The SH-dependent proteases (I and II) responsible for the development of Arthus hypersensitivity reaction were extracted in the euglobulin fraction of the skin lesions, and highly purified by column chromatography using Sephadex G-50, DEAE-Sephadex A-50 and GE-cellulose in this order. They behaved each as an almost homogeneous substance on electrophoresis. The optimum pH of these proteases was 7.1, which was a pH value adequate for their action in the Arthus skin site. They were different from cathepsins D and E. Intradermal injections of these SH-dependent proteases (I and II) induced rapid development of local cutaneous lesions similar to those of the Arthus skin lesions in both gross and microscopic features. On the other hand, another SH-independent protease was also isolated from the Arthus skin lesions, but it was ineffective in causing inflammatory reaction on experimental injection; this SH-independent protease may not play a significant part for the development of Arthus reaction.
The specific inhibitor of SH-dependent skin protease responsible for the development of Arthus-type inflammation was isolated from the skin site and highly purified by chromatography. The gradual cessation of the inflammatory process was associated with a local increase of the inhibitor. The inhibitor (polypeptide) behaved as a homogeneous substance in electrophoresis and ultra-centrifugation. The constituent amino-acids of the polypeptide were as follows: Cys, Met, Asp, Thr, Ser, Glu, Pro, Ala, Gly, Val, Len, Ileu, Phe, Lys, His, Arg and HO-pro. The labeled amino-acids (35S-methionine or 35S-cystine) given intravenously were incorporated into the inhibitor; approximately 87 per cent of radioactivity in the hydrolysed inhibitor was found in methionine and approximately 13 per cent in cystine. The observations suggested possible synthesis of this inhibitor in the inflamed skin site.
Hyperpolarization by the vagus stimulation of the quiescent sinus of bullfrog's heart was recorded. The slope and magnitude of hyperpolarization varied with the pattern of vagal impulses. The hyperpolarization became larger with increase in the number of shocks, but after the magnitude of hyperpolarization attained its maximum the potential fell slowly toward the initial level during the stimulation. The optimal interval for the slope and magnitude of hyper-polarization was about 50 to 100 msec. Outside these intervals, the slope and magnitude of hyperpolarization were slow and small. Secondly, the electrogram was recorded from the tortoise's heart and the relation between the pattern of vagus stimulation and the quiescent period after the stimulation was investigated, and similar results were obtained. Of course, the phenomenon of escape occurred on continued vagus stimulation. The results were explained on the assumption of accumulation of the transmitter, its diffusion or destruction and the failure of nervous impulses, but the reduction of potential as well as the vagus escape in the later period of stimulation were interpreted as suggesting a development of the desensitization to the transmitter. Moreover, delayed response, change of firing potential, shift of pacemaker and rebound excitation were described.
Pulmonary vagotonia is regarded as the fundamental cause of asthma, both allergic and non-allergic. It is heightened by hyperactivity of both the carotid body and carotid sinus reflexes. Although this hyperactivity is usually reversible in most cases of asthma, it is irreversible in some intractable cases. The irrever-sibility of both hyperactive reflexes that may be proved by the NaCN-test and pressure upon the carotid sinus provides a reliable criterion for the utility of glomectomy and/or carotid sinus denervation. Since the pulmonary vagotonia is usually too stubborn to be eradicated merely by such surgery, much cannot be expected therefrom. Therefore, surgical treatments are indicated only in such intractable cases where the disease has resisted all the internal treatments excepting the use of corticosteroid. To make the effect of surgery last long and to further improve the disease or to treat unimproved patients, non-specific treatment such as mechanical or inflammatory stimulation to the skin is recommendable because it usually improves effectively the pulmonary vagotonia. Even when asthmatic attacks have disappeared completely after the surgery, the rubbing of the whole body surface should be practiced until the effectiveness of the treat-ment can be established.
Rural children were administered riboflavin, pyridoxine and other vitamins in various combination in an attempt to determine whether the urinary excre-tion of 17-ketosteroid and 17-hydroxy corticoid would reflect the administration of these vitamins. In addition, tryptophan-load-test was conducted to investigate the effect of vitamin other than pyridoxine on the metabolism of tryptophan. The result was that the urinary pattern of 17-hydroxy corticoid was improved significantly, and xanthurenic acid excretion was decreased remarkably after sup-plementation of not only pyridoxine but also of riboflavin. From the data pre-sented here it seems that some of the children were deficient in riboflavin and pyridoxine, and this may cause stresses to and disorder of tryptophan metabo-lism among them.
Experiments were performed on 9 conscious and 5 anesthetized dogs. The animal was immobilized by strapping supine or prone to the animal table for 60 minutes. The adrenal venous blood was collected before, during and after the period of immobilization and was analyzed for 17-hydroxycorticosteroids (17-OHCS). The adrenal 17-OHCS secretion rate in conscious dogs before immobiliza-tion was 0.02-0.21μg/kg/min. In most cases it increased markedly during the immobilization period and reached 0.81-1.80μg/kg/min. This increase was attributable to elevated 17-OHCS concentration of adrenal venous blood. The 17-OHCS secretion rate in dogs anesthetized with sodium pentobarbital did not show any definite change during and after the immobilization period.
The relationship between radiation effect and fraction number was studied in a case of metastatic lung cancer. Three radiotherapeutic fields were taken from multiple pulmonary metastatic foci of squamous-cell carcinoma from the lower jaw. The same total dose was given to each field with the same over-all time, but with three different daily doses. In each radiation field several nodular shadows of metastases were contained, one of which was measured for diameter periodically. Radiation effects were summarized in the formula: log Rn/Ro=(α/t-β)T Where Ro is the tumor size before treatment, Rn is that after irradiation, t the interval of time between fractions, T the over-all time, and α and β constants related to the daily dose.
A case of intrahepatic cholestasis with mental and growth retardation, which was considered to be familial, was presented. The jaundice appeared at the age of 6 months, being preceded by marked steatorrhea, and persisted throughout his life with fluctuation. He died of acute pneumonia after a laparotomy at 2 years 6 months. The patient had marked itching and steatorrhea which were probably manifestations of bile salt retention, acholic stools, and short stubby hands and foots with thickened and brownish skin. Biochemical characteristics of the serum were hyperbilirubinemia (over half being conjugated), moderately elevated alkaline phosphatase, slightly elevated GOT and GPT activities and α2- and β-globulins, and normal to subnormal cholesterol. There were also marked retention of B.S.P., presence of bilirubin in the urine and decreased fecal excretion of bilirubin and bile salts. Analysis of bile salts in the serum indicated an increase of cholic acid. Normal intra- and extrahepatic biliary passage was confirmed at operation and at autopsy. Light microscopic examination of the liver revealed periportal fibrosis and bile thrombi in the bile canaliculi, and electron microscopic examination of the liver revealed distortion of mitochondrial limiting membrane, dilatation of the bile canaliculi, blunted and diminished microvilli of the canalicular membrane and existence of a number of encapsulated bodies with a speckled appearance of obscure origin. These conditions of our patient are considered to be similar to those of patients, which have been recently reported by Clayton et al. (1965), Gray et al. (1966) and Juberg et al. (1966), except for some minor differences.
Specific monoclonal immunoglobulins (Igs) were purified from myeloma sera and urines, and the proteins were submitted to physicochemical treatments including ultrasonic irradiation, heat aggregation and reduction by mercaptoethanol. By using these protein preparations, their inhibitory effects upon the agglutination of anti-D sensitized erythrocytes with anti-globulin serum (anti-globulin reaction) were investigated. Some of the monoclonal IgGs were found to exert no inhibitory action and were not fixed onto cells. Monoclonal Igs other than IgG did not inhibit the anti-globulin reaction (AGR). Neither ultrasonic irradiation nor heat aggregation altered the inhibitory activity of monoclonal IgG, whereas a little loss of inhibitory activity was observed in cases of reduction of IgG. These results clearly indicate that the anti-D antibody is of the IgG type. Neuraminidase treatment of erythrocytes and the presence of red cell stromal substance (RCSS) in the reaction mixture disturbed the inhibitory activity of IgG. High contents of carbohydrates were observed in IgGs having the inhibitory action, but no significant difference in amino acid composition was observed among IgGs with or without the inhibitory activity.
The postural effect of lateral decubitus position on the distribution of pulmonary arterial blood flow was assessed in 9 normal subjects and 31 patients with pulmonary tuberculosis by radioisotope perfusion scanning of the lungs. The perfusion of the dependent lung was larger than that of the supine lung with out exception. In both normal and tuberculous subjects, the average overall ratio of the pulmonary arterial blood flow in the dependent lung was 1.1 to 1.2 times that of the supine lung in any of the right and left lateral decubitus positions, and this was assumed to be due to gravitational effect. It was clarified that the increase in oxygen uptake in the dependent lung so far reported by many investigators was due to increased distribution of the pulmonary arterial blood flow which was related to gravitational effect.