Joseph Roberts

Glutaminase induced prolonged regression of established Ehrlich carcinoma

Abstract Glutaminase treatment of mice bearing an asparaginase-resistant Ehrlich carcinoma resulted in complete regression of one week established tumors in 67 to 80 percent of animals and more than 200 percent prolongation of survival time to date. Combination of glutaminase with asparaginase did not produce a better therapeutic effect than glutaminase alone.

Kinetics of uptake and activity in mouse liver of glutaminase coupled to desialated orosomucoid

Desialised orosomucoid (alpha-1-acidic glycoprotein) was coupled to Pseudomonas 7A glutaminase-asparaginase by glutaraldehyde, iodinated and injected into mice. The half-life of radioactivity and glutaminase activity in plasma was about 7 min. Radioactivity and glutaminase activity in the liver reached a peak at about 20 min. The radioactivity in liver then declined with a half-life of about 20 min. Enzyme activity in liver declined with a half-life of about 10 min. The ratio of enzyme activity to radioactivity was lower in the liver than in plasma at all times during the experiment, indicating rapid hepatic inactivation of the enzyme. Uptake into the liver could be blocked by excess desialised orosomucoid. Glutamine levels in the liver were about 10% of normal for 44 min but returned to 50% of normal by 93 min. Intestines, kidney and spleen failed to exhibit any appreciable uptake of desialated orosomucoid glutaminase-asparaginase.

The changing faces of cholangitis.

A variety of diseases are included under the umbrella term ‘cholangitis’, including hepatobiliary diseases with an autoimmune pathogenesis (such as primary sclerosing cholangitis, primary biliary cholangitis, and IgG4-associated sclerosing cholangitis) and disease processes associated with intraductal stones and infectious etiologies (such as ascending bacterial cholangitis, recurrent pyogenic cholangitis, and liver fluke-associated cholangitis). Recent advances in the pathophysiologic bases of these disorders, particularly with respect to the autoimmune variety, are allowing improved diagnosis and prognostication as well as providing the opportunity to refine and re-imagine treatment modalities. The aim of this review is to highlight selected advances in cholangitis research that point to novel insights into the pathophysiology, diagnosis, and treatment of this diverse array of disorders.

Active enzyme sedimentation of antitumor asparaginase and glutaminase enzymes

Abstract Active enzyme sedimentation of five asparaginase and glutaminase-asparaginase enzymes with antitumor activity was studied. The catalytically active species of each enzyme appeared to have a molecular weight greater than 100,000 g/mole. Gel filtration and disc gel electrophoresis confirmed the absence of catalytically active smaller species.

Endoscopic resection of gastric adenocarcinoma by use of a full-thickness resection device

Figure 2. Representative axial CT image showing sequelae of cirrhosis A 62-year-old man with hepatitis C mediated Child’s A cirrhosis and severe chronic obstructive pulmonary disease presented for esophageal variceal screening with upper endoscopy. In addition to small varices, a small 6-mm irregular lesion was found in the gastric fundus (Fig. 1), which underwent biopsy and was found to be a gastric adenocarcinoma with signet ring features. Staging CT of the chest, abdomen, and pelvis did not reveal any distant metastases or other masses, although we did observe marked intra-abdominal vascular collaterals and splenomegaly (Fig. 2). EUS revealed a mucosal mass extending into the level of the submucosa, without adjacent lymphadenopathy. Surgical consultation was obtained, and, given the small size of the lesion and the significant comorbidities associated with an open total gastrectomy, the patient opted for an attempt at endoscopic removal with the full-thickness resection device (FTRD). Using an Olympus 1T190 endoscope (Olympus Corp, Tokyo, Japan), we identified the lesion and marked the borders with cautery (Fig. 3). The 1T endoscope was removed, and the Olympus 2T180 endoscope was fitted