To study the mechanism of the induction of nephritis, chronic serum sickness (CSS) was induced in Fisher rats and the kinetics of immune complex formation and immunohistological glomerular alterations were studied up to the 13th week following pre-immunization with bovine serum albumin (BSA).
Serum circulating immune complexes (CIC) were detectable in high titer from the 8th week (intravenous stage). After immunization with BSA, serum anti-BSA antibodies increased gradually and remained high in titer even after injection of BSA. At the 9th week, BSA, IgG and C3 were detectable transiently by immunofluorescence in glomerular capillary lumens. Light and electron microscopic findings were normal. At the 12th week, BSA, IgG and C3 were observed by immunofluorescence in glomerular basement membrane and increased in intensity with time. Urinary protein excretion was detected at the 11th week and the amount excreted increased with time.
In conclusion, the change in antibody titer and CIC level indicated a smaller amount of antigens than antibodies during the induction of nephritis and CIC seemed to be formed in antibody excess. In addition, there was a time-lag of several weeks between the onset of nephritis (the onset of proteinuria and the deposition of IC in a glomerulus) and the rise of the CIC titer. The continuation of the high CIC titer and the saturation of the reticuloendothelial system seemed to be necessary to induce CSS nephritis in rats.

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The kinetics of immune complexes, the immune deposits and glomerular changes were studied in nephrotic rats. Chronic serum sickness was induced in rats and examined for 80 weeks, injections of bovine serum albumin (BSA) having been stopped at the 13th week.
The amount of ciculating immune complexes (CIC) was significantly lower in nephrotic rats than in non-nephrotic rats at the 13th week. To study the short-term kinetics of CIC, 2 mg of BSA was administered intravenously to both groups of rats at the 13th weeek and serum CIC were tested for 24 hrs. Injection of BSA was followed by an acute rise in the titer, which disappeared more rapidly in nephrotic than non-nephrotic rats (12% vs 45% of peak CIC level, 24 hrs after injection). The kinetics of CIC after the injection of ¹²⁵I·BSA was also studied. The ¹²⁵I·BSA level, 24 hrs after injection in a nephrotic rat was 8% in blood and 68% in urine. CIC titer seemed to be lowered rapidly due to urinary losses.
Histologically, light microscopic changes mainly involved irregularity, thickening and disruption of glomerular basement membrane (GBM). By the 80th week, all changes had resolved apart from persistent GBM thickening. By electron microscopy, subepithelial deposits had been decreased in number after the stoppage of injection of BSA and some of the subepithelial deposits had been completely resolved and some had been covered by a layer of lamina densa-like material and transformed into intramembranous deposits. Deposits had been lucent peripherally and became lucent completely at the 60th week. Subepithelial deposits disappeared after 80 weeks from the GBM. By immunofluorescent staining, BSA decreased in intensity and became negative by the 15th week. Similarly C3 became negative by the 20th week but rat IgG persisted until the 45th week. The presense of lucent deposits correlated with the loss of biological activity as detected by immunofluorescence.
Thus the resolution of immune deposits in this model conformed to previously described changes in resolving human membranous nephropathy.

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To evaluate the effect of antithrombotic therapy, serial changes in platelet aggregability were investigated in 103 patients who had received heart valve replacement. All patients received warfarin and were divided into three groups: warfarin alone (control), and combined with trapidil and dipyridamole. Both antithrombogenic drugs were given at a dose of 300 mg/day. Platelet count and aggregation were evaluated out every three months for 36 months.
Antiplatelet drugs had no affect on the platelet count during the course. The platelet aggregation did not change in the control group, but were decreased at 24 and 30 months in the trapidil group and 24 months in the dipyridamole group. The platelet aggregation was significantly suppressed by trapidil compared to the control at 30 months. The incidence of thromboembolism in control, trapidil and dipyridamole groups was 9.0%, 4.3% and 7.7% respectively. These results indicate that anti-platelet drugs given with warfarin are safe and effective for patients with a prosthetic valve to prevent thromboembolism.

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We report a rare case of primary aldosteronism with severe hypokalemic myopathy in a 59-year-old female who had suffered from hypertension since 1979. Because of severe muscle weakness, especially of extremities, she became unable to rise from her bed and was admitted to the Kitagawa hospital on July 10, 1989. Symptoms such as tetany, polyuria, and diarrhea were not observed. Her consciousness was clear. The blood pressure was in the range of 152 mmHg systolic and 104 mmHg diastolic. Systolic heart murmur (Levine II), cardiac arrythmia, and slight edema on the legs were noticed. She did not have any sign of muscular atrophy. Serum aldosteron level was 220 pg/ml, and plasma renin concentration was less than 0.5 ng/ml/h. The serum level of potassium was 1.7 mEq/l, sodium 150 mEq/l, GOT 47 IU/l, LDH 507 IU/l, CPK 850 IU/l (MM type 99%), and aldolase 9.2 mIU/ml. Computed tomography (CT) after intravenous contrast injection revealed a round low density mass (1.6 cm in diameter) in her left adrenal gland. CT also revealed the gallbladder adenomyomatosis. Her left adrenal gland and gallbladder were surgically removed on July 26, 1989. After the operation, the blood pressure and laboratory data including serum potassium returned to normal, and she became able to pursue her ordinary life. Endoscopy revealed a gastric polyp which was hyperplastic. Histopathologically the removed adrenal gland showed an adrenocortical adenoma consisted of clear cells and nodular hyperplasia of the glomerular zone.

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The clinical and angiographic findings in cases of juvenile Moyamoya disease were reviewed and functional images of cerebral perfusion were observed to clarify the mechanism of transient ischemic attack (TIA) which is the characteristic symptom of this disease. A total of fifty two patients with Moyamoya disease were seen in our hospital between 1963 and 1980. Twenty seven were pediatric patients and twenty five were adults. TIA was observed in nineteen of the twenty seven pediatric cases. In thirteen of these nineteen children, TIA was precipitated by physical exercise or emotional upsets such as running, crying or hyperventilation during EEG recording. Angiograms revealed no correlations among the clinical symptoms, the development of the cerebral basal rete, and the degree of the stenosis of the carotid artery. However, the arterial vascularity of the Sylvian group was reduced on the side related to TIA. In seven of the pediatric patients with TIA, cerebral perfusion images were observed during continuous intracarotid infusion of the solution of Kr-81m. The patients were hyperventilated under infusion of the tracer and the changes in cerebral perfusion were detected by a gamma camera. Prolonged and marked reduction of cerebral perfusion was observed in the fronto-pareital convexity region during and after hyperventilation in six of seven patients. This prolonged reduction of perfusion in the fronto-parietal region seems to be responsible for TIA which often occurred following hyperventilation or strenuous exercise.

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To reduce the side effects during hemodialysis treatment, we used FUT-175 (FUT), which has anticomplementary activity as an anticoagulant during hemodialysis. On 9 dialysis patients and 8 domestic rabbits, we used heparin or FUT as an anticoagulant during dialysis and studied their effects on anticoagulant action, white blood cell count, complement activity and lipid metabolism. FUT exerted a stronger local anticoagulant action than heparin. Although FUT did not suppress hemodialysis leukopenia, it suppressed complement activity. FUT suppressed the decrease in triglyceride and the increase in free fatty acids observed during heparin administration.
In conclusion, FUT could be an anticoagulant superior to heparin.

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The effects of serum protein concentration (SPC) on serum protein/gas partition coefficient and of hematocrit ratio (HT) on red cell/gas partition coefficient during halothane, enflurane or isoflurane anesthesia were examined in dogs. Furthermore, their effects on Minimum Alveolar Concentration (MAC) of the three anesthetics were also studied.
Serum protein/gas partition coefficient and red cell/gas partition coefficient were significantly changed by the alteration of SPC and HT, respectively, in vitro. Concentrations of these anesthetics in blood at 1 MAC were only related to SPC in vivo. This suggeste that the solubility of inhalation anesthetics may be influenced by the composition of red cells and serum protein. In vivo, as SPC increased, MAC of these anesthetics increased linearly (p<0.01). MAC of enflurane was affected most by SPC and followed by that of isoflurane. MAC of halothane and enflurane was not affected by HT, but that of isoflurane increased linearly (p<0.01) as the HT increased. This suggested that the protein concentration difference between brain tissue and serum alters the action of the anesthetics and that HT alone alters the action of isoflurane only.

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To clarify the immunological characteristics of small airway areas, an unlabelled antibody peroxidase method for the detection of IgG, IgA, IgM, IgE & complement (C₁q) was applied to human peripheral lung tissues from patients with or without immunological respiratory diseases. Normal lung tissues were obtained from 8 surgically resected lungs with primary carcinoma.
In normal peripheral lungs, immunoglobulin containing cells were mainly distributed around the bronchiolar mucosa, but were sometimes found in alveolar septa. IgA containing cells were most numerous (mean 64.6%), followed by IgG containing cells (mean 20.1%) and IgM containing cells (mean 13.7%). IgE containing cells were virtually absent from small airway areas. No interstitial deposition of immuoglobulins or complement was detected in normal peripheral lung tissues.
In peripheral lungs with interstitial lung diseases, immunoglobulin containing cells were generally increased in number compared with normal lungs. Among them, IgG containing cells were dominant especially in interstitial pneumonia cases. In peripheral interstitium, various immune depositions were observed. Marked IgG and C₁q deposits were seen in thickened septa of interstitial pneumonia and around granulomas of sarcoidosis, suggesting a relation between immune complex and these diseases. In diffuse panbronchiolitis, there were many IgG containing cells around the bronchiolar area.
These findings indicate that the IgA antibody was dominant in the immunological defence mechanism of the normal peripheral lung, whereas IgG antibody and complement as well as IgA antibody were important in immuological respiratory diseases.

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The distribution of immunoglobulin containing cells and interstitial deposition of immunoglobulins and complement were observed aroud small airway areas of bronchial asthmatics. Transbronchial lung biopsy was performed to obtain peripheral lung tissues of bronchial asthmatics in non-attack stage. The peroxidase antiperoxidase technique was applied to detect IgG, IgA, IgM, IgE antibodies and C₁q using routinely processed paraffin sections.
The proportion of IgA containing cells was lower in the peripheral airway of bronchial asthmatics than in normal peripheral lungs.
In atopic asthmatics, the proportion of IgE containing cells was higher than that in non-atopic asthmatics and normal controls.
In non-atopic asthmatics, the proportion of IgG containing cells was higher than that in atopic asthmatics and normal controls.
In non-atopic asthmatics, interstitial depositon of IgG antibody to alveolar septa and bronchiolar mucosa was characteristic.
These findings suggest that the IgG antibody plays an important role in the pathogenesis of non-atopic asthma, whereas the IgE antibody is involved in atopic asthma.

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Between April 1984 and March 1989, anti-erythrocyte irregular antibodies (Abs) were detected in 329 (4.0%) of 8, 208 patients by a screening test using saline, bromelin and Coombs' methods. Most of them were anti-P₁, Lewis, M, Rh-D, -E, and -c Abs. Of the detected Abs, 174 were reactive at 37°C, with 79 Abs (45.4%), 131 Abs (75.3%) and 150 Abs (86.2%) being detected by the saline, bromelin and Coombs' methods, respectively. Our Ab screening test was found to be 99.99 per cent effective in preventing the transfusion of incompatible blood.
We also examined blood utilization during surgery for 28 different types of elective operation in 1976 patients. By analysis of the results of this examination, it was possible to decide on preoperative crossmatch guidelines, i.e. a maximum surgical blood order schedule, for 9 operations in abdominal surgery, 2 in lung surgery, 5 in cardiac surgery, 2 in neurosurgery, 2 in orthopedic surgery and 1 in gynecologic surgery. Arrangements for blood transfusion were unnecessary for cholecystectomy and 6 other operations, but the introduction of “type and screen” appears to be the best way to avoid an urgent order from the surgeon and for improvement in blood availability.

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Granulomatous inflammation was induced in rats by subcutaneous implantation of formalin-soaked filter paper and lipid classes in inflammatory tissue were investigated.
An increase in triglyceride content was observed in parallel with the formation of adipose tissue in the early stage of inflammation. In the stage of growth of granulomatous tissue, phospholipids increased with the gradual decrease in triglyceride content. In the early stage of granulomatous tissue formation, triglycerides contained mainly saturated fatty acid (16:0) and unsaturated fatty acids (18:1 (ω-9), 18:2 (ω-6) and 18:3 (ω-3)). Phospholipids in the growing stage of granulomas contained mainly polyunsaturated fatty acids (20:4 (ω-6) and 22:4 (ω-6)). Rapid and selective in vitro and in vivo incorporation of radio-labelled unsaturated fatty acids (20:3 (ω-6), 20:4 (ω-6), 20:5 (ω-3)) into phospholipids was observed in granulomatous tissue.
These results suggested that fatty acids released by lipolytic degradation of triglycerides in adipose tissue in the early stage of granulomatous inflammation are converted into phospholipids in cells accumulating in maturing granulation tissues, and also that these dynamic changes in lipid metabolism play important roles in the progress of inflammatory processes.

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Fatty acid dynamics in phospholipids and incorporation of radio-labelled fatty acids into phospholipid fractions were examined, using granulation tissue induced by the implantation of formalin-soaked filter paper in rats. The effects of anti-inflammatory drugs on lipid dynamics were also studied.
Concomitant with the progress of granulomatous inflammation, an increase in polyunsaturated fatty acids (mainly 20:4 (ω-6)) content of phospholipids was observed. Differing from saturated fatty acids, labelled polyunsaturated fatty acids (20:3 (ω-6), 20:4 (ω-6) and 20:5 (ω-3)) were easily incorporated in vivo into phosphatidylinositol and phosphatidylethanolamine in addition to phosphatidylcholine of granulation tissue. Indomethacin, tenoxicam and dexamethasone administered p. o. inhibited the granuloma formation. Indomethacin and tenoxicam had no marked effect on the tissue lipid composition. However, in dexamethasonetreated rats, tissue lipids were almost exclusively composed of triglycerides. Indomethacin and tenoxicam slightly decreased the percentages of 18:2 (ω-6) and 20:4 (ω-6) in phospholipid fractions.
Thus, polyunsaturated fatty acids released by lipolysis from fat cells accumulated in local inflammatory tissue in the early stage may be transferred into membrane phospholipids of inflammatory cells of later stage of inflammation and influence their functions. Antiinflammatory drugs may cause functional changes in cells accumulated in granulation tissue by changing the fatty acid components of the phospholipids.

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To investigate the efficacy of intravenous fat emulsion for total parenteral nutrition (TPN), oxidation of fat was evaluated using ¹⁴C labeled nutrients in rats. Animals were divided into five group depending the content of fat emulsion of TPN e. i. 0%, 20%, 40%, 60%, and 80%, respectively.
Oxidation rate of intravenous glucose was unaffected by content of fat emulsion. Cumulative ¹⁴CO₂ production for 7 hours was about 62% in all groups. On the other hand, the oxidation rate of intravenous fat emulsion was suppressed by increased glucose content. There was a negative linear relationship between oxidation rate of intravenous fat and glucose intake (r=-0.92, p<0.01). The oxidation rate of intravenous fat was increased proportionaly to fat intake and not completely suppressed when fat-free TPN was provided. Percentage of energy to be infused as fat should be about 20%.

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The changes in isozyme pattern of lactate dehydrogenase (LDH) and calculated ratios of heart muscle type (H)/skeletal muscle type (M) were studied by thin layer acrylamide gel electrophoresis in 65 tissue extracts from 9 human benign astrocytomas, 13 malignant astrocytomas, 3 medulloblastomas, 3 metastatic brain tumors, 19 meningiomas, 9 neurinomas, 5 pituitary adenomas, and 4 other tumors. The isozyme patterns were compared to those obtained from three normal human brain tissues. The average of H/M ratios of normal brain tissues was 1.51±0.03. Benign astrocytomas showed H/M ratios above 1.4 with their average of 2.4±0.7. Malignant astrocytomas showed H/M ratio below 0.9 with their average of 0.58±0.15. There was a decrease in the H/M ratio with increasing the degree of de-differentiation of all gliomas studied. Three medulloblastomas and three metastatic tumors also showed cathodal shifts of LDH isozymes. No characteristic pattern of LDH isozymes was seen in meningiomas, neurinomas, and pituitary adenomas. Analysis of LDH isozyme patterns of the tumors was found to be useful in the estimation of the degree of biological malignancy of gliomas.
In four astrocytomas (2 benign and 2 malignant astrocytomas), a supernumerary band of LDH which migrated cathodic to LDH-2 was observed. This extra band was exclusively found in gliomas but not observed in other kinds of tumors. This extra band of LDH might be related with the de-differentiation of glial cells.

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The effect of organic phosphates and chloronaphthalenes, which are used in new pesticides on mitochondrial oxidative phosphorylation in the rat liver was examined.
Chlorpyrifos and phoxim decreased State 3 respiration in a dose-dependent manner, but pyridaphenthion, α-and β-chloronaphthalene had only a slight effect. Degree of their effect in the order of chlorpyrifos>phoxim>β-chloronaphthalene>α-chloronaphthalene>pyridaphenthion. Chlorpyrifos, pyridaphenthion, α-and β-chloronaphthalene affected on the State 4 respiration, but phoxim did not. Consequently, they lowered the respiratory control index and the effect being in the order of chlorpyrifos>β-chloronaphthalene>phoxim>α-chloronaphthalene>pyridaphenthion.
All the compounds tested stimulated latent ATPase activities, but DNP - stimulated ATPase activities were not affected by these compounds. Their effect on latent ATPase activities were in the descending order of chlorpyrifos>phoxim, β-chloronaphthalene>α-chloronaphthalene>pyridaphenthion.
These findings suggest that chlorypyrifos, pyridaphenthion, phoxim, α-chloronaphthalene and β-chloronaphthalene impede mitochondrial oxidative phosphorylation.

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Inhibition of cholinesterase (ChE) activity was examined by experiments on enzyme activity of ChE of rat administered intraperitoneally chlorpyrifos and enzyme kinetic study of ChE in plasma.
Plasma ChE activity was inhibited more highly than erythrocyte ChE activity in rat 12 hrs after administration. Plasma ChE activity was recovered 1 month after administration but erythrocyte ChE activity was not recovered. No difference between frontal cortex and striatum ChE activity was recognized. Changes in brain ChE activity was similar to those in erythrocyte ChE activity.
PAM affected the inhibition of ChE activity by chlorpyrifos on 3 hrs after administration but other ChE activities were not.
Uncompetitive inhibition between chlorpyrifos and ChE was proved by Lineweaver-Burk plots.
Inhibition of ChE isoenzyme was found on bands 4 and 7 by electrophoresis.
These results suggest that plasma ChE was effective for exposure monitoring and erythrocyte ChE was effective for effect monitoring.

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