The height, the size and the interval space of the valves of the vena saphena magna and the ductus thoracicus of adult dogs were measured. As a result it was found that except for a slight difference the height of the valves could be represented by 1/4 wave length, and the interval space between the upper margins of the valves by 1/2 wave length. Such a slight difference seems to be due to the difference in the growth of the venous and thoracic duct wall. From the vascular structure the structural mechanisms of the valves have been described hemodynamically.
The arterial wall is all consisted of the chain of fibroblasts that run stereoscopically crisscrossing with each other in the Archimedes spiral formation, as viewed from the upper surface, originating from the endothel cells in the initial embryonic stage, and also with the heterogenous fibroblasts that continue in the same spiral direction. The endothel cells form the elastic prefibers of the subendothelial layer, while the fibroblasts of tunica media which form Archimedes spiral, construct elastic and collagenous fibers and transform into smooth muscle cells. On the other hand, heterogenous fibroblasts construct collagenous and elastic fibers of tunica adventitia. This chain of the smooth muscle cells of tunica media that retains Archimedes spiral, as viewed from the upper surface, is the muscular-type artery and the one that has differentiated and each smooth muscle cells have bridged between elastic membranes is the elastic-type artery.
From both the light and electron microscope observations of histological structure and mechanisms of contruction of arterial wall, the functional, formative mechanisms of elastic membrane of arterial wall may be explained as follows: The fundamental type of artery is the muscular-type artery in which the chain of smooth muscle cells runs criss-cross wise from left to right or vice versa in Archimedes spiral formation as viewed from the upper surface. That further differentiates and the chain disintegrates, resulting in individual smooth muscle cells bridging between the elastic membranes to form an elastictype artery. In the case of the muscle-type artery of a relatively high differentiation, the smooth muscle cell chain is divided into equal parts each of which forms an individual Archimedes segment composed of original elastic components. In the case of elastic-type artery within such a segment, cells become individual smooth muscle cells. The elastic component ejected from the cytoplasm of each smooth muscle cell forms the elastic fiber sheath by its kinetic movement. This sheath in the muscle-type is divided into two equal numbers in the center of the above segment, and longitudinal sheath-segments of about one fourth of the original size separate to left and right, then at the horizontal level they form Archimedes segments with the original elastic networks by attaching themselves to the anterior-posterior surfaces and the lateral surface. However, only the inner layer of the internal elastic membrane is formed by the elastic prefibers of high ascending angle produced by endothel cells. In the case of elastic-type artery, the elastic sheath containing the individual smooth muscle cell is similarly divided into two equal parts at the center, which are further split up longitudinally that reinforce the original elastic network to form an elastic membrane. In each elastic sheath there are formed a spiral ascending fiber in the direction of the longitudinal axis and a fiber of approximately circular shape, the former of which becomes an ascending fiber and the latter becomes the longitudinal fiber of the elastic membrane. Therefore, the ascending angle of fiber of the elastic membrane is equal at the opposite surface of the stroma. In addition, the reason why the ascending angle of fiber is higher in the outer-layer fiber than in the inner-layer fiber is because the twisting phenomenon by contracting movement of the smooth muscle cells is stronger in those of the outer layer and the ascending angle of the fiber of elastic sheath is lower in the outer side.
Light and electron microscope studies on the spheroid alveolar epithelial cells of the lung in mice were conducted. By the light microscopy it was found that in the case of the intraperitoneal injection of H3-thymidine, S35-DL-cysteine and S35-H2SO4 into mice, most of siliver particles deposit in the cytoplasm and nucleus of spheroid alveolar cells. In observing this phenomenon by the electron tracers, the above tracers enter not only into the nucleus but also into mitochondria, degenerated mitochondria, and into inclusion bodies of myelin-type or lamellar microbodies in the cytoplasm of the spheroid alveolar cells. From these results it is understood that the inclusion body not clarified at present is formed by the degeneration of mitochondria. This inclusion body seems to be a kind of cytolysomes and by various enzymes contained in it, nucleic acids, proteins, mucopolysaccharides, phosphoric acid ester, and glucuronide are dissolved and finally they are reduced into the myeline figure substance as the endproduct. The endproduct is to be secreted into the alveolar lumen from the spheroid alveolar cell.
The authors reported the results of field survey on acatalasemia and hypocatalasemia during the year of 1972 and 1973. Seventeen hypocatalasemias were seen in the test of 7, 475 individuals at Oahu Is. of Hawaii, U.S.A. Among them two Englishmen, one Portugese and three Filipinos were included. One new acatalasemia case was reported in 1972. Consequently, the total of reported acatalasemias were 97 cases of 47 families by the end of 1973.
Cell-mediated immunity in chronic myelogenous leukemia (CML) was investigated by means of three kinds of skin tests, including purified protein derivated of tuberculin (PPD), candida and dinitrochrolobenzene (DNCB), and macrophage migration inhibitory test (MIT). Immunological examinations were made on 21 patients with CML, who have been admitted to our hospital or controled in our outpatient department since October 1974, at the same, 20 healthy adults were used as control study. The following results were obtained: I. Skin tests: 1) Thirteen (61.9%) of 21 patients showed positive reactions to the PPD at least once throughout clinical course of each patient, while positive in 18 (90.0%) of 20 controls. 2) Candida test was attempted on a total of 13 patients. One (7.7%) of these 13 patients showed positive reaction to the candida, while positive in 9 (45.0%) of 20 healthy subjects. 3) Seven (41.2%) of 17 patients showed positive reactions to the DNCB sensitization, while all of 20 controls proved to be positive. 4) The results of PPD skin test were analyzed according to the stages in clinical course of each individual. Positive reactions were obtained from 50% of the patients at pretreatment stage, 66.6% at remission stage, 20% at relapse stage and 16.6% at blastic crisis. 5) The PPD skin test changed from negative, or false positive, to positive in 5 of 21 cases who had achieved remission during the observation period, while it changed from positive to negative in one case who had relapsed during the same period. It kept positive in 4 of 8 cases who had maintained remission, and kept negative in one relapsing case having failed to achieve remission. In 2 of 6 cases who had a blastic crisis during the observation period, it was positive before the crisis and became false positive after the crisis. According to these results a significant correlation was found between PPD and clinical stage of CML. II. Macrophage migration inhibitory test (MIT): 1) In the preliminary studies, the optimal ratio was determined that 106 lymphocytes react properly to 0.1ml antigen fluid, which is equivalent to 0.11-0.03μg of protein level and is extracted from the leukemic cells by means of sonication. 2) Eight (53.3%) of 17 patients were regarded as positive in allo-antigen system of MIT and 5 (55.5%) of 9 patients in auto-antigen system. Because of the difficulty of collecting lymphocytes, all MIT were conducted only in the remission stage of each patient. From these results, the following conclusion can be made. Cellular immunity in CML is somewhat impaired at pretreatment or relapsing stage. It is, however, repaired mostly at remission stage and it has a close correlation to clinical stage of CML.
To study the humoral reactivity in chronic myelogenous leukemia (CML), the author examined immunoglobuline levels, immune adherence hemagglutination test (IAHA) and lymphocytotoxicity test on the 24 patients admitted to our clinic. The following data were obtained: 1) The 19 patients, whose serum immunoglobuline levels were examined, were all within normal range with mean values of IgA 203±74mg/dl, IgG 1463±275mg/dl and IgM 182±67mg/dl. 2) IAHA was positive in 4 of 24 patients (16.7%) and the reactivity was correlated with the number of peripheral leukemic cells used as antigen; it was positive in 3 of 9 patients (33.3%) with leukemic cells over 4×104/μ l, but in only one of 15 patients (6.7%) with leukemic cells below 4×104/μ l. The IAHA test was also correlated with the disease state; none of 4 patients (0%) during blastic crisis of CML showed a positive reaction to their own leukemic cells. 3) Sera from 12 of 17 patients (70.6%) showed a positive lymphocytotoxicity to normal lymphocytes. In its correlation with the disease state, it was positive in 8 of 13 patients (61.5%) during remission and in all the patients (100%) during relapse. From these results it could be concluded that humoral immunity in CML is not so impaired through the clinical course except for blastic crisis.
Further investigation concerned on the antigenicity of the lymphocyte membrane was performed in this paper using C57B1 mice and purified lymphocyte membranes which were preparated from either calf thymic lymphocyte (TM) or bovine intestinal lymphnode lymphocyte (LM). The detail of the methods for the purification of lymphocyte membrane were described in the part I of this article. Intraperitoneal injection of 5, 10 or 100γ of lymphocyte membrane was performed once a week untill 5 weeks. The peripheral blood pictures, diameter of lymphocyte, histological studies on the thymus, lymphnode and spleen, serum protein electrophoresis, immunoelectrosyneresis, RFC and PHA reactivity were examined in these immunized mice. The lymphocytes both in the peripheral blood and lymphatic organs were diminished profoundly in the mice immunized with TM. Especially the lymphocytes in the T dependent area of spleen and lymphnode as well as in the cortical area of the thymus decreased intensively in contrasting with a decrease of B cell area of spleen and lymphnode in the mice immunized with LM. The lymphocyte depletion in the lymphoid organs of the mice immunized with 100γ LM had a similar pattern to those of mice immunized with TM indicating the contamination of TM into the LM preparation up to approximately 6-8%. Temporary increase of α1-globulin, α2-globulin and α3-globulin in this order was noted in serum of the mice immunized with TM, being followed by hypergammaglobulinemia. On the other hand an increase of α3-globulin and then of γ-globulin appeared rapidly in the mice immunized with LM. The discrepancies on the tissue reaction and protein fraction of these two groups suggested the difference of antigenicity between TM and LM on the activation of antibody-forming system.
The serum DBH (Dopamine-β-Hydroxylase) activity in a total of 177 individuals was determined in this study during the period from June 1974 to June 1975. The subjects were 103 manic-depressive psychosis patients and 43 patients with other diseases who had visited the Neurology Department of the Hiroshima City Hospital and 31 healthy subjects included for comparison. Among the 103 manic-depressive psychosis cases, there were 55 cases, 40 with unipolar depression and 15 with bipolar depression, in whom determination of activity was made during both the depressive and remission phases. Further, in 25 unipolar depression and 6 bipolar depression cases, the diurnal variation of activity was measured and studied in detail. The following results were obtained from the above findings. 1. There was marked individual difference in serum DBH activity. Great individual difference was observed in healthy persons also, but in the same individual the value obtained by repeat test perform 9 months after the initial test showed almost the same result and the rate of variation was less than ±10%. 2. Comparison of the mean values of serum DBH activity among various diseases showed the values to be high in the order of schizophrenia, neurosis, unipolar depression and bipolar depression, but the differences from healthy persons were not significant. 3. Variation in serum DBH activity in manic-depressive psychosis strongly suggested the heterogeneity of unipolar and bipolar depressions. Further it was also assumed that there were heterogeneous diseases mixed among the unipolar or bipolar depression cases, and thus further subclassification was performed. 4. Cases with unipolar depression were classified into 3 groups according to whether the differece in value of serum DBH activity was significantly higher in the depressive phase than the remission phase (Group I), unchanged (Group II) and significantly lowere (Group III). The respective clinical characteristics were as follows: Group I consisted of 40% of the unipolar depression cases, was made up predominantly of women and a strong feeling of anxiety prevailed, but the subjects responded well to tricyclic antidepressants. Group II was composed of 32.5%, the subjects were highly irritant and many did not respond well to tricyclic antidepressants. Group III consisted of 27.5%, was made up predominantly of males, severe psychomotor retardation was present and the subjects responded well to tricylic antidepressants. 5. All cases with bipolar depression presented the characteristic finding of lower activity values during the depressive phase than the remission phase. Cases with manic phase activity values lower than the remission phase were classified as Group I and those with higher values Group II. The respective clinical characteristics were as follows: Group I was composed of 69.2% of the bipolar depression cases of whom many changed to mania within a short period of time after their depressive phase making it appear as if the depressive and manic phases were one single continuous phase. Group II was composed of 30.8% and was frequently found in those with a marked manic phase only or in those whom the manic or depressive phase developed independently. 6. The diurnal variation of serum DBH activity in manic-depressive psychosis was not of a fixed pattern such as being low in the morning and high at noon. However, many presented a similar rhythm for both the depressive and remission phases of the disease, but the rate of diurnal variation was greater during the depressive or manic phase than the remission phase. The rate of diurnal variation during the remission phase was about±10%.
The exercise electrocardiogram of the patients with left ventricular hypertrophy was studied, especially on its STT change. Seventy six patients with essential hypertension, who were under good control, were included for the study. They were 52 males and 24 females. Their ages ranged from 33 to 70 years (the average was 51.6±7.8 years of age). The patients were divided into four groups according to changes in ST segment and T wave on standard 12 lead ECG (III, aVR were excluded): Group A consisted of 10 subjects, whose ECG showed so-called “Strain Pattern”; Group B included 22 subjects, showing ischemic depression less than 0.5 mm below the isoelectric line or low T wave (T/R≤1/20 and R≥10 mm); Group C included 17 subjects, junctional depression was equal to or exceeded 1.0 mm; Group D included 27 subjects without marked STT change. Twenty healthy men (6 males and 14 females) were studied as control. They ranged in age from 20 to 62 (the average was 36.7±14.1 years of age). As a rule, they were subjected to the Master's test (double two step). In the pre-exercise electrocardiogram of Group A, QRS voltage, LAD and QT ratio were significantly greater than any other groups. In the post-exercise electrocardiogram, Group A showed chiefly T wave changes without ST deviation. I could not find any cases in the group with positive responce. Therefore, the “Strain Pattern” with marked QRS high voltage might be secondary STT changes. On the other hand, patients in Group B and D showed mainly ST changes and most of them were determined to have positive responce of the test. So, the STT changes without marked QRS high voltage might be primary changes.
Effect of anti-anginal drugs on the distribution of blood flow in the left ventricular free wall has been studied using thirty anesthetized open-chest dogs. The regional myocardial blood flows in the inner-(subendocardial) and outer-(sub-epicardial) layer were continuously monitored by heated cross-thermocouples designed according to Grayson's heat exchange principle. The techniques used were essentially the same as that described by Uchida (1970). The antianginal drug (nitroglycerin, 20μg/Kg; prenylamine, 1mg/Kg; dipyridamole, 0.3mg/Kg; or dilazep, 0.2mg/Kg) was administered intravenously. The results were as follows: (1) No difference in the regional myocardial blood flow between the inner- and outer-layer was observed. The flow ratio of the inner- to the outer-layer (I/O ratio) was 0.97±0.17. (2) Nitroglycerin produced a slight decrease in the flow through the inner-layer in spite of a remarkable drop in coronary perfusion pressure, while it did a marked decrease through the outer-layer. As the result, I/O ratio was significantly elevated after the injection. (3) Prenylamine produced a moderate increase in the flow through the both layers in spite of a remarkable fall in the coronary perfusion pressure. The ratio was rather elevated after a significant initial decline. (4) Dipyridamole caused a marked increase in the flow through the both layers, whereas I/O ratio was only minimaly lowered. (5) A change similar to that caused by dipyridamole was observed except a slight elevation of the ratio from 20 to 30 minutes when dilazep was injected. As mentioned above, these anti-anginal drugs produced different effects on the flow in the both layers. One of the explanation of these differences observed might be that these drugs have different effects on sites of coronary vessels, large intramural conductive vessels or small resistive vessels. Another explanation could be that these drugs cause different effects on the systemic hemodynamics. For the studies on effect of anti-anginal drugs on the intramyocardial distribution of blood flow, it is necessary that the regional myocardial blood flow must be monitored continuously since the intramyocardial distribution of the blood flow can be changed from time to time after the administration.
For the purpose to elucidate immunopathological significance of immunoglobulin in liver tissue of various liver diseases, localizations of three kinds of immunoglobulins, namely IgG, IgA and IgM, in liver tissue from 30 patients with chronic hepatitis (18 cases with history of blood transfusion and 12 cases without history of blood transfusion) were studied by direct fluorescent antibody technique. The localization of the specific HBs (HB surface) antibody in liver tissue from 5 patients examined HBs antigen in those sera, were observed by the use of direct fluorescent antigen method. IgG in immunoglobulins was localized as a pattern of immune deposits in the following areas, where the focal necrosis, piecemeal necrosis, destruction of the limiting plate, and the exudative areas of sinusoidal capillary walls, peripheral regions of the portal veins and central veins were observed. Also IgG in immunoglobulins was localized in the cytoplasm of Kupffer's cells as a phagocytic granule and in the mononuclear cell as a produced pattern in portal areas. Intensities of specific fluorescence of IgA and IgM were observed in a lesser degree than that of IgG in the same area. Localizations of HBs antibody was found in the areas where the infiltration of plasma cells, destruction of limiting plate and piecemeal necrosis were observed in the patients with positive HBs antigen in the serum.
For the purpose to elucidate immunopathogenetical role of complement for immunological phenomenon in chronic liver diseases, localizations of two kinds of complement components, namely C3 and C4 in liver tissue from 19 patients including 2 cases of acute hepatitis, 6 cases of chronic hepatitis, 3 cases of liver cirrhosis, 2 cases of hepatocellular carcinoma, 1 case of hepatoblastoma and 5 cases of control, were studied by direct fluorescent antibody technique. The intensities of specific fluorescence of C3 and C4 were observed in same degree as that of IgG in the same areas, where the focal necrosis, piecemeal necrosis, destruction of the limiting plate, and the exudative areas of sinusoidal capillary walls, peripheral regions of the portal veins and central veins were observed. Two components were observed diffusely in a lesser degree as a produced pattern in the normal hepatic cells, hepatocellular carcinoma cells, hepatoblastoma cells and hepatic cells of embryo and fetus than that of immune deposits. On the other hand, the intensities of two components other than liver tissue were observed in a lesser degree in the middle sized lymphocytes in lymph nodes and spleen, reticulum celllike cells in spleen, parietal cells of stomach and a few of epithelial cells of small intestine, but could not observed in the tissues of heart, lung, thymus, thyroid gland, kidney, skeletal muscle and testis.
Physiological effects of 4-M-1, administrated intraperitoneally or orally in mice, were investigated. The quantity of LD50 and LD100 was determined by the acute toxicity test of mice. An excited condition without convulsion was observed in the range from LD20 to LD25.
The examination of quantitative analysis of 4-M-1 absorbed in the organs after ip injection into rat was carried out. A quantitative analysis of 4-M-1 in the organs was established. It was carried out by three methods; paper chromatography, thin-layer chromatography and gas-liquid chromatography and then the detectable limit of 4-M-1 was determined on each of them. The spot test was useful in qualitative analysis.
The absorbance localization of 4-M-1 in organs of rat after ip injection and the relation of time and quantity in excretion of 4-M-1 were examined. The results were summarized as follows. The absorbant rate of 4-M-1 five minutes after ip injection was higher in intestine, blood, liver, stomach and kidney in that order. Excretion of 4-M-1 began about 30 minutes after injection and its quantity amounted roughly to 90% from 4 to 8 hours.
Physiological and biochemical data in rat injected subacute toxicity dose of 4-M-1 were investigated. Obtained results were as follows. Some rats had hypertrophic liver after intraperitoneal injection, but had no biochemical difference from others that hypertrophy was not observed.