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The aim of this study is to obtain data for improving a training program for patients with diabetes mellitus. One hundred eighty-seven patients with non-insulin dependent diabetes mellitus were tested with 20 questions about their knowledge for self-management of diabetes mellitus. Then to draw out factors in their personal backgrounds relating to their correct answers, multiple regression analyses were conducted. As a result, four factors showed significant differences in the following order: Educational careers > ages > duration of disease > socioeconomic strata. The results of the present study have shown for the first time, that these four factors closely concern patients to acquire the necessary knowledge for their self-management of the disease. In addition, this study has raised some fundamental problems regarding the training program for patients: how education should be given to patients.

Early diagnosis of rejection and timely immunosuppression are absolutely important in clinical lung transplantation. We studied surface markers of peripheral blood lymphocytes (PBL), graft infiltrating lymphocytes (GIF) and bronchoalveolar lavage fluid (BALF) in a rat using flow cytometric monitoring to diagnose rejection. Left lung transplantation was performed on Brown Norway (BN) rats and Lewis (LEW) rats in the following groups; Group 1: LEW-LEW (isograft), Group 2: BN-LEW (allograft; no immunosuppression), Group 3: BN-LEW (allograft; treated with Cyclosporine A at a dose of 15 mg/kg/day i.m.). In each group, rats were killed 3, 5, 7 days postoperatively (n = 6 on each day). Monoclonal antibodies investigated in this study were W3/25 (anti-helper T lymphocyte), OX8 (anti-suppressor/cytotoxic T lymphocyte), and OX39 (anti-interleukin 2 receptor). Histological classification of rejection in Group 2 showed vascular phase at 3 days, alveolar phase at 5 days, and destructive phase at 7 days, respectively. No evidence of rejection was found in Group 1 or 3. In Group 2, W3/25 positive cell proportion in GIL and BALF significantly decreased as the rejection progressed, but OX8 positive and OX39 positive cell proportion increases were significantly greater than in Groups 1 and 3 as the rejection progressed. These results lead us to speculate that the studies of T cell subsets in GIL and BALF lymphocytes are useful for diagnosis of rejection in lung transplantation.

A ten year follow-up study was made of 107 hips of 97 patients to find if derotation osteotomy affected the growth of the hip joint. The anteversion angles before and after treatment were measured in four groups classified according to treatment method: Pavlik harness, frog plaster, Colonna operation and derotation osteotomy. The difference in the angle was greatest in the derotation osteotomy group. However, no significant relation between the CE angles and the anteversion angles or the degree of derotation at the time of the follow-up study was found. The author concluded that the growth of the hip is not influenced by the extent of anteversion as much as was previously believed before.

The differences in physiological and safety conditions of one-man buses and two-man buses were examined from the view point of occupational fatigue. This survey consisted of a work load study which included a time study, study of subsidiary behavior, auditory task, memory test, Galvanic Skin Response (GSR) and physiological function tests and a self-administered questionnaire which involved items concerning safety and subjective fatigue complaints. The visual and postural restrictions in the one-man bus were greater than in the two-man bus. The mental capacity of the one-man bus drivers was found to be less. Greater mental fatigue and stress were observed in the one-man bus. More subjective fatigue complaints were observed in the one-man bus. More cases of near accidents were observed in the one-man bus. From these results it was concluded that the one-man bus caused bus drivers a greater mental and physical work load.

We examined the activity of peripheral blood monocytes in patients with autoimmune hemolytic anemia (AIHA) using an in vitro assay of monocyte-macrophage interaction with erythrocytes and an antibody-dependent cell-mediated cytotoxicity (ADCC) assay. The monocytes of AIHA patients in the hemolyzing period phagocytized autologous sensitized red cells and anti-D coated red cells more avidly than normal control monocytes. There was no significant relationship between phagocytic activity and ADCC activity. The activated monocytes phagocytized autologous sensitized red cells, but had no ADCC activity in a short time 51Cr release assay. Phagocytic activity of the patients' monocytes against autologous erythrocytes rapidly decreased after treatment with prednisolone even though the red cell sensitization with antibody remained almost the same as during the hemolyzing period. We postulated that the activation of monocytes in AIHA was due to the "arming" effect of anti-erythrocyte antibody, but we think that other mechanisms may also be involved in the activation of monocytes.

In order to approach human cancer immunotherapy, the author carried out the immunotherapy with BCG on mice having homotransplanted cancer, observed the posttransplantation results with lapse of time, conduced daily macrophage inhibition test (MI test) and found the immunotherapy to be effective. At the same time the MI test proved to be a useful criterion in determining the course of cancer progress and effectiveness of the immunotherapy.

Attempts were made to identify menstrual blood by means of paper electrophoresis with preparation of extracts of menstrual blood isolated under various conditions and mixed with human fibrin. Also similar analyses were conducted with blood aspirated from the median cubital vein of a woman during menstruation as well as from a man as the control, also with extracts of lochial blood from a woman after normal delivery, and of the blood obtained at arrtificial abortion. Animal fibrins (from rabbit, mouse, steer, and guinea pig) were also used to see the lytic action of the bloods. The following are the results of the present experiments. 1. The identification of menstrual blood by means of paper electrophoresis is a simple method in legal medicine and its electrophorogram is an excellent method to offer an evidence of proof for mentrual blood. 2. By this method it is possible to identify the menstrual bloodstain even after the lapse of time as much as 6 months. 3. It is possible to identify even putrefied menstrual bloodstain. 4. In the case where the material stained with menstrual blood is found in water, it is not possible to identify the menstrual blood by this method. 5. When the menstrual blood is heated at 60°C over 30 minutes, it becomes impossible to identify it by this method. 6. In the case of venous blood during menstruation fibrinolytic product can be detected only on the first day of menstruation, but since it appears only in trace, it is easy to differentiate it from menstrual blood. 7. As for lochial blood the fibrinolytic product can be detected only in the blood obtained on the first and second days of puerperium, but the amount being so slight that it can readily be distinguished from menstrual blood. 8. In the case of the blood obtained at artificial abortion fibrinolytic product appears just as much as in the case of menstrual blood, and thus it is impossible to differentiate it from mentrual blood by this method. 9. As for the use of human fibrin it is best to employ it while it isdresh, but the human fibrin up to 6 days old can be used. However, the older is the human fibrin the lesser the fibrinolytic product detectable. 10. In the case using animal fibrins mixed with the extract of menstrual blood some do produce fibrinolytic product in trace, but since there is a danger of also producing the fibrinolytic product-like substance in venous blood, it is advisable not to use animal fibrins.

The human tumor H. Ep. #3 maintained in rats could be transferred for 1-8 generations in treated guinea pigs. H. Ep. #3 grew in the subcutaneous and intramuscular sites in each host at the same time. The treatment with the combination of X-ray 250 r. and 80 mg/kg of cortisone turned out to be the optimal conditioning studied. The number of tumor takes averaged 95.7-100 per cent in the subcutaneous site in guinea pigs treated with optimal conditioning, but in the intramuscular site, the number of tumor takes was 65.2-93.8 per cent. Host mortality varied from 4.2-37.5 per cent in the hosts treated with optimal conditioning. The subcutaneous tumor weights in hosts treated with optimal conditioning averaged 3.3 gm, and their intramuscular tumor weights averaged 5.6-6.2 gm. Tumor weights in hosts treated with only cortisone averaged 1-2 gm in both subcutaneous and intramuscular sites. Histological findings. for the original tumors were found to be the same as that for the successful transplanted tumors in the guinea pigs. The malignancy of the tumor was evaluated by the criteria of anaplasia, invasion, rapidity of growth, and ease of maintenance of transplants. There was no metastasis found in any organs.

Homogenous grafting of the ovary to patients of ovarian dysfunction all proved to be effective, but the degree of the effectiveness and the time of appearance of effect of the grafting were not fixed. Moreover, there was no relationship between the effectiveness of grafting and the type of blood. If the various conditions at the time of grafting are taken into· consideration as above mentioned, this operation utilizing as it does the ovary usually discarded at operation may be expected to bring about quite a satisfactory therapeutic result.

With an improved method of tissue culture of peripheral leucocytes of our own design, the authors carried out systematic observations on the peripheral leucocyte culture from the normal, various kinds of leukemias, leukemoid reactions, and hypoplastic anemia. As for the culture method we have devised a method of silicon oil coating on the blood containers, a method which will least affect the cell function as compared with the conventional culture method. As the results we have found that the tissue growth in the case of peripheral leucocyte culture of normal persons ceases after six-hour culture and also we have recognized a peculiar finding, a growth like a corona-shape, in which an empty space appears in the inner part of growth area along with the lapse of time. In every leukemic case, without presenting growth area like a corona, the cell density is high and the outer zone of growth area becomes sharply demarcated as in the case with bone-marrow culture and also the growth continues even after 12 hours. At this instance we have noticed many mitoses of immature cells. Moreover, the maturation of immature cells has been observed and it has also been possible to distinguish to what type these immature cells belonged. In the leukemoid reaction no growth pattern Characteristic to the leukemia can be recognized, and at a glance it can easily be differentiated from the leukemia. In the case of hypoplastic anemia although the growth area is like that of the normal presenting a corona-like shape, the cell density is lower and the function of leucccytes is lesser than the normal. From these results we believe that the peripheral leucocyte culture is clinically useful.

By mixing ferric iron with serum protein, 20 cc of serum and 1 cc of ferric chloride or ferric ammonium sulfate (l0 mg ferric iron/cc in each), in the range of pH 5.4 to 8.2, a transparent brownish red colored solution can be obtained. Paperelectrochromatography proved the iron can mainly be detected in β-globulin fraction in bovine serum and in &#945-globulin and albumin fractions in human and rabbit sera. But the absorption spectrum proved that there is no formation of any new compound, giving almost the same absorption curve as in the serum protein itself. And by lowering the pH of media below 5.4, the solution gives immediately the positive reaction of ferric iron. From these rerults it is suggested that iron will be maintained in a colloidal state keeping the stability of this state in the presence of protein molecules. Freezing and drying are the procedures quite useful for keeping this material for a long period of time without changing the chemical characteristics.

To study the effect of partial liquid ventilation (PLV) with perfluorocarbon on acute respiratory failure, 3 groups of 17 rabbits were examined to compare. After acute respiratory failure was induced by lung lavage with sea water in 12 of the 17 rabbits, 7 of the 12 rabbits were treated with conventional mechanical ventilation (AC group) and 5 of the 12 rabbits were treated with PLV using perfluorocarbon (AP group). The remaining 5 normal rabbits without acute respiratory failure were treated with PLV with perfluorocarbon as a control group (PL group). In the PL group, PaO2, PaCO2, blood pH, pulmonary compliance or pathological findings were not so changed after PLV. In the AC and AP groups, PaCO2 significantly increased, and in contrast, PaO2 and pulmonary compliance significantly decreased after lung lavage. However, these findings improved to almost the same levels as those of a control group within 2 h after the PLV treatment in the AP group, but in the AC group, these gradually deteriorated over time. As for the pathological findings, pulmonary vascular congestion, alveolar hemorrhage and inflammatory infiltration were observed in the AC group. However, these findings were not observed in the specimens of the AP group. From these results, PLV with perfluorocarbon was shown to be useful to improve gas exchange and pulmonary functions without major side effects.

Intrathymic (i.t.) injection of allogenic cells without administration of anti-lymphocyte serum (ALS) in neonatal recipients has induced donor-specific tolerance to subsequent cardiac allografts in rats. This study examines whether similar tactics can be successfully applied to a hamster-to-rat cardiac xenotransplantation model. Lewis neonates on their first day of life underwent i.t., subcutaneous (s.c.), intraperitoneal (i.p.), or intravenous (i.v.) injections of 5 x 10(7) Golden Syrian hamster splenocytes. After six weeks, the rats underwent heterotopic cardiac transplantation of hamster hearts. Cyclophosphamide (CyP) was administered on the day before surgery and postoperatively to suppress antibody-mediated graft rejection. Rats given splenocytes with 80 mg/kg of CyP had the following graft survival times: 8 to 12 days for i.t. injection (mean, 9.4 days); 5 to 7 days for s.c. injection (mean, 6.6 days); 4 to 11 days for i.p. injection (mean, 7.4 days); and 4 to 13 days for i.v. injection (mean, 7.9 days). Only the extension of graft survival produced by i.t. injection was statistically significant in comparison with the rats given only CyP treatment (mean, 7.5 days; P < 0.05). Thus, it appears that i.t. injection of xenogenic splenocytes in neonatal recipients with administration of CyP, but without ALS, can prolong xenograft survival. This biological intervention may be most useful in pediatric xenotransplantation when combined with other immunomodulation techniques.

In order to elucidate factors influencing the prognosis of small-cell lung cancer (SCLC), we reviewed the records of 253 patients with SCLC and evaluated 20 pretreatment prognostic factors by univariate analysis and Cox's multiple regression analysis. Recursive partitioning and amalgamation (RPA) was employed to identify subgroups with similar survival rates. Cox's multiple regression analysis identified five significant factors: extent of disease, number of metastatic sites, serum albumin, serum lactate dehydrogenase, and presence of weight loss. Among these, extent of disease was the most influential factor. RPA analysis revealed three subgroups predicting significantly different prognoses. The median survival time and 3-year survival rate were 18.4 months and 20.6%, respectively for the good-risk group (limited disease without weight loss), 13.5 months and 9.1%, respectively for the intermediate-risk group (limited disease with weight loss or extensive disease with less than two metastatic sites), and 9.2 months and 0%, respectively for the poor-risk group (extensive disease with two or more metastatic sites). These results will be useful for development of new staging system or subsequent stratification for randomized trials.

3-(3-methyl-3-butenyl)-1,2,3,4,5,6-hexahydro-6, 11-dimethyl-8-hydroxy-2,6-methano-3-benzazocine (KF-1820) is a derivative of benzomorphan and is different from pentazocine only in the site of the double bond. KF-1820 showed potent analgesic activity in all tests performed. KF-1820 was 6 to 12 times and 30 to 40 times more potent than morphine and pentazocine, respectively, when administered subcutaneously. KF-1820 had little or no narcotic antagonist property. Physical dependence liability tests indicated that KF-1820 may be a little less, or as liable as, pentazocine to produce physical dependence. ID50 values of KF-1820, pentazocine and morphine for depression of contractions of isolated guinea pig ileum to coaxial stimulation correlated well with their analgesic activities in the rodent. The dissociation equilibrium constant of KP-1820 confirmed the in vivo finding that KF-1820 had little or no narcotic antagonist property.

Drug effects were studied on anaphylactic histamine release from rat mast cells sensitized in vitro with mouse IgE antibody. When histamine release was elicited by adding Ca-++ at various times after antigen-stimulation of sensitized cells in Ca++-free medium, the drugs to be tested were added shortly before each Ca++ addition. Quercetin was effective only when added before or immediately after antigen. Theophylline and disodium cromoglycate (DSCG) were active irrespective of the time interval between antigen and Ca++ addition. Verapamil was more effective when added before or simultaneously with antigen than when added later. When tested in the two-stage experiments, quercetin showed inhibition only in Stage 1 and verapamil was inhibitive primarily in Stage 1, while theophylline and DSCG wee only inhibitive in Stage 2. It seems that quercetin selectively and verapamil primarily act to block calcium-gate opening resulting from antigen-antibody interaction on the mast cell membrane, while theophylline and DSCG selectively inhibit the passage of calcium through open calcium channels.

A permeable cell system has been developed by treatment with saponin for studying in vitro replication of DNA and chromatin. DNA replication of simian virus 40 nucleoprotein complexes (SV40 chromatin) in saponin-treated permeable cells was found to be more efficient than that in digitonin-treated permeable cells. Autoradiography of the agarose-gel revealed that [alpha-32P]dCTP was incorporated into SV40 DNA I, II and replicating intermediates. The time course of the incorporation indicated complete replication of SV40 DNA and chromatin with a full number of nucleosomes. The saponin-treated permeable cell system will serve as a useful system for studying in vitro replication of DNA and chromatin in eukaryotic cells.

<p>The kinetics in tumor cells and various factors affecting the tumor accumulation of 67Ga-citrate and 201Tl-chloride were studied in vitro. 67Ga was taken up gradually by tumor cells and its excretion from the cells decreased with time. 201Tl was taken up rapidly by tumor cells. Its excretion was very rapid, indicating that the two nuclides had entirely different kinetics in tumor cells. The uptake of 201Tl by culture cells correlated with that of 42KCl and was inhibited by Ouabain. 201Tl was hardly taken up by nonviable tumor cells. These facts indicate that active transport involving Na-K ATPase is involved in the tumor accumulation of 201Tl. The uptake of 67Ga and 201Tl by tumor cells was not affected by the administration of anticancer agents. The uptake of 67Ga by tumor cells was dependent upon the concentration of transferrin in the medium, which apparently plays a role as one of the pathways of tumor accumulation of 67Ga.</p>

The usefulness of liposomes (in neutral, positively and negatively charged forms) as a carrier for adriamycin (ADM) was studied by examining the distribution of ADM and related fluorescent compounds in Ehrlich solid tumor-bearing mice. The mice were given free or liposome-entrapped ADM intraperitoneally. The distribution of ADM and related fluorescent compounds between the administration of the free form and liposome-entrapped form was measured by high performance liquid chromatography : The distribution was dependent on the form of the liposomes. The amounts of ADM and its metabolites in the mouse serum 20 min after administration of neutral-liposome-entrapped ADM were 10 times those after the administration of free ADM, 6 times those after the administration of a negatively charged form, and 3.5 times those in the administration of positively charged form. There was no marked difference in the concentrations of these compounds 5 h after administration. The concentration of these compounds in the liver 60 min after administration of each liposome-entrapped form of ADM were in inverse correlation with the concentrations in the serum obtained at 20 min after administration. Total concentrations of ADM and its metabolites in the tumors 20 min after administration of each entrapped form of ADM were 4-5 times that in administration of free ADM after 20 min. There were no marked differences in the concentration of ADM for administration of the various liposome forms. Statistically significant decreases in mean tumor weight were seen in the groups given neutral, positively and negatively charged liposome-entrapped forms compared to corresponding control groups given with free ADM.

By physically destroying typhoid bacilli and centrifuging at a high speed, an insoluble granular fraction (P1) and soluble fraction (S1) were obtained. Chemical and enzymologic properties of these substances as well as their influences on the protective ability against infection were studied; and the following results were attained: 1. P1 contains an extremely small amount of proteins when compared with S1. 2. The enzymologic activity of P1 is entirely different from that of S1. In P1 the respiratory enzyme system of only lactate and succinate is localized. 3. Although both P1 and S1 possess the antibody-producing ability in serum of rabbit to the same high degree, P1 imparts to mice a markedly high protective ability against infection. 4. By the heat-treatment of P1 its antigenicity is lost at the same time.