Biomedical subjects
Publications and source records attributed to S I Said.
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Immunohistochemical studies have demonstrated that immunoreactive vasoactive intestinal peptide is present in, and restricted to, the differentiating and mature ganglion cells in a variety of normal and neoplastic neural tissues. In a composite pheochromocytoma-ganglioneuroma (associated with the syndrome of watery diarrhea, hypokalemia, and hypochlorhydria), five ganglioneuroblastomas, five ganglioneuromas (two of which were associated with diarrheal syndromes), an unusual mixed neuroblastoma-ganglioneuroma, and four normal sympathetic ganglia, vasoactive intestinal peptide was present in differentiating and mature ganglion cells. The peptide was also demonstrated in isolated ganglion cells in two pheochromocytomas but was not present in pheochromocytes, Schwann cells, or undifferentiated neuroblastic cells in the neuroblastomas and ganglioneuroblastomas. These studies indicate that the presence and presumably the production of vasoactive intestinal peptide thus reflect a particular line of neuroblastic differentiation and are not merely a reflection of common derivation of these tissues. Our identification of vasoactive intestinal peptide in neurogenic tumors associated with diarrhea supports the contention that the peptide might be an important diarrheogenic factor in these tumors.
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In animals, the effects of vasoactive intestinal polypeptide (VIP) include peripheral vasodilation, hyperdynamic circulation, hyperglycemia, and hyperventilation. Because these phenomena are noted in patients with cirrhosis, it has been postulated that VIP might be escaping hepatic inactivation and entering the systemic circulatory system and contributing to these abnormalities. The major purpose of this study is to establish whether or not VIP levels are elevated in patients with cirrhosis. Additional goals are to determine if VIP levels are elevated in acute liver disease and in chronic illnesses with secondary liver involvement. The data demonstrate that patients with cirrhosis and those with acute liver disease or chronic illnesses with secondary hepatic involvement have a wide range of VIP levels with mean values significantly above that of normal individuals and patients with chronic illness and no liver involvement.
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Symptoms of hypersensitivity pneumonitis in three employees in an office building led to an investigation of their work environment. An open spray water air cooling system was implicated when inhalation challenge with the spray water caused acute illness in one of them. A questionnaire survey of the 4,023 co-workers identified 48 other suspect cases, and laboaratory studies confirmed hypersensitivity pneumonitis in three additional workers of this group. A significant change in pulmonary function, occurring only after exposure to the work environment, was the most useful laboratory finding and was found in five workers with no other pulmonary abnormalities, but not is asymptomatic workers or controls, since five of the six patients with hypersensitivy pneumonitis worked in offices cooled by the spray water system and since three had positive responses to inhalation challenge, use of the spray water system was discontinued. The affected workers improved after they were removed from the office complex.
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The 23-peptide 15-lysine-secretin-(5-27) [S(5-27)] was synthesized on an insoluble support. The residue in position 15 of secretin, aspartic acid, was replaced by lysine, which occupies that position in the vasoactive intestinal polypeptide (VIP), a member of the secretin family. The resulting analogue showed increased VIP-like activity on smooth muscle preparations and unaltered secretin-like activity on pancreatic juice secretion in the rat. The affinity of the new analogue was high-affinity secretin receptors in acinar cells from guinea pig pancreas was less than that of S(5-27) but was higher than that of S(5-27) for high-affinity VIP receptors in the same cells.
Cyclic adenosine 3',5'-monophosphage (cyclic AMP) levels in guinea-pig tracheal rings increased on incubation with the vasoactive intestinal peptide (VIP). The effect was potentiated by the addition of theophylline. The results suggest that the tracheo-bronchial relaxant action of VIP may be mediated by stimulation of tracheal adenylyl cyclase.
Vasoactive intestinal polypeptide (VIP) was tested on neurons in the rat sensory motor cerebral cortex and on the isolated hemisected toad spinal cord. Iontophoretically applied VIP excited deep, spontaneously active cortical neurons, including identified corticospinal neurons. The excitation had a latency of onset varying from several seconds to over 1 min and often lasted for a minute or longer after cessation of the application. Desensitization of the effect occurred with repeated applications. VIP caused a depolarization of motoneurons and dorsal root terminals in the isolated amphibian spinal cord. Threshold for this effect was about 10(-6) M. The effects of VIP on both preparations were comparable with those of another peptide, substance P.
The effects of synetic porcine vasoactive intestinal peptide (VIP) on pancreatic and biliary secretion and on glucose, insulin and calcium blood levels were examined in the dog and compared with the effects of natural porcine VIP. Synthetic VIP was a secretin-like partial agonist of pancreatic and biliary secretion with efficacies relative to secretin of 0.27 and 0.41, respectively. Consistent with its weak secretin-like action, synthetic VIP augmented the pancreatic response to CCK-OP and the submaximal but not the maximal response to secretin. Synthetic VIP also produced a dose-dependent increase in blood glucose levels and a synchronous and proportionate increase in blood insulin levels. A slight increase in total calcium levels was equivocal. The effects of antural VIP on pancreatic and biliary secretion and on glucose and insulin blood levels were identical to those of synthetic VIP. The identity of effects supports the validity of the postulated structure of porcine VIP. Although elicited at high doses, the effects of VIP on exocrine and endocrine secretion may be relevant physiologically in the context of a neurocrine or paracrine role for VIP.
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Environmental lung injury may take the form of acute tracheobronchitis, asthma, pulmonary edema, chronic bronchitis, emphysema, allergic pneumonitis, fibrosing alveolitis, pleurisy, and neoplastic disease. Environmental factors eliciting these responses include irritant gases and fumes, oxidants, organic allergens, inorganic dust, bacterial enzymes, and high partial pressures of oxygen. The basic pulmonary reactions to these toxic agents--bronchoconstriction, vasoconstriction, increased vascular permeability, inflammation, carcinogenesis--may be mediated, aggravated, or modulated by biologically active substances. These humoral agents include biogenic amines (e.g. histamine): peptides (e.g., bradykinin, vasoactive intestinal peptide, and spasmogenic lung peptide); enzymes (e.g., proteases, superoxide dismutase, and mixed function oxidases); and acidic lipids (e.g., prostaglandins, prostaglandin endoperoxides, and thromboxanes).
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