A monoclonal antibody against gamma-glutamyltransferase from human primary hepatoma: its use in enzyme-linked immunosorbent assay of sera of cancer patients

A monoclonal antibody, gamma-120, was raised against a highly purified gamma-glutamyltransferase (gamma GT) from human primary hepatoma. The antibody preferentially bound to the small subunit of gamma GT from human hepatoma and kidney as evidenced by immunoblot analysis. Weak binding to the normal liver enzyme could be detected by solid-phase enzyme-linked immunosorbent assay (ELISA). With the use of this antibody, an ELISA was developed for the quantitation of immunoreactive gamma GT in human serum. Sera of 188 normal control subjects displayed a low level (9.4 micrograms/ml) of immunoreactive gamma GT. Highly elevated levels of immunoreactive gamma GT were detected in the sera of patients with primary hepatoma, metastatic liver cancer, pancreatic cancer, and certain types of lung cancer. Slightly elevated levels of immunoreactive gamma GT were seen in the sera of patients with liver cirrhosis. The levels of gamma GT were within a normal range in the sera of patients with gastrointestinal cancers and patients with nonmalignant diseases such as hepatitis and gallstones. The antibody has been shown to be useful for the diagnosis of some of the neoplastic diseases.     

Effects of fexofenadine hydrochloride in a guinea pig model of antigen-induced rhinitis

Allergic rhinitis is an inflammatory disease of the nasal mucosa, induced by histamine, leukotrienes, and other substances released from mast cells. Fexofenadine hydrochloride, the active metabolite of terfenadine, is a novel, nonsedating antiallergic drug having H1 receptor antagonistic activity. Fexofenadine is effective for the treatment of allergic rhinitis. However, its mechanism of action in attenuating nasal congestion has not yet been elucidated. Therefore, we first examined the effects of fexofenadine on a guinea pig model of antigen-induced rhinitis. We also evaluated the effects of mepyramine, zafirlukast and ramatroban in this model; these drugs are an H1 receptor antagonist, a selective leukotriene antagonist and a selective thromboxane antagonist, respectively. Rhinitis was induced by ovalbumin (OVA) instillation into the nasal cavity of animals that had been sensitized by two earlier OVA injections (s.c. and i.p.). The nasal airway resistance was measured for 45 min after the challenge. Fexofenadine hydrochloride (20 mg/kg) and terfenadine (20 mg/kg) administered orally 70 min prior to the challenge significantly inhibited (fexofenadine, p < 0.001, terfenadine, p < 0.05) the increase in nasal airway resistance. Ramatroban (30 mg/kg) administered orally 60 min prior to the challenge also significantly inhibited (p < 0.05) the increase in nasal airway resistance. In contrast, mepyramine (3 mg/kg i.v.) and zafirlukast (3 mg/kg p.o.) failed to reduce the increase in nasal airway resistance. These results suggest that thromboxane may be involved in the increase in the nasal airway resistance in this model. Accordingly, fexofenadine may reduce the increase in nasal airway resistance by inhibiting the release of chemical mediators, including thromboxane, that are involved in the increase in nasal airway resistance in this model.     

Negative inotropic action of propofol is enhanced in the acute ischemic myocardium of dogs

Purpose We investigated the effects of propofol on contractility and oxygen balance in acute ischemic myocardium and compared them with those of normal myocardium using a coronary microembolization model in dogs.Methods In open-chest dogs, the left anterior descending coronary artery (LAD) was perfused through an extracorporeal bypass from the carotid artery. Regional myocardial contractility and myocardial oxygen balance were evaluated along with segment shortening (%SS), regional myocardial oxygen consumption (MVO₂), and lactate extraction ratio (LER) of the area perfused by the LAD. Acute ischemia was produced by repeated injection of microspheres into the LAD-perfused area until %SS decreased by 50% of baseline.Results In normal myocardium, intracoronary infusion of propofol at doses of 1.2 and 2.4mg·kg^–1·h^–1 caused slight decreases in %SS to 83% ± 8% and 80% ± 10%, respectively. In ischemic myocardium, propofol caused greater decreases in %SS (59% ± 18% and 35% ± 20%, respectively). The changes in MVO₂ after propofol infusion generally paralleled the changes in %SS, but LER was not changed in either ischemic or normal myocardium.Conclusion Propofol causes a greater decrease in the contractility of acute ischemic myocardium as compared with normal myocardium in which myocardial oxygen imbalance is not involved as a mechanism.