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Biomedical subjects

J U Balis

Publications and source records attributed to J U Balis.

At least 55 records · Page 3Linked to original sources
PubMed1979

Inhibition of the contractile action of bradykinin on isolated smooth muscle preparations by derivatives of low molecular weight peptides.

The carbonyl terminal tripeptide sequence of bradykinin (Pro-Phe-Arg) is molecularly manipulated to obtain agents with potent antagonistic activity towards the smooth muscle contractile activity of bradykinin. Screening of various peptide derivatives revealed that heptyl amides or esters of H-D-Pro-Phe-Arg, and H-D-Phe-Phe-Arg possessed relatively stronger antibradykinin activity on the isolated smooth muscle preparation. The parent tripeptides, H-D-Pro-Phe-Arg-OH, and H-D-Phe-Phe-Arg-OH, and their amino acid components, i.e. D-Proline, D-Phenylalanine, L-Phenylalanine and Arginine, did not possess any antibradykinin activity in concentrations of up to 10(-4) M. When the heptyl derivatives of these peptides were incubated with either heparinized or citrated whole blood or plasma, the antibradykinin activity was not lost. Incubation of these peptide derivatives with either carboxypeptidase A or B did not result in any loss of the pharmacological effect. However, pancreatic protease extract produced a significant loss of the anti-oxytocic action on the isolated rat uterus preparation. H-D-Pro-Phe-Arg-NH-lauryl derivative also blocked the action of bradykinin and this effect sustained for a longer period of time comparative to the blockade with H-D-Pro-Phe-Arg-NH-heptyl derivative. In concentrations of 10(-7) M and 10(-8) M and 1 min incubation, which blocked the contractile action of bradykinin (1 nmole) on the isolated guinea pig ileum, these peptide derivatives did not block the action of acetylcholine, histamine, and serotonin. However, in concentrations of about 10(-6) M and higher with 5 min. incubation histamin is also blocked. On the isolated rat uterus preparation the contractile action of acetylcholine, angiotensin, oxytocin and vasopressin was blocked at concentrations of 10(-6) M. These findings warrant a differential pharmacological evaluation and in vivo testing of these peptide derivatives to investigate their therapeutic potential.

Acetylcholine↗
PubMed1978

A primate model for prolonged endotoxin shock. Blood-vascular reactions and effects of glucocorticoid treatment.

A primate model was developed to study sequential blood-vascular responses, primarily of the lung and liver, and hematologic changes during prolonged endotoxemia with or without glucocorticoid treatment. In this model, pairs of animals, one with intermittent glucocorticoid regimen, were continuously infused with endotoxin throughout the experimental period. The duration of the experiment and the onset of progressive shock could be adjusted by changing the rate of endotoxin infusion. Endotoxemia at a rate of 10 mg. per kg. per hour resulted in progressive shick which was significantly delayed with glucocorticoid treatment. Endotoxin-induced hematologic alterations included early leukopenia and gradual development of disseminated intravascular coagulation. Morphologic studies revealed margination of neutrophils and mononuclear cells in the microcirculation of lung and liver. These changes were associated with sustained phagocytosis of endotoxin by the sequestered leukocytes and Kupffer cells, degranulation of the hepatic sinusoids and spaces of Disse contained extensive fibrinous deposits which in advanced stages of shock were accompanied by midzonal and centrilobular necrosis. Pulmonary lesions included margination, degranulation and fragmentation of leukocytes, early appearance of fibrin in hepatic sinusoids, and rapid development of disseminated intravascular coagulation, endothelial damage and associated lesions of lung and liver. The results indicate that events relating to sustained phagocytosis of endotoxin by the marginating leukocytes initiate a state of intravascular inflammation with disseminated intravascular coagulation and play a vasic role in the pathogenesis of pulmonary and hepatic lesions during prolonged endotoxemia leading to shock. The findings also suggest that glucocorticoid treatment attenuates endotoxin-induced blood-vascular reactions thereby providing an early protection against the development of shock and structural damage to the lung and liver.

Animals↗
PubMed1977

Isolation and characterization of proteins associated with the lung surfactant system.

Rabbit lung washings and purified lung surfactant were delipidated without precipitation or loss of protein. This enabled effective study of the proteins by electrophoretic and immunoelectrophoretic techniques. The lung washings contained secretory immunoglobulin A and several serum proteins. The protein composition of purified lung surfactant was the same as the unfractionated lung washings confirming our previous study which indicated that there is no specific protein associated with surfactant phospholipids obtained by alveolar lavage with isotonic saline.

Animals↗
PubMed1975

Perinatal reactions of the rabbit lung to maternal endotoxemia.

The reactions of the fetal and newborn lung to in utero injury were investigated in rabbits using as a model maternal administration of Escherichia coli endotoxin, 2 to 4 mug per kg. of body weight, injected intravenously at the 29th gestational day. At 6 hours after endotoxin injection, the lung revealed diffuse alveolar damage-sparing type II cells which appeared resistant to injury but more mature than type II cells from control lungs. These changes were followed by a reparative phase which over a 2-day period resulted in increased interstitial cellularity, replacement of the damaged type I cells by proliferated type II cells, and marked intraalveolar accumulation of myelin figures. The above reactions were associated with an average increase of 100 per cent in the phospholipid content of the surfactant fraction isolated from lung washing. Postnatally, the lungs showed structural changes resembling those seen in hyaline membrane disease of the newborn. The findings suggest that the response of the alveolar epithelim to injury inudced late in gestation follows a pattern similar to that described previously in adult lung, and is assoicated with in utero increased release of surfactant. It is proposed that alveolar injury and repair, including reduction of the intracellular surfactant reservoir occurring prior to breathing, may interfere postnatally with formation and maintenance of a normal surfactant layer, thereby predisposing to respiratory distress.

Animals↗
PubMed1975

Characterization of lung surfactant: factors promoting formation of artifactual lipid-protein complexes.

Because uncertainty exists as to whether dipalmitoyl phosphatidylcholine, the major component of lung surfactant, is part of a lipoprotein molecule, a study was designed to investigate the relationships between the phospholipids and proteins of rabbit lung washings obtained by lavage with aqueous solutions. Surface-active sediments contained phospholipid and protein in ratios directly dependent upon the ratios in the washings from which they were obtained. Comparison of negatively stained lung washings and sediments revealed that sedimentation caused extensive aggregation of surfactant "liposomes". Analytical ultracentrifugation revealed that both cell-free washings from lungs and suspension of pure phosphatidylcholine contained components with flotation rates ranging from 25 to 400. Density gradient centrifugation of washings, without prior sedimentation, resulted in the appearance of a phospholipid band associated with only a small amount of protein. The density of the band varied depending upon temperature. No qualitative differences in the protein compositions of the phospholipid band and other gradient fractions were found by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Albumin, IgG, IgM, and several nonplasma proteins were present. These results indicate that little, if any, protein is specifically attached to the phospholipids of lung surfactant; rather, the lipid-protein complexes of lung washings are the result of a nonspecific association caused by removal of water-soluble surfactant from the lung and promoted by sedimentation.

Animals↗