Kinetic studies on the fragmentation of the third component of complement (C3) by trypsin

The kinetics of cleavage of C3 by trypsin was analyzed by electrophoresis in agarose and in polyacrylamide gels containing sodium dodecyl sulfate and the data obtained were used to construct an anatomical model for C3 showing the sites of tryptic attack, the fragments generated, and their composition. Trypsin was shown to cleave C3 in a stepwise fashion. The attack was initially directed at the alpha-polypeptide chain and resulted in the generation of C3a and C3b. Further cleavage of the alpha-chain of C3b, converted it into C3b1 and then into C3d and C3c. Cleavage of the beta-chain by trypsin occurred only at the C3c stage with the release of a small peptide (m.w. 12,000) from C3c and the formation of C3c'. On immunoelectrophoresis, C3c' had a less anodal mobility compared to the beta1A mobility of C3c. C3a, once formed could be further cleaved to give residual fragments with decreasing net positive charge. Exposure of C3 to acid conditions, pH 5.0 or below, rendered the molecule exceedingly susceptible to tryptic degradation.     

Correlation between regional cerebral blood flow and oxidative metabolism. In vivo studies in man

To test the hypothesis that regional cerebral blood flow (rCBF) is normally regulated by regional metabolic activity, rCBF and the regional cerebral metabolic rate for oxygen (rCMRO2) were compared in selected human subjects. In normal subjects and patients with chronic, stable diseases of brain, rCBF correlated well with rCMRO2. In one individual with mild dementia, rCBF and rCMRO2 were measured before and during exercise of the hand and forearm contralateral to the hemisphere studied. Appropriate parallel changes occurred in both rCBF and rCMRO2 during hand exercise. In patients with acute diseases affecting the hemisphere studied, however, the correlation between rCBF and rCMRO2 was unpredictable.     

Incidence and pathophysiological changes in chronic two-kidney hypertension in the dog

Unilateral renal artery plication in dogs reduced renal blood flow by 80% and produced a sustained elevation in arterial pressure whereas plasma renin activity increased for only 4 days. Sodium was retained for 3 days after plication, but this response is similar to that after a sham operation. Of seven dogs studied chronically, elevated arterial pressure was sustained for 27 days or longer in six animals. In three dogs hypertension continued for 2 mo before collateral vessels developed and arterial pressure fell; ligation of these collaterals restored hypertension. Arterial pressure was unaffected by an infusion of [1-sarcosine, 8-alanine] angiotensin II in chronic hypertensive dogs on a normal sodium intake. This angiotensin antagonist lowered arterial pressure after sodium depletion, but became ineffective following rapid sodium repletion. Chronic hypertensive dogs showed normal responses to deoxycorticosterone acetate. These findings suggest that the renin-angiotensin system is not critically involved in maintenace of chronic two-kidney renovascular hypertension in the dog. The data also show that the homeostatic role played by the renin-angiotensin system in the maintenance of arterial pressure remained intact in chronic hypertension.     

Gastric erosions: radiological and endoscopic aspects

Varioliform gastric erosion is a common lesion which can be reliably diagnosed radiologically. The diagnosis was established in 27 (1.7%) of 1,600 detailed radiological examinations made in 1975. There was a good correlation with gastroscopic findings.     

Analyte and label binding assay read by flow cytometry

A new immunometric two-site sandwich assay is introduced, in which a label-scavenging binding partner is added to the sample in addition to the analyte-binding partner. The scavenger binding partner binds excess label antibody, giving a signal proportional to the amount of excess label antibody in the sample solution. A set of two calibration curves is obtained from the two binding partners simultaneously, and a combination of the two signals gives an unambiguous determination of the analyte concentration, even for high analyte concentrations where the hook effect may occur. Two-particle immunofluorometric assays developed for placental alkaline phosphatase and human chorionic gonadotropin on the basis of this principle and yielding signals measured by flow cytometry gave rapid results (2 h) and had working ranges in excess of 5 and 6 orders of magnitude for the respective analytes.