Chiyo Chiba

Protein and Nucleic Acid Synthesis During the Reparative Processes Following Myocardial Infarction

The effect of myocardial infarction upon protein and nucleic acid synthesis of the heart was studied. Myocardial infarction was produced in dogs by ligation of branches of the anterior or posterior descending coronary artery. The rate of incorporation of glycine-2-C14 into heart muscle protein was studied over a period of six weeks. The infarcted tissue showed a rapid diminution in protein synthesis after infarction; on the third day the incorporation into the infarcted tissue rose above normal and reached a maximum on the fourth. The borderline tissue also demonstrated an early increase in protein synthesis with a maximum incorporation 48 hours after infarction. The changes in the concentration of RNA paralleled those of the incorporation of glycine-C14. The concentration of DNA increased on the second day after infarction and reached a maximum on the tenth day. Studies on the incorporation of glycine-C14 into subcellular fractions showed an early renewal of cell material in the infarcted area. Incorporation into nuclear ribosomal fraction increased first, followed by mitochondria and microsomes. The incorporation into “contractile proteins” remained subnormal. The earliest increase in nucleic acid synthesis was observed for “nucleolar RNA” (p-RNA) followed by nuclear ribosomal RNA. DNA showed an increase in incorporation 48 hours after the infarction. The studies demonstrate the rapid reaction of the heart muscle to injury and the increase in protein and nucleic acid synthesis of infarcted and borderline tissue. The first step in these reactions is the synthesis of nuclear material followed by the reconstruction of mitochondria and microsomes.

Measurement of coronary blood flow using rubidium84 and the coincidence counting method

Abstract The concepts on which the coincidence counting method for the measurement of myocardial blood flow by using rubidium 84 are based were re-evaluated and critically analyzed. Contrary to recent reports from this laboratory, it was shown in the isolated dog heart that alterations in coronary blood flow resulted in a change of the mean extraction ratio. As flow increased, the myocardial extraction ratio of rubidium 84 decreased; an increase in the mean extraction ratio occurred when coronary flow was reduced. This does not invalidate the calculation of flow as obtained by extrapolation of the myocardial clearance to time zero; at this time, the extraction ratio is theoretically one, provided the myocardium is extracting all the isotope at this time. In addition, it was shown that the myocardial extraction ratio early in the experiment was not 100 per cent but averaged 63.5 per cent and probably signified the presence of anatomic or functional shunts. Therefore, it was suggested that the calculated flows should be referred to as nutrient or effective coronary flows. It was demonstrated that the radioactivity of blood in the cardiac chamber could be neglected in the calculation of the myocardial uptake of rubidium. 84 The observation was confirmed that nitroglycerin increases the myocardial uptake and/or flow in patients without coronary artery disease; it failed to do so in patients with coronary artery disease. Because of this different response to the administration of nitroglycerin, the coincidence method as used here is of diagnostic aid in the recognition of coronary artery disease.

Catecholamines in Homologous Heart Grafts.

Summary Complete denervation of puppy hearts was accomplished by homologous transplantation. Cardiac content and intracellular distribution of catecholamines remained unaffected the first 24 hours following transplantation. Within this time period accelerated rejection did not influence the catecholamine content of the heart graft. After 72 hours no catecholamines could be detected in transplanted heart.

The Selective Irradiation Of Canine Lymph Nodes By Means Of Intralymphatic Injection Of 32p

Intralymphatic injection of radioactive chromic phosphate produced a severe destruction of a majority of lymph nodes, and subsequent marked lymphopenia in dogs. Selectivity of radiation was evidenced by histological study of other major organs and blood counts. Antibody production of these animals against human serum albumin was significantly inhibited; however, the reactivity to the allografted heart was not altered.

Cross species immunosuppressive effects of antilymphocyte serum in mice and rats.

SUMMARY The immunosuppresive effect of cross species antilymphocyte serum (CSALS) on skin homograft reactions was tested in mice and rats. The effect of CSALS was significant in rats and particularly noticeable when Donryu rats were used as graft donors. Nine of 11 grafts survived longer than 40 days and the longest time was 324 days. The effect of CSALS was greatly influenced by the administration schedule, 11 consecutive injections producing a stronger effect than 11 injections, of which 5 were given before and 6 were given after transplantation. The immunosuppressive effect of antirat antilymphocyte serum (ALS) was not as strong in mice as that seen in antimouse ALStreated rats. It is concluded that CSALS can be an effective immunosuppressive regimen if the proper animal species is chosen as immunizing lymphocyte donor, the administration schedule is carefully established, and the genetic disparity between the graft donor and recipient is minimized through histocompatibility testing.

Studies on the Transplanted Heart. Role of Gamma-Globulin in Transplantation Immunity.

Summary Sensitization of the recipient animal with spleen homogenate resulted in a significant increase in the serum gamma globulin fraction and subsequent accelerated rejection of the graft. In exceptional cases in which serum gamma-globulin level did not increase, the accelerated rejection was absent. Treatment with 6-MP reduced the gammaglobulin level and the grafts in these animals showed prolonged survival. Reduction of gamma-globulin by exchange transfusion failed to prolong survival time of the graft. These results are in accord with the view that humoral factors present in the gammaglobulin fraction play an important role in homograft rejection.

Demonstration of Cytotoxic Humoral Substances during the Course of First Set Skin Allograft Rejection

Summary Cytotoxic humoral substances, which are most likely produced by the stimulation of first set skin allograft, were demonstrated by utilizing Millipore diffusion-chamber technique. The cytotoxic effect of the substance was much stronger in the animals which had rejected their grafts, whereas it was least in the animals bearing viable grafts. The presence of such cytotoxic humoral substances was observed as early as 8 days after grafting, and lasted for at least 6 weeks. The results obtained at the twelfth week of grafting suggested the virtual disappearance of the cycotoxic substances. Lymphocytes originating from a rat other than the skin graft donor were also killed rapidly when implanted into recipient rats which had rejected grafts, indicating cross-reactivity within the animals used in this study.

Einfluß einer durch Autoimmunreaktion hervorgerufenen Lymphopenie auf die Transplantatabstoßung beim Hund

ZusammenfassungEine auf einer Autoimmunreaktion beruhende Methode zur Erzielung einer experimentellen Lymphopenie wird geschildert. Dabei wurde keine Granulopenie beobachtet. Nach Auftreten der deutlichen Lymphopenie wurden an Herzen bei Hunden heterotop transplantiert. Die Überlebenszeit der Transplantate war nicht signifikant verlängert.SummaryThis report describes an autoimmune method for inducing experimental lymphopenia in dogs. The lymphopenia was not accompanied by granulocytopenia. Following the appearance of lymphopenia hearts were transplanted heterotopically. The survival time of the transplants was not significantly prolonged.

Serum Electrophoretic Changes Following Heart Allotransplantation.

Summary Serum electrophoretic changes in animals receiving allotransplantation of the heart were studied. Two major changes were observed: an early elevation in alpha-2 globulin and a late (post rejection) increase in gamma globulin fraction. The rise of alpha-2 globulins could not be correlated with cytotoxic changes leading to rejection. It is therefore felt that the initial rise in alpha-2 globulin represented a non-cytotoxic graft specific antibody. The change in gamma globulin seemed to be closely related to rejection and possibly represented cytotoxic graft specific antibody.

Production of Enhanced Immunity to Autologous Material by Means of Coupling to an Antigenic Protein Carrier.

Excerpt The possibility was explored of establishing a state of active immunity by means of coupling components of autologous body material to an antigenic protein carrier and injecting this comple...