Calvin A. Saravis

Sustained Depressor Effect of Renal Medullary Extract in the Normotensive Rat

Crude homogenates of rabbit, medulla produced a sustained depression of blood pressure when injected intravenously into the normotensive, anesthetized, pentolinium-treated rat. Similar activity was present in rat medulla, but not in extracts of renin-free cortex or certain nonrenal tissues. The sustained depressor activity of medulary extract possessed different physiological and chemical characteristics from the shortacting nucleotide depressor activity which is present in both cortical and medullary extracts. In addition, prolonged medullary depressor activity was separable from medullary nucleotide activity by column chromatography. The activity responsible for sustained depressor activity was a dialyzable, ethanol soluble, low molecular weight(<4500 mol wt) substance(s) which was resistant to a mixture of peptide hydrolases and destroyed by heating for one hour at 100°C.

Direct tissue isoelectric focusing in agarose.

We are isoelectric focusing small amounts of tissues placed directly on electroendosmosis-free agarose gels instead of using the saline extracts of tissue homogenates. More numerous proteins are extracted during isoelectric focusing of the solid tissues than present in the same tissues.

Signet ring carcinoma of the pancreas, a rare variant with very high CEA values. Immunohistologic comparison with adenocarcinoma.

SummarySignet ring carcinoma of the pancreas is rare. We report a case which was remarkable for (1) diffuse, infiltrating growth which suggested chronic pancreatitis at laparotomy, and (2) an associated very high circulating carcinoembryonic antigen (CEA) level of 6400 ng/ml. The case report and autopsy are presented. Twelve other cases of pancreatic adenocarcinoma (non-signet ring) are compared with the signet ring carcinoma with respect to CEA staining and circulating levels. We conclude immunocytochemical staining of biopsy tissue for CEA is a useful adjunct in the interpretation of circulating CEA levels in pancreatic carcinoma.

Perfusion techniques in temporary human—Isolated ex vivo porcine liver cross circulation: Possible adjunct in the treatment of hepatic failure

Summary Techniques of patient cannulation, isolated ex vivo porcine hepatic cannulation and flushing, and the perfusion and monitoring circuitry involved in clinical repeated short-term cross circulation between a subject and the ex vivo porcine liver are described. These methods have been applied in 9 clinical trial perfusions, the longest lasting 9 hours. Their possible continued utilization to support patients in far advanced, but reversible, hepatic failure or patients in terminal hepatic failure prior to homotransplantation, as it becomes available, is envisioned.

Techniques of obtaining and preparing the porcine liver for experimental and clinical temporary ex vivo perfusion

Summary Methods have been presented of porcine preoperative maintenance, induction and maintenance of anesthesia, intraoperative heparinization and hemodilution, prophylactic buffering prior to and during surgery along with the details of hepatectomy including hazards and rationales of the phases involved. These techniques have been utilized in 30 experimental preparations for isolated ex vivo perfusion studies and in 5 clinical perfusions. In the latter situations wherein the human-ex vivo perfused porcine liver is utilized as a possible therapeutic adjunct in the treatment of terminal hepatic failure, the avoidance of the initial phase of vasoconstriction secondary to an increase in transhepatic vascular resistance3,4 in the excised liver becomes of paramount importance in maintaining adequate flow rates to support prolonged ex vivo porcine hepatic viability.

Studies of the renin-renin substrate reaction in man; kinetic evidence for inhibition by serum.

Increasing evidence suggests that the renin-renin substrate reaction is regulated by factors other than the concentrations of enzyme and substrate. Partially purified human renin and renin substrate extracted from the plasma of each of eight human subjects were used to construct substrate-velocity curves comparing the rate of substrate cleavage in the whole serum of each individual with the rate in a corresponding system containing purified autologous substrate, or purified substrate plus a small amount of autologous serum. Linear regression analysis of the double reciprocal plots were used to compare the kinetic constants in paired experiments. Maximal reaction velocity (Vmax) was significantly lower (p > .05) when the reaction rate was measured in whole serum, in seven of the eight patients, while Km did not differ significantly, suggesting the presence of noncompetitive inhibition by human serum. The mean Michaelis constant in serum was 449 ng/ml while the average native substrate concentration of the five normal subjects was 629 ng/ml, an excess of less than twofold. The data suggest that plasma renin activity in man depends upon the concentrations of inhibitor and substrate, as well as upon the concentration of renin.

Angiotensinase Activity of Fractionated Human Plasma.

Summary Electrophoresis and column fractionation of plasma, SPPS, and the albumin peak of SPPS after electrophoresis, demonstrated that the described angiotensinase activity is normally present in a fraction distinct from albumin, alpha-2, beta and gamma globulins. Its physical characteristics generally tend to classify it as an alpha-1 globulin of a single species or of several species having very similar characteristics. That it is a protein is strongly supported by the fact that protein precipitation techniques were used in its purification, that it was nondialyzable, and that it was completely destroyed by heating to 100°C.

Production of Antibodies to Carcinoembryonic Antigen in Tolerant Rabbits

Antisera reacting with carcinoembryonic antigens isolated from metas-tases of colonic cancer were produced in mature rabbits injected at birth with heterologous proteins. The antisera were examined by the agarose gel diffusion, immunoelectrophoresis, counterimmunoelectrophoresis, and radioimmunoassay techniques. The anti-CEA antisera did not need absorption with extracts of normal liver and colon to remove antibodies to them and were interchangeable with goat anti-CEA antisera for use in assay systems for circulating CEA. The immunizing procedure using aluminum hydroxide gel as an adjuvant is described.