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Using a cell line (SBC-3/ADM) of human small cell lung cancer, which is 30-fold more resistant to adriamycin than the parent cell line (SBC-3), the activity of a variety of anticancer agents was analyzed by soft agar clonogenic assay to search for a means of circumventing drug resistance. The SBC-3/ADM cells were markedly resistant to some anthracycline antibiotics in comparison with the SBC-3 cells: 28-fold for daunomycin, 26-fold for 4'-epiadriamycin, 18-fold for THP-adriamycin, and 8.4-fold for aclarubicin. However, the cells were as sensitive to mitoxantrone, one of the anthraquinone derivatives, as the parent cells. The cells were resistant to structurally or pharmacodynamically unrelated compounds such as vincristine, mitomycin C, and an active form of ifosfamide, whereas they were susceptible to cisplatin to some extent. The in vitro radiosensitivity of both cell lines was also evaluated, and they were found to be equally sensitive to X-ray. These results suggest that mitoxantrone and cisplatin may exert sufficient activity for small cell lung cancer which has acquired resistance to adriamycin, and that consolidative chest irradiation may be clinically useful after combination chemotherapy including adriamycin.

Primary cultures of surgically obtained noncancerous portions of human liver tissues were made. Liver tissues were poorly dissociated with collagenase, but well dissociated with dispase. The yield and viability of cells were improved somewhat when dissociated with collagenase followed by dispase. The mean cell yield was 1.1 X 10(6) cells/g liver. The epithelial-like morphology of the dissociated liver cells was maintained for about one week, but thereafter degenerative alteration of cells was observed. In liver explant culture, an active outgrowth of cells was observed for more than one month. Albumin production in culture fluids from dissociated livers was detectable for about 2 weeks, but later became undetectable, while that from explant culture was detectable for at least one month. These data demonstrate that adult human hepatocytes can be isolated from noncancerous portions of livers with relatively high yield, and that albumin production of the dissociated cells is detectable for several days.

Maximal expiratory volume-time and flow-volume (MEVT and MEFV) curves were drawn for young male nonsmoking healthy adults and for young male nonsmoking asthmatic patients. Eleven parameters, two MEVT (%FVC and FEV1.0%), six MEFV (PFR, V75, V50, V25, V10 and V50/V25), and three MTC parameters (MTC75-50, MTC50-25 and MTC25-RV) were used for the multivariate analysis. The multivariate analysis in this study consisted of correlation coefficient matrix computation, the test for mean values in the multivariates, and the linear discriminant analysis using the all possible selection procedure (APSP). Correlation coefficients among flow rate parameters and flow rate related parameters in high lung volumes were different between the two groups. In the eleven-parameter discriminant analysis by APSP using single parameters, PFR, V75 (flow rate at 75% of forced vital capacity), and FEV1.0% were considered to be the effective parameters. In the seven-parameter discriminant analysis using the parameter groups, the group of all parameters and the %FVC and flow rate-related parameter group were considered to be the effective numerical alternatives to MEFV curves discriminating between healthy adults and asthmatic patients.

Vital observation on the cellular morphology of the normal human blood cells was conducted by means of bone marrow culture successfully in conjunction with vital staining with Janus green B and neutral red. A special attention was paid for the alterations of the cellular structures in the course of the culture. The findings are summarized as follows : 1) Intracellular particles with affinity to Janus green B or neutral red were classified into minute granules, granules, vacuoles, and mitochondria. Morphologic features of each type of the particles were studied in detail. 2) Two types of granules are present in neutrophilic and eosinophilic blood cells, whereas one type of granules is present in basophilic blood cells. Eosinophilic and basophilic granules show characteristic pole formation in them at the terminal stage of the staining. 3) The rosette formation in the mature monocyte and the aggregations of neutral red vacuoles in the mature neutrophil and the mature lymphocyte were characterized. 4) The cluster of neutral red vacuoles is characteristic of the erythroblast. 5) The mitochondria of the mature neutrophil and the mature monocyte participate in producing neutral red vacuoles.

Within the range of our investigations the most important biochemical characteristics in the brain of idiopathic epileptic patients seem to be defect in the production of and the attendant decrease in free amino acids of the brain. On account of these phenomena there seem to occur the acceleration of the ChE activity and a poor utilization of glucose. Of the free amino acids in the brain the combined amount of glutamic acid, glutamine and γ-aminobutyric acid (GABA) will occupy the major portion of the total free amino acids found in brain, and thus diminution in the contents of glutamic acid and GABA in the brain of idopathic epileptic patients has quite an important meaning. At the present stage it is not yet possible to give any definitive answer to the question why such decrease occurs but it is believed that the most urgent problem facing us today is the amino acid metabolism that is associated with glutamic acid and the comparative studies of the amino acid metabolism in the epileptic brain to that in the non-epileptic brain are required. The fact that γ-amino-β-hydroxybutyric acid (GABOB), the substance that suppresses the central excitation, is decreased seems to indicate biochemically the existence of a defect in the processes of excitation in the brain of idiopathic epleptic patients.

1. Adrenalin, when acting directly on eosinophils, brings about a diminution in the wandering velocity of eosinophils but it has no influence on the number of the cells. Judging from the movement patterns of eosinophils this drug acts as to impede the motive function. 2. Acting directly on eosinophils, cortisone markedly decreases the wandering velocity of these cells and also brings about the diminution in the number of the cells. Likewise from the movement patterns of eosinophils, this drug markedly impedes the motive function of the cells. 3. ACTH (adrenocorticotropic hormone), when acting directly on eosinophils, enhances the wandering velocity of eosinophils but it in no way affects the number of eosinophils. Judging from the eosinophil movement patterns, this drug markedly promotes the motive function. 4. Although adrenalin brings about a decrease in the number of peripheral eosinophils in hypophysectomized dogs, the rate of the decrease is less than that observable in the case of normal dogs. 5. Cortisone brings about no significant change in the number of peripheral eosinophils in hypophysectomized dogs, but is induces a decrease in peripheral eosinophils of normal dogs. 6. ACTH acts as to decrease the number of peripheral eosinophils to an equal. degree in both hypophysectomized and normal dogs. 7. When cortisone is administered simultaneously with Adrex, a marked decrease in peripheral eosinophils is brought about in hypophysectomized dogs. 8. By means of the bone-marrow tissue culture of hypophysectomized dogs it has been confirmed that the blood plasma of hypophysectomized dogs lacks an essential factor for cortisone to induce eosinopenia in perpheral blood. 9. The decrease in eosinophils of peripheral blood induced by cortisone has been proved to be dependent upon the presence or absence of the pituitary body. 10. Taking the decrease in peripheral eosinophils by cortisone administration as the criterion, the author has carried out clinical observations with this method and obtained anticipated results.

The vector electrocardiographic method was applied on 126 healthy young Korean adults without any evidence of cardiac diseases. The range of the age of the subjects were between 19 and 34. The normal values of the magnitude and direction of the mean QRS, T, P vectors, ventricular gradient and QRS-T angle in frontal plane were presented and discussed in comparison with those previously reported in the literature. Considering the age of the subjects under study, our results were in general agreement with those previously reported by other authors.

1) I designed a new micro-method for complement fixation test by means of a capillary pipette. 2) By this method, the complement-fixing antibodies in an individual mouse could be tested without taking its life. 3} The complement fixation titers in mice immunized with Japanese B encephalitis had a considerable individuality. 4) An adjuvant containing anhydrous lanoline and paraffin-oil, when mixed with Japanese B encephalitis vaccine, was effective to potent complement-fixing antibody productions in mice to this antigen.

In such animals not having any organic changes in their brains during the initial stage showed a descendence of convulsive threshold. abnormal findings in their electroencephalogram and ascending activity of ChE. But what is the cause of these functional changes? First, from the fact that though there was no organic changes, they were sensitized and reiniected by a known antigen, which is obviously an antigen-antibody reaction. Second, from the fact that we got a histological.change, which was acknowledged as C.L.A. changes by increasing the concentration of these solution and the number of injections, it could be thought that these functional changes were caused by what I called latent C.L.A.. That is, it seems it could be thought that it would give functionally a permanent hypersensitivity, which is called convulsive arrangement. Furthermore, a similar histological findings as seen in old epileptics were made experimentally after prolonged and repeated injections of very diluted antigens. I believe it can be said, also from this histological point that they are experimental epileptics. But I am not trying to say that idiopathic epilepsy is the same allergic disease as asthma. If it was so, it should offer clinically a problem of eosinophilia in the blood of epileptics. But actually there is no eosinophilia in epileptics. Also, in adult epileptics, convulsive attacks is not often seen soon after introduction of antigens. Consequently, my theory that epilepsy is allergic, does not mean that allergy is the direct cause of epileptic attacks. What I mean is, the causal genesis of idiopathic epilepsy is hypersensitivity of nerve cells in the brain. This hypersensitivity was attained as a tissue reaction by some allergic mechanism without any organic changes. This functional change gives the nerve cell a hypersensitive state, which becomes the base of the beginnihg of convulsion. Its inducement of attack could be water stagnation in the body, anemic state of the brain, alkalosis, or introduction of allergens. In short, the cause of attack does not always come from allergic reactions.

The aim of this study was to explore muscle strength and its relation to exercise habits in Japanese. We used data from 3,018 men and 6,881 women aged 20-69 years and not using medications in a cross-sectional study. Exercise habits and muscle strength, i.e. grip strength and leg strength, were measured. Age-related changes in muscle strength were noted. Exercise habits were found in 984 men (32.6%) and 1,664 women (24.2%). For subjects of both sexes over 50 years, grip strength was significantly decreased with age. However, the ratio of leg strength to body weight significantly decreased with age as early as 30 years in men and 40 years in women. Grip strength, leg strength and the ratio of leg strength to body weight in subjects with exercise habits were significantly higher than those without exercise habits after adjusting for age in both sexes. This standard mean value may provide a useful database for evaluating muscle strength in Japanese adult subjects.

The present study was performed to clarify the effect of hypertonic saline infusion into the lung parenchyma on radiofrequency ablation (RFA) of the lungs. A total of 20 ablation zones were created in 3 pigs. The ablation zones were divided into 3 groups. Group 1 (n6) consisted of ablation zones created by applying smaller radiofrequency (RF) power without saline infusion;group 2 (n5) zones were created by applying greater RF power without saline infusion;and group 3 (n9) zones were created by applying greater RF power with saline infusion. The techniques of saline infusion included administration of hypertonic saline 1ml before RFA, followed by continuous administration at a rate of 1ml/min during the first 2min after the initiation of RFA. The ablation parameters and coagulation necrosis volumes were compared among the groups. Group 3 had a tendency toward smaller mean impedance than group 1 (p0.059) and group 2 (p0.053). Group 3 showed significantly longer RF application time than group 2 (p0.004) and significantly greater maximum RF power than group 1 (p0.001) and group 2 (p0.004). Group 3 showed significantly larger coagulation necrosis volume (mean, 1,421mm3) than group 2 (mean, 858mm3, p0.039) and had a tendency toward larger necrosis volume than group 1 (mean, 878mm3, p0.077). Although this small study had limited statistical power, hypertonic saline infusion during RFA appeared to enlarge coagulation necrosis of the lung parenchyma.

We report 2 cases of small cell carcinoma (SmCC) of the stomach with distant metastasis that were treated with the same chemotherapeutic regimens as used to treat small cell lung cancer. Although the mean survival of patients with SmCC of the stomach is reported to be only 7 months, our patients survived for 15 and 14 months, respectively. In our experience, these chemotherapeutic regimens might provide a survival benefit for patients with SmCC of the stomach, although they demonstrated no remarkable antitumor effects.

Conventionally, the carrying angle of the elbow is measured using simple two-dimensional radiography or goniometry, which has questionable reliability. This study proposes a novel method for estimating carrying angles using computed tomography that can enhance the reliability of the angle measurement. Data of CT scans from 25 elbow joints were processed to build segmented three-dimensional models. The cross-sectional centerlines of the ulna and the humerus were traced from the 3D models, and the angle between 2 vectors formed from the centerlines of the humerus and the ulna was defined as the "three-dimensional carrying angle." These angles were compared with those measured by simple radiograph. Two cases of angular deformity were underwent surgery based on this preoperative surgical planning, and the postoperative 3D carrying angles were evaluated using the proposed method. The mean value of the calculated three-dimensional carrying angle was 20.7 degrees +/-3.61, while it was 16.3 degrees +/-3.21 based on simple radiography without statistical difference. Based on the 3D carrying angle estimations, 2 surgical cases of cubitus deformities were planned by comparison with the normal contra-lateral elbow. Postoperative angle estimations confirmed that the corrected angles were nearly identical to the planned angles for both cases. The results of this study showed that the carrying angle can be accurately estimated using three-dimensional CT and that the proposed method is useful in evaluating deformities of the elbow with high reliability.

Toremifene citrate is expected to prevent drug resistance in cancer patients by inhibiting p-glycoprotein activity. The safety and efficacy of combination therapy with high-dose toremifene citrate and paclitaxel were investigated. Between December 2003 and June 2004, 15 women with a mean age of 53 years old with metastatic breast cancer were enrolled. The administration schedule was 80mg/m2 of paclitaxel given on Days 1, 8, and 15, and 120mg/day of toremifene citrate orally administered starting on Day 18. On Days 32 and 39, paclitaxel was concurrently administered again. Toxicities, response rate, and time to treatment failure were assessed. All patients had been treated with endocrine or chemotherapy. Grade 3 leukopenia occurred in 2 patients on the administration of paclitaxel alone, and grade 3 febrile neutropenia occurred in 1 patient given the combination therapy. There was no grade 3 or greater non-hematological toxicity. There was no complete response and 1 partial response, producing a response rate of 6.7%. Median time to treatment failure was 2.7 months. Combination therapy of paclitaxel and toremifene was safe and well tolerated with minimal toxicity. Further clinical trials targeting patients with functional p-glycoprotein are warranted.

The annual number of suicides in Japan increased sharply in 1998, and since that time it has consistently exceeded 30,000 per year. In this study, we analyze a database of personal and background characteristics of 824 cases (605 men, 219 women) who completed suicide in Okayama Prefecture in 2002 and 2003. The data were obtained with cooperation from the police. Using the methodologies in a previous European study as a model, we classified the suicide methods into 8 categories. To examine the generational and regional differences in the choice of methods, we stratified the sample into 4 age groups (<-24, 2544, 4564, and >-65) and 2 regional groups (Okayama/Kurashiki vs. other areas). Our results on gender differences in 7 of the suicide methods were mostly similar to the European data. However, our data showed a remarkably higher proportionate male-to-female mortality ratio for poisoning by other substances (ICD-10, X65-X69 codes) (1.83, 1.15-2.92). In terms of generational differences in the choice of suicide methods, the Mantel-Haenszel test of homogeneity was significant for most of the categories in our study, suggesting an impact of age on how people commit suicide. There were no remarkable regional differences in our sample. An epidemic curve for suicides via carbon monoxide poisoning using charcoal briquets revealed a trend of time clustering not observed in the other 6 means. The database constructed and used in this study contains richer information than conventional death statistics and is expected to provide helpful knowledge and insights for future epidemiological studies.

Protective effects of clinically used drugs against adriamycin (ADM)-induced toxicity were studied in ICR mice. The control mice, which were administered 15 mg/kg of ADM twice, survived 7.48 +/- 1.99 days (mean +/- S.D.). The survival times of mice treated with the following drugs, expressed as a percent of that of the control group, were 293.6% for coenzyme Q10 (Co Q10, 2 mg/kg), 402.2% for dextran sulfate (MDS, 300 mg/kg), 121.6% for flavin adenine dinucleotide (20 mg/kg), 236.3% for adenosine triphosphate disodium (50 mg/kg), 213.7% for reduced glutathione (100 mg/kg), 121.6% for phytonadione (50 mg/kg), 155.2% for inositol nicotinate (Ino-N, 500 mg/kg), 335.5% for nicomol (1000 mg/kg), 157.5% for nicardipine (10 mg/kg) and 123.3% for dipyridamol (50 mg/kg). Anti-hyperlipemic agents such as MDS, nicomol, Ino-N and Co Q10 strongly protected against the ADM-induced toxicity, and the mice administered these drugs lived significantly longer than the control mice. The mechanism of the protective effect was discussed.

The extra-anatomical bypass formation and the exclusion of thoracic aortic aneurysms by the "paired clamp method" applied to the thoracic aorta of mongrel dogs, and the development of hind leg paralysis was studied experimentally in relation to the ratio between the mean excluded cavity pressure and the mean aortic pressure ratio (EA-ratio). The relationship between thrombus formation in the excluded cavity and the EA-ratio was also studied. Animals were divided into 4 groups: Group 1 underwent the cross-clamping of the descending thoracic aorta for 8 min; Group 2 underwent exclusion of the entire thoracic aorta under permanent bypass; Group 3 underwent ligation of 2/3 of the proximal intercostal arteries which branched from the excluded thoracic aorta; and Group 4 underwent division of the excluded thoracic aorta into 3 parts by ligation. No animals in group 1 developed paralysis. When EA-ratios were higher than 0.48, animals in groups 2 and 3 were not paralyzed, whereas all but 1 animals with EA-ratios lower than or equal to 0.48 were paralyzed. There was statistically significant difference between the EA-ratio of the non-paralyzed animals and that of the paralyzed animals in groups 2 and 3. Four out of 5 animals in group 4 were paralyzed. However, there was no statistically significant difference between the EA-ratio in these 4 paralyzed animals and that in the non-paralyzed animals in groups 2 and 3. When the EA-ratio was lower than or equal to 0.59, all but 1 excluded cavities of groups 2 and 3 animals were fully thrombosed 7 or 8 days after the operation. None of these animals showed the aggravation of the paralysis during the observation period and, conversely, the paralysis of almost all animals was ameliorated. These results suggested that the EA-ratio is useful in predicting the development of paralysis and thrombus formation in the excluded cavity after the operation of thoracic aortic aneurysms by the "paired clamp method".

Thirty-eight patients were operated on for mitral stenosis between March 1979 and September 1981. Thirty-six of them were examined as to their age, symptom duration, chest roentgenograms, electrocardiograms and echocardiograms to obtain various indices of left ventricular function. The usefulness of these indices as preoperative risk factors for predicting postoperative low cardiac output syndrome (LOS) was investigated. Cases which had values of ejection fraction, cardiac index, percent fiber shortening or mean velocity of circumferential fiber shortening less than 0.45, 2.0 l/min/m2, 25% and 0.80 circ/sec, respectively, in the preoperative echocardiographic examination were associated with a greater chance of postoperative LOS. Each of these factors was independently useful as a risk factor in cardiac surgery for mitral stenosis. Moreover, it was revealed that the combination of a preoperative percent fractional shortening (%FS) of less than 30% and a cardiac index smaller than 2.0 l/min/m2 indicated a strong predisposition toward postoperative LOS.

Antibody activity, especially that involved in the reaction of antibody-dependent cell-mediated cytotoxicity (ADCC), of five commercially available human gammaglobulin preparations (standard, pepsin-treated, plasmin-treated, polyethylene glycol-fractionated and S-sulfonated gammaglobulin) was measured. All these gammaglobulin preparations had high titers of hemagglutination inhibition and neutralizing antibody against measles virus. In ADCC reaction, the pepsin-treated gammaglobulin preparation showed no antibody activity. The standard gammaglobulin preparation showed weak activity only when highly diluted. The remaining three preparations showed high activity. Though the S-sulfonated gammaglobulin preparation showed no activity in ADCC reaction, it showed high activity after reconversion by means of oxidation and reduction in vitro. The plasmin-treated gammaglobulin preparation showed greater activity than the polyethylene glycol-fractionated preparation of the optimal concentration. In ADCC tests using the plasmin-treated gammaglobulin preparation, K cell activity was strongly inhibited by Hg (thimerosal), while, in those using the standard gammaglobulin preparation, the activity was hardly influenced by Hg, suggesting that the low ADCC activity of the standard gammaglobulin preparation of high concentrations was due to the inhibitory effect of aggregated immunoglobulin G molecules.