Differential hypothermia (D. H.) for the treatment of brain tumor, a method in which the tumor is kept normothermic while the body is kept hypothermic (Popovic et al., 1965) was examined. In order to clarify the effect of D. H. on tumor metabolism, histological and histochemical examinations were performed on adenovirus type 12 induced tumors transplanted into the cheek pouches of 50 Syrian golden hamsters. The animals were anesthsized with 5% pentobarbital sodium given intraperitoneally. The tumors were immersed in a warm water bath to keep the tumor temperature at 37°C while the total body was kept hypothermic (12°C) by placing it in ice water for 10 hours. Tumor growth was examined in 20 animals. Fifty percent of the tumors disappeared completely with no regrowth within 1 month after D. H., and 35% showed marked regression. However 15% showed no regression. Histological and histochemical examinations performed on 30 animals disclosed degenerative changes of the tumors treated with D. H., such as enlarged lumen of blood vessels and edema around tumor cells immediately after the treatment. Pyknoses and karyorrhexes became obvious 24 hours after the treatment. Histochemical examinations were performed immediately, 12, 24, 48 and 96 hours after D. H. Three hydrolytic enzymes [alkaline phosphatase (ALP) and acid phosphatase (ACP), Burstone's method, and adenosine triphosphatase (ATPase) Wackstein-Meisel's method] and 8 glycolytic enzymes [lactate dehydrogenase (LHD), malate dehydrogenase (MDH), glucose-6-phosphate dehydrogenase (G-6-PHD) and β-hydroxybutyrate dehydrogenase (β-HDH), Mori's method, succinate dehydrogenase (SDH), Nachlas's method, cytochrome oxidase (CYO), Burston's method, glutamate dehydrogenase (GDH), Barka-Anderson's method, and monoamine oxidase (MAO), Glenner, Burster and Brown's method] were examined. Enzymatic activities of LDH and MDH obviously decreased in the tumor cells immediately after D. H. and also slightly but significantly thereafter. On the other hand, the activities of β-HDH, SDH, CYO, GDH and MAO obviously increased in the tumor cells up to 12 hours after D. H. These results indicate that acceleration of fatty acid and amino acid metabolism and aberrant glycolysis occurs. These metabolic changes are suggestive of degenerative changes of tumor cells following D. H. ALP, ACP, ATPase and G-6-PDH showed no activity in the tumor cells before or after D. H. In the tumor stromas, the activities of ALP and ACP increased immediately and over 24 hours after D. H. The activity of ATPase was confined only to the endothelium of blood vessels and decreased up to 48 hours after D. H. These changes in ALP, ACP and ATPase activity in the tumor stromas suggest metabolic disturbances and increased permeability of the blood vessel walls following D. H. The other enzymes showed no remarkable changes in the tumor stromas after D. H.
Eight children under 15 years of age and 8 adults with basal cerebral rete (so called Moyamoya disease) were examined. Regional cerebral blood flow (rCBF) was measured in 12 of these patients under normocapneic, hypercapneic, hypocapneic and hypotensive states by a 133Xe-intracarotid injection method using a gamma camera. Patients with neurological deficits due to completed stroke (CS) had angiographically poor normograde vascularization of cortical branches of the middle cerebral artery (MCA) and poorly developed collateral circulation. Hemispheric cerebral blood flow (HCBF) in the resting state tended to decrease according to the severity of neurological deficits, but was within the normal range in patients with no neurological deficits. However, focal reduction of rCBF was seen in half of the patients with transient ischemic attacks. Development of leptomeningeal anastomosis of MCA territories from the posterior cerebral artery seemed to have a more important role than basal rete in maintaining cerebral blood flow. There was a significant reduction of the HCBF under the hypocaneic state, but no significant increase under the hypercapneic state. The lack of a CBF response to increased arterial CO2 tension seemed to be due to maximum dilatation of cerebral arterioles.
The effects of an expanding supratentorial mass on the neural function and local cerebral blood flow (1-CBF) in the brain stem were investigated. A balloon was into the supratentorial epidural space of 32 cats and inflated at a constant rate (0.0197 ml/minute). The auditory brain-stem response (BER) and the short-latency somatosensory evoked response (S-SER) were employed to evaluate the electrical conduction through the auditory and lemniscal pathway, respectively. The blink reflex was also monitored to investigate the neural function of the brain-stem reticular formation. The 1-CBF was measured in the inferior colliculus (IC), medial lemniscus (ML), pontine reticular formation (PRF) and reticular formation of the medulla oblongata (MORF) by the hydrogen clearance method. While the ICP was raised to 40-60 mmHg, the values of IC- and PRF-CBF markedly decreased as compared with those of ML- and MORF-CBF. Blink reflex R2 disappeared at 40-70 mmHg ICP, prior to the disappearance of BER wave V, S-SER II components, and blink reflex R1. At the stage of appearance of anisocoria, the BER wave V disappeared in all cats while the S-SER components were preserved in 4 of 18 cats. When both BER wave V and S-SER II components disappeared, 1-CBFs in IC and ML decreased to less than 50% of the control. The balloon was deflated within 15 minutes after anisocoria occurred. One hour after the deflation, blink reflex R2 remained absent in all cases. S-SER II components and BER wave V recovered in 10 of 14 cats and 4 of 18 cats, respectively. The 1-CBF of the brain-stem improved in the majority of the cats in which the neural function of the corresponding region recovered. These results suggest that the circulation and the neural function of PRF and IC are more vulnerable to intracranial hypertension than those of ML, and an hardly restored by decompression after the evidence of tentorial herniation.
Urokinase was administrated to 36 patients for the thrombolytic treatment of 63 instances of Björk-Shiley prosthetic valve thrombosis. Patients were diagnosed either from clinical findings or from the maximum opening angle of the prosthetic valve. By means of administration of urokinase, the maximum opening angle of the prosthetic valve, heart rate and cardiothoracic ratio improved significantly. It was considered that fibrinolytic treatment with urokinase against prosthetic valve thrombosis is more effective in the asymptomatic phase, and for this reason, early detection of abnormal prosthetic valve sounds and periodical measurement of the maximum opening angle of the prosthetic valve are significant.
Urokinase was administrated to 9 patients for the thrombolytic treatment of 10 instances of Björk-Shiley prosthetic valve thrombosis in the mitral position. Patients were diagnosed either from clinical findings or from the maximum opening angle of the prosthetic valve. Before and after administration of urokinase, Doppler echocardiography was performed in all patients. By means of fibrionlytic treatment, the peak velocity of rapid filling into the left ventricle, the peak pressure gradient, the pressure half time and the mean diastolic gradient decreaed, while the effective valve area increased. It was considered that thrombolytic tretment with urokinase is effective for Björk-Shiley prosthetic valve thrombosis,
The protective effect of a calcium antagonist on reperfused myocardium was investigated, with particular reference to cardiac sarcoplasmic reticulum (SR). SR function, which is closely related to cardiac diastolic function, was measured before and after coronary reflow. Verapamil (2mg/L), a calcium antagonist, was added to a cardioplegic solution, and its protective effect against SR injury was compared with that of potassium (K+, 20mEq/L) by measurement of SR function and cardiac functions. In 7 dogs, the left ventricular myocardium was resected to prepare SR for measurement of its Ca2+-binding function as a control. Another 24 canine hearts were placed on cardiopulmonary bypass (CPB). Then, intermittent aortic root infusion of each cardioplegic solution (0°C, pH 7.40, 360mOsm/L) was performed during 2 hours of aortic clamping. The myocardial temperature was kept at 15±3°C. After 2 hours of ischemia with either verapamil solution (Group I-A: n=5) or potassium solution (Group II-A: n=5), each myocardium was resected before reperfusion, and SR was prepared for measurement of its Ca2+-binding function. Fourteen canine hearts, which were protected with either verapamil solution (Group I-B: n=7) or potassium solution (Group II-B: n=7), were reperfused and cardiac functions were measured for 60 minutes after weaning from CPB. Then, the Ca2+-binding function of SR prepared from each reperfused myocardium was measured. With regard to Ca2+-binding function of SR, there was no significant difference between Group I-A and Group II-A, but a significant decrease was seen in Group II-B compared with Group II-A and Group I-B. There was no difference in contractility between Group I-B and Group II-B, but performance and diastolic parameters, especially the time constant T, were well preserved in Group I-B compared with Group II-B. It was concluded that after 2 hours of global ischemia of the myocardium, SR function was well preserved with verapamil and potassium. After reperfusion, SR function was impaired in both groups, but verapamil preserved SR function better than potassium. Therefore, cardiac functions, especially performance and diastolic parameters, appeared to be well preserved with verapamil. These results suggest that SR injury after reperfusion can be reduced with calcium antagonists.
A simplified method for measuring complement-mediated inhibition of immune precipitation (IIP) using peroxidase (PO) as an antigen was studied. IIP was measured in 48 patients with systemic lupus erythematosus (SLE). Immune precipitation of PO and anti-PO rabbit IgG at equivalence was inhibited principally via the classical complement pathway in the serum. When the substrates H2O2 and 5-aminosalicylic acid were added to the supernatants (soluble PO immune complex and free PO) of antigen, antibody and fresh or heat-inactivated serum mixture, their absorbance (O. D.) at 450nm increased in a dose-dependent manner. The IIp of the complement in the serum was shown by the difference in absorbance between fresh serum and heat-inactivated serum. The IIP in SLE was lower than that in normal subjects and patients with other collagen diseases. There were correlations between IIP and CH50 (r=0.47, p<0.01), C3 (r=0.67, p<0.01) and complement-mediated solubilization of immune complex (r=0.45, p<0.01). The IIP in SLE was reduced only in the earlier active state and normalized very rapidly. The above results suggest that the formation of an immune complex lesion in SLE is not due to the acquired depression of complement-mediated inhibition of immune precipitation as seen in the complement deficiency state.
An exercise tolerance test with a bicycle ergometer was carried out in 40 patients prior to pulmonary resection. During the test, expiratory gas was analyzed, and the alterations in the blood gas level and lactic acid value were studied. Nine patients had postoperative cardiopulmonary complications, and 31 had no postoperative complications. It was found that both Vo2 max and Vo2 max/body weight were good parameters for indicating significant differences between patients with and patients without postoperative complications. Patients with a Vo2 max value less than 1100 ml/min and/or Vo2max/body weight below 20 ml/min/kg after an exercise tolerance test with a bicycle ergometer have a high risk of developing postoperative cardiopulmonary complications.
To examine the relationship between aging and pancreatic exocrine function, fecal chymotrypsin activity (FCA) was measured by a photometric method in 62 healthy controls (20 to 87 years old, with a mean age of 51.0), 43 patients with non-pancreatic diseases (31 to 83 years old, with a mean age of 55.7), 40 controls with no known digestive diseases in an old-age home (63 to 92 years old, with a mean age of 77.6) and 22 patients with chronic pancreatitis (17 to 72 years old, with a mean age of 52.9). Pancreatic exocrine function decreased significantly with aging as indicated by: (a) a significant inverse correlation between aging and FCA in the 62 healthy controls (r=-0.56, p<0.001), in the 43 patients with non-pancreatic diseases (r=-0.58, p<0.001), and in the 40 controls in an old-age home (r=-0.52, p<0.001): and (b) a significantly lower FCA in the 21 healthy controls over 65 years of age (designated as B-group of healthy controls) than the 41 healthy controls under 65 years of age (designated as A-group of healthy controls). The 40 controls in an old-age home showed significantly lower FCA than the B-group of healthy controls. This result was ascribed to the fact that the former group comprised significantly older subjects than the latter. No significant difference was found in FCA between patients with chronic pancreatitis and B-group of healthy controls as well as controls in an old-age home. When the mean-2SD of the A-group of healthy controls was set as the lower limit of normal, 59.1 percent of patients with chronic pancreatitis, 52.4 percent of B-group healthy controls and 62.5 percent of controls in an old-age home showed abnormally low levels of FCA. This result indicates that the FCA value should be carefully interpreted with respect to the age of the patient before making the diagnosis of pancreatic disease.
The effect of spa-drink therapy (Misasa hot spring) on exocrine pancreatic function was studied in 25 patiens after their physical and psychological conditions had stabilized about two weeks following their hospitalization. Patients were randomly divided into the following two groups: nine patients into the control group (continuance of spa-bathing) and 16 patients into the spa-drink therapy group (continuance of spa-bathing plus commencement of spa-drink therapy). Spa-drink therapy refers to drinking 200 ml of warm spa-water (40°C) two times a day between meals, in the morning and in the afternoon. Exocrine pancreatic function was evaluated by: fecal chymotrypsin activity (FCA), which was determined by a new colorimetric method with Monotest Chymotrypsin supplied by Boehringer Mannheim; and cumulative % PABA recovery in 6-hour urine, which was determined with N-BT-PABA supplied by Eisai. The 2-week spa-drink therapy significantly improved the FCA value in four of the 16 patients (25%) while none of the controls showed a significant improvement in the FCA value. The 2-week spa-drink therapy significantly improved the PFD value in seven of the 16 patients (43.8%), while only 11.1% of the controls showed an improvement. These improvements with the spa-drink therapy were probably due to an enhancement of exocrine pancreatic secretion in four patients, and an improvement of gastric secretory or motor function in three patients. With 4 weeks of spa-drink therapy, however, these improvements tended to become less prominent, with FCA and PFD approaching the pre-treatment values. The 2-week spa-drink therapy improved the digestive function in some individuals either by enhancing exocrine pancreatic function or by improving the gastric secretory or motor function. However, the effect became less prominent thereafter, a phenomenon known as “adaptation” in the field of balneotherapy.
Liver tissue cathepsin B (EC 3. 4. 22. 1) activity was measured with N-benzyloxy-carbonyl-L-arginyl-L-arginine-4-methyl-7-coumarilamide (Z-Arg-Arg-MCA) as the substrate in order to clarify the role of this enzyme in tumor invasion or metastasis of liver cancer. Serum inhibitory factor of cathepsin B activity was also determined in cirrhotic patients with hepatocellular carcinoma and in patients with other liver diseases. Cathepsin B activity of liver cancer tissues in patients with lung metastasis was higher than that in non-cancerous tissue sourrounding the main tumor. The levels of serum inhibitory factor of cathepsin B activity in patients with hepatocellular carcinoma were lower than those in healthy subjects or non-malignant chronic liver diseases. Furthemore, in hepatocellular carcinoma patients with portal invasion, serum levels of inhibitory factor of cathepsin B activity were much lower than those with no portal invasion. The results suggest that cathepsin B activity participates in tumor invasion and metastasis of liver cancer due to imbalance of enzyme-inhibitor relationship.
The 24-hour Holter ECG monitoring was performed in 79 patients with old myocardial infarction, 46 with anterior infarction and 33 with inferior infarction, and the daily profile of ventricular premature contractions (VPCs) prevalence was studied. Fifteen healthy subjects served as controls. The prevalence rate of VPCs in a day varied within a small range (mixed type) in patients with anterior infarction, while VPCs in patients with inferior infarction appeared more frequently during the daytime than at night (daytime type). The LV ejection fraction did not influence the daily profile of the VPC prevalence rate. VPCs tended to be more frequent during the night in patients under 60 years of age with anterior infarction, but the inferior infarction group of patients undergo mainly showed the daytime pattern. Complex VPCs including grade 3 or more of Lown's classificasion had a tendency to be more frequent in patients with the daytime type VPC profile than VPCs of less than grade 3 of Lown's classificasion. Grade 4 VPCs mainly appeared during daytime in both the anterior infarction and inferior infarction groups. These characteristic daily profiles of VPC prevalence suggest different mechanisms of VPCs between anterior infarction and inferior infarction, and would be of use for the medical treatment of VPCs.
Sinusoidal endothelial cells were isolated from a rat liver by collagenase perfusion and centrifugal elutriation. The cells attached poorly to a plastic dish without coating it even after 24 hr of culture. In the collagen-coated dish, a large number of cells attached to the dish and spread within 24 hr of culture. Centrifugation of the dish immediately after seeding lead to much better attachment of the cells. Fresh rat serum obtained from the portal vein did not increase the attachment, but was essential for the maintenance of the attached cells after the initial 24 hr of culture, when the fetal calf serum was not replaced. The rat serum also induced cell proliferation as determined by thymidine uptake. Its effect was abolished by heattreatment of 56°C for 30 minutes.
The influence of the occupations of factory workers on their health needs was analyzed by reviewing their health records. The study was carried out on the male workers at a paper factory managed by the national government. Five types of occupations were defined: management personnel, foremen, shift-workers, day-workers with the experience of shiftwork, and day-workers without any experience of shift-work. The frequency of receiving medical services and medical expenditures was high among the day-workers with shift-work experience, among whom there existed many workers who quit shift-work because of health problems. Among management personnel and foremen, the frequency of receiving medical services, especially those at medical institutions outside the factory, was low. The ratio of medical service provided by an occupational health doctor to that provided by medical institutions outside the plant was high among the management personnel, because they have difficulty in leaving the plant during working time, while other workers are allowed to go out to receive medical service without any salary reduction. Among management personnel and foremen, the frequency of sick leaves was low, but the length of one sick leave tended to be longer. This result shows that the management personnel and foremen have difficulty in taking sick leaves at the early stage of the disease, so that the length of the leave becomes long when they take a sick leave. These results suggest that the consideration of workers' occupations is important, as well as their age and sex pointed out in the first report, to provide adequate health services to the workers.
The lipid and fatty acid metabolism of tissues and plasma of rats was studied one week and three months after insulin deficiency was induced in the rats by treatment with streptozotocin. The fatty acid content was analyzed by microcapillary column gas-liquid chromatography. In the liver, significant decreases in triglyceride, cholesterol and phospholipids were observed after one week, and significant decreases in triglyceride were observed after three months. No changes were observed in the heart. In the lung, remarkable decreases in triglyceride and phospholipids were observed after three months. Significant decreases in arachidonic acid were observed in the liver, heart and lung. Significant decreases in palmitic acid were observed in the lung and adipose tissue.
In order to study the lipid and fatty acid metabolism in the insulin deficient state, the in vitro incorporation of 1-14C-sodium acetate into major lipid fractions and fatty acids of liver slices and whole blood cells was determined. Rats were studied one week, one month and three months after insulin deficiency was induced by administration of streptozotocin. The net incorporation of 14C into lipid fractions and total fatty acids of liver slices significantly decreased after one week. On the other hand the net incorporation of 14C into the lipid fractions and total fatty acids of whole blood cells showed a tendency to decrease after three months. The net 14C incorporation into free cholesterol decreased significantly and that into phospholipids increased significantly in liver slices after one week. The net 14C incorporation into free cholesterol of whole blood cells decreased significantly on the same day. A significant decrease in the percent incorporation of 14C into oleic acid was observed in both liver slices and whole blood cells after one month and three months.
The properties of catalases in the liver homogenate of acatalasemic (C3H/CsbCsb), hypocatalasemic (C3H/CscCsc), acatalasemic heterozygous (C3H/CsaCsb) and normal (C3H/CsaCsa) mice were analyzed directly by agarose isoelectric focusing. Homogenates of mouse liver were prepared with isotonic sucrose solution and separated from the subcellular fractions by repeated centrifugation followed by ultra-centrifugation (105, 000×g). Agarose isoelectric focusing was performed in a pH 3-to-10 Pharmalyte gradient gel at 8°C. Isoelectric range of catalase in liver supernatants was compared normal and mutant mice which were designated acatalasemia, hypocatalasemia and acatalasemic heterozygous. Liver catalases of CsbCsb, CscCsc, CsaCsb and CsaCsa were focused to a band at pl 5.9-7.6, pl 5.8-7.3, pl 5.6-7.0 and pl 5.4-7.0, respectively. The difference in the isoelectric points of catalases among CsbCsb, CscCsc, CsaCsb and CsaCsb suggested the presence of some structural differences in the catalase molecule between normal and mutant mice. The homegenates of liver from CsaCsa and CsbCsb were separated into four fractions (noncatalase fraction and A, B and C catalase fractions) by DEAE cellulose column chromatography with a discontinous buffer system of 1mM, 3mM, 10mM and 100 mM phosphate buffer. The eluates were concentrated to 1.5 PU/ml by ultrafiltration, and pl values of the fractions were examined by isoelectric focusing. Acatalasemic fractions B and C focused at a more alkaline pl than normal fractions B and C.
Blood samples were taken from the orbital sinus (venous) of normal (C3H/CsaCsa), acatalasemic (C3H/CsbCsb) and hypocatalasemic (acatalasemic heterozygote, C3H/CsaCsb) mice. Packed red cells prepared from mice were washed three times with cold 0.9% NaCl solution to remove the huffy coat. One volume of red cells was hemolyzed with 1.5 volumes of distilled water. The various mouse hemolysates were fractionated into A, B and C fractions by DEAE cellulose column chromatography with a discontinous buffer system. Catalase activity in the eluate was determined by the perborate method, and the eluate was concentrated to 1.0PU/ml. Agarose isoelectric focusing was performed in a pH 3-to-10 Pharmalyte gradient gel at 8°C. The distribution of catalase in the erythrocyte fractions A, B and C from normal and mutant mice were examined. The activity ratio of the C fraction to the total fraction was greater in the descending order of CsaCsa, CsaCsb and CsbCsb mice. Catalase of fraction A of CsbCsb, CsaCsb and CsaCsa focused to band at pl 6.5-7.3, pl 5.7-6.5 and pl 5.4-5.9, respectively. Similarly, catalase of the fraction C of CsbCsb, CsaCsb and CsaCsa focused to a band at pl 6.3-7.2, pl 5.9-6.5 and pl 5.0-6.0, respectively. Thus the isoelectric points of catalases in fractions A and C obtained from the blood of CsbCsb were higher than those of CsaCsa. The isoelectric points of catalases in fractions A and C of CsaCsb were between those of the CsbCsb and CsaCsa. The results also indicate that the isoelectric point of catalase in fraction A was higher than that of fraction C in each group of mice.