[Extracorporeal immunomodulation].
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Biomedical subjects
Publications and source records attributed to Z Yamazaki.
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In order to selectively remove pathogenic macromolecular reactants, a biological affinity type adsorbent (a DNA colloidin charcoal column or protein A sepharose CL4B = Prosorba) has been developed and used for the treatment of immune disorders, alloimmunization and cancer. However, because physiologically active materials are required in this procedure, it is difficult to ensure an adequate supply of raw materials (and their handling, sterilization and preservation as an immunoadsorbent. To overcome the above-mentioned problems, we developed physicochemical type immunoadsorbents IM-TR and IM-PH, which consist of polyvinyl alcohol gel where tryptophan, in the former, and phenylalanine, in the latter, is used as a ligand. IM-PH has a better selectivity than IM-TR, however, IM-TR is a more efficient adsorbent of anti-acethylcholine receptor antibody than IM-PH. IM-PH plasma perfusion has been successfully used with patients with rheumatoid arthritis, systemic lupus erythematosus (SLE), and multiple sclerosis (MS).
AST-120 is a specially synthesized carbonaceous adsorbent for oral use. It mainly adsorbs low to middle molecules in the alimentary tract. In the present study, AST-120 was administered to hepatic failure dogs, and blood metabolites were analyzed by high performance liquid chromatography (HPLC). Thirty adult mongrel dogs underwent posta-cavae (P-C) shunts with 40% and 70% hepatectomies. They were divided into two groups, the AST group (n = 19) and control group (n = 11). The AST group received about 0.5 g/kg of the adsorbent intermittently with diet after the operation. The control group was fed the ordinary diet. Body weight, blood ammonia, plasma bile acids were measured, and blood metabolites were analyzed by the multi-column HPLC system. P-C shunt dogs with 70% hepatotectomies died within three months showing about 40-50% body weight loss. HPLC analysis of their plasma showed some specific peaks for middle molecules, about 3000-5000 daltons. After administration of the adsorbent, these peaks were not detected, so it was considered that these substances had been adsorbed.
UNLABELLED: A pneumatic massage apparatus has been developed for the treatment of peripheral lymphedema. The stagnant lymph and venous blood are displaced toward the heart by this pneumatic massage. It has been applied to more than 650 patients with edematous limbs in the authors' Hadomer clinic over the last ten years. Satisfactory results were obtained, including decrease in swelling, pain, and induration. The authors' clinical experiences and statistical analysis of the patients are reported here. STATISTICAL ANALYSIS: 9 primary (4 males and 5 females) and 646 secondary (28 males and 618 females) patients with lymphatic edema of extremities have been treated. The majority of the patients had postmastectomy edema of the upper extremity. CLINICAL STUDIES: The circumference of the edematous limb was measured before and after pneumatic massage treatment of forty to sixty minutes, daily or every second day. (Formula: see text). The rate of swelling was calculated by the formula described above. Twenty-six cases, treated with pneumatic massage for more than fifteen months, have been investigated. A decrease in the rate of swelling was observed in 14 cases (54%), there was no change in 7 (27%), and an increase was seen in 5 (19%). Electric impedance plethysmographic analysis of peripheral lymph volume and blood flow indicated that pneumatic massage was effective in the treatment of edema of the limbs, and its effectiveness was confirmed also by core temperature measurement of the hand during pneumatic massage. The decreased circumference of the edematous limb was kept constant for a long period of time by daily repeated pneumatic massage and ordinary conservative treatments. In conclusion, most lymphedema is of a secondary type. Pneumatic massage was effective in the treatment of peripheral lymph edema, and the improvement was maintained by repeated daily pneumatic massage and ordinary conservative treatment. Therefore, before it becomes worse, lymphedema of the limb should be treated by use of conservative treatments, including pneumatic massage continued as a long-term schedule.
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Tumor oriented anticancer agents with estrogen as a carrier have been extensively studied since 1950's. Only Estracyt and bestrabucil have been evaluated to be useful in clinical trials. Although the use of estrogen as a carrier for anticancer agents aimed at the development of the anticancer drug for the receptor mediated chemotherapy, these two drugs did not show any affinity to estrogen receptor. The history tells us that the development of anticancer agents for the estrogen receptor mediated chemotherapy is extremely difficult. Estracyt is reported to exert its anticancer effect on prostate cancer through the specific binding to the estramustine binding protein (EMBP) which is present only in the prostate gland and cancer. Bestrabucil shows the selective uptake by the various malignant cells and is indicated that bestrabucil exerts its anti-cancer effects on various malignant tumors including breast cancer and hematopoietic malignancy, through the affinity to malignant cells. The mechanism is unknown and to be elucidated.
Nafamostat mesilate (FUT-175) is a strong protease inhibitor and is used as an anticoagulant in extracorporeal circulation. In the present study, we administered FUT and dipyridamole as anticoagulants during donor plasmapheresis, and the additional effect of dipyridamole was examined. In dogs weighing about 15 Kg, donor plasmapheresis was performed using a cellulose triacetate membrane plasmaseparator (PEX-15, Nipro), and 300 ml of filtrated plasma was obtained within 30 minutes. These dogs were divided into two groups, 50 mg/h of FUT alone was infused (group A, n = 10), and the same dose of FUT and 25 mg/h of dipyridamole were infused (group B, n = 5) during plasmapheresis. Changes of the coagulation system, blood cell counts and complement system were investigated. In clinical cases, an artificial liver support therapy using FUT as an anticoagulant was performed on 8 patients with acute liver failure, and blood compatibility was examined. In dogs, RBC counts and hematocrits were almost stable, but WBC counts were decreased to about 70% of the previous value. Platelets counts were about 60% and 80% of the previous value, in group A and group B, respectively, at the end of the plasmapheresis (P less than 0.01). Clotting factor VII was diminished to about 20% and 35% of the previous value in group A and B, respectively. In clinical cases, all patients received the plasma exchange combined with hemodialysis using FUT as an anticoagulant, and no distinct side effect was observed during plasma exchange.
Our hepatic assist device is composed of a membrane plasma separator, blood and plasma pumps, hemodialyzer and controller. Using this device, the patients plasma is replaced with fresh donor plasma in a 5000 ml amount daily. This procedure of plasma exchange takes place in the intensive care unit, until the patient recovers consciousness or cerebral death is confirmed. In the initial results of this plasma exchange, 5 out of 10 patients with fulminant hepatic failure survived. Even with fatal cases, prolongation of survival time was observed. Our hepatic assist device, performing an easy and safe procedure for plasma exchange, appears to be the most promising method of providing long-term hepatic support for acute liver failure at the present time.
By the introduction of Sabin oral poliovirus vaccine, the circulation of wild type polioviruses has virtually disappeared in Japan. However, an outbreak of poliomyelitis associated with sporadic transmission of type 1 wild strain occurred in Nagano in 1980. Furthermore, we found that some type 1 wild strains were introduced into Japan from abroad in 1981. In recent surveys, the two poliovirus type 1 isolates which have non-vaccine-like antigenic character were detected in Aichi. Then, an investigation to trace the origin of these strains was performed, by using intratypic serodifferentiation and biochemical techniques. Electrophoretic migration patterns of their structural polypeptides were quite different from the vaccine virus. In the oligonucleotide mapping, however, one of them gave patterns very similar to those of the vaccine virus. We could conclude that one originated most probably from wild strains, and the other was an antigenic variant derived from the vaccine virus. It showed that oligonucleotide mapping was a very useful method for identification of antigenic modified Sabin type 1 derivatives.
Based on the assumption that middle molecules that induce hepatic coma occur in the plasma of patients with fulminant hepatic failure (FHF), the authors have developed a hemodiafiltration (HDF) method using a large-pore poly(methylmethacrylate) (PMMA) membrane that allows proteins to pass through. PMMA HDF resulted in complete recovery of deep coma and long-term survival in a patient with severe FHF. Although a large-scale controlled trial is needed, PMMA HDF is believed to be promising as a future artificial liver support.
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An artificial liver should in fact be called an artificial liver assist device or system because at this point in its development it is unable to prolong the life of an ahepatic animal, whereas, an artificial heart or an artificial kidney enables the animal to live without a heart or kidneys for a long period of time. The hepatic assist devices are classified into three types: Artificial (charcoal hemoperfusion, PAN membrane dialysis or filtration); biological (baboon liver perfusion, cross dialysis between pig liver and patients systemic circulation); and hybrid (combined form of artificial and biological). Our hepatic support system is composed of a membrane plasma separator, blood and plasma pumps, hemodialyzer and controller. Using this system, the patients plasma is replaced with fresh donor plasma in amount of 5,000 ml daily. This procedure are taken place in the intensive care unit, until the patient recovers consciousness or his cerebral death is confirmed. A national survey of the patients with fulminant hepatic failure, revealed that the survival rate of the patients treated with plasma exchange was 34.1% (15/45), while that of the patient untreated with plasma exchange was 14.3% (5/35). The difference is statistically significant. However, plasma exchange requires a large amount of fresh plasma which occasionally induce hepatitis or allergy and its detoxication of the patients plasma was insufficient in severe cases. To overcome these problems, specific adsorpton of hepatic toxins and a combined therapy of blood purification with plasma exchange will be studied further.
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