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Biomedical subjects

H Ohyanagi

Publications and source records attributed to H Ohyanagi.

At least 91 records · Page 5Linked to original sources

Study of the excretion mechanism of a perfluorochemical emulsion.

The excretion mechanism of perfluorochemicals (PFC) via the lung has been studied by physicochemical and histochemical methods. Monocytes that had phagocytized PFC particles were found in the lung capillaries, and alveolar macrophages that had phagocytized PFC particles were found in the alveoli. Vacuolated macrophages were observed microscopically in the alveolar space of rats injected with PFC emulsions. The PFC content in alveolar macrophages reached a maximum level of 1.44 mg/l x 10(8) cells 72 h after injection. It was confirmed by means of a wavelength dispersive x-ray analyzer that fluorine atoms were present in the vacuolated alveolar macrophages. The peroxidase activity of the PFC-phagocytizing macrophages suggest that monocytes phagocytize PFC particles in the circulation and migrate to the alveolar space. This study shows that the monocyte/macrophage system is related to one mechanism for excretion of PFC after intravenous injection of PFC emulsions.

Animals↗

[Comparative studies on monoclonal antibody KM10 and anti-CEA monoclonal antibodies].

The specificity of KM10 was evaluated in comparison with newly developed anti-CEA monoclonal antibodies (A10, B9, JA4, AH3). Both KM10 and all anti-CEA monoclonal antibodies reacted with CEA in ELISA system, and with adenocarcinoma of the stomach, colon, and pancreas in the immunohistochemical assay. B9, JA4, and AH3 were suggested to react with CEA related antigens, such as NCA and BGPI, whereas KM10 and A10 were suggested to recognize the distinctive part of CEA. The antigenic determinant of CEA reactive with KM10 and A10 was revealed to be protein moiety after enzyme treatment. The competitive binding inhibition assay, however, indicated that epitopes of KM10 and A10 were different each other. Enzyme immunoassay using both KM10 and A10 could detect CEA. These findings showed the possible use of both KM10 and A10 for clinical diagnosis and treatment by means of targeting for the distinctive part of CEA.

Adenocarcinoma↗

[Extracorporeal adriamycin-removal following hepatic artery infusion: use of direct hemoperfusion combined with veno-venous bypass].

Systemic toxicity of adriamycin (ADR) has limited its high dosage application in hepatic artery infusion. We developed a new extracorporeal device combining direct hemoperfusion (DHP) and veno-venous bypass to eliminate ADR following hepatic artery infusion. Mongrel dogs were divided into three group, I: controls without DHP (n = 3), II: DHP under single venous bypass from IVC to left external jugular vein (n = 3) and III: DHP under hepatic venous isolation using veno-venous bypass (n = 5). Blood specimens were obtained to determine plasma drug levels until 60 min after ADR injection (3 mg/kg body weight, 1 min). Blood flow through DHP, which was averaged 200 ml/min in both groups II and III, was monitored with ultrasonic flowmeter. In groups I and II, peripheral ADR levels rapidly increased, reaching the peak values of 5.61 +/- 2.42 and 1.17 +/- 0.31 micrograms/ml respectively at 1 min after injection. The peak level in group III was markedly reduced, the value being 0.42 +/- 0.17 microgram/ml, which was 7.5% of the peak value of group I. The removal rates in groups II and III were 10.9 and 27.5% respectively. In conclusion, DHP under hepatic venous isolation can be an useful method to reduce systemic distribution of ADR during hepatic artery infusion.

Animals↗

Hemodynamic study of occlusion of the splenic vein caused by carcinoma of the pancreas.

The most common cause of occlusion of the splenic vein is pancreatic disease, such as pancreatitis or carcinoma of the pancreas. As compared with benign causes, carcinoma of the pancreatic body or tail may readily involve not only the splenic vein, but also, eventually, the splenic artery. Therefore, the clinical features of occlusion of the splenic vein may be profoundly altered according to the nature of the underlying causes. In an attempt to clarify the pathophysiologic findings and hemodynamic mechanism of occlusion of the splenic vein associated with carcinoma of the pancreas, three patient reports were selected from our past experience. Upon analyzing the clinical course of these patients, three consecutive phases may be distinguished. Phase 1 is the insidious or latent phase represented by Patient No. 1. The splenic vein is partially occluded and gastric varices or splenomegaly has not developed. Phase 2, the collateral developing phase, is represented by Patient No. 2. The splenic vein is completely occluded while the splenic artery is patent, resulting in marked gastric varices and splenomegaly. Phase 3 is the vanishing phase and is represented by Patient No. 3. The occlusion of the splenic artery is superimposed on the occlusion of the splenic vein, causing gastric varices to vanish and the enlarged spleen to shrink.

Aged↗

[Splenic vein occlusion due to pancreatic disease: regional portal hypertension from hemodynamic points of view].

The purpose of this study is to clarify the clinicopathophysiology of splenic vein occlusion due to pancreatic disease from hemodynamic points of view. We reviewed the angiographic findings and medical records of 82 patients who had pancreatitis, pancreatic cyst or pancreatic cancer in the pancreatic body and tail. According to the site of occlusion in 16 patients with complete splenic vein occlusion, this entity may be divided into two categories: Type A, an occlusion close to the spleen in which short-gastric system seems to be major collateral, and Type B, an occlusion distant from splenic hilum in which gastroepiploic system becomes prominent as collateral. As compared to 7 patients with incomplete splenic vein occlusion, gastric varices and splenomegaly were frequently observed with the patients having complete occlusion. Among these 16 patients, splenic arterial occlusion was superimposed in 3 patients with pancreatic cancer in whom gastric varices were not detected. Thus, clinical features of this entity must be carefully assessed according to the nature of the underlying disease. Based on these observations, three consecutive phases: Phase 1 Insiduous or latent phase, Phase 2 Collateral developing phase, Phase 3 Vanishing phase may be distinguished for splenic vein occlusion secondary to pancreatic disease.

Adult↗

Mode of inhibitory action of cholecystokinin in amylase release from isolated rat pancreatic acini--inhibition of secretory process post to protein kinase C-calcium ion systems.

The incubation of isolated rat pancreatic acini with low doses (1 x 10(-11)-1 x 10(-10) M) of cholecystokinin-octapeptide (CCK8) induced amylase release. This CCK8-induced amylase release has been shown to be mediated through the protein kinase C activation and the Ca2+ mobilization which are linked to the phospholipase C-mediated hydrolysis of phosphoinositides. However, the incubation of the acini with high doses (1 x 10(-9)-1 x 10(-7) M) of CCK8 reduced amylase release to the level less than that induced by the maximally effective dose (1 x 10(-10) M) of this secretagogue. Under the same conditions, the high doses of this secretagogue did not inhibit the phospholipase C-mediated hydrolysis of phosphoinositides. The stimulatory action of the maximally effective dose of CCK8 in amylase release was mimicked by the simultaneous addition of protein kinase C-activating 12-O-tetradecanoylphorbol-13-acetate (TPA) and Ca2+ ionophore A23187. A high dose (1 x 10(-7) M) of CCK8 reduced the amylase release induced by the combination of TPA and A23187. These results suggest that the high doses of CCK8 inhibit the secretory process post to the protein kinase C-Ca2+ systems and thereby reduce the amylase release induced by the maximally effective dose of CCK8 in rat pancreatic acini.

Amylases↗

The prevention of experimental cholesterol gallstones by ileectomy in mice.

After a lithogenic diet containing 0.5 per cent cholesterol and 0.25 per cent sodium cholate was fed to a group of normal Crj-ICR male mice for 10 days, cholesterol gallstones developed. No formation of gallstones occurred, however, in a group of mice from which 20 cms of terminal ileum had been removed prior to the feeding of the lithogenic diet. The biliary concentrations of cholesterol, phospholipids and bile acids were markedly lower in the ileectomized mice, with the decrease in cholesterol concentration being most significant. On the other hand, fecal excretion of sterols and bile acids increased in the ileectomized mice. The pool size of bile acids increased after the feeding of the lithogenic diet, but ileectomy decreased the pool size in mice fed the ordinary or lithogenic diets. The biliary concentration of cholic acid increased after the feeding of the lithogenic diet, but decreased with ileectomy. The biliary concentration and fecal excretion of deoxycholic acid markedly increased, while those of beta-muricholic acid and its secondary bile acids, omega-muricholic acid and hyodeoxycholic acid, decreased. The increase in plasma and liver cholesterol levels after the feeding of the lithogenic diet was prevented by ileectomy. These data suggest that ileectomy prevents the formation of cholesterol gallstones after the feeding of a lithogenic diet due to a decrease in cholic acid absorption.

Animals↗

A monoclonal antibody, KM10 reactive with human gastrointestinal cancer and its application for immunotherapy.

A monoclonal antibody, KM10 (IgG1) was produced by fusing spleen cells from a human gastric cancer cell (MKN45)-primed BALB/c mouse with the murine myeloma cell line X63-Ag8-653. The antibody reacted strongly with the plasma membrane of human gastrointestinal carcinoma. Sections of the malignant and benign tissues were tested with immunoperoxidase. All of 10 (100%) large intestinal cancers, 26 of 31 (84%) gastric cancers, 5 of 7 (71%) pancreatic cancers and all of 3 (100%) ampullary cancers reacted positively. Moderate or weak reactivity was observed with normal human tissues, hepatoma and carcinomas of mammary, thyroid and adrenal glands. According to a study of the distribution of 125I-labeled KM10 in nude mice bearing human gastric cancer, KM10 selectively localized in tumor tissue rather than normal tissue. Whole body autoradiography also supported such a selective distribution. Destruction of antigenic properties by pronase digestion demonstrated its protein nature and by Western blot analysis, it was identified as a protein with an Mr of 180-200 kd. KM10-adriamycin (ADM) conjugate was prepared via an oxidized dextran bridge and this immunoconjugate retained the binding activity against human gastric cancer. MKN45 cells were inoculated subcutaneously into athymic mice and intravenous treatment was begun when the tumor became measurable. A dose-dependent antitumor activity was observed in vivo with KM10-ADM conjugate, while this conjugate was less toxic than free ADM.

Animals↗

Therapeutic effect of plasma exchange with the biliary drainage in the treatment of obstructive jaundice.

The effect of therapeutic plasmapheresis combined with biliary drainage was evaluated in obstructive jaundice animal models. Plasma exchange (PE) using fresh-frozen plasma was carried out with biliary drainage (BD) on a canine jaundice model created by the ligation and resection of bile duct. Routine biochemical analyses were done following PE and BD. The result was compared with that of a BD only group. Plasma bilirubin level abruptly dropped after PE and was kept at a lower level, whereas the bilirubin level of the drainage alone group decreased gradually. Decreased plasma mitochondrial GOT level in the PE group suggests improvement of liver cell damage in obstructive jaundice. Mitochondrial function of liver tissue was evaluated following partial hepatectomy, which was carried out 2 days after PE along with BD in jaundice rat. Mitochondrial respiratory control ratio and ADP/O ratio following hepatectomy were improved in the PE group. The results suggest the improvement of hepatic functional reservoir by a single PE treatment in addition to BD treatment. These results show that PE can shorten the icteric period and may improve the hepatic functions after the treatment of malignant obstructive lesion in the biliary tract.

Animals↗

Recent studies on perfluorochemical (PFC) emulsion as an oxygen carrier in Japan.

In summary, we have discussed PFC emulsions as oxygen carriers, and concluded as follows: PFC emulsions which are clinically usable at present, such as Fluosol-DA, have some negative points. For instance, there is the requirement of relatively high FiO2 level, short retention time in the blood stream, slow excretion rate from the organs, limited dosage for infusion, and so on. However, in the clinical cases of moderate acute anemia, the consumed oxygen in the PFC phase was nearly 30% of that in the hemoglobin phase in the administration of only 1,000 ml of Fluosol-DA. It strongly suggests that PFC emulsion can carry a considerable amount of oxygen to the tissues and play an important role in improving the tissue hypoxia. Moreover, we surgeons wish to say that there is a great difference for the surgeons' mental state during a surgical operation between the cases where no blood transfusion is allowed for a religious or other reason, and the cases where we may use Fluosol-DA depending on the patients' condition. In the former cases, surgeons will be under stress such that he or she might cause the patients to lose blood excessively. On the other hand, when the surgeon has something in reserve, that is, when he or she may use Fluosol-DA if needed, a good result will usually be obtained in the operation, even without actually using Fluosol-DA. One might be led to say that a key point for the success of operations is the surgeon's mental condition, freedom from anxiety.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport↗

Discussion and considerations for the excretion mechanism of perfluorochemical emulsion.

It has been assumed that a mononuclear phagocyte system is related to the excretion of PFC emulsions: PFC particles are phagocytized by blood monocytes to be expelled through the lung alveoli. This monocyte-related mechanism may well explain excretion at an early stage when PFC particles are abundant in the blood stream. It does not, however, fully explain the manner by which PFC cells are released from the RES cells into the blood stream and into the adipose tissue. To explain this, the following mechanism has been proposed and discussed based on some experimental results. PFC emulsion particles taken up by the RES organs, are stripped at their surfactant layers in the cells and move across the cell membranes to the blood vessels and into other tissues such as adipose, at a rate that depends on the lipophilicity of the PFC's. In the blood stream, PFCs are delivered by lipoproteins to the lung and excreted into the expired air. Pharmacokinetical analysis with a compartmental model for the excretion also supported this proposed mechanism.

Adipose Tissue↗

Experimental studies on fluosol DA administration in acute pancreatitis.

Therapeutic use of the perfluorochemical emulsion, Fluosol DA, in acute pancreatitis was experimentally discussed in view of maintaining the local blood flow and oxygen supply in the pancreas to avoid further aggravation of pancreatitis. Acute pancreatitis was induced by deoxycholate injection into the pancreatic duct in adult mongrel dogs. Fluosol DA or 6% hydroxyethylstarch (HES) solution as control was transfused at 20 ml/kg/hour for the first 3 hours. Fluosol DA and HES solution improved the depressed cardiac output and pancreatic blood flow to normal levels. Compared with HES solution, Fluosol DA administration revealed a prominent increase in oxygen tension in the pancreatic tissue, which had decreased severely from onset of pancreatitis. Fluosol DA administration brought about better preservation of pancreatic mitochondrial functions. Despite no significant differences in blood levels of other pancreatic enzymes between Fluosol DA and HES solution, the sharp decrease in plasma postheparin phospholipase A2 suggested the protection of involved systemic organs including pancreas. Thus, maintaining pancreatic blood flow and increasing the oxygen transport by Fluosol DA administration seemed to play a positive role in inhibiting the progress of pancreatitis, though improvement of survival rate in acute pancreatitis was incomplete by Fluosol DA administration alone.

Acute Disease↗

[A monoclonal antibody, KM10 reactive with human gastrointestinal cancer].

A monoclonal antibody, KM10 (IgG1) was produced by fusing spleen cells from a human gastric cancer cell-primed BALB/c mouse with the murine myeloma cell line X63-Ag8-653. The antibody reacted strongly with the plasma membrane of human gastro-intestinal carcinoma. Sections of both malignant and benign tissues were tested with immunoperoxidase. Ten of 10 (100%) large intestine cancers, 26 of 31 (84%) gastric cancers, 5 of 7 (71%) pancreatic cancers and 3 of 3 (100%) ampulla of Vater cancers reacted positively. Moderate or little reactivity was observed with normal human tissues and carcinomas of the liver, mammary, thyroid and adrenal glands. According to a study of the distribution of 125I-labeled KM10 in nude mice bearing human gastric cancer, KM10 selectively localized in tumor tissue rather than normal tissue. Whole-body autoradiography also supported such selective distribution. By enzyme treatment and Western blot analysis, the antigenic determinant of KM10 antigen was demonstrated to be protein with a MW of about 240,000.

Animals↗

[Perfluorochemical emulsion as a perfusate in 24-hour liver preservation prior to transplantation in the rat].

Perfluorochemical (PFC) emulsion as a perfusate of liver preservation prior to transplantation was evaluated in continuous hypothermic perfusion for 24 hours followed by orthotopic transplantation in inbred male Lewis rat. Three different contents of PFC emulsion that is, 20% (original Fluosol DA), 10% and 0% PFC solution were prepared as a perfusate. Isolated liver was stored for up to 24 hours using a continuous non-pulsatile perfusion technique of closed circuit with each perfusate. Gas content, GOT, GPT, LDH, potassium and glucose of the perfusate were measured. Oxygen consumption of perfused liver was higher in PFC emulsion than non PFC perfusate. Biochemical analysis of perfusate suggested that liver was preserved best in 10% PFC emulsion. Histological findings, especially, acid phosphatase staining, showed better result in PFC groups. One week survival rates after liver graft were 4/6 (66.7%) in 10% PFC solution, 1/6 (16.7%) in 20% and 0/6 (0%) in 0% solution. In spite of the highest oxygen consumption of perfused liver in early phase, 20% PFC emulsion did not bring the good preservation of perfused liver because of impaired circulation due to higher viscosity in low temperature. Ten percent PFC solution is considered the best in hypothermic preservation of the liver.

Animals↗