The effect of mono-, di-, tri-, and tetra-chlorinated benzene on mitochondrial oxidative phosphorylation was determined and the following results were obtained. 1) Chlorinated mono-aromatic hydrocarbons inhibited respiratory control strongly by increasing state 4 respiration and decreasing state 3 respiration. 2) Lower concentrations of mitochondrial protein showed higher inhibitory effects for 1, 2, 3-tichloro benzene on respiratory control. 3) The respiratory control index decreased with increase in the number of chlorine. 4) The respiratory control index decreased with increase in the concentration of chlorinated benzene. 5) Decrease in respiratory control index was in the order of orth>meta>para-dichloro benzenes. There were differences between the isomers.
The effects of synthetic neurotensin and xenopsin on plasma glucagon and insulin secretion were investigated using dogs. Neurotensin and xenopsin were injected rapidly or infused for 30 min into the superior pancreaticoduodenal artery. Plasma glucagon and insulin in the superior pancreaticoduodenal (pancreatic) vein and femoral vein were measured by radioimmunoassay. In normal dogs, rapid administration of neurotensin (10μg/kg body weight) brought about mild hyperglycemia and a rapid and sharp increase of plasma glucagon and insulin levels in the pancreatic and femoral veins. Though the plasma glucagon level in the pancreatic vein showed a nider at 45 min, the glucagon response maintained a significant increase for 120 min. A biphasic insulin response with the second peak at 30 min was noted in the pancreatic and femoral veins. The blood pressure was 30% of the initial value at 2 min after neurotensin administration and returned to the initial level at the end of the experiment. An insignificant elevation of the plasma cortisol level was observed after neurotensin administration. These vaso-circulatory changes and the increase of plasma cortisol concentration by neurotensin administration were assumed to influence the increase of glucagon in the latter period of the experiment and the formation of second peak of insulin level. In normal dogs, neurotensin (0.5μg/kg/min) infusion brought about mild hyperglycemia and a rapid and sharp increase of plasma glucagon and insulin in the pancreatic and femoral veins, during the infused period of 30 min; however these responses were smaller than those for the rapidly injected neurotensin. In hypophysectomized dogs, the basal level of plasma glucose, pancreatic glucagon and insulin decreased to 52%, 48%, 11% of normal dogs respectively. Neurotensin (10μg/kg body weight) administration resulted in no elevation of blood glucose. Neurotensin has little effect on glucagon and insulin secretion. A biphasic insulin secretory pattern observed in normal dogs was not demonstrated in hypophysectomized dogs. It seems that the pituitary gland plays some role in the neurotensin-induced insulin secretion. In normal dogs, rapid administration of xenopsin (10μg/kg body weight) brought about mild hyperglycemia and a rapid and sharp increase of plasma glucagon and insulin in the pancreatic and femoral veins. Glucagon secretory activities were the same as with neurotensin but insulin secretory activities were smaller. Neurotensin and xenopsin appeared more potent inducers of glucagon in the present experiment. Neurotensin and xenopsin appeared to stimulate glucagon and insulin secretion not only by neurogenic vasodilatation, but also by a direct action on pancreatic alpha and beta cells.
The concentration of urinary free light chains was measured in 61 patients with systemic lupus erythematosus (SLE) by single radial immunodiffusion. The concentration was significantly increased in these patients, and was associated with hypocomplementemia and a high level of antibody to DNA. It also correlated with the clinical disease activity of SLE. It is postulated that increased free light chain in the urine of SLE patients is derived mostly from increased synthesis of light chain rather than from increased breakdown of intact immunoglobulins or decrease of catabolism during renal insufficiency. The measurement of urinary free light chains may offer information for evaluating disease activity in SLE patients.
By the use of radioimmunoassay, urinary β2-microglobulin concentration was mesured in 49 patients with systemic lupus erythematosus (SLE). The urinary β2-microglobulin was significantly elevated in SLE (p<0.01). The level of urinary β2-microglobulin did not correlate with the level of serum complement, antibody to DNA or the massive proteinuria. It was associated with urinary free light chain and the degree of renal tubular damage, but not with the glomerular lesions observed in renal biopsy specimens. The elevated level of β2-microglobulin in urine was most likely due to increased excretion of β2-microglobulin from involved tubulus or direct secretion from lymphocytes infiltrating the interstitium. The measurement of the level of urinary β2-microglobulin is useful for estimating the extent of renal interstitial damage in patients with SLE.
The isolation of monocytes in human peripheral blood by discontinuous density gradients was studied. Discontinuous density gradients were obtained by successive layering of bovine serum albumins into three layers in 10ml glass tubes. Buffy coat cells were layered on top of a gradient and centrifuged under various conditions of centrifugation. Optimal isolation was achieved by centrifugation on a three layer of 35-32-28% bovine serum albumin at 490g for 60 minutes. The purity, yield and recovery of monocytes at the interface between 35% and 32% bovine serum albumin were 54.0%, 7.0×105 and 22.0% respectively. After centrifugation on Conray-Ficoll mixtures, the interface fraction containing lymphocytes was removed and the bottom fraction containing monocytes and other cells was centrifuged under various condition. The optimal condition was on a three layer of 35-32-28% bovine serum albumin at 400g for 40 minutes. The purity of monocytes by this method increased to 75% but the yield and recovery declined to 2.5×105 and 4.5% respectively. From these data I concluded that isolation of monocytes from blood only on density gradients was difficult because of a partial overlap between monocytes and lymphocytes in the density distribution profiles.
Absolute peripheral blood monocyte counts and the β-galactosidase activity of monocytes were studied in 60 patients with lung cancer, 20 with malignant lymphoma, 17 with other malignant diseases, 13 with sarcoidosis and 28 normal individuals. The monocyte count was 296.3±176.8/cmm in lung cancer, 315.6±160.0/cmm in malignant lymphoma, 217.8±89.6/cmm in sarcoidosis, and 298.6±144.1/cmm in normal individuals. Although there was no significant differences in the monocyte count of malignant and non-malignant diseases, all patients with lung cancer or malignant lymphoma had monocyte counts less than 100/cmm. In patients with lung cancer and malignant lymphoma, there was no significant differences in histological types or clinical stages. The monocyte count in lung cancer patients treated with streptococcal agent OK-432 was elevated to 484.9±269.0/cmm, as compared with 315.5±107.7/cmm before administration. A nadir of monocyte counts was found at one week after combination chemotherapy but recovery to normal value was observed by 3 weeks after. On the other hand, white blood cell counts reached a nadir 2 weeks after chemotherapy and recovered by 4 weeks after. The percentages of β-galactosidase positive monocytes were 21.5±11.5% in patients with lung cancer, 20.1±7.5% in malignant lymphomas, 19.1±6.8% in other malignant diseases and 25.3±12.4% in normal individuals. There was no significant differences in β-galactosidase activity related to histological types or clinical stages of patients with lung cancer and malignant lymphoma. No changes in β-galactosidase activity were found between before and after combination chemotherapy.
The effects of oral administration of propranolol on the electrocardiogram (ECG), vectorcardiogram (VCG) and plasma potassium levels were studied in the following groups: healthy controls, and patients with neurocirculatory asthenia (NCA), ischemic heart disease (IHD), hypertension and persistent juvenile T wave pattern. ECG and VCG were taken before, 30, 60 and 90 minutes after oral administration of propranolol in a single dose of 10mg. The results were as follows: 1) RR, PQ and QT intervals were prolonged while the rate-corrected QT interval was shortened in each group. 2) The amplitude of the T wave and the magnitudes of spatial maximum T vector and of ventricular gradient (V.G.) were increased in the healthy control group. 3) In the NCA group, which was characterized by a low T wave, small T loop, small V.G. and posteriorly directed V.G. before propranolol administration, the T wave, T loop and V.G. were enlarged and V.G. was rotated toward anteriorly. 4) In the IHD group, which was characterized by a low T wave and small T loop and V.G., the changes were unremarkable after the administration of propranolol. 5) In the well controled hypertensive group the effects resembled those of the healthy control group. In the hypertensive group without sufficient treatment, the effects were similar to those of the IHD. 6) In the persistent juvenile T wave group, a typical pattern was the location of the T loop and V.G. in the left posterior quadrant. The drug rotated the T loop and V.G. anteriorly. 7) Little change was found in the R wave amplitude and spatial maximum QRS vector in each group. 8) Plasma potassium level was not effected by the drug. 9) No undesirable effects were seen during the study. 10) The maximum effects were obtained within 60 to 90 minutes after the administration of propranolol. From the above results, propranolol appears to be useful in differentiating T wave changes associate with increased beta-sympathetic tone from changes due to other causes.
(1) The uptake of metallic mercury by catalase purified from spinach was observed with and without H2O2. Purified catalase solution took metallic mercury up more than crude catalase solution. (2) In comparison with the mercury uptake from air saturated with mercury vapour, crude spinach extract of catalase with H2O2 showed a 38% decrease with H2O2 plus KCN, a 86% decrease with H2O2 plus NaN3, and a 19% decrease without H2O2. Uptake by purified extract with H2O2 decreased by 47% with H2O2 plus KCN, decreased about 100% with H2O2 Plus NaN3, and 65% without H2O2 in comparison with the mercury uptake from air saturated with mercury vapour.
This study was conducted to determine effective chemotherapy for preventing perioperative hematogenous metastases, particularly hepatic metastases, by measuring plasma concentration of 1-(2-tetrahydrofuryl)-5-fluorouracil (Tegafur, TF) in the portal system as an index. 1) TF suppositories of 750 mg/day for 8 days were inserted in the lower portion of the rectum pre-operatively. The plasma concentrations of 5-FU in the portal vein, the inferior vena cava, and the peripheral vein were 0.01 mcg/ml during surgery and this was maintained for 24 hours post-operatively. 2) The plasma 5-FU concentration in the portal vein was higher than that in the peripheral vein when TF was given in the jejunum as a single shot. The plasma concentration in the portal vein averaged 0.025 mcg/ml 2 hours after the administration. 3) With a combination of TF suppositories (750 mg/day) for 8 days pre-operatively and TF (800 mg) in the jejunum intra-operatively, the plasma 5-FU concentration stayed at 0.04 mcg/ml in the portal and peripheral veins for 4 hours. After 24 hours, the concentration of the peripheral vein decreased to 0.02 mcg/ml. This combination method was maintained higher 5-FU concentrations in the portal vein for longer periods. 4) It was also found in an experimental study using dogs that TF given into the jejunum was partly activated to 5-FU. It was concluded that the chemotherapy combining pre-operative administration of TF suppositories and intra-operative administration of TF into the jejunum was the perioperative treatment of choice to prevent surgery-induced metastases through the portal system, particularly hepatic metastases in cancer of the gastrointestinal tract.
Superoxide dismutase (SOD) activity and the lipoperoxide level of synovial fluid in patients with rheumatoid arthritis (RA) were investigated. SOD activity was checked with xanthine and xanthine oxidase reaction according to Fridovich. Lipoperoxide level was checked with thiobarbituric acid reaction according to Naito. Synovial fluid SOD activity, synovial fluid leucocyte SOD activity and synovial fluid lipoperoxide level were checked in comparison with those of osteoarthritis (OA). The correlation between SOD activity and inflammatory sings such as leucocyte count, relative viscosity, lysosomal enzyme activity (acid phosphatase activity) and C-reactive protein (CRP) concentration was checked in synovial fluid from patients with RA. The correlation between lipoperoxide level and inflammatory sings was checked similarly. The results are summarized as follows: 1) Synovial fluid SOD activity in RA was higher than in OA. Synovial fluid leucocyte SOD activity was significantly higher than that of OA. 2) The synovial fluid lipoperoxide level of RA was significantly higher than that of OA. 3) A significant correlation was present between synovial fluid SOD activity and leucocyte count, lipoperoxide level, acid phosphatase activity. 4) A significant correlation was present between synovial fluid leucocyte activity and leucocyte count, lipoperoxide level, acid phosphatase activity, CRP concentration. 5) A significant correlation was present between synovial fluid lipoperoxide level and leucocyte count, acid phosphatase activity. 6) Superoxide and lipoperoxide may be an inducer of inflammation in view of RA inflammation. It is premature to pass judgement on the generally accepted idea that SOD is an antiinflammatory protein.
Cepharanthin was administered intraarticularly to rheumatoid arthritis (RA) patients who showed no beneficial response to intraarticular RA treatment. Joint symptoms, volume, leucocyte counts, relative viscosity, lysosomal enzyme activity, C-reactive protein concentration, lipoperoxide level, superoxide dismutase (SOD) activity of synovial fluid and SOD activity of synovial fluid leucocytes were tested before and after intraarticular injection of Cepharanthin. Furthermore the therapeutic effects on hydroarthrosis were investigated. I divided these RA patients into three groups. Group 1 consisted of patients who received only Cepharanthin-intraarticular injection. Group 2 consisted of patients who received Cepharanthin-intraarticular injection and corticosteroid-intraarticular injection about one week later. Group 3 consisted of patients who received simultaneous intraarticular injection of both Cepharanthin and corticosteroid. The results are summarized as follows: 1) The decrease of knee puncture frequency and the reduction of synovial fluid volume were prominent in 5 out of 9 (55.5%) cases in Group 1, 5 out of 5 (100%) cases in Group 2, and 4 out of 4 (100%) cases in Group 3. 2) Cepharanthin had no effect on leucocyte counts, relative viscosity, lysosomal enzyme activity or C-reactive protein concentration. 3) Cepharanthin had no effect on lipoperoxide level, synovial fluid SOD activity or synovial fluid leucocytes SOD activity. 4) All four cases who had Cepharanthin of 20 mg or 30 mg injection experienced a postinjection flare up-like phenomenon. Three out of 14 (21.4%) cases who had Cepharanthin 10 mg experienced a slight postinjection flare up-phenomenon. Postinjection flare up-like phenomena did not appear in Group 3. 5) Simultaneous intraarticular injection of both Cepharanthin of 10 mg and corticosteroid was the most effective method. It was considered that simultaneous intraarticular injection of both Cepharanthin 10 mg and corticosteroid was a useful measure for treatment of the so-called wet type of RA.
The present study was undertaken to study the relationship between changes in platelet monoamine oxidase (MAO) activity and schizophrenia. In addition, some biochemical characteristics of human platelet MAO were examined. The results are as follows; 1) There was no evidence to suggest that differences in methods used in the determination of platelet MAO activity caused the conflicting results in the literature. 2) It was confirmed from a kinetic study that MAO reaction in platelets proceeded via a ping-pong mechanism as previously reported in brain and liver. 3) The frequency distribution for the Michaelis constant (Km) and maximal velocity (Vmax) in apparently healthy subjects exhibited a skewed unimodal pattern. The mean of the Vmax value for females was significantly higher than the corresponding value for males. 4) Platelet MAO activity was determined in 8 schizophrenics and non-schizophrenic members from a North-Swedish pedigree with a high frequency of schizophrenia. There were no statistically significant differeneces in apparent Km and Vmax values between schizophrenics and their non-schizophrenic relatives, although a tendency to lowered Vmax and increased Km values was observed among the schizophrenic subjects. 5) MAO activity was assayed in platelets from 22 (8 monozygotic and 14 dizygotic) twin pairs. At least one twin (proband) of each pair suffered from serious psychiatric disorders including schizophrenia. The correlation between proband and control twins was high for both apparent Km and Vmax. No differences in kinetic properties were found between schizophrenic and non-schizophrenic twins. The monozygotic twin pairs showed very high correlations (Km; r=0.93, Vmax; r=0.86) as compared to dizygotic twins (Km; r=0.81, Vmax; r=0.50) and apparently healthy subjects (Km; r=0.46, Vmax; r=0.33).
Two B-cell lines, a hairy cell leukemia (HCL) line (ZK-H) and a normal lymphoblastoid line (ZK-N), were established in long-term culture from Peripheral blood of the same patient with HCL. An anti-HCL serum was prepared by immunizing a rabbit with ZK-H cells, rendered HCL-specific by absorption with ZK-N cells and tested in indirect membrane immunofluorescence. The absorbed antiserum reacted with 3 of 3 HCL lines but not with another 21 hemic cell lines, including 4 non-T, non-B cell lines, 6 T-cell lines, 9 B-cell lines and 2 myeloid cell lines. When tested against fresh normal and leukemic cells, positive reactions were observed in 5 of 5 HCL cases but not in 6 normal persons or in another 26 cases of various leukemias, except for a low percentage positive reaction in 2 of 6 cases of CLL. These results suggest that HCL cells possess a specific HCL-associated antigen which is shared by certain CLL cells but which is distinct from a B cell antigen. The method of production of hetero-antiserum used in the present experiment appears to obviate problems related to histocompatibility antigens and would be useful for the immunodiagnosis of leukemias.