Biomedical subjects
Publications and source records attributed to K Satake.
The amino acid sequence of the beta chain of hemerythrin from Lingula unguis was determined. The sequence consists of 117 amino acid residues. The sequence shares 25 amino acid residues in common with other known hemerythrin sequences, including myohemerythrin, with which it shares an insertion of 5 amino acids. This is the first complete sequence from a heteropolymeric hemerythrin.
The kinetics of binding of Cu(II), Tb(III) and Fe(III) to ovotransferrin have been investigated using the stopped-flow technique. Rate constants for the second-order reaction, k+, were determined by monitoring the absorbance change upon formation of the metal-transferrin complex in time range of milliseconds to seconds. The N and C sites appeared to bind a particular metal ion with the same rate; thus, average formation rate constants k+ (average) were 2.4 x 10(4) M-1 s-1 and 8.3 x 10(4) M-1 s-1 for Cu(II) and Tb(III) respectively. Site preference (N site for Cu(II) and C site for Tb(III] is then mainly due to the difference in dissociation rate constant for the metals. Fe(III) binding from Fe-nitrilotriacetate complex to apo-ovotransferrin was found to be more rapid, giving an average formation rate constant k+ (average) of 5 x 10(5) M-1 s-1, which was followed by a slow increase in absorbance at 465 nm. This slow process has an apparent rate constant in the range 3 s-1 to 0.5 s-1, depending upon the degree of Fe(III) saturation. The variation in the rate of the second phase is thought to reflect the difference in the rate of a conformational change for monoferric and diferric ovotransferrins. Monoferric ovotransferrin changes its conformation more rapidly (3.4 s-1) than diferric ovotransferrin (0.52 s-1). A further absorbance decrease was observed over a period of several minutes; this could be assigned to release of NTA from the complex, as suggested by Honda et al. (1980).
Various cannulae have been devised to serve in experiments for collecting pancreatic juice. In this study we created a pancreatic fistula in dogs through a modification of Herrera's method. Since it is advisable to make as small a duodenal pouch as possible to collect almost all the secreted pancreatic juice, both ends of the pouch were closed by an inverted continuous all-layer suture. The lateral flange of the cannula was then introduced into the pouch to sample the pancreatic juice. Duodenoduodenostomy was performed to restore continuity of the alimentary tract, and the other end was inserted into the duodenum 3 cm distal to the anastomosis on the anal side. The exocrine pancreatic secretion of these dogs responded well to food ingestion, with a peak level of 14.5 +/- 5.4 ml/15 min appearing after 30 to 45 min in a postprandial state. Moreover, the animals were able to survive and be utilized for experiments for a period of 3 to 5 months. This experimental model is therefore considered to be of great value for the investigation of exocrine pancreatic secretion.
A patient with transpyloric prolapse of a pedunculated polypoid gastric carcinoma is reported. Only three previous cases have been reported in the international literatures. However, in Japan, 33 cases of prolapsed gastric carcinoma have been reported during the past 30 years. Prolapsed gastric carcinoma should be included in the differential diagnosis of localized intraluminal filling defects in the duodenal bulb. Endoscopy and biopsy are essential for correct diagnosis.
The coagulation disturbance observed during severe acute pancreatitis before and after the infusion of a new synthetic low molecular weight protease inhibitor (Fut-175) was compared. The coagulo-fibrinolytic changes after acute pancreatitis was induced by the intraductal injection of an autologous bile and trypsin mixture showed decreased platelet counts, decreased plasma fibrinogen levels, prolonged partial prothrombin time and increased fibrinogen degradation products. In addition, markers of hypercoagulation showed increased fibrin-peptide A and decreased antithrombin III. The two markers of fibrinolysis showed increased B beta 15-42 immunoreactive peptide and decreased alpha 2 antiplasmin. After the infusion of Fut-175, the coagulo-fibrinolytic abnormalities, which were observed during severe acute pancreatitis without infusion of Fut-175, were improved. Furthermore, Fut-175 could suppress the rise in fibrino-peptide A and B beta 15-42 immunoreactive peptide and decrease in antithrombin III and alpha 2 antiplasmin. Thus, Fut-175 seems to be an effective inhibitor of protease-mediated hypercoagulation and fibrinolysis in severe acute pancreatitis.
This study reports the serial histologic changes of the healing process of relapsing edematous and hemorrhagic acute pancreatitis induced in rats by the close duodenal loop. Serum amylase levels in single, second and third attacks of edematous acute pancreatitis, and single and second attacks of hemorrhagic acute pancreatitis were elevated significantly compared with that of preligation levels (P less than 0.01), but the concentrations were similar in the five groups. However, the histologic findings were different. The results showed that repeated attacks may lead to more obvious damage to the pancreas compared with the first attack of either edematous or hemorrhagic acute pancreatitis. After elimination of causal factors the single attack of edematous acute pancreatitis healed completely but the destructive and hemorrhagic acute pancreatitis usually healed with scarring. Repeated attacks of edematous acute pancreatitis may lead to more chronic pancreatic damage and repeated attacks of destructive and hemorrhagic acute pancreatitis healed with more chronic pancreatic damage than that of repeated attacks of edematous acute pancreatitis.
Thirty four murine monoclonal antibodies were produced against mucin which was isolated from nude mouse xenografts of the SW1990 pancreatic adenocarcinoma cell line. Twelve of them reacted with formalin-fixed SW1990 cells. The antigenic determinants of these antibodies were composed of carbohydrates and their immunoreactivities were predominant at CsCl fraction #6. The remaining 22 antibodies did not react with formalin-fixed cells, 5 epitope specificities of which antibodies are present in the polypeptide part or the part of linkage between oligosaccharide and polypeptide and the immunoreactivities were predominant at CsCl fraction #5. Immunohistochemical study showed that the incidence of epitope expression of the latter 22 antibodies were higher in pancreatic cancer tissues and lower in normal pancreatic tissues than that of the former 12 antibodies. The incidence of Nd2 (one of the 22 antibodies) expression was highest in pancreatic cancer tissues and lowest in normal tissues. ELISA showed that Nd2 antigen was non-secreting type. In vivo tumor distribution studies showed that Nd2 antibody tended to accumulate in cancer tissues. These results seem to support the clinical availability of Nd2.
Progressive systemic sclerosis (PSS) commonly involves the esophagus. Dysphagia and heartburn are the most common esophageal symptoms. In this study we evaluated the relationship between esophageal symptoms and esophago-gastric motility. On esophageal manometry, loss of peristalsis, peristaltic contraction amplitude of distal esophagus less than 30 mmHg and decreased LES pressure were critical for esophageal symptoms. The degree of symptoms correlated to esophageal dysmotility. The gastric emptying in PSS patients was delayed, but there was no significant difference in gastric emptying between the patients with and without reflux esophagitis. Esophageal dysmotility is considered to be much responsible for the reflux esophagitis in PSS patients than gastric emptying.
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Hemerythrin, a non-heme Fe-protein, of Lingula unguis has an octamer structure. We demonstrated that the protein is composed of two distinct subunits (alpha and beta), in equal amounts by investigation of their composition and partial terminal sequence. The cross-linking reaction of the native protein with dithiobis-(succinimidyl propionate) provided evidence for the presence of a dimer composed of alpha and beta subunits.
Basic evaluation of SPan-1 assay (SPan-1 RIA. BEAD) and clinical significance of serum SPan-1 levels for the diagnosis of pancreatic cancer were studied. This assay was reproducible, reliable and simple to perform. It required minimal samples (duplicate 50 microliters) and may be done within 4 hrs. Normal subjects (N = 1182) had serum SPan-1 antigen levels which ranged 0 to 42.8 units/ml with a mean of 7.5 units/ml and above 40 units/ml was considered to be positive. SPan-1 antigen levels in cultured medium of four out of five pancreatic cancer cell lines showed more than 1000 units/ml by this assay. While over 90% of pancreatic cancer patients had elevated levels of serum SPan-1 antigen, only 0-17% of patients with other malignant and non malignant gastrointestinal diseases such as pancreatitis (chronic or acute), gastric cancer or colon cancer had above normal levels. Furthermore, levels of serum SPan-1 antigen correlated well with treatment and recurrence of disease in patients with pancreatic and gastric cancer. These results suggest that determination of serum SPan-1 antigen levels by this assay kit is useful for the diagnosis and monitoring of pancreatic cancer.
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The amino acid sequence of hemerythrin from Siphonosoma cumanense was determined. The sequence consists of 113 amino acid residues. High homology is conserved in the regions of amino acid residues coordinating two iron atoms as its active site. The invariant sequences observed from the proteins in the same family were considerably altered except for the residues in the active site.
We studied clinical significance of serum SPan-1 antigen, which is human pancreatic cancer associated antigen, in hepatobiliary and pancreatic diseases employing newly developed kit. The sensitivity of serum SPan-1 antigen levels for pancreatic cancer, gallbladder carcinoma, hepatocellular carcinoma, bile duct cancer were 90.9%, 77.8%, 60.7%, 60.0% respectively. No correlation was found between serum SPan-1 antigen levels and total bilirubin levels. SPan-1 positivity in patients with hepatic disease including hepatocellular carcinoma was rather high, but there were few cases more than 100 U/ml. The mechanism of the elevated level was supposed to be release of the antigen from bile-duct epithelium, and this must be taken into consideration at diagnosis referred to serum SPan-1 antigen level.
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To investigate the hemodynamic changes of the liver in acute pancreatitis the microcirculation of the liver, portal venous flow, hepatic artery blood flow, cardiac index were measured in 15 dogs with acute pancreatitis induced by autologous bile and trypsin injection into the main pancreatic duct during the experimental period for 5 hrs. The effect of protease inhibitor (PATM) in a dose of 3 mg/kg/kg/hr on those hemodynamic changes was investigated in another series of acute pancreatitis in dogs. In acute pancreatitis hepatic microcirculation decreased to 26 +/- 15 ml/min/100g at 5 hrs after onset of pancreatitis, portal venous flow and hepatic artery flow decreased to 86 +/- 16 ml/min and 66 +/- 30 ml/min at 5 hrs, respectively. The administration of PATM maintained the portal blood flow during the first 2 hrs and showed a trend of decreasing to 219 +/- 93 ml/min at 5 hrs. The hepatic microcirculation showed 77 +/- 25 ml/min/100g and 72 +/- 14 ml/min/100g at 1 and 2 hrs respectively and then decreased to 47 +/- 21 ml/min/100g at 5 hrs. We concluded hemodynamic and microcirculatory changes of the liver in acute pancreatitis was disturbed due to the decreased portal and hepatic artery flow, however, the administration of PATM has an effect of improvement of liver microcirculation.
Pancreatic inschemia, especially due to pancreatic microcirculation disturbance, has been considered to trigger and aggravate acute pancreatitis. In this work experimental acute pancreatitis was produced by autologous bile and trypsin in mongrel dogs to study the time-course changes in systemic and local hemodynamics in association with disease progress. In addition, the effects of a new synthetic pancreatic protease inhibitor (PATM, 3 mg/kg/hr, i.v.) on systemic and local circulation were examined. In animals with untreated pancreatitis the mean baseline pancreatic microflow was 55.6 +/- 17.0 ml/min/100g before the onset of pancreatitis and this decreased by 22% and 52% at 1 hr and 5 hr, respectively. The femoral arterial pressure and cardiac index also decreased during the 5 hr experiment at period in comparison with the respective preoperative levels. The portal venous flow showed a sharp reduction immediately after the onset of pancreatitis, staying at a low level thereafter. The pancreatic microflow was significantly improved by PATM treatment for the first 60 min and the portal venous flow for the first 120 min. PATM treatment prevented the decrease in femoral arterial pressure, although it failed to exert any appreciable effect upon the cardiac index. These findings suggest that intravenous administration of PATM might be of value for improving the pancreatic microflow and portal venous flow, at least in the early stage of experimental acute pancreatitis in dogs.
Hemerythrin from Siphonosoma cumanense has a trimeric structure consisting of identical subunits, which have no cooperativity nor Bohr effect on oxygen-binding. The trimer was dissociated into its monomers by the modification of the SH group of its cysteines with p-chloromercuriphenylsulfonic acid (PCMPS), which was monitored by stopped-flow of both spectrophotomeric and small angle X-ray scattering methods. The results showed that the process involved sequential modification of the SH groups, dissociation into monomers, and auto-oxidation of ferrous iron in the active center. The modification of the SH groups with PCMPS followed second-order kinetics with a rate constant of 1.8 M-1.s-1. The dissociation and auto-oxidation followed first-order kinetics with rate constants of 4 X 10(-3) s-1 and 5 X 10(-4) s-1, respectively. The obtained rate of auto-oxidation was much faster than that in the native state. These findings lead to the conclusion that the trimeric state of S. cumanense hemerythrin is necessary to prevent auto-oxidation.