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Biomedical subjects

K Satake

Publications and source records attributed to K Satake.

At least 109 records · Page 6Linked to original sources

Negative cooperativity of chicken ovotransferrin on Al(III)-binding.

Chicken ovotransferrin, an iron binding protein, has two metal binding sites (amino (N) and carboxy (C) terminal sites). It binds Cu(II), Al(III), Co(II), and other metals, as well as Fe(III). In this study, the selectivity and cooperativity of the N and C sites on Al(III), Co(II), and Tb(III) binding were investigated. Metals were classified into two groups according to their site preference. Co(II) and Al(III) bound to the N site more preferably than to the C site, whereas Tb(III) bound to the C site more preferably. On Fe(III) binding, the binding constant of Fe(III) becomes larger when the other site is already occupied. Thus, positive cooperativity is seen. In the present study, the binding cooperativities of Co(II), Tb(III), and Al(III) as to the N and C sites were investigated. On Co(II) and Tb(III) binding, no cooperativity was observed, as in the case of Cu(II) [Yamamura, T. et al. (1985) in Proteins of Iron Storage and Transport (Spik, G., Montreuil, J., Crichton, R.R., & Mazurier, J., eds.) pp. 53-56, Elsevier Science Publ. B.V., Amsterdam]. In contrast, negative cooperativity was observed on Al(III) binding. Based on a model proposed by Yamamura et al. [Yamamura, T. et al. (1985) ibid.], the ratio of the binding constants, KC/KN, and the stacking coefficient, Kst, were estimated. KC/KN is 2.2 +/- 0.4 for the Tb(III) ion, 0.5 +/- 0.1 for the Co(II) ion, and 0.12 +/- 0.02 for the Al(III) ion. Kst (= 1 in a non-cooperative case) is 0.98 +/- 0.02 for the Tb(III) ion, 1.03 +/- 0.02 for the Co(II) ion, and 0.55 +/- 0.22 for the Al(III) ion.

Aluminum↗

Human monoclonal antibody prepared from lymphocytes of pancreatic cancer patients.

We have succeeded in establishing a human monoclonal antibody (MoAb) OC2D against pancreatic cancer cells using lymphocytes from pancreatic cancer patients and a human lymphoblastoid cell line HO323. The reactivity of OC2D using various cell lines and immunoperoxidase staining showed a rather specific effect for malignant cells such as those of pancreatic, gastric, and colon cancers. The antigen recognized by OC2D appeared to be nonsecreting and was mainly found on the cell surface, and various enzyme treatments showed that the epitope was an asialosylated carbohydrate. The hybridoma OC2D has continued to produce human MoAb for 10 months after fusion and grew stably in serum-free medium as well as in serum-containing medium. These results suggest that this human MoAb OC2D is useful for both imaging and targeting therapy.

Antibodies, Monoclonal↗

[Percutaneous recording of gastric electrical activity (electrogastrography): its technique and analysis].

In 1922, Alvarez made some electrical recordings from cutaneous electrodes, but the method has not been widely adopted. It has been caused by the technical difficulties in recording, and in extracting consistent information from the recording. Therefore in an effort to improve the ability to routinely obtain a recording of the gastric electrical activity, using cutaneous electrodes (electrogastrography, EGG), we have investigated different electrodes placement and bipolar recording techniques. We studied 10 healthy asymptomatic volunteers. Frequency and power product have been used to help interpret the potential change. We found significant frequency component at approximately 3 cycle/min. Recordings from the upper part of epigastrium were better than those from the lower part of epigastrium. This suggests that these recordings are taken from electrical activity of the stomach. We found the good placement of cutaneous electrodes and good recording techniques.

Action Potentials↗

Plasma beta-endorphin and the effect of naloxone on hemodynamic changes during experimental acute pancreatitis in dogs.

The effect of endogenous pituitary and pancreatic beta-endorphins in the physiopathologic factors of acute pancreatitis and the effect of opiate antagonist naloxone in these conditions were studied. Pancreatitis was induced by the injection of 0.5 milligram per kilogram of autologous bile mixed with 10,000 units per kilogram of trypsin into the main duct after ligating the accessory duct. After the induction of acute pancreatitis, plasma beta-endorphin concentrations in systemic and portal blood and cardiovascular function were measured. Ten dogs (control group) were given an intravenous injection of 10 milliliters per kilogram per hour of lactate Ringer's solution one hour before the induction of acute pancreatitis. Six (naloxone group) received an intravenous bolus injection of 2 milligrams per kilogram of naloxone at one hour after the induction of acute pancreatitis and then an intravenous infusion of 2 milligrams per kilogram per hour of naloxone was given under the same conditions as for those in the control group. Beta-endorphin in systemic and portal venous blood in those in the control group increased significantly during the experiments. Beta-endorphin and adrenocorticotropin hormone in systemic venous blood both in the control and naloxone groups increased simultaneously. However, blood pressure, pulse pressure and cardiac output improved quickly after the bolus injection of naloxone and were well maintained during intravenous infusion of naloxone. Also, naloxone improved the survival time from acute pancreatitis and decreased plasma lactate concentrations. Our data show that beta-endorphin, released mainly from the pituitary gland and not from the pancreas, may have an important role in subsequent cardiovascular depression. Also the opiate antagonist naloxone may be effective in the treatment of acute pancreatitis.

Acute Disease↗

[Diagnostic usefulness and limitation of measuring pancreatic cancer associate antigen, SPan-1, in patients with pancreatic cancer].

Serum levels of SPan-1 were determined in patients with various gastrointestinal cancers including pancreatic cancer and benign disorders, as well as from healthy subjects, by using a newly developed SPan-1 antigen immunoradiometric assay (SPan-1 RIABEAD, Dainabott). In addition, usefulness of diagnosis for pancreatic cancer by determination of Serum SPan-1 antigen was compared with that of other tumor markers such as CA 19-9, DU-PAN 2, CA 50, CEA and elastase 1 in the same patients. Serum SPan-1 antigen levels in healthy controls ranged from 0 to 156 U/ml with a mean of 7.7 U/ml (+/- 15.0, 2 S.D). Thirty U/ml of serum SPan-1 antigen levels was set as the cut-off value, and 98.9% of healthy controls were within this cut-off value (30 U/ml). Serum SPan-1 antigen levels in pancreatic cancer were distributed from 0-353, 900 U/ml with a mean of 14,466 U/ml (+/- 16.616 SD). Sensitivity of SPan-1 antigen in pancreatic cancer was 81.9%, which was the highest among gastrointestinal cancers, and eight of nine pancreatic cancer patients with stage II showed above normal limits (30 U/ml). Although serum SPan-1 antigen levels in biliary tract cancer and liver cirrhosis showed a high percentage (70.3%, 56.8%), the mean values of SPan-1 antigen levels in these groups were 477 U/ml and 62.8 U/ml, respectively, which was lower than that of pancreatic cancer. False positive ratio of SPan-1 antigen in benign pancreatic disease was lower than that of CA 19-9. Also, comparative studies of SPan-1 antigen and various tumor markers between pancreatic cancer and benign gastrointestinal diseases revealed that SPan-1 antigen showed the highest sensitivity and accuracy in diagnosis for pancreatic cancer among other tumor markers. From these results, measurement of SPan-1 antigen appeared to be the most useful marker in the diagnosis of pancreatic cancer.

Antigens, Neoplasm↗

Auto-oxidation of Lingula unguis and Siphonosoma cumanense hemerythrins induced by some perturbants.

Auto-oxidation of human adult hemoglobin and Siphonosoma cumanense and Lingula unguis hemerythrins were investigated in the presence and absence of perturbants. In the presence of urea, there were no drastic increases in auto-oxidation rates for the three proteins. In contrast, thiocyanate and laurate enhanced the auto-oxidation rates remarkably. In the presence of thiol reagents such as PCMB and NEM, auto-oxidation rates were enhanced with dissociation into subunit, but not enhanced so much with SH-modification only. Thus oligomerization is probably necessary to protect auto-oxidation.

Animals↗

Lex and Ley antigen expression in human pancreatic cancer.

Carbohydrate antigens are useful markers for the serological detection of pancreatic cancer. However, data concerning the expression of structurally well-defined carbohydrate antigens in normal and malignant pancreatic tissue is quite limited. The Lex and Leg antigens are closely related carbohydrate antigens synthesized on type 2 blood group oligosaccharide side chains of glycolipids and glycoproteins. Monoclonal antibodies anti-SSEA-1 and AH6 recognize "simple" Lex and Ley epitopes, respectively, regardless of the length of the carrier carbohydrate. Other monoclonal antibodies recognize Lex (FH4), sialyl Lex (FH6, IB9) or Ley (KH1, CC-1, CC-2) carried only by elongated type 2 side chains with or without internal alpha 1,3 fucosyl substitution. The present comparative immunohistochemical study used tissues of normal pancreas, chronic pancreatitis, and pancreatic cancer to determine the normal expression of Lex and Ley antigens in the pancreas and to elucidate any cancer-associated alterations. Lex-related antigens were not expressed in normal pancreas, expressed in only 10-20% of chronic pancreatitis tissues, but expressed in 50-70% of pancreatic cancer tissues. The frequency of Lex-related antigen expression in pancreatic cancer tissues was lowest in poorly differentiated cancers. Within a given specimen, at least three or all four of the Lex recognizing monoclonal antibodies were simultaneously expressed. Unlike Lex antigens, Ley-related antigens were expressed in 32-77% of specimens of normal pancreas, with similar frequencies in specimens of chronic pancreatitis and pancreatic cancer. In normal pancreas, simple Ley was expressed by both ductal and acinar cells, but extended Ley antigens were expressed only by acinar cells. In pancreatic cancer, extended Ley antigen expression was found in less than 10% of poorly differentiated tumors. Coexpression among the Ley-related antigens was less common than with the Lex-related antigens. Also in cancer specimens, simple Lex and simple Lex antigens were often concordantly expressed, whereas extended Lex and extended Ley antigen expression was often discordant. Hyperplastic ducts and ductules associated with pancreatic cancer expressed Lex-related antigens more frequently than morphologically similar lesions associated with chronic pancreatitis. These results demonstrate that Lex-related antigens are cancer-associated determinants in the human pancreas. The discrepant expression between Lex and Ley antigens in these tissues implies altered regulation of fucosyltransferase activity associated with the malignant state.

Antibodies, Monoclonal↗

The measurement of serum immunoreactive pancreatic secretory trypsin inhibitor in gastrointestinal cancer and pancreatic disease.

The clinical usefulness of serum pancreatic secretory trypsin inhibitor (PSTI) in pancreatic disease and gastric and colorectal cancer has been examined. The results showed that serum PSTI in acute pancreatitis was significantly higher than in normal subjects and it was also raised in acute exacerbations of chronic pancreatitis. Although the sensitivities of serum PSTI, amylase and elastase I were similar, serum PSTI in necrotizing hemorrhagic pancreatitis was 2.7 times higher than in mild acute pancreatitis. Only a few patients with chronic pancreatitis showed increased concentrations and the mean value was near normal. The mean PSTI in patients with pancreatic and colorectal cancer was higher than normal, although that of gastric cancer was within normal limits. The sensitivity of serum PSTI measurements in patients with these three malignant diseases was only about 30%. The results suggested that the measurement of serum PSTI could be useful in the diagnosis of acute pancreatitis, but of limited value in the diagnosis of other disease which we examined.

Amylases↗

Different stability of N- and C-domain of diferric ovotransferrin in urea and application to the determination of iron distribution between the two domains.

The study of guanidine-HCl or thermal denaturation of diferric ovotransferrin (Fe2Tf) has revealed a simultaneous unfolding of the two domains of the protein (Ikeda et al. (1985) FEBS Lett. 182, 305-309). In urea denaturation of Fe2Tf, however, two distinct steps of unfolding were observed in the urea concentration range from 4.5 to 9 M at pH 8.0 and 37 degrees C by measuring the residual iron-bound protein (absorbance at 465 nm) and the remaining folded structures (circular dichroism at 222 nm). From a study of urea denaturation of partially iron-saturated Tf whose iron preferentially occupied the N-domain, it was found that the first and the second steps of denaturation corresponded to those of the N-terminal (4.5-6 M urea) and C-terminal domains (over 7 M urea), respectively. The N-domain of Fe2Tf was selectively unfolded in 7 M urea and digested with trypsin to provide an iron-bound C-terminal fragment (42 kDa) in good yield (about 80% of theoretical). The kinetic analysis of the decrease in A465 of Fe2Tf in 9 M urea showed that the N-domain unfolded 3 x 10(2) times faster than the C-domain. With partially iron-saturated Tf, the decrease of A465 in 9 M urea also proceeded in a biphasic manner and the ratio, the decrement in A465 of the rapid phase/the decrement in A465 of the slow phase, gave the value of iron distribution as Fe at the N-site/Fe at the C-site.

Binding Sites↗

Serial histologic study of the development, progression, and healing of acute pancreatitis in the rat.

This study was undertaken to investigate serially the development, progression, and healing of acute pancreatitis which was induced in rats by the closed duodenal loop technique. Edematous changes appeared within 2 to 4 h. Pancreatic blood flow increased at 1 h and tended to decrease after 3 h. After injection of fesin into the loop, fesin appeared in the periacinar space and acinar cells after 4 h. Electron microscopy showed that partial destruction of the plasma membrane occurred and serum amylase increased considerably at the same time, suggesting that the initial inflammatory changes caused the release of pancreatic enzymes at approximately 4 h. After elimination of the causal factors, edematous pancreatitis healed completely but hemorrhagic acute pancreatitis was not completely healed 6 months later.

Acute Disease↗

[Studies on the muscarine receptors in rat gastric smooth muscle].

It has been reported that the two types of muscarinic receptors, "M1" and "M2", exist in the opossum lower esophageal sphincter. The presence of these muscarinic receptor subtypes had been confirmed with the discovery of the M1 selective antagonist, pirenzepine. But little is known about muscarinic receptor subtypes in gastric smooth muscle. The aim of this study was to identify the muscarinic receptor subtypes on the gastric smooth muscle responsible for the contraction of rat gastric muscle strip. Also, we examined the mechanism of the action of aclatonium napadisilate on rat gastric smooth muscle in vitro. The stimulation of M2 receptor caused the contraction of the gastric smooth muscle. McN-A-343, selective M1 agonist, caused weak contraction of the gastric smooth muscle, and this response was not affected by the selective M1 antagonist, pirenzepine. Aclatonium napadisilate stimulated M2 receptor and caused the gastric smooth muscle contraction. We conclude that the contraction of the gastric smooth muscle is caused by the stimulation of the M2 receptor and this reaction was not affected by tetrodotoxin, suggesting the M2 receptor is located directly on the gastric smooth muscle. The weak contraction of the gastric smooth muscle caused by McN-A-343 was not affected by the selective M1 antagonist, pirenzepine, suggesting that McN-A-343 may not be a pure M1 selective agonist. The action of aclatonium napadisilate is supposed to stimulate the M2 receptor.

Acetylcholine↗

[Effect of cisapride on delayed gastric emptying in diabetic patients].

Delayed gastric emptying is supposed to affect glycemic control in diabetic patients by relative over dosing of insulin to blood glucose level due to delayed absorption of nutrients. Therefore, treatment of delayed gastric emptying is important in diabetic patients. Cisapride, a potent gastrokinetic agents, has been reported to activate the motility from stomach to colon. We evaluated the effect of acute oral administration of cisapride in seven diabetic patients (aged 46-62) with delayed gastric emptying. All patients complicated with autonomic neuropathy. Ten mg of cisapride was administered orally 30 minutes before breakfast and lunch on the day of study. Gastric emptying study was done using 99mTc-tin colloid labeled omelet meal served with 2 slices of toast and 200 ml of milk. With cisapride, the retention rate at time of 150 minutes decreased from 76 +/- 10% to 47 +/- 13% (mean +/- SD) (p less than 0.001) and starting index shortened from 86 +/- 28 minutes to 38 +/- 27 minutes (p less than 0.05). Gastric emptying speed became faster from 0.31 +/- 0.16%/min to 0.43 +/- 0.12%/min (0.2 greater than p greater than 0.1). Blood glucose level before meal decreased from 117 +/- 27 mg/dl (mean +/- SE) to 74 +/- 7 mg/dl (n.s.), and difference between basal and maximal blood glucose level became larger from 46 +/- 27 mg/dl to 84 +/- 30 mg/dl (n.s.). We conclude that acute oral administration of cisapride has significant effect in improving delayed emptying of solid meal in diabetic patients.

Administration, Oral↗

[The effect of cisapride on intestinal transit].

Cisapride is known to accelerate gastrointestinal motility in various diseases with gastrointestinal motor abnormalities, and in normal subjects. In this study, we developed a new method to evaluate intestinal transit by radio-opaque markers, and evaluated the effect of oral doses of cisapride on intestinal transit in 6 normal subjects. Twenty markers were ingested with breakfast, and abdominal X-ray pictures were taken at 6, 24, 48 and 72 hours later, markers on the films were scored according to estimated their location. Geometric mean of the markers and half-dose transit-time (HT) at selected points of the colon were calculated. Cisapride 7.5 mg, 15 mg per day or placebo, were given in random order, in double blind fashion. Cisapride accelerated intestinal transit at every point calculated. HT at anus was shortened to 23.3 +/- 10.2 hours (mean +/- SD) (p less than 0.05) with cisapride 15 mg/day from 42.3 +/- 16.9 hours with placebo. Geometric means at 24-hour were 3.7 +/- 1.4 with placebo, 5.3 +/- 0.9 (p less than 0.05) with cisapride 7.5 mg/day, and 5.1 +/- 1.5 with cisapride 15 mg/day. No serious side effects were noted. Our new method to evaluate intestinal transit using radio-opaque markers is easy to perform, and is able to quantify the state of transit. Cisapride accelerated intestinal transit without diarrhea. This effect of cisapride on intestinal transit may be useful in patients with constipation.

Administration, Oral↗

[Results of long follow-up study for peptic ulcer patients treated with gastrectomy].

This clinical study was based on 307 peptic ulcer patients treated with gastrectomy over a 15-year period in our department. Numbers of surgical cases for peptic ulcer remarkably decreased after the introduction of cimetidine in 1980. A median age of gastric ulcer patients was in sixth decades, whereas duodenal ulcer in fifth decades. Surgical indications were 60 percent in intractable ulcer, 30 percent in complication as bleeding, stenosis and perforation, and 10 percent in suspicious malignancy. After cimetidine introduction intractable cases decreased from 63 percent to 44 percent. There was no remarkable difference in the fasting and peak plasma secretin concentrations in postprandial period between peptic ulcer patients and normal controls, however, in gastrectomized patients the plasma secretin response decreased in postprandial state. Follow up study was made on a point of postoperative recurrence and postgastrectomy syndrome. Small stomach syndromes such as insufficient food intake and body weight loss were observed in 10 and 30 percent in the gastrectomized patients, but 86 percent of the patients were satisfied with the results of operation. We concluded that gastrectomy for peptic ulcer was treatment of choice from the point of low recurrence rate and no severe postgastrectomy disorders.

Adult↗

[Renal microcirculation in experimental acute pancreatitis of dogs--the effect of pancreatic protease inhibitor and dopamine].

To understand the renal microcirculation in acute pancreatitis is important to know the pathophysiology of renal insufficiency frequently observed as one of multiple organ failures in severe acute pancreatitis. In mongrel dogs acute pancreatitis was experimentally introduced by autologous bile added trypsin injection into the pancreatic duct. The effect of new synthesized pancreatic protease inhibitor (PATM) and dopamine in a dose of 3mg/kg/hr and 10 micrograms/kg/min were investigated, respectively. In acute pancreatitis dogs, renal arterial blood flow and renal tissue blood flow immediately fell and gradually decreased in time course of experiment and renal vascular resistance increased from 2 hours after onset of pancreatitis. When pancreatic protease inhibitor (PATM) was infused in acute pancreatitis dogs, blood pressure and pulse pressure relatively preserved during the experiment. Renal blood flow and renal tissue blood flow were maintained during the first 1 hour and thereafter slightly decreased, however which was less than that of no PATM treated dogs. When dopamine was infused in acute pancreatitis dogs, blood pressure was maintained during the first 90 minutes thereafter remarkably decreased. Renal blood flow was maintained within 60 minutes, however it remarkably decreased at the end of the experiment. This study suggested that renal microcirculation was disturbed from early period of acute pancreatitis in dogs and pancreatic protease inhibitor (PATM) had a beneficial effect of maintain the renal microcirculation.

Acute Disease↗