipid of pulmonary surfactant, disaturated phosphatidylcholine (DSPC) was unaffected in T2P treated with PT, but was stimulated in cells exposed to CT or BT. Neither CT nor BT altered release of lactate dehydrogenase. In cells treated with AMP or with isoproterenol DSPC secretion was stimulated six- to eightfold; preexposure of the cells to CT reduced the response to either agonist by 70%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate Ribose

Stretch-related changes in lung cAMP after partial pneumonectomy.

In rats, left pneumonectomy (PNX) initiates rapid compensatory hyperplastic growth of the right lung. Previous work indicated that increased polyamine uptake associated with post-PNX distortion or "stretch" of the remaining tissue and altered adenosine 3',5'-cyclic monophosphate (cAMP) metabolism may play a role in the early phase of the growth response. Evidence was sought to link these observations with the goal of understanding control of compensatory growth. At day 1 or 3 after left PNX in vivo, increased right lung cAMP was associated with activation of the cAMP-dependent protein kinase (PKa). Total PKa activity was unaffected, but the PKa activity ratio (-cAMP/+cAMP) doubled, providing evidence for PNX-associated activation of the kinase in vivo. Neither cAMP nor PKa was altered in sham-operated control lungs. To determine whether increased distension of the right lung after PNX might initiate these changes, lungs of unoperated animals were perfused 40 min in vitro, either without ventilation or with a distending constant positive airway pressure (CPAP) of 20 cmH2O. CPAP rapidly increased uptake of the polyamine spermidine (SPD; 1.5 microM), tissue cAMP, and the PKa activity ratio, in a manner similar to that observed after PNX. Both tissue cAMP and the kinase activity ratio increased with 1 microM forskolin (FSK), as expected, but SPD uptake was unaffected by FSK. FSK did not diminish the CPAP-associated elevations of SPD uptake (P less than 0.01) or cAMP (P less than 0.05), but the kinase was not further activated by CPAP with FSK present.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Inflation-associated increases in lung polyamine uptake: role of altered pulmonary vascular flow.

Unilateral pneumonectomy in rats leads to rapid compensatory growth of the remaining lung. Previous studies showed that postoperative increases in lung mass are preceded by enhanced uptake of exogenous polyamines and by alterations in adenosine 3',5'-cyclic monophosphate (cAMP) metabolism. These effects are both mimicked in lungs of intact animals subjected to increased inflation in vitro. Partial pneumonectomy also leads to increased flow to the contralateral lung associated with reduced pulmonary vascular resistance. This raises the possibility that the postoperative metabolic response is initiated by changes in pulmonary artery pressure (Pa) or flow, rather than altered inflation. The present studies were designed to investigate this issue. Uptake of exogenous [14C]spermidine by isolated perfused rat lungs was examined over a wide range (greater than 4-fold) of pulmonary flow and ventilation at fixed PaS. Assessment of tissue metabolism from rates of protein synthesis suggested stability of the isolated lung preparations. Apnea (0 ventilation) had no effect on spermidine uptake or flow rate, compared with lungs evaluated under normal conditions of ventilation (inspiratory pressure, 15 cmH2O; positive end expiratory pressure, 2 cmH2O; rate, 70 breaths/min). At both high and low Pa (at a flow rate of 37 +/- 1 and 11 +/- 2 ml/min, respectively, with 0 ventilation), removal of the left lung from the perfusion circuit increased specific right lung flow rate greater than 30% but had no effect on spermidine uptake. Similar alterations in flow rate to the right or both apneic lungs had no effect on the tissue content of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Biochemical mechanisms of cardiac hypertrophy.

Rapid cardiac growth in adult rats and neonatal pigs involves more efficient use of existing components of the protein synthesis pathway and synthesis of new ribosomes and mRNA to increase the capacity for protein synthesis. Greater efficiency of synthesis can be induced by mechanical perturbations that stretch the ventricular wall, including increased cardiac work and increased ventricular pressure development in beating hearts, and increased aortic and intraventricular pressure in arrested-drained hearts. The biochemical signal linking stretch to more efficient protein synthesis has not been identified. Preferential synthesis of new ribosomes occurs in the first two hours of exposure of Langendorff preparations to high aortic pressure or within four hours after injection of thyroid hormone into normal rats. The rate of protein degradation is either accelerated or unchanged in hypertrophing hearts but is inhibited by induction of cardiac work or high aortic pressure in Langendorff preparations. Overall, increased capacity for, and efficiency of, protein synthesis are the major factors accounting for cardiac growth.

Aging

[Hodgkin's lymphoma with nodular sclerosis. A report of a case with an unusual sternal location at the onset].

The authors report the case of a boy, 9 years old, with a mass in the sternum and the anterior region of the mediastinum. A biopsy of the sternal mass was performed and demonstrated a Hodgkin disease variety nodular sclerosis. The disease was classified as stage III A after that two lymph nodes on the right side of the groin were revealed by lymphography. Therapy consisted of 6 alternate MOPP/ABVD cycles, followed by mantle and inverted Y field radiotherapy for a total of 25 Cg and 5 Cg booster on a sternum. During chemotherapy there was a complete regression of the disease in all sites. At present the patient is healthy and in complete remission and "off therapy", with a follow-up of 32 months. The most interesting aspect of this case is the sternum involvement as the initial manifestation of the nodular sclerosing form of Hodgkin's disease.

Biopsy

Professionalism.

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Humans