In the course of studying the precipitin reactions between sera from patients with connective tissue diseases and the saline soluble extracts of young rabbit thymus acetone powder, a new precipitin system was observed, tentatively called the Tu system after the original serum.
The Tu antigen activity was unaltered by heating up to 60°C for 30 minutes, and was stable at pH values of 4 to 10. The precipitin activity was resistant to digestion by DNase and RNase, but partially sensitive to trypsin digestion, suggesting that a glycoprotein was associated with antigenicity. The average molecular weight of the Tu antigen was estimated to be 70, 000 as determined by Sephadex G-200 chromatography analysis. The Tu antigen was localized in the cell cytoplasma, but not in cell nuclei nor nucleoli, as observed by indirect immunofluorescence and the peroxidase enzyme antibody technique. Cell fraction analysis by centrifuge methods clarified that the Tu antigen activity was in the microsomal fraction, mostly in the rough endoplasmic reticulum fraction.
The Tu antibody was found in 31% of patients with progressive systemic sclerosis, in 20% with systemic lupus erythematosus, in 22% with mixed connective tissue disease and in 10-20% with other connective tissue diseases. The patients with this precipitin antibody in their sera also had antibodies to various non-histone nuclear protein antigens, including RNP, Sm, Scl-70, SS-A and SS-B.
The Tu system was completely different from immune systems previously reported by others which included anti thyroid-specific microsomal antibodies, ubiquitous tissue antigen (UTA) and liver/kidney microsomal systems because of the non-identical precipitin lines and the difference in their disease distribution.

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Fifty-two patients with extensive small lung cancer entered a study of cyclic alternating combination chemotherapy between February 1981 and December 1984. The chemotherapy consisted of a four-drug combination of cyclophosphamide (CPA), vincristine (VCR), methotrexate (MTX) and procarbazine (PCZ), and a three-drug combination of etoposide (VP-16), adriamycin (ADM) and nimustine hydrochloride (ACNU). The doses and schedule were as follows: CPA, 270 mg/m², i. v., day 1-5; VCR, 1.4 mg/m², i. v., day 1; MTX, 6.5 mg/m², i. m., day 1-5; PCZ, 65 mg/m², p. o., day 1-5; VP-16, 140 mg/m², p. o., day 29-32; ADM, 40 mg/m², i. v., day 29; ACNU, 40 mg/m², i. v., day 29. Cycles were repeated every 8 weeks. Of 52 patients, 45 were fully evaluated for tumor response and toxicity. The overall response rate was 89%, and the complete response rate was 33%. The median survival time of all the patients who could be evaluated was 11.0 months: 16.5 months for complete responders, 10.0 months for partial responders, and 6.5 months for non-responders. Responders lived significantly longer than non-responders. The major toxicity was myelosuppression. However, patients tolerated the chemotherapy well, and no patients encountered life-threatening complications. The cyclic alternating chemotherapy appears beneficial compared to the four-drug combination of CPA, VCR, MTX and PCZ.

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In order to compare the efficacy and toxicity of cis-platinum and mitomycin C in advanced non-small cell lung cancer (NSCLC), randomized trial has been conducted since June 1982. Forty-eight previously untreated patients with advanced NSCLC were administered either PVB (a combination of cis-platinum, vindesine, and bleomycin) or MVB (mitomycin C, vindesine, and bleomycin), and 47 of them were fully evaluated for tumor response and toxicity. The partial response rate was 35% for 23 patients receiving PVB compared to 29% for patients treated with MVB. The projected median survival time were 10.0 months for PVB, and 8.5 months for MVB. There were no statistical differences in response rate and survival time between PVB and MVB. Myelotoxicity and neurotoxicity were comparable for the two treatments. Upper G. I. toxicity and nephrotoxicity were significantly more frequent in patients given PVB than in those receiving MVB, but these toxicities were generally mangeable. Cis-platinum thus appears to have no significant advantage over mitomycin C in the treatment of advanced NSCLC.

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Guanidino compounds in blood products, including red cell concentrate, platelet concentrate and liquid plasma, were fluorometrically analyzed with a guanidino compound analyzer. Highly toxic guanidino compounds such as methylguanidine and guanidinosuccinic acid were not found in any blood product under usual storage conditions. The levels of guanidinoacetic acid and creatinine in these products changed little during storage. On the other hand, the concentration of arginine decreased markedly over storage time and reached approximately 20% of the initial value after 7 days of storage. Addition of arginine at a final concentration of 1 mmol/l to the red cell concentrate resulted in better maintenance of the 2, 3-DPG level and morphology score of red cells. Moreover, arginine showed a protecting effect against hemolysis. These data indicate that adverse reactions due to guanidino compounds may be neglected in blood transfusion, and that arginine should be useful as a blood preservative.

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Mononuclear cells in gastric cancer lesions of 42 patients were immunohistologically classified into functional subpopulations using various antibodies such as OKT3, OKT4, OKT6, OKT8, OKT9, OKT10, OKIa1, OKM1, OKM5, OKB7, Leu7, Leu8, Leullb, DRC1, anti-IL-2 receptor, anti-S-100 protein antibody and anti-lisozyme antibody.
Most of these cells, which were T-cells, NK/K cells and IL-2 receptor positive cells in the early stage, were clearly greator in number when compared with the control group, but their numbers decreased as the disease stage progressed. In the histologically poorly differentiated type, there were fewer T-cells (mainly OKT4 positive cells). and in the scirrhous type, fewer NK/K cells were observed. On the other hand, in the higher grade of lymphocyte infiltration around cancer lesions, an increase in the number of NK/K cells and lymphfollicles with DRC1 positive cells was noted. When immunomodulator (OK-432) was locally injected into the tumor endoscopically, cells with IL-2 receptors, NK/K cells, dendritic reticulum cells and anti-S-100 protein antibody positive cells remarkedly increased.
This study indicated that the endoscopic injection of immunomodulators into gastric cancer might activate immunologically important cells which have anti-tumor effects. The method should be tried in the clinical field.

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Rats were administered chlordane emulsion orally, and changes in the liver function were studied. The levels of certain chemicals in the serum of chlordane wokers also were determined. The increase in the body weight of rats administered chlordane was suppressed compared to control rats. Liver weights of rats administered chlordane were significantly (p<0.01) greater than those of control rats. Levels of moisture, total lipid, triglycerides and phospholipid per gram liver of rats administered chlordane were significantly (p<0.05) higher than those of control rats. Levels of lipid peroxide of rats administered chlordane were significantly (p<0.05) higher than those of control rats, and increased according to increases in the amount of chlordane administered. Levers of DNP-stimulated ATPase activity in the liver mitochondria of rats administered chlordane were lower than those of control rats. State 4 respiration in the mitochondria of rats administered chlordane was greater than those of control rats. State 3 respiration was the same in both groups. As a result, the respiratory control index (RCI) of administered rats was lower than those of control rats. Levels of triglycerides, total cholesterol and γ-GTP activity in the serum of rats administered chlordane were significantly (p<0.05) higher than those of control rats. Levels of blood suger of rats administered chlordane were significantly (p<0.05) lower than those of control rats. Levels of total cholesterol, triglycerides, activity of CPK and LDH of several tested chlordane wokers were higher than the upper limit of normal persons.

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Since Bast et. al. reported that patients with ovarian carcinoma had elevated levels of CA125 in serum, the attention has been paid to CA125 in serum as a tumor maker.
Serum CA125 levels in 88 patients with gynecological disease were measured. Among 15 patients with malignant ovarian tumor, CA125 values were above 35 U/ml in 80%, and above 65 U/ml in 73%, of serum samples assayed. By increasing the values of CA125 considered normal from 35 to 65 U/ml, the positive rate of benign ovarian tumor and carcinoma of the uterus was markedly reduced. Therefore, it was more efficient as a screening test for gynecological disease that the value of CA125 considered abnormal be above 65 U/ml. Serum CA125 levels were correlated with efficacy of therapy and the clinical course.

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Both protection and sensitization of E. coli NIHJ and C 57 BL mice against ⁶⁰Co γ-rays by sulfur-containing amino acid derivatives (S-alkyl-L-cysteines, S-alkyl-2-methyl-DL-cysteines and their hydantoin derivatives, and sulfoxides of these compounds) were examined. E. coli cells (10⁶/ml) in 20 mM aqueous solution of the sulfur compounds was irradiated with 60 Gy (6 krad) of γ-rays. Mice (5-week-old males) were subjected to 7.5 Gy (750 rad) of γ-rays after a single intraperitoneal injection of 0.75m mol/kg body weight of each compound.
In the case of E. coli, S-alkyl compounds were more effective than S-propyl ones for protection, and sulfoxide amino acids exhibited a radiosensitization effect. The replacement of the α-hydrogen of S-substituted cysteines by methyl groups decreased the radioprotective effect. On the other hand, the hydantoin derivatives, such as DL-5-allylthiomethyl-hydantoin, were much more radioprotective than the original amino acids. In mice, DL-5-allylthiomethyl-5-methlhydantoin and DL-5-n-propylthiomethylhydantoin (0.75 m mole/kg) had a remarkable radioprotective effect. The survival ratios were 6.33 and 6.67, or the dose reduction factors (DRF) were 1.41 and 1.53, respectively. On the other hand, DL-5-allylthiomethyl-5-methylhydantoin sulfoxide had a radiosentizing effect: survival ratio, 0.333; DRF, 0.517.

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In order to clarify the pathogenesis of peptic ulcers and erosions in patients with liver cirrhosis (LC), I studied concentrations of antral mucosal gastrin (Ant-Ga) and somatostatin (Ant-St), and gastric mucosal blood flow (MBF) in patients with LC. Furthermore, using rats with chronic liver damage induced by carbon tetrachloride, I studied gastric acidity, pepsin activity, serum gastrin (Se-Ga), Ant-Ga and Ant-St concentrations, and MBF.
Of 155 patients with LC, peptic ulcers or erosions were observed in 121 patients (78.1%). Ant-Ga was significantly raised in the LC patients without mucosal lesions compared to the LC patients with mucosal lesions and in control patients without liver cirrhosis. MBF was significantly lower in the LC patients compared to the control patients.
In the rats with carbon tetrachloride injured livers, gastric acidity, pepsin activity, Ant-St and MBF were significantly lower than in control rats with intact livers. In contrast, Se-Ga and Ant-Ga in the rats with the injured livers were significantly higher than those in the control rats.
These results suggest that impairment of the defensive factor represented by MBF rather than the aggressive factor represented by the gastrin level, gastric acidity and pepsin activity play an important role in the pathogenesis of the gastric mucosal lesions in LC.

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Morphological changes of basophil granulocytes from 5 atopic asthmatics after addition of specific antigen (house dust) were observed with a phase-contrast microscope. The motility of basophils from atopic asthmatics was less active than that of basophils from healthy subjects. The motility of basophils from healthy subjects did not change after the addition of antigen. On the other hand, the motility of basophils from atopic asthmatics significantly increased after addition of antigen, and some basophils showed degranulation. Basophils with oriented movement resembling that of neutrophils (A₂ type) characteristically appeared in atopic asthmatics after addition of antigen. No degranulation was observed in basophils from healthy subjects. Basophils showed a decrease in motility before becoming swollen, at which time the incidence of A₃ type basophils, with movement resembling that of monocytes, characteristically increased. Swollen basophils (B from) were stained variously from poor to well by toluidine blue. The mean diameter of basophils was larger among the poorly stained cells than among the well stained cells.

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Morphological changes, i.e., increased motility and degranulation, of basophils of 5 atopic asthmatics after antigen stimulation were observed in differenctial-interference microscopic motion pictures. Among basophil granulocytes with increased motility and without degranulation after antigen stimulation, the incidence of A₁ type basophils, which showed random movement, and A₂ type basophils, which showed oriented movement, clearly increased during the 15-min. microscopic observation. Among basophil granulocytes with degranulation after addition of antigen, the incidence of A₁ type basophils slightly increased, and A₃ type basophils, which are a pre-swollen cell, characteristically appeared before degranulation. No A₂ type basophils were observed for 15 min.

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The functional and morphological changes in the left ventricle were assessed in 43 patients with mitral stenosis (MS) using echocardiography. The MS patient group consisted of 24 patients with sinus rhythm and 23 with atrial fibrillation. The cardiac functions of the patients were from I to III according to the New York Heart Association (NYHA) classification. The control group included 14 normal subjects and 3 with lone atrial fibrillation. The left ventricular ejection fractions (EF) at rest and in response to a bicycle ergometer (10 watts for 3 min) were examined by echocardiography. Comparison of the EF by echocardiography to the index by radionuclide angiography proved the efficacy of echocardiography for estimating LV function in patients with MS. Morphological changes in the left ventricle were caused by submitral lesions. These changes were quantitatively represented by a deformity ratio (DR). The EF at rest in the MS patients with atrial fibrillation was lower than in the remaining groups, and the MS patients with sinus rhythm showed an EF similar to that of normal subjects and lone atrial fibrillation patients. Some of the MS patients with atrial fibrillation had a higher EF while others had a lower EF. After exercise, the EF of the MS patients with sinus rhythm, who had NYHA class III cardiac function, decreased due to reduction of left ventricular end-diastolic dimension (LVDd) caused by an increased heart rate (HR) and total peripheral resistance (TPR). EFs of the remaining subjects were augmented after exercise. The relationships between the resting EF and other hemodynamic parameters measured were investigated to verify which factors influence left ventricular function in MS patients. There were no significant relationships between EF and mitral valve area (MVA), LVDd, HR or TPR. However, the DR closely correlated to the EF with a correlation coefficient of -0.75. Surgical treatment of the mitral valve improved both the cardiac function as to the NYHA class and the EF at rest, along with significant recovery of the DR. The percent change in the EF varied inversely with that in the DR (correlation coefficient, -0.57). Response of the EF to exercise was also improved after surgery. Therefore, it is concluded that left ventricular deformities of patients with MS induced by subvalvular lesion limits the left ventricular function and causes a lower EF.

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