Biomedical subjects
Publications and source records attributed to H Yuu.
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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.
The secretion of insulin, glucagon, pancreatic juice, and amylase in response to a 20-min iv infusion of synthetic caerulein were studied simultaneously in the anesthetized rat. Caerulein, a chemical analogue of cholecystokinin, was used in doses of 1-1000 ng/kg.min. The maximum stimulatory effect of caerulein on pancreatic juice volume and amylase output was obtained with doses of 10 ng/kg.min. With increasing doses, the effect decreased progressively. On the other hand, the release of insulin and glucagon was stimulated only by supramaximal doses of caerulein, which had little or no effect on pancreatic exocrine secretions. These results raised the question of whether, under physiological conditions, cholecystokinin regulates the secretory activity of the endocrine pancreas.
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On the assumption that a rise in the pancreatic type isoamylases may not necessarily indicate underlying pancreatitis, genetic studies of human serum and urinary amylase isoenzymes have been performed with the use of electrophoresis. Although the preponderant increase in the two principal pancreatic isoamylases Amylase-1 and 2 has been accepted to be a specific index of pancreatic involvement, 1.68% of normal persons had Amylase-2 with an elevated amylase activity (named "Dominant Amylase-2") up to the same levels as the major isoenzymes. Results of pancreozymin-secretin test and other laboratory findings of these persons with Dominant Amylase-2 were all within normal ranges. Pedigree studies confirmed an autosomal dominant mode of inheritance for this variant. The important of serial determination and pedigree investigations has been shown to distinguish normal persons having Dominant Amylase-2 from patients with pancreatitis without elevated amylase activity. The existence of an inherited trait of pancreatitis-like isoamylase pattern in healthy individuals must be born in mind before coming to a conclusion when amylase isoenzymes are used for clinical medicine, though preponderance of the pancreatic type isoenzymes in serum and urine has been revealed to be a characteristic finding in pancreatitis. Knowledge of amylase genetic polymorphism provides a scientific basis for amylase isoenzyme interpretation.
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Several investigations in vivo and in vitro have shown that gastro-intestinal hormones stimulate insulin secretion. However, the reports on the insulinotropic activity of pancreozymin are contradictory. The conflicting results are probably due to the fact that pure native preparation of this hormone has not been obtained in "physiologic" doses. In the present study this problem has been investigated by exposing rat pancreas to caerulein in vitro. Caerulein, an active decapeptide isolated from the skin of the Australian amphibia Hyla caerulea, resembles pancreozymin in chemical structure, including C-terminus. This active polypeptide of nonmammalian origin has been shown to possess all the biological activities of pancreozymin. The present investigation was undertaken to evaluate the significance of the interactions of exocrine and endocrine pancreas using perfused rat pancreas in vitro. Biphasic insulin release was demonstrated with caerulein at concentrations higher than 1 ng/ml. Insulin response of the first phase was proportional to the dose up to 1 microgram/ml. The second phase of insulin release was, however, almost constant, regardless of the concentrations of caerulein. Release of glucagon was stimulated by the same concentrations of caerulein which stimulated insulin release. Maximal response of the pancreatic amylase and pancretic juice output were observed with 1 ng/ml of caerulein. With higher doses, significantly less secretory responses were observed. The dissociation of the response to caerulein between endocrine and exocrine pancreas was found.
Amylase isoenzyme analysis of serum and urine has been performed in 4001 normal persons and 500 patients with various disease 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.
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We describe an atypical serum creatine kinase isoenzyme in the serum of a woman with cancer of the left breast. This isoenzyme migrated toward the cathode, closely following the MM isoenzyme on agarose gel electrophoresis. Its relative molecular mass was estimated to be about 325,000, fourfold that of normal creatine kinase. It is more heat-stable and is inhibited more by urea than the normal MM isoenzyme. Isoenzyme monomer B activity was observed to be 20 U/liter in the serum, as measured with use of an antibody against the M monomer. On anion-exchange column analysis, creatine kinase activity was observed only in the MM fraction, in spite of the fact that B activity was observed in the patient's serum. Results of the immunological investigation make it unlikely that the atypical isoenzyme is linked to immunoglobulin or beta-lipoprotein. It may have been present as the result of modification of normal creatine kinase by the therapeutic radiation the patient was receiving.
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Serum and urinary amylase isoenzymes were studied in an attempt to evaluate the usefulness of isoamylase analysis in the diagnosis of pancreatic diseases. The amylase in human serum and urine was separated into 4 to 5 distinct isoenzymes, which have mobilities consistent with those of the pancreatic isoamylases (Amylase-1, -2, -4 and -6) and the salivary isoamylases (Amylase-3, -5 and -7). The normal isoamylase pattern was Amylase-1, -2, -3 and -5. Amylase-4 and -6 could not be found in normal serum and urine. Amylase activity in Amylase-1 and/or -2 increased remarkably, having the normal isoamylase pattern, in the patients with elevated serum amylase activity after stimulation with pancreozymin-secretin or after endoscopic retrograde cholangiopancreatography. However, in the patients with acute pancreatitis, salivary type isoamylases disappeared and only the pancreatic type components were identified. It seems that the appearance of Amylase-4 and disappearance of the salivary components indicate severe pancreatic inflammation and that the apparent specificity of this isoenzyme pattern affords a mean for conforming the diagnosis of acute pancreatitis. However, the occurrence of an inherited trait in the pancreatic isoamylases of healthy individuals suggests that a rise in the pancreatic components may not necessarily indicate pancreatic disorders.
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.
The nature of the postoperative hyperamylasemia in 27 patients undergoing open-heart surgery was investigated. An increase in serum amylase activity was found in 56% of the patients. Isoamylase analysis revealed that the rise was in the salivary-type isoamylase in all of these patients. Since the level of serum amylase activity was increased in the postoperative state with prolongation of extracorporeal circulation, it is conceivable that cellular hypoxia due to inadequate tissue perfusion may cause disturbances in cellular metabolism with a release of intracellular amylase. The finding of the salivary-type amylase in normal lung tissue, transient salivary-type hyperamylasemia in acute respiratory distress and increased amylase activity of the salivary-type in serum specimens from the left atrium compared to those from the right ventricle suggest that the origin of the amylase responsible for the transient postoperative hyperamylasemia in the salivary-type is due to the amylase released from lung tissues under hypoxia during and after operation.
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, pleural fluid and tumor extracts, and to determine whether amylase might be produced ectopically in tumor tissues. Our data not only confirmed 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.
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