Hosai Yuu

Discrepancies between the Doses of Cholecystokinin or Caerulein-Stimulating Exocrine and Endocrine Responses in Perfused Isolated Rat Pancreas

The effects of highly purified natural porcine cholecystokinin (CCK) and synthetic caerulein on the rate of flow of pancreatic juice, the rate of output of amylase, and the rate of release of immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) were simultaneously investigated in the isolated perfused rat pancreas. The maximal flow rate of pancreatic juice was obtained with concentrations of CCK ranging from 0.5 to 10 mU/ml, whereas amylase output was maximal at CCK concentrations from 1 to 10 mU/ml. Caerulein at concentrations of 0.05-1 ng/ml induced a similar maximal flow rate and amylase secretion. Supramaximal stimulatory concentrations of these peptides resulted in lower rates of release of fluid and amylase than with the maximally effective concentrations. Stimulation of IRI and IRG release was elicited only with concentrations of peptides supramaximal for effects on the exocrine responses. The demonstration of very similar discrepancies between the doses of caerulein required to elicit maximal exocrine responses and those required to elicit endocrine responses provide strong evidence that the pattern of the effect of the porcine CCK is accounted for by CCK itself. Although caerulein had no influence on IRI response when superimposed on 100 or 150 mg/100 ml glucose stimulation, preperfusion of caerulein led to a significant enhancement of IRI response to a subsequent glucose stimulation in both phases. The augmentation effect was completely separate from the direct IRI-stimulating effect of caerulein, because the CCK-like peptide requires no glucose for insulinotropic action. Because the concentrations of the peptides necessary for stimulation of endocrine responses were inhibitory in their effects on exocrine responses, it may be inferred that it is unlikely that the endocrine effect is physiologically important, though the results of caerulein for augmenting glucose-stimulated IRI release suggests a possible role for CCK in carbohydrate metabolism.

Amylase in the lung.

Although elevated amylase levels in serum, pleural fluid, and extracts of tumor tissue in primary lung cancer have been reported, electrophoretic and column‐chromatographic studies have not revealed the ectopic production of amylase but have merely shown an increase of amylase activity of chiefly the salivary type in these materials. The present study was designed to make clear the nature of the amylase or amylase‐like substance in the serum, pleaural fluid and tumor extracts, and to determine whether amylase might be produced ectopically in tumor tissues. Our data not only comfirmed that the hyperamylasemia in some cases of primary lung cancer was due to an increase in salivary type isoamylases, but also showed that the same isoamylase pattern occurs in serum, pleural fluids, and diseased lung tissue of patients with pneumonia. However, the elution pattern of amylase in these materials in column‐chromatography on Sephadex G‐75 Superfine was different from that of salivary amylase. On the basis of our observations, it seems reasonable to conclude that the salivary type hyperamylasemia in some cases of primary lung cancer may be due to an increase in the amylase contained in normal lung tissues, resulting from activation and release into the blood stream by some inflammatory process. However, ectopic production of amylase was demonstrated in one particular case of primary lung cancer in which a high amylase content and a peculiar isoamylase were found both in the primary and metastatic lesions.

Salivary-type hyperamylasemia in primary lung cancer: Observation of a possible precursor of the salivary-type isoamylase

Although recent studies by column chromatography and electrophoresis showed that elevated amylase activity in the body fluids and tumor extracts in patients with primary lung cancer was mainly in the salivary-type isoamylase, neither mechanism nor mature of elevation of amylase have been clarified yet. This study was undertaken in order to make clear the nature of amylase elevated in the body fluids and tumor extracts of patients with primary lung cancer. In addition, amylase contained in the extracts of normal lungs and diseased lungs of patients who had died of various diseases was also studied. Our results revealed that amylase elevated in the body fluids and tumor extracts in patients with primary lung cancer was the salivary-type isoamylase and, moreover, that small amounts of salivary-type isoamylase in normal lung tissues and large amounts in diseased lung tissues were also contained. These facts suggested that salivary-type isoamylase was physiologically contained in normal lung tissues and large amounts in diseased lung tissues were also contained. These facts suggested that salivary-type isoamylase was physiologically contained in normal lung tissues and might be activated through pathological processes, such as inflammation, circulatory disturbance or tumor formation. Two peculiar isoamylases with cathodic mobility on polyacrylamide gel electrophoresis were found. One of them was so unstable that it was converted to the stable salivary-type isoamylase, suggesting the precursor of human salivary isoamylase.

Serum pancreatic secretory trypsin inhibitor in pancreatic disease

The clinical usefulness of serum pancreatic secretory trypsin inhibitor (PSTI) in pancreatic diseases was evaluated. The mean serum PSTI level of 41 healthy normal persons was 9.4 ng/ml (ranging from 5.2 to 16.7 ng/ml). Serum PSTI levels were abnormally raised in all patients with acute pancreatitis ranging from 35.0 to 4500 ng/ml, but were almost within normal range in patients with chronic pancreatitis, pancreatic cyst, acute abdominal emergencies such as perforated ulcer and intestinal obstruction, and macroamylasemia. There was no correlation between serum PSTI levels and total or pancreatic-type isoamylase activity. Patients with acute pancreatitis in whom the elevation of serum PSTI was transient and occurred after that of serum amylase activity had relatively mild symptoms and recovered along with normalization of serum PSTI levels. On the other hand, patients whose serum PSTI values became increased coincidentally with serum amylase activity and remained elevated, had severe clinical symptoms and unfavorable clinical outcome. Of 2 patients who underwent partial pancreatectomy, the serum PSTI level increased markedly in one who developed postoperative pancreatitis but not in the other without pancreatitis. In contrast to patients with acute pancreatitis, the serum response to the secretin stimulation in patients with chronic pancreatitis, was only small and transient, reaching the maximum at 10 min after administration of secretin. These results suggest that measurement of serum PSTI concentration may be useful in the diagnosis of acute pancreatitis and that the degree of rise and the duration of the elevated levels of serum PSTI are closely related to the severity of acute pancreatitis.

Pancreatic exocrine secretion and immunoreactive secretin release after intraduodenal instillation of 1-phenyl-1-hydroxy-n-pentane and HCl in rats.

Portal plasma immunoreactive secretin (IRS) concentrations, pancreatic juice flow, and amylase output were simultaneously measured in response to intraduodenal infusion of 1-phenyl-1-hydroxy-n-pentane (PHP), as well as infusion of hydrochloric acid (HCl). These data were compared with those obtained from intravenous bolus injections of synthetic porcine secretin in anesthetized rats. The intraduodenal infusion of PHP or HCl at a rate of 2 ml/min for 2 min produced a dose-related increase in portal plasma secretin concentrations, pancreatic juice flow, and amylase output. However, the mechanism of secretin release by PHP seems to differ from that of HCl. The secretin response to 0.1 N HCl infused at a rate of 0.1 ml/min for 30 min was complete after 10 min, despite continued infusion, while PHP stimulated a secetin release which persisted for 10 min after cessation of infusion. The pH in the second portion of the duodenum, following PHP infusion, remained consisitently greater than 6.3. PHP-stimulated pancreatic exocrine secretions were only partially suppressed by somatostation, while secretin release was almost completely inhibited. However, intraduodenal PHP may stimulate the release of secretin along with other gastrointestinal hormones, and the endogenous release of these hormones may not be inhibited by somatostatin.

The characteristics of amylase activity and the isoamylase pattern in serum and urine of infants and children

Determination of amylase activity and isoamylase patterns were performed in serum and urine of normal newborns, infants and children of different ages. In the serum of newborn infants measurable amounts of amylase were present. The activity increased with the age and reached the normal adult level by approximately 8 months of age. Isoamylase analysis revealed that the low level of serum amylase in infants was mainly due to deficiency of the pancreatic-type isoamylase. The absence of the pancreatic isoamylase in newborns and young infants is a physiological and developmental phenomenon. Great caution is therefore necessary when amylase isoenzymes are used in the diagnosis of abnormal pancreatic function and such results have always to be interpreted in relation to the age of the child.

Exocrine and endocrine secretion from isolated perfused rat pancreas with islet cell tumors induced by streptozotocin and nicotinamide

Pancreatic exocrine and endocrine function in the rat with islet cell tumors induced by streptozotocin and nicotinamide was studied in thein vitro isolated perfused pancreas. The tumor-bearing pancreas secreted significant amounts of insulin even at 2.8 mM glucose stimulation. Further, insulin response to 8.3 mM glucose stimulation was greater in the tumor-bearing pancreas than in the control. Not only endocrine, but also exocrine, disorders were found in the rat pancreas bearing islet cell tumors. In contrast to the increased response of insulin, amylase output in response to 0.1 ng/ml cerulein was significantly lower in the tumor-bearing than in the control pancreas, although there was no difference in pancreatic juice flows from both groups. These results suggest that enzyme secretory function of the pancreas with islet cell tumors may be suppressed in the presence of some interrelationship between the exocrine and endocrine portion of the pancreas with islet cell tumors.

Clinical evaluation of the pancreatitis-like isoamylase pattern in normal persons.

SummaryAmylase isoenzyme analysis of serum and urine has been performed in 4001 normal persons and 500 patients with various diseases using electrophoresis on thin layer polyacrylamide gel.Although elevation of amylase activity in amylase-1 and 2 has been reported to be the specific findings in patients with pancreatitis, 1.69% of normal persons had an elevated Amylase-2 (named “Dominant Amylase-2”) up to the same levels as major isoenzymes (Amylase-1 and 3), along with Amylase-1. Pedigree study confirmed an autosomal dominant mode of inheritance for Dominant Amylase-2. Knowledge of the genetic polymorphism is of importance in clinical assessment of amylase isoenzymes in patients having an elevated Amylase-2 suggestive of pancreatitis.Predominance of the pancreatic components in serum and urine has been revealed to be a specific index of pancreatic involvement. However, the existecne of an inherited trait of pancreatitis-like isoamylase pattern in healthy individuals must be borne in mind.On the basis of the present study, it may be concluded that a rise in the pancreatic type isoenzymes may not necessarily indicate underlying pancreatitis, especially in the absence of elevated amylase and lipase levels.

Electrophoretical and biochemical study of amylase in the lung

Electrophoretical and biochemical characteristics of amylase in the extracts of lung tissues were investigated.Amylase activity in the extracts of the diseased lung tissues was significantly higher than in the normal lung tissues. However, electrophoretical properties of amylase in these tissues were revealed to be the same as salivary amylase on polyacrylamide gel electrophoresis.Heat treatment at 56°C demonstrated that amylase in the extracts of lung tissues was more stable than that of saliva or pancreatic juice.Amylase activity in saliva and the extracts of lung tissues was suppressed similarly by rabbit antiserum against human salivary amylase.Km value of amylase in the extracts of lung tissues for Blue Starch was almost same as that of saliva, indicating that both have the same enzymatic nature.