Hideyuki Wakasugi

Plasma human pancreatic polypeptide response in chronic pancreatitis

SummaryThe changes of plasma pancreatic polypeptide (PP) and the relationship between PP response and exocrine pancreatic function in chronic pancreatitis are reported. In 260 healthy control subjects, plasma PP levels increased gradually with aging. Basal levels of PP in 30 patients with chronic pancreatitis were significantly lowered in comparison with age matched control subjects (control 95.0 ± 10.3 pg/ml, chronic non-calcifying pancreatitis 45.0 ± 7.3 pg/ml, chronic calcifying pancreatitis 40.4 ± 6.0 pg/ml). Plasma PP response by insulin induced hypoglycemia, test meal ingestion, and pancreozymin-secretin injection represented a significant decrease in patients with chronic pancreatitis. Additionally, maximum PP response, especially in pancreozymin-secretin injection, had a good correlation with exocrine pancreatic function. These results suggest that the determination of plasma PP response is useful for the diagnosis of chronic pancreatitis.

Clinical investigation of serum deoxyribonuclease: II. Clinical studies of serum deoxyribonuclease activity in pancreatic disease.

SummarySerum Deoxyribonuclease (DNase) of normal persons and of patients with chronic pancreatitis, pancreatic cancer, Diabetes Mellitus, or other malignant diseases was determined with (32P) DNA as substrate. Serum DNase activity was much lower in patients with chronic pancreatitis, pancreatic cancer, or other malignant diseases than in control subjects, and serum DNase activity was almost normal in patients with Diabetes Mellitus.There was no correlation between serum DNase and serum amylase, but there was a good correlation between serum DNase and DNase I output in duodenal juice. There was an inverse correlation between serum DNase and serum RNase.These results imply that in the diagnosis of possible pancreatic disorders serum DNase may be a good indicator and thus may be useful for the detection of malignant diseases.

Serum ribonucleases in pancreatic cancer: Relation to tumor histology

SummarySerum Ribonuclease (RNase, EC. 3.1.4.22) of normal persons and of patients with chronic pancreatitis, or pancreatic cancer was determined with poly (C) as substrate.Strikingly abnormal elevations occured in the serum RNase of patients with pancreatic cancer (p<0.001). Average serum RNase values of 18 normal persons, 10 patients with chronic pancreatitis and 26 patients with pancreatic cancer were 92, 118, and 249 units, respectively.In patients with pancreatic cancer, we compared the RNase level with four histologic types (ductar cell adenocarcinoma, anaplastic cell carcinoma, acinar cell carcinoma, and islet cell carcinoma). Adenocarcinoma showed higher activity than the other histologic types (p<0.005).When we compared the serum of pancreatic cancer and pancreatic cancer tumor extract with normal serum and normal pancreas extract, strikingly different phosphocellulose Chromatographie pattern were evident. The correlation of increased serum RNase levels with tumor histology and different Chromatographie pattern may explain the new enzyme production in cancer patients, and have biological significance in the development of pancreatic cancer.

Clinical studies on human pancreaticdeoxyribonuclease I

SummaryDuodenal juice collected after administration of Boot’s pancreozymin and secretin to patients with various pancreatic diseases was subjected to deoxyribonuclease I (DNase I) assay, as well as measurements of total volume, amylase output and maximum bicarbonate concentration. It was observed that the DNase I output is well correlated with each of the three latter factors. The DNase I output was much lower in patients with chronic pancreatitis or pancreatic cancer than in control subjects, and DNase I output was even found to be low in patients suspected of having chronic pancreatitis, who did not give abnormal results with other assay methods. These results imply that DNase I output may be a good indicator of exocrine function of the pancreas, and thus may be useful for early detection of pancreatic diseases.

Studies on intestinal malabsorption in chronic pancreatitis

SummaryPancreozymin-secretin test (PS test) and intestinal absorption tests were performed in 21 patients with chronic calcific pancreatitis and 32 patients with chronic noncalcific pancreatitis to evaluate exocrine functions of the pancreas. And the following results were confirmed.(1)Fecal fat excretion increased in 33% of chronic pancreatitis (47% of calcific pancreatitis and 25% of noncalcific pancreatitis). Serum carotene leves showed significantly low levels in 44% of chronic pancreatitis (67% of calcific pancreatitis and 27% of noncalcific pancreatitis).(2)D-xylose tolerance test was abnormally low in only 6% of chronic pancreatitis, but Schilling test was evaluated abnormally low in 29% of chronic pancreatitis (50% of calcific pancreatitis and 11% of noncalcific pancreatitis).(3)Fecal fat excretion increased in cases of severe exocrine insufficiency of the pancreas with decreased amylase output and decreased maximum bicarbonate concentration in PS test.(4)Correlation of fecal fat excretion to maximum bicarbonate concentration was statistically significant, but those to amylase output or volume of pancreatic juice were not significant.(5)Antacid drugs combined with pancreatic extracts seems to be indispensable in the treatment of chronic pancreatitis as far as malabsorption in chronic pancreatitis is concerned.

Evaluation of Exocrine Pancreatic Function by Oral Administration of N-Benzoyl-L-tyrosyl-p-aminobenzoic Acid (PFD Test) in Primary Diabetes mellitus

Exocrine pancreatic function was evaluated in patients with primary diabetes mellitus by oral administration of N-benzoyl-L-tyrosyl-p-aminobenzoic acid (pancreatic function diagnostic test, PFD test) and p-aminobenzoic acid (PABA absorption test). In both primary diabetes mellitus and chronic pancreatitis, the mean excretion of PABA in the urine in the PFD test was significantly less than in the controls, and in 19 of 31 (61.3%) patients with primary diabetes mellitus and 11 of 12 (91.7%) patients with chronic pancreatitis there was a low PABA excretion rate. In contrast, the mean excretion of PABA in the urine in the PABA absorption test was significantly less in those with primary diabetes mellitus than in the controls. Therefore, to detect disturbances of pancreatic exocrine function in patients with primary diabetes mellitus, differences in the excretion of PABA in the urine between PFD test and PABA absorption test should be calculated. According to this method, the rate of abnormality was 12.9% in primary diabetes mellitus and 100% in chronic pancreatitis. There was a significant correlation between the excretion of PABA in the urine in the PFD test and results of renal function tests in primary diabetic patients with a normal range of serum creatinine levels. The serum PABA levels in the PFD test remained high in patients with primary diabetes mellitus and decreased in cases of chronic pancreatitis, as compared with the controls.

Biochemical and clinical studies on human pancreatic deoxyribonuclease I inhibitor

SummaryHuman pancreatic Deoxyribonuclease I (DNase I), inhibitor was partially purified from duodenal juice of healthy subjects collected in the Pancreozymin-Secretin test, by a procedure which included ammonium sulfate fractionation, DEAE cellulose fractionation, Sepharose 4B affinity chromatography, and gel filtration. The final preparation inhibited DNase I only, and had no inhibitory activity on pancreatic RNase, and trypsin. The inhibitor had a molecular weight of approximately 40,000, as determined by gel filtration, and showed the same mobility as skeletal muscle actin on SDS gel electrophoresis.Then clinical studies were made on the DNase I inhibitor in duodenal juice obtained after administration of Pancreozymin and Secretin to patients with various pancreatic diseases. In patients with suspected chronic pancreatitis with whom the ordinary test, containing the assay of the total volume, amylase output and maximum bicarbonate concentration of duodenal juice had produced normal results, the DNase I inhibitor output was observed to be higher than that in control subjects. While it was lower in patients with confirmed chronic pancreatitis than in control subjects. There results imply that DNase I inhibitor output may be an indicator of the pancreatic inflammation state and be useful for the early detection of pancreatic diseases.

Clinical studies on carcinoembryonic antigen in pancreatic cancer.

SummaryWe studied serum carcinoembryonic antigen (CEA) levels in 82 patients. Thirty-four of these had benign diseases while 48 had malignant diseases. Highest incidence and levels of CEA occurred in the sera of patients with pancreatic cancer and stomach cancer. In this paper we focused our particular attention on the serum CEA of 25 pancreatic cancer patients, and examined differences in serum CEA levels in relation to histologie differentiation and sites of pancreatic cancer. No statistical difference in serum CEA level was found among various histologic types and sites of the pancreatic cancer. Clinical courses of two patients with pancreatic cancer were also studied. Serial determinations of CEA levels are most useful in assessing the effect of operation or chemotherapies and are a useful indicator for differentiating pancreatic cancer from chronic pancreatitis but cannot be a conclusive factor for the diagnosis. Finally, we correlated serum CEA levels with those of RNase and confirmed a positive correlation.

Clinical investigation of serum deoxyribonuclease: I. Analysis of serum deoxyribonuclease activity in comparison with normal and after endoscopic retrograde pancreatography.

SummarySerum Deoxyribonuclease (DNase) micro-assay method was developed using32P-labelled E. coli DNA as substrate.The serum DNase showed maximum activity at pH 7.5. It required Mg++ for activity, and was inhibited by EDTA or EGTA. The enzyme was also inhibited by actin (60-65%) or bovine pancreatic DNase I antibody (40-45%). The serum DNase activity was markedly increased following endoscopic retrograde pancreatography (ERP) examination. These results imply that serum DNase activity is mostly at least 60–65% pancreatic DNase I.

Comparison of somatostatin distribution in pancreatic duct ligated rats and streptozotocin diabetic rats

SummaryThe somatostatin content in the pancreas and gastrointestinal tract was examined in normal, streptozotocin (STZ)-diabetic and pancreatic duct ligation (PDL) rats. The somatostatin content in the pancreas and gastric antrum in the STZ-diabetic group showed a higher concentration compared with those in the normal control group (p<0.001). The somatostatin content in the duodenum in the PDL group showed a higher concentration compared with those in the sham-operated group (p<0.02). There was no significant increase in the lower gastrointestinal tract in the normal, STZ and PDL groups.These facts suggest that the concentration of somatostatin varies according to tissues and organs and that the distribution of somatostatin in chronic pancreatic injury caused by PDL is different from that in diabetes mellitus cases or controls.