Experimental acute intoxication from cadmium chloride in the rat was studied with specific reference to change in the activity of mitochondrial oxidative phosphorylation in the liver and kidney. Various concentrations of cadmium chloride (2.5, 5.0, 10.0 mg/Kg) were given by intraperitoneal injection. Two hours after cadmium injection, the activity of liver and kidney mitochondrial oxidative phosphorylation had decreased, suggesting that cadmium uncoupled oxidative phosphorylation in liver and kidney mitochondria. A dose response relationship of cadmium uncoupling was observed in liver mitochondria, but was not observed in kidney mitochondria indicating that kidney mitochondria were more sensitive to cadmium than liver mitochondria were. A single injection of 250 mg/Kg of magnesium chloride prevented the uncoupling action of cadmium in liver mitochondria but not in kidney mitochondria. Magnesium did not prevent the uncoupling action of mercury chloride in liver or kidney mitochondria. The preventive action of magnesium chloride was evident in in vitro liver mitochondria but not in in vitro kidney mitochondria. The effect of magnesium on cadmium action was discussed.
Effect of PCNs on normal isolated mitochondrial membrane was studied and the results obtained were as follows. 1) PCNs inhibited the state 3 respiration, and stimulated the state 4 respiration (namely uncoupling action). 2) The proportional relationship between a decrease in RCI and an increase in concentration of Halowax 1001 (PCN) was recognized, and a decrease tendency of ADP/O ratio was observed within the range of PCN concentration measured. 3) PCNs induced a K+ release in mitochondria and the release effect was the strongest in Halowax 1031 (PCN). 4) Discussion was made that effects of PCNs on the mitochondrial membrane were seemed to be related to their complex characters which are the content of chlorine and their isomers.
PCN was dissolved in olive oil and given to rats intraperitoneally. The effect of PCN on liver mitochondria was compared with control rats given olive oil only. The results were as follows: The RCI of liver mitochondria had decreased significantly one hour after the injection of PCN. It was slightly decreased after 24 hours. The ADP/O ratio was slightly decreased one hour and 24 hours after the injection of PCN. The TBA value of the PCN injected group had increased significantly after 1 and 24 hours compared with the control, indicating that peroxidation of liver lipid had occurred. The level of ATP had decreased significantly compared with that of the control group 24 hours after the administration of PCN. Liver mitochondria showed greater uptake of components with shorter retention times than of those with longer retention times.
The influence of cadmium (Cd2+) on adenine nucleotide concentration in a reaction mixture consisting of rat liver mitochondria and ADP was studied using high performance liquid chromatography. The results were as follows: An increase in AMP concentration was brought about by the addition of Cd2+. This increase in AMP concentration occurred in parallel with increase in Cd2+ concentration. The appearance of AMP was thought to be due to an ATPase reaction and an adenylate kinase reaction stimulated by Cd2+ although further studies on the adenylate kinase reaction stimulated by Cd2+ are needed. An increase in AMP may influence metabolism via glycolysis. As lanthanium (La3+) is related to Ca2+-binding sites, the effect of La3+ on the K+-release of rat liver mitochondria induced by Cd2+ was also studied. The results were: K+-release induced by Cd2+ was inhibited by La3+. The Cd2+-binding site was thought to be related to the Ca2+ carrier of mitochondria.
Rats were injected intraperitoneally with cadmium chloride (5 or 10 mg/kg body weight) and calcium chloride (50 mg/kg body weight) simultaneously. Rats were killed after 2 hours. The accumulation of cadmium and calcium in the liver and kidney, and in liver and kidney mitochondria was examined. The mutual effect of cadmium and calcium on the respiration of the mitochondria was also investigated. The results were as follows: 1) concentrations of cadmium in the liver were lower in the presence of calcium than in its absence, but the accumulation of cadmium was marked. 2) concentrations of cadmium in liver mitochondria were lower in the presence of calcium than in its absence. 3) the decrease in respiratory control index and ADP/O ratio of liver mitochondria was lower in the presence of calcium than in its absence. 4) the same statements are true for kidney and kidney mitochondria. 5) The concentrations of calcium in the liver and kidney in the presence of both cadmium and calcium were similar to the those when calcium was absence.
The serum β2-microglobulin levels of 112 senior high school students were determined by radioimmunoassay and were analyzed statistically. Its measured values were transformed into logarithms and the distribution type was decided and also mean values. (m), standard deviation (SD), 95% confidence intervals and 5% rejection limit of logarithm transformed values and the actual values were calculated. The urinary β2-microglobulin levels of 18 senior high school students were statistically analyzed, and its measured values were transformed into logarithms and then the same calculations were performed. The results obtained were as follows: 1. The distribution type of the serum β2-microglobulin level was adapted by x2-test to the log normal type rather than to the normal distribution. 2. The statistical values of the serum β2-microglobulin, as they are adapted to the log normal type, were as follows: The logarithm transformed mean value was 0.158 mg/l, m±SD (logarithm) was 0.158±0.088 mg/l, m±2SD was -0.018-0.334 mg/l, 95% confidence interval was 0.142-0.175 mg/l and 5% rejection limit was -0.335 (upper) mg/l. The actual mean value (antilog) was 1.44 mg/l, m±SD (antilog) was 1.44±0.82 mg/l, m±2SD (antilog) was 0.96-2.16 mg/l, 95% confidence interval was 1.39-1.50 mg/l and 5% rejection limit (upper) was 2.16 mg/l. 3. The statistical values of urinary β2-microglobulin, as adapted to the log normal type, were as follows: The logarithm transformed mean value was 2.114 μg/l, m±SD (logarithm) was 2.114±0.179 μg/l, m±2SD (logarithm) was 1.758-2.472 μg/l, 95% confidence interval (logarithm) was 2.023-2.205 μg/l and 5% rejection limit (upper, logarithm) was 2.513 μg/l. The actual mean value (antilog) was 130 μg/l, m±SD (antilog) was 130±1.51 μg/l, m±2SD (antilog) was 57.3-296 μg/l, 95% confidence interval (antilog) was 105-160 μg/l and 5% rejection limit (upper, antilog) was 326 μg/l.
In order to quantitate the increase in urinary β2-microglobulin after exercise urine samples were taken immediately before and after soccer or judo. The titers of β2-microglobulin were measured by radioimmunoassay. The results were: 1. Both the acutual and the corrected β2-microglobulin levels increased significantly after exercise soccer, although not before. 2. The total protein tended to be increased after hard exercise soccer. 3. Urinary β2-microglobulin levels showed similar tends whether the exercise was soccer or judo.
Urinary levels of β2-microglobulin in healthy non-pregnant and pregnant women were determined. None of the women showed urinary protein, urinary glucose or urobilinogen. The results were: 1. The actual amount of urinary β2-microglobulin, the amount corrected for specific gravity (1.024), and β2-microglobulin/creatinine ratios were significantly higher in pregnant women than in non pregnant women. 2. The logarithms of corrected urinary β2-microglobulin levels were significantly higher in pregnant women than in non-pregnant women.
Ulcerative colitis in childhood is a rare disease in Japan. A 10-year-old male child was admitted to Okayama University Hospital with a chief complaint of mucous and bloody diarrhea. He had been treated conservatively in another hospital, but the symptoms had not improved. Barium enema examination revealed, from the sigmoid to the transverse colon, abnormal barium coating, numerous small niches, disappearance of the network pattern, and faint spiculations along the margins. Endoscopy demonstrated slight edema, hyperemia, easy bleeding and some purulent secretion. Biopsy specimens showed infiltration of lymphocytes, plasma cells and eosinophilic leucocytes in the mucosa. We made a diagnosis of ulcerative colitis. The patient responded poorly to Salazopyrin and Penicillin, but improved considerably with corticosteroids.
This report concerns 2 autopsy cases of Creutzfeldt-Jakob disease (CJD) in which the relationship between changes in serial electroencephalograms and the course of the disease is analysed. The importance of timing when periodic synchronous discharge (PSD) occurs was indicated. i.e., the appearance of PSD paralleled clinical manifestations of the apallic syndrome and was most distinct when the disease was at its worst. We reviewed the EEG findings in autopsy cases of CJD reported in Japan. Fifteen cases of typical PSD were found and these were examined clinico-pathologically. The findings were: 1. PSD was recorded within three months of the onset of the disease in two thirds of the 15 cases. 2. In 13 cases the clinical manifestations when PSD occurred were those of apallic syndrome or of similar conditions. 3. Following characteristics were found in the distribution of pathological changes in the brain; (a) The presence of extensive changes in the cerebral cortex was the only finding common to all cases. (b) The cerebral changes mainly occurred in the corpus striatum of the basal ganglia and in the medical nuclei of the thalamus. (c) Disturbances were least in the brain-stem below the level of the midbrain. (d) No definite tendency was apparent in the changes of the cerebral white matter and cerebellum. In conclusion, the mechanism of PSD may be accounted for by disturbances of the cortico-thalamic circuit. This circuit is said to be regulated by diffuse thalamic projection system. It is presumed that the extensive pathology in the cortex and medical nuclei of the thalamus plays an important role.
A survey of the ECG changes in 1906 cases in three districts of Okayama Prefecture was conducted over the past 10 years with particular emphasis on those exhibiting Minnesota Code 1-0. 1) Of the 741 cases which were ECG Code 1-0 in 1966, 77.1% remained Code 1-0 in 1970 and 57.2% in 1976. 2) Many cases which were initially ECG Code 1-0 in 1966 but with concomitant high blood pressure had changed to Code 3, Code 3+4+5, or Code 3+5 during the next 10 years. 3) Females constituted most of the Code 4+5 and Code 5 patients. 4) Those with Code 1-0 in 1966 and normal blood pressure, urinalysis and other physiological parameters dropped to 84.9% in 1976. 5) In those cases which remained Code 1-0 for 10 years, no significant changes were noted in the QT-interval, PR-interval, QRS-complex, or the size of the T-wave of their ECGs. 6) Among the 66 cases which were initially ECG Code 3 (only 1 subcode) in 1966, some had progressed to Code 3+4+5 or Code 3+5 and some had returned to Code 1-0 by 10 years later. It was concluded that aging has very little effect on the ECG. Other factors appear to be more important in causing ECG changes.
Changes in fluorescent intensity of the cyanine dye, 3, 3'-dipropyl-2, 2'-thiodicarbocyanine iodide [diS-C3-(5)], were monitored in Ehrlich ascites tumor cells (EATC) in correlation with glycolytic energy metabolism and endogenous respiration. After addition of glucose to EATC, membrane potentials monitored by diS-C3-(5) increased. The cyanine dyes were incorporated into EATC in proportion to the membrane potentials, and inhibited the endogenous respiration of EATC by more than 85% at a concentration of 100 μM. The inhibited respiration was partially released by addition of an uncoupler of oxidative phosphorylation (DNP). The respiratory activity of NAD-linked substrates in mitochondria (2.7 mg protein/ml) was also inhibited by diS-C3-(5), which inhibited the Rotenone-sensitive sites of the respiratory chains (Site 1) and increased Mg++ATPase activity. The inhibition by diS-C3-(5) of endogenous respiration in EATC in vivo was also effective even 24 hours after administration of the dye into the peritoneal cavity. The mean survival times of EATC-bearing mice were significantly prolonged by the administration of diS-C3-(5). The data suggest that the cell membrane potential is a useful factor when administering therapeutic drugs into target cells.
Lymphocyte-mediated cytotoxicity and serum blocking factor, their classification according to the stage, and the follow-up observations before and after operation were investigated in 40 cases of colon cancer. For the control group, the cytotoxicity test was conducted on 12 cases of cancer other than colon cancer. Cytotoxicity was detected in only one of these. Cytotoxicity was detected in 30 cases of colon cancer. There were no significant differences due to the stage of cancer. Serum blocking factor was investigated in 34 cases and 25 of them showed positive blocking. Classification by stage showed tendency for the blocking index to increase with advance of the cancer. Follow-up observations before and after operation were conducted on 14 cases. The cytotoxicity rose transiently after operation then decreased progressively in cases undergoing therapeutic surgery. Cytotoxicity reappeared in the cases of recurrence. The serum blocking factor decreased after operation showing transient negative blocking, then disappeared. In the cases of non-curative surgery, cytotoxicity rose transiently after operation and did not disappear throughout the entire course of observation. Serum blocking factor after operation showed transient negative blocking, then returned to positive.
The present status and the history of Inbred Strains of Experimental Animals, Animal Experimental Center, Okayama University Medical School, otherwise known as “The Mouse colony of Okayama University Medical School” are described.
Pathohistologic changes in various organs of eels kept for 14 days in water tanks containing crude oil with and without various oil detergents were studied. The results were: 1. Eels kept in water containing crude oil showed marked degeneration of proximal renal tubules. There was some regeneration of tubular epithelial cells and an increase in hemosiderin-like substance in the interstitial tissue of the kidney and spleen, suggesting accelerated hemolysis. The increased deposition of hemosiderin-like substance seemed to be due to hemolytic activity of the benzine, toluene and xylene contained in crude oil. No marked changes were seen in the liver, gills, muscle, intestine or other organs examined. 2. Eels exposed to oil detergents also showed kidney damage, tubular necrosis and regeneration. Increased deposition of hemosiderin-like granules was evident. The activated hemolysis seemed to be due to cytolytic activity of the surface active agents. 3. In the cases where crude oil was given with oil detergents pathologic changes were most marked. Severe degeneration of the proximal renal tubules was observed with poor regeneration of the epithelial cells. These severe changes may be due to accelerated migration of crude oil components into the fish body by oil detergents rather than to synergistic effects of the agents and crude oil. 4. Of the substances contained in crude oil those that are known to penetrate into the living body are, in the mammal, all liver-damaging but not kidney damaging. The same substances, however, may cause kidney damage in fish, because the function of fish kidneys is very different from that of mammal kidney.
Wistar rats were made polycythemic by daily injections of massive numbers of red cells for one week. The injections were made into the peritoneal cavity and the Ht level rose to between 70 and 75%. This plethoric state resulted in suppressed erythropoiesis of the bone marrow. At this stage, a quantity of blood was drawn from the orbital sinuses with concomitant transfusion of a saline-glucose-blood serum mixture. This withdrawal-transfusion process took about 30 minutes and the Ht value decreased from 75 to 25%. Distinct proliferation of erythroblasts and basophilic erythroblasts was observed 6 to 9 hours after blood withdrawal. Polycythemic animals had many large blast-like cells having relatively large clear cytoplasm. In each of these cells, the nucleus had fine chromatin nets and an ambiguous nucleolus. At 3 hours after blood withdrawal proerythroblast like cells with basophilic cytoplasm had appeared, but there were no basophilic erythroblasts. Typical proerythroblasts having characteristic nuclear chromatin nets and deep blue cytoplasm were prominent after 6 to 9 hours. More mature, poly- and orthochromatic erythroblasts appeared between 9 and 12 hours after blood letting. At 72 hours after blood letting, the cytohistologic picture of the bone marrow of polycythemic animals had returned to nearly normal. Possible erythroid cell differentiation from precursors in the bone marrow and from circulating blood is discussed.
Radiotherapy is an important mode of therapy for malignant tumors in the oro-mandibular area and the changes in vascularization which it causes are considered good indicators of both healing and the results of combined surgery and chemotherapy. The author studied the effects of radiotherapy on teeth and mandibular vascularization in 60 adult dogs. Cobalt irradiation of the lower right mandible was followed by intravascular injection of chloropercha to delineate the three-dimensional morphology of the changes. The histopathology, X-ray and macroscopic characteristics were also studied. The results were: (1) With 600 rad, fine capillaries around the roots of teeth increased. With 900-1, 500 rad, the course of blood vessels became irregular. With 1, 200 rad, there was a marked increase in capillary vessels which extended meanderingly. With 4, 500 rad, the number of blood vessels was markedly decreased. Some vessels were irregular and unclear. (2) Vessels in the dental pulp showed mild meandering with 900 rad. They increased markedly with 1, 200 rad and showed meandering. With 4, 500 rad, the number of blood vessels decreased. (3) The histopathology showed that, with comparatively small amounts of irradiation, marked vascular disturbance accompanied by vascular dilation and edema had occurred. As the amount of irradiation increased, increased fibrosis of interstitial tissue, decreased numbers of blood vessels, and aseptic necrosis occurred, resulting finally in bone absorption and bone necrosis. (4) X-ray examination showed that mild constriction of the pulp cavity occurred. with 3, 000 rad. This became marked with 4, 500 rad and showed absorption. (5) Macroscopically, 900 rad caused mild edema in the cheek skin. With 3, 000 rad, the oral cavity showed some ulceration. With 4, 500 rad, necrosis of the gingiva occurred. (6) A certain correlation in the changes of blood vessels, X-ray findings, macroscopical, and pathohistological findings was evident.
The purpose of this study was to investigate the therapeutic prognosis of adult patients with epilepsy during long-term follwo-up. The subjects of the present study were 286 epileptic patients seen by the author at the Department of Neuro-Psychiatry, Okayama University Hospital and Tsuyama Sekizen Hospital. All patients had been on therapy for more than five years. The age, onset of seizure and period of treatment of these patients were in order 35.1±11.5 y.o. (mean±SD), 15.9±10.2 y.o. (mean±SD), and 12.4±4.9 years (mean±SD). As classified by the criteria of the International League Against Epilepsy, the present study consisted of cases with; Partial Seizures 167 (58.4%) Primary Ceneralized Seizures 115 (40.2%) Secondary Generalized Seizures 4 (1.4%) The clinical course over the past three years was used as the period to determine the therapeutic prognosis. To describe the therapeutic prognosis, four categories were created taking types and frequency of seizures into consideration; i.e., “seizure-free”, “mild”, “moderate”, and “severe”. Results were: 1) “Seizure-free” 99 (34.6%), “mild” 91 (31.8%), “moderate” 54 (18.9%), and “severe” 42(14.7%). 2) In 187 patients, seizures were not abolished. In 89 cases (47.6%) change of seizure type occurred under treatment. The facts elucidated were; a) Partial seizures were resistent even to continued therapeutic efforts. b) Tonic-clonic general convulsions in primary generalized seizures and partial seizure with secondarily generalized responded well to therapy, disappearing promptly and permanently. c) “Abortive-minor seizure” occurred under treatment. d) The change from primary generalized seizures to partial seizures was seen in several cases. 3) Multidimensional comparisons regarding factors which may influence therapeutic prognosis were conducted. In “seizure-free” and “severe” cases, factors which showed statistically significant differences were as follows; In “seizure-free” cases, the first of each following pair showed the better prognosis; a) Seizure types: Primary generalized seizures and partial seizures. b) Etiology: “hereditary” and “residual”. c) Etiology: “cryptogenic” and “residual”. d) Duration prior to therapy: “within 3 years” and “over 3 years”. In “severe” cases, the first of each following pair showed the poorer prognosis; a) Seizure types: partial seizures and primary generalized seizures. b) Etiology: “residual” and “cryptogenic”. c) Sexual differences: women and men. 4) Psychiatric problems were observed in 143 cases (50.0%). These patients had a poor prognosis. Patients with partial seizures had more psychiatric problems than patients with primary generalized seizures.
The experiment was undertaken to determine the optimal amino acid solution for total parenteral nutrition (TPN) in 20 rats. Four different amino acid solutions were used, namely A, B, C and D, of which the E/N ratios were in order 0.8, 1.0, 2.0 and 3.0. TPN was introduced to rats of non-operated and operated groups, using these amino acids. Body weight change, nitrogen balance and plasma and urine aminograms were studied for assessment of the effect. The results were as follows; Non-operated group: Although all groups showed weight gain and positive nitrogen balance, group B with an E/N ratio of 1.0 was the best, followed by C, A then D. Blood aminograms showed markedly elevated levels of Thr in all groups, especially in B, C and D. This may be due to overdosage of Thr for rats. D group had increased urinary loss of Lys, Thr and Glu. These data suggest that B was the best amino acid solution for TPN in the non-operated group. Operated group: A small intestinal bypass operation was performed in rats and TPN was begun after operation. Weight gain and positive nitrogen balance were less than in the non-operated group. The best result was obtained in group C. Marked rise of Thr was observed as in the non-operated group. The typical pattern of postoperative change of aminogram was not seen, i.e., Phe, Met, branched amino acid did not increase. The aminogram of group C was close to the normal pattern. In the operated group, C with an E/N ratio of 2.0 was the optimal amino acid solution.
In our observation of leukemia and malignant lymphoma, many cases with slight changes in the IgM precipitation line (“abnormal IgM”), suggestive of small amounts of M-component, were detected by immunoelectrophoretic analysis. In these cases, determination of the light chain type seemed necessary for the diagnosis of M-component. However, typing was difficult by conventional methods because of the low amount of M-component. In this report, a new method for typing of the light chain of the IgM type of M-component, using FITC labelled anti-light chain specific antisera, is discussed. With this method, the light chain type of M-component was determined by the difference in strength of FITC specific fluorescence between the reaction of FITC conjugated anti-kappa and -lambda chain sera at the abnormal parts of the immune precipitation, which were prepared by agar immunoelectrophoresis using anti-heavy chain specific antisera. This method was applied to 11 cases with usual M-component, in which the light chain types were determined only by agar immunoelectrophoresis utilizing anti-light chain specific antisera or by combination with gel-filtration. In all cases, the types were determined in agreement with previous methods. Compared with cellulose acetate electrophoresis or agar immunoelectrophoresis using anti-heavy chain specific antisera, the immunofluorescent method had a sensitivity similar to agar immunoelectrophoresis and more sensitive than cellulose acetate electrophoresis. This method was applied to 7 cases with “abnormal IgM” which were found in leukemia and malignant lymphoma. In all 7 cases, differences in the strength of FITC specific fluorescence at the abnormal parts of the precipitation line were observed. As a result, 1 case with both kappa and lambda types, 2 cases with the kappa type and 4 cases with the lambda type of M-component were found. These results indicate the usefulness of this method for light chain typing of low amounts of M-component with IgM type. It seems likely that the slight changes in the IgM precipitation line, detected in leukemia and malignant lymphoma, result from M-components.