It is valuable for the research of pathological anatomy to detect the distributions of active hematopoietic organ in the patients with various blood dyscrasias. 99mTc sulfur colloid was applied on 5 normal subjects as a control and 7 patients with hypoplastic anemia using a Type III gamma scintillation camera (Nuclear Chicago Ltd.), for studying the distribution of active hematopoietic bone marrow. After 30min. of intravenous infusion of 5 to 10mCi of 99mTc sulfur colloid, a black and white polaroid film (ASA 3000: 3000speed/107 type) was exposed under the 1000 hole multicollimeter of the Type III gamma scintillation camera total counts were adjusted to be 1-5×104. Blood picture was examined periodically. And, among these date, one considered the results to be most appropriate which were obtained on the closest date when the patient was studied for the distribution of 99mTc sulfur colloid. The 59Fe-ferrokinetics were performed using a modified method of Pollycove and Hoffe. In normal subjects, the active hematopoietic bone marrows, namely the positive uptake of 99mTc sulfur colloid, was distributed in the skull, sternum, thoracic and lumbar spines, pelvic bone, femur and humerus. The positive uptake was also occasionaly obtained in the joints of both elbow and knee, in contrast to the bones of foot and hand. The intensity of the figures was higher in the proximal part of tubular bone than in the distal part. The distributions of active hematopoietic organs in the patients with hypoplastic anemia were classified as follows depending on the intensity and figure of 99mTc sulfur colloid uptake. Type I was a narrow distribution of the diffuse and obscure figure. This Type I was subclassified further: In Type Ia, active marrow was scarcely figured out. In Type Ib, active marrow was figured out more widely than in Type Ia although its image was obscure and diffuse. And in Type Ic, the active hematopoietic marrows was restricted only in the vertebrae with clearer uptake of 99mTc sulfur colloid. Type II is the narrow islet form with clear and distinctive high density figure and with the obscure and low density in background. Hypoplastic anemia showing Type I figure belonged to the Types II and IV according to the classification made in our Department. This demonstrated a typical hematological findings of hypoplastic anemia with a pancytopenia in the peripheral blood, hypocellularity in the bone marrow, a prolongation of plasma iron disappearance time (PIDT), and decrease in percentage red cell utilization (%RCU) in 59Fe-ferrokinetics, and low uptake of 59Fe into the bone marrow. On the other hand, the patient showing Type II figure belonged the Type I of hypoplastic anemia in our classification. This demonstrated a hypercellularity in the bone marrow, relatively normal %RCU in 59Fe-ferrokinetics, and prolonged retention of 59Fe uptake in the bone marrow.
Detection of the distributions of active hematopoietic bone marrow with 99mTc sulfur colloid using a scintillation camera is effective for the prognosis and therapeutic effects on the various hematological disorders, especially in the hypoplastic anemia. Two types of 99mTc sulfur colloid uptake into the bone marrow can be classified in the hypoplastic anemia, i.e., the islet form and the diffuse form, as reported in the Part I of this paper. The comparative studies of the distributions of 99mTc sulfur colloid in the bone marrow and hematological findings in various blood disorders other than hypoplastic anemia were described in this part. The examinations were performed using the same methods as described in the Part I. Seventeen patients observed were 5 leukemia, 3 multiple myeloma, 2 liver cirrhosis, and one each of erythroleukemia, malignant lymphoma, sarcoidosis, congenital hemolytic anemia, folic acid deficiency anemia, hemochromatosis and hemophilla B. As general, clear images were determined during shorter exposure time on the sternum, thoracic and lumbar spine. This indicated that the hematopoiesis, or the distribution of reticuloendothelial cells, in these marrow was more prominent than others, when the relationship of exposure time and image density of photography per 10, 000 counts were classified in 4 degrees. The most distinct images of bone marrow, i.e., active hematopoietic images in the general bone marrow including the hands and feet, were obtained from the patient with the congenital hemolytic anemia, erythroleukemia, and liver cirrhosis. Increased distributions of these acitve proliferation of erythroblasts in the patients with the congenital hemolytic anemia and with the erythroleukemia. On the other hand, the fat cells in the bone marrow of a patient with the liver cirrhosis were replaced with reticulum cells proliferating actively coinciding with the proliferation of the Kupffer's cells in the liver. Clearer and wider distributions of active hematopoietic marrow were able to be detected in a patient with the malignant lymphoma, multiple myeloma, sarcoidosis or liver cirrhosis than in a normal subject. From these evidence a good correlation of distribution is considered to be exist between the active hematopoietic marrow and the proliferation of either tumor cell, epitheloid cell or reticulum cell. Therefore, it may be concluded that 99mTc sulfur colloid uptake in useful for making the diagnosis as well as for appreciating the therapeutic effect on the patients with various blood dyscrasias which involve the bone marrow. The above results indicated a good correlation of a 99mTc-sulfur colloid uptake in the reticuloendothelial system with a 59Fe in the erythroblastic series of myeloid cells, in almost all the patients studied. Therefore, we may conclude that this method is useful for the destribution of active hematopoiesis in the body with hypoplastic anemia, and in helpful for treating and justifying the prognosis on these patients.
Synthetic dye, aluminon has been demonstrated to cause swelling of isolated nuclei, decondensation of chromatin fibers, and dissociation of histones from chromatin. These phenomena are similar to those caused by high molecular weight polyanions such as heparin. In this paper, nuclear swelling with aluminon was studied in more detail in order to establish the role of aluminon as a probe for nuclei and chromatin. Studies were also done on the binding of aluminon to nuclei, and on its effect on RNA synthesis in vitro. Nuclear swelling was monitored from changes in turbidity of nuclear suspension. A stoichiometrical relationship was suggested between the amount of aluminon needed for maximal swelling and that of nuclear DNA in the system. The swelling velocity at pH 5.4 was much slower than that at pH 7.9 and the time course of the swelling was shown to be consisted of four distinct successive processes in which the swelling velocity was constant. Centrifugation of treated chromatin in a linear density gradient of sucrose revealed a decreased density of chromatin and dissociation of histones and certain nonhistone proteins from chromatin. Aggregation of arginine rich histones after dissociation was observed. The release of histones from chromation was also deduced from the fact that aluminon removed the restriction of chromatin template when transcribed with homologous RNA polymerases. Above results indicate that aluminon may be a useful tool for studies on structure and function of chromatin.
Spontaneous internal biliary fistula implys an abnormal communication between the biliary tract and other organs which is non-surgically formed most commonly by spontaneous passage of gall stones. It has been reported that the incidence of spontaneous biliary fistula is low and that cholecyst-duodenal fistula is the most common type of fistula. Author's experience, however, indicates that the actual incidence is not so low as previously considered and that choledocho-duodenal fistula is far more frequently found than cholecyst-duodenal fistula. This report is concerned with clinical, radiological and endoscopic studies on 33 cases of spontaneous choledocho-duodenal and cholecyst-duodenal fistula which were found preoperatively by duodenofiberscopic examination in the past 5 years at the author's clinic. Followings are the conclusions obtained. 1) 33 cases of spontaneous internal biliary fistula was found among 246 cases of gall stone disease. The incidence (13 percent) is much higher than the figures indicate because the author's experience shows that not a few cases heal to close in a short period. In contrast to the previous report, choledocho-duodenal fistula (30 cases) was much more frequently found than cholecyst-duodenal fistula (3 cases). Author's experience suggests that many cases of choledocho-duodenal fistula have been overlooked without duodenofiberscopic examination. 2) Clinical evaluation revealed a characteristic attack of severe abdominal pain just like labor pain in 80 percent of cases. 3) Radiological evaluation revealed air shadow in the biliary tract in 36 percent of cases. The air shadow can be detected only by careful observation. 4) Choledocho-duodenal fistula was divided into three types, thpe I, type II and type III, according to the site of fistula orifice. What type of fistula is formed depends on not only the size of stones but also the structual abnormality of the Vaterian bile duct. 5) The fistula either heals to close within 4 to 14 weeks or otherwise remains open with epithelization of the orifice. Final outcome of the fistula depends on the presence or absence of the obstructive lesions of the biliary tract distal to the fistula orifice. As a result, most of I type of choledocho-duodenal fistulae heals to close, most of III type remain open and II type takes either course half and half. 6) As for a clinical course, cases with residual gall stones in the biliary tract tend to have attcks of cholangitis as compared to those without stones. However, one third of cases without residual gall stones may have attacks at some time of clinical course. As a result, a surgical intervention is indicated to cases with residual gall stones. In cases without residual stones, however, an indication to the surgical intervention depends on the clincal course.
Mitral valvar diseases would be ones in which hemodynamic study was frequently required to follow up patients, regardless of undergoing surgical treatment. Therefore, it would be ideal if hemodynamic study could be done under non-invasive technique. In this respect RI cardiograph (radiocardiograph) seems to be suitable because a needle puncture to inject a dose (10 mCi) of radioisotope (99mTc pertechnetate) is only one thing to be done under invasive technique. This study is to show applicability of RCG and to determine criteria for its use. Instrumentation employed for data processing was DAP 5000-2 (Toshiba, Ltd. Tokyo, Japan) and the data obtained were processed by computer. RI dilution curves recorded on the right ventricle, the left lung, the left ventricle were analyzed to obtain following parameters, namely interventricular peak to peak time, down-slope of RI dilution curve of the left lung, and the up- and the down-slopes of RI dilution curves of the left ventricle. Patients studied were 37 ranging from 15 to 64 years of age. Preoperatively, interventricular peak to peak time was prolonged and RI dilution curves of the left lung and the left ventricle were widened. Postoperatively these parameters were resumed to normal or close to normal. Coefficient of correlation (r) of up-slope of the left ventricle to NYHA classification was turned out to be -0.64 and that of down-slope to NYHA to classification was 0.63. It was concluded that the parameters studied, including down-slope and up-slope of RI dilution curves of the left ventricle and down-slope of the left lung, reflected reasonably well hemodynamic alterations of patients with mitral valvar diseases, and that RCG should have great advantage for following up patients with mitral valvar diseases because of its non-invasive technique and ready repeatability.
A regimen consisting of 5-fluorouracil, vincristine, bleomycin, cyclophosphamide and mitomycin C (FOBEM) was used for the treatment of advanced lung cancer patients. 5-fluorouracil (250mg) was administered every other day. Vincristine (1mg), bleomycin (15mg), cyclophosphamide (400mg) and mitomycin C (4mg) were each administered once a week for six consecutive weeks. Fourteen (28.6%) of 49 evaluated patients had significant tumor regression and included two patients with small cell carcinoma who shows complete regression. Histological classification indicated 17.6% of adenocarcinoma, 35.3% of squamous cell carcinoma and 57.0% of anaplastic carcinoma. And 12.5% of patients were diagnosed cytologically or clinically. Patients responding to FOBEM survived about two times longer after the initiation of chemotherapy than non-responders, and the survival was slightly longer in patients treated with FOBEM than in those administered one or two of these drugs. In aged patients pulmonary toxicity of bleomycin was the major dose limiting factor rather than the mild myelosuppressive toxicity, and the cumulative pulmonary toxicity necessitated the reduction of this drug. This FOBEM regimen warrants further investigation in the management of small cell and squamous cell carcinoma of the lung.
Cellular immunity in lung cancer was studied by means of lymphocyte transformation by phytohemagglutinin (PHA), purified protein derivative (PPD) skin test, absolute counts of peripheral lymphocytes and leucocyte migration inhibition test. The lymphocyte transformation by PHA was reduced in lung cancer patients in comparison with healthy controls, and correlated with the disease stage, but not with the histology type. The lymphocyte transformation became further depressed by cancer chemotherapy. PPD skin reaction or absolute counts of peripheral lymphocytes did not correlate with the disease stage. However, all the three tests correlated with the disease stage. Therefore, these tests appeared to be general indices of the immunologic status. Inhibition of leucocyte migration was demonstrated in about a half of the patients with lung cancer, but not in patients with other cancers or infectious lung diseases or in healthy controls. These findings suggest the presence of tumor-associated antigens in lung cancer. Concerning the effect of the streptococcal agent, OK-432, enhancement of the function of lymphocyte was observed in the parameters such as lymphocyte transformation by PHA, PPD skin test and leucocyte migration inhibition test. In addition, OK-432 yielded a longer survival in lung cancer patients when used in combination with chemotherapy than with chemotherapy alone.
Since tumor-antitumor agent-host correlation must be considered in the treatment of neoplasms, the qualitative change of serum protein and hemolytic plaque forming cell (HPFC) production against sheep red blood cells (SRBC) in mice were carefully studied in part 1 to investigate the effect of a new antileukemic agent, Neocarzinostatin (NCS), on humoral immunity. Serum gamma globulin significantly decreased by the 4th day and returned to normal by the 12th day after a single injection of NCS. After 4 consecutive days of NCS administration gamma globulin value showed no change, but after 7 consecutive days of NCS 0.50mg/kg/day administration marked gamma globulin reduction was observed. Marked reduction of HPFC was observed in the -8th and -4th day groups of the single injection of NCS, but the -12th, 0, +2nd and +4th day groups showed only moderate reduction (Immunization by SRBC was done on 0 day.). After 4 consecutive days of NCS injection only 0.50mg/kg/day group showed HPFC reduction. But after 7 consecutive days of NCS administration 0.005mg/kg/day group showed moderate and 0.05mg/kg/day group showed marked reduction of HPFC. All mice in 0.50mg/kg/day group died. These data suggest that NCS suppresses the humoral immunity of mice to some extent and it affects almost all phases of the immune response but mainly the afferent phase. Furthermore, immunosuppressive effects of NCS are related to the daily dose and the number of consecutive days of NCS administration.
In part 2 peripheral lymphocyte count, the total number of spleen cells, the weight and histology of the spleen, in vitro proliferative response of spleen cells to phytohemagglutinin (PHA) and delayed cutaneous hypersensitivity to picryl chloride were studied to see the effects of a new antileukemic agent, Neocarzinostatin (NCS), on the cellular immunity of mice. A single administration of NCS decreased the peripheral lymphocyte count, the spleen weight, the total number of spleen cells and in vitro proliferative response to PHA on the 4th and 8th day after NCS administration but its suppressive effects on these factors almost disappeared on the 12th day. NCS suppressed the delayed cutaneous hypersensitivity to picryl chloride and its suppressive effect was dependent on the daily dose of NCS. But its suppressive effect weakened after 10 days of drug free interval. The above data suggest that NCS suppresses the cellular immunity of mice to a certain degree and its immunosuppressive effects are dependent on the daily dose and the number of consecutive days of NCS administration, and on the days of drug free interval.
Cortisol and corticosterone were measured on 27 excited acute schizophrenic patients, 17 deteriorated chronic schizophrenic patients, and 16 general paresis patients. Cortisol and corticosterone were concurrently measured by the Van der Vies fluorimetric procedure. ACTH (water soluble regular ACTH) at 25 I. U. was injected once intramuscularly. Blood and cerebrospinal fluid (CSF) samples were collected one week prior to and 120 minutes after the ACTH injection. The results were as follows: 1. The mean total blood concentrations of cortisol and corticosterone were higher in the general paresis group than in either schizophrenic group. Almost no difference was present between the acute schizophrenic group and the chronic schizophrenic group. Blood concentrations of corticosterone were higher in the chronic schizophrenic group and general paresis group than in the acute schizophrenic group. The ratio of blood cortisol to corticosterone was high in the acute schizophrenic group while the chronic schizophrenic group and general paresis group showed low ratios. 2. Blood cortisol levels of the acute schizophrenic group and the general paresis group were markedly increased after ACTH administration, but the chronic schizophrenic group did not show such a marked increase. 3. The blood corticosterone level of the chronic schizophrenic group decreased after ACTH administration. This finding suggests that ACTH administration might induce some unknown responses on the metabolic pathway from progesterone to cortisol or from progesterone to corticosterone. 4. The ratios of blood cortisol to corticosterone induced by ACTH injection were reversed between the acute schizophrenic group and the chronic schizophrenic group, due presumable to the inefficient increase of cortisol in the chronic schizophrenic group. 5. Blood and CSF corticoid levels were high in the general paresis group. This may be due to atrophy of the frontal lobe cortex and impairment of the blood-brain barrier. 6. The ratios of plasma cortisol to CSF cortisol before and after ACTH administration were almost the same. However, the ratios of plasma corticosterone to CSF corticosterone before and after ACTH administration differed. 7. Blood and CSF corticoid levels of the chronic schizophrenic group before and after ACTH injection indicated that this group had a distinctive response pattern compared to the acute schizophrenic group. 8. A characteristic feature of the chronic schizophrenic group was a decreased response to ACTH injection and a high level of plasma corticosterone. 9. Atrophy of the frontal lobe cortex seemed not to interfere with the acute stress response.
198Au sodium thiomalate was administered intramuscularly to two groups of mature rabbits. One group was pretreated intramuscularly with non radioactive gold prior to injection of 198Au sodium thiomalate. The other group recieved no pretreatment. 1) Serum radioactive gold level reached a peak at 3 hours after injection. Serum radioactive gold level decreased more rapidly in the pretreated group than in the non-treated group. 2) Serum gold concentration was higher in the pretreated group than in the non-treated group. 3) Urinary excretion of radioactive gold was more rapid in the pretreated group than in the non-treated group. 4) In peripheral blood of both groups, the radioactive gold level was in the descending order of serum, plasma and whole blood. 5) The effective half life of radioactive gold in the pretreated group was 2.51 days in serum, 2.50 days in whole blood and 2.16 days in plasma. From this finding and (4), gold salt probably did not combined with fibrinogen. 6) Radioactive gold level in feces in both groups reached a plateau at 48 hours and gradually decreased at 96 hours. 7) Gold salt distribution was detected in the descending order of renal cortex, renal medulla, spleen, lymphonode and liver. 8) Histologically, gold salt was detected in epithelial cells of the urinary tubules, in kupffer's cells and around the lymphoid follicles. 9) By zone electrophoresis, 50.6% of radioactive gold on 100% of non-radioactive gold was combined with albumin fraction. By paperchromatography, 79.1% of radioactive gold was combined with albumin fraction. 10) Gold salt did not attach to red cell surfaces.
The influence of gold salt on the hypothalamo-hypophyseo-adrenocortical (PHA) function was studied experimentally and clinically. The following results were obtained. 1) The food intake of mature female CBA mice injected with gold thioglucose (GTG) increased significantly before a body weight increase and the level of plasma comp. B increased temporarily compared to control subjects. 2) The plasma comp. B level in mature female rabbit reached a peak at 2 or 3 days after an injection of gold sodium thiomalate (GTM). 3) Urinary 17KGS of RA patients injected GTG or GTM increased temporarily at accumulation dose of about 140mg of total gold salt. 4) By PHA function test in RA patients, endocrine system abnormalities may originate at a more anatomical cranial site than hypophysis. 5) The response of the ACTH-Z, metopirone, LVP and insulin test were more higher than in RA patients before chrysotherapy than in the same patients after chrysotherapy. 6) These results suggest that the PHA system was stimulated by gold salt. This response was one of the pharmacological actions of gold salt but it was not anti-rheumatic action in RA.
The pathogenesis of rheumatoid factor (RF), especially IgG RF, in rheumatoid arthritis (RA) and the influence of gold salt on RF were studied clinically. The following results were obtained. 1) The incidence of RF sera was 78.9% by the RA test, 90.9% by the Heller FII method and 72.7% by the Heller Svartz method. In RA synovial fluid, the incidence of RF was 94% by the RA test, 100% by the Heller FII method and 72.7% by the Heller Svartz method. In osteoarthritis (OA) synovial fluid, the incidence of RF was 14.3% by the RA test and 33.3% by both the Heller FII and Heller Svartz method. 2) The RF titer of same RA serum was higher by the Heller FII method than by the Heller Svartz method. 3) RF response in RA serum and synovial fluid was identical in 76.2% of cases by the RA test. In 19% of the subjects, RA test was positive in synovial fluid but negative in serum. 4) No relationships were found between RF titer and white cell count or RA cell count in RA and OA synovial fluid. 5) The mean value of IgG RF was almost equal in seronegative and seropositive RA. 6) A statistically significant relationship was present between higher erythrocyte sedimentation rate and higher RF titer in RA patients. 7) No relationships were found in positive and negaitve C-reactive protain in the three RF subtypes in RA patients. 8) A correlation was present between a high grade of bone destruction and IgG RF value above the mean in RA serum and synovial fluid. 9) In RA synovial fluid, IgG RF level was parallel to total beta glucuronidase activity. 10) In effective cases of chrysotherapy in RA, serum and synovial fluid gold concentration did not decrease but the IgG RF level decreased slightly. 11) In non-effective cases of chrysotherapy in RA, serum and synovial fluid gold concentration decreased slightly but the IgG RF level was stationary or increased slightly.