Katsumi Iwase

Changes in Superoxide Dismutase Activities and Concentrations and Myeloperoxidase Activities in Leukocytes from Patients with Diabetes Mellitus

To investigate whether the two free-radical scavengers, Cu, Zn- and Mn-superoxide dismutase (SOD), are changed in leukocytes of diabetic patients, and the alteration of these enzymes correlates with the diabetic state, we measured the activity and concentration of these enzymes in leukocytes from diabetic patients. Both Cu, Zn-SOD and Mn-SOD activities in neutrophils and lymphocytes were significantly lower in patients with non-insulin-dependent diabetes mellitus than in healthy controls. The concentrations of these enzymes in leukocytes from diabetic patients, however, did not differ from those in controls. Cu, Zn-SOD and Mn-SOD activities in neutrophils inversely correlated with HbA(1c) concentrations. Myeloperoxidase activity in leukocytes was significantly reduced in NIDDM patients. These findings suggest that changes in these enzymes may affect the susceptibility to infection and immunocompetence of patients with diabetes.

High activity of cyclic 3',5'-nucleotide phosphodiesterase in sera of patient with phaeochromocytoma

Our previous observations that serum cyclic 3′,5′‐nucleotide phosphodiesterase activity varied in thyroid disorders and was positively correlated with thyroid function stimulated us to investigate the phosphodiesterase levels in sera of patients with pituitary and adrenal disorders, and the response to glucagon in normal subjects. Both serum cyclic AMP phosphodiesterase (cyclic AMP‐PDE) and cyclic GMP phosphodiesterase (cyclic GMP‐PDE) activities were measured at a low substrate concentration. Serum cyclic AMP‐PDE activity was elevated in five patients with phaeochromocytoma and was not elevated in patients with Cushings syndrome or acromegaly, compared to the level in normal subjects. Increased enzyme activities returned to normal after resection of the tumours. Intramuscular injection of glucagon to five healthy subjects elevated cyclic AMP levels and cyclic AMP‐PDE activity in plasma. These results imply that the increased cyclic AMP level by the activation of cyclase may have induced cyclic AMP‐PDE in the target organ and the soluble cyclic AMP‐PDE may leak into blood vessels from target organs.

Immunohistochemical Study of Neuron- Specific Enolase and CA 19-9 in Pancreatic Disorders The Value of Neuron-Specific Enolase as a Marker for Islet Cell and Nerve Tissue

Immunohistochemical studies of neuron-specific enolase were performed on pancreatic tissues from patients with insulinoma, nonfunctioning islet cell tumor, chronic pancreatitis, and pancreatic adenocarcinoma, and from 5 normal patients. The concentration of neuron-specific enolase was also measured in the sera of patients and in the pancreatic tissue, and the tissues were stained for carbohydrate antigen 19-9 by immunohistochemical techniques. Neuron-specific enolase was localized in nerve fibers, normal islet cells, and islet cell tumors; its concentration was elevated only in the tissue of islet cell tumors and in serum from patients with insulinoma. In the pancreatic tissue of pancreatitis or pancreatic adenocarcinoma, various changes in acini and islets were present. The altered islets stained clearly for neuron-specific enolase and could easily be distinguished from altered, unstained acini in cases of pancreatitis or pancreatic adenocarcinoma. Islets in the pancreatic tissue remained intact with various morphologic changes, although acini had degenerated severely. Carbohydrate antigen 19-9 was localized in all the carcinoma cells in the pancreatic tissue and in some of the normal pancreatic ducts. No cells were simultaneously immunostained by anti-neuron-specific enolase and anti-carbohydrate antigen 19-9 antibodies. Thus, neuron-specific enolase is a good marker for islet cell tumor, and is valuable for examining islets in pancreas with various disorders both alone and in combination with other tumor markers.

Effect of Somatostatin and Dopaminergic Agents on Bovine Pituitary Phosphodiesterase Activity

The effects of somatostatin and dopaminergic agents on pituitary cyclic nucleotide phosphodiesterases that had been partially purified through DEAE cellulose column chromatography were studied. Somatostatin, L-dopa, dopamine and CB-154(2-bromo-alpha-ergocriptine) competitively inhibited the pituitary cyclic AMP phosphodiesterase activity, especially that of the low Km enzyme. This inhibition was most potent in the case of somatostatin and CB-154.

Inhibitory effect of thyroid hormones on pituitary cyclic AMP phosphodiesterase activity in vitro

Thyroid hormones effectively inhibited partially purified cyclic AMP phosphodiesterase from the anterior and posterior lobes of bovine pituitary gland competitively with the substrate, but thyronine, diiodotyrosine, monoiodotyrosine, thyrotropin, thyrotropin releasing hormone, dexamethasone, and luteinizing hormone releasing hormone did not inhibit this enzyme activity.Ki values were found to be 1.0 and 2.5 μM for thyroxine, and 8.0 and 13.5 μM for triiodothyronine in the anterior and posterior lobes, respectively.