Levels of renal bicarbonate threshold in response to oral administration of sodium bicarbonate were determined by analysis of urine samples from voluntary micturition in 30 cases including 8 normal subjects and 22 patients with various features of renal tubular acidosis. In the normal subjects, the lower limit of renal bicarbonate threshold was assessed as 25 mEq/liter. Levels lower than this limit were identified in 5 of 8 patients with multiple tubular dysfunction, all 3 with primary hyperparathyroidism, 1 with malabsorption syndrome, and 1 of 3 with pseudohypoparathyroidism. On the other hand, all 7 patients with distal renal tubular acidosis showed levels of renal bicarbonate threshold compatible with or higher than the control figure. It is concluded that this method of defining renal bicarbonate threshold is worthy of clinical application for distinguishing between Proximal and distal renal tubular acidosis.
The clinical significance of serum and urinary lysozyme estimation was evaluated in patients with hematologic and non-hematologic disorders. Markedly increased serum lysozyme ranging from 17.0 to 150.0 μ/ml with the mean of 48.1 μ/ml and profuse lysozymuria with the mean daily excretion of 938 mg were observed in monocytic leukemia. Slight to moderate increases of serum lysozyme were found in chronic myelocytic leukemia with the mean of 16.7 μ/ml and polycythemia vera with the mean of 15.1 μ/ml, and in the former disease lysozymuria was less marked, except for one excreting 110 mg per day, than that in monocytic leukemia. In cases of acute and chronic lymphocytic leukemias, lysozyme levels lower than normal serum levels were detected. With regard to lysozyme activity in reactive monocytosis, a case of miliary tuberculosis with pulmonary and hepatosplenic involvement was presented in which moderately elevated serum lysozyme and a large amount of lysozyme in urine to such an extent as suggestive of monocytic leukemia were found by serial estimations. Two other patients with miliary tuberculosis, who were undergoing chemotherapy, showed increased serum lysozyme activities. An additional case with possible diagnosis of cholecystitis exhibited peripheral monocytosis and greatly increased serum and urinary lysozyme concentrations. Such cases suggest that proliferation of monocytic cells, not only in leukemia but also in the rare conditions including prominent reactive monocytosis (3-5×1011 monocytes in the body), can cause marked increase of lysozyme when the amounts of lysozyme exceed the capacity to dispose the enzyme by catabolic mechanism. Pulmonary tuberculosis with varied degrees of disease activity did not cause an increase of lysozyme, while in patients with sarcoidosis elevated serum lysozyme activities were observed, indicating that total mass of monocytic cells were increased in the latter conditions. On the other hand, proliferation of lymphoid cells and reticuloendothelial cells resulted in no increase of lysozyme. Non-hematologic disorders such as hepatic, cardiac disorders and neoplasm except for renal disease caused no increase of lysozyme.
Serum and urinary lysozyme values were assayed in 51 patients with chronic glomerulonephritis and 10 undergoing regular hemodialysis. Renal threshold for lysozyme was in the range from 15 to 20 μ/ml, but no correlation was obtained between serum and urinary lysozyme concentrations. Significant correlations were found between serum lysozyme activities and commonly employed parameters of renal dysfunctions, such as blood urea nitrogen level (r=0.77), serum creatinine level (r=0.86), and creatinine clearance (r=-0.80). The majority of patients with markedly diminished glomerular filtration rates smaller than 20 ml/min exhibited urinary excretion of more than 3 mg of lysozyme per day and elevated serum lysozyme, while in patients with mildly to moderately impaired renal function, serum and urine lysozyme concentrations were within normal limits. Therefore, positive lysozymuria and increased serum lysozyme activity may be taken as evidence of severe renal damage, whereas the lysozyme determination may not serve as sensitive indicators in mildly to moderately injured renal diseases.
Experiments were designed to ascertain whether hyperlipemia produced by chronic alcohol intake would accelerate cholesterol-fed experimental atherosclerosis. Young male rabbits (134-139 days after birth) were kept on a diet containing cholesterol (0.5%) and lard (5%) and some of them were kept on 5% or 10% ethanol in drinking water for thirteen weeks. There was no significant difference in the increase of body weight and in diet intake. Plasma lipids levels were significantly higher in the ethanol-fed groups than in the control group kept on plain water. The atherosclerotic changes of the aorta, however, were significantly less in the ethanol-fed rabbits than in the controls and even less in the rabbits kept on 10% ethanol than in those on 5% ethanol. The results suggest that ethanol has an inhibitory effect on cholesterol-induced experimental atherosclerosis despite its hyperlipemic action.
The isolated right atrium of the dog was perfused with blood led from a support dog. The selective injection of dipyridamole into the sinus node artery at a dose of 1-10 μg induced a slight negative chronotropic and positive inotropic effect. The administration of 0.3-10 μg of adenosine caused a negative chronotropic and inotropic effect. The effects induced by adenosine were potentiated by a single injection or a continuous infusion of dipyridamole usually in the duration of adenosine action and frequently in the maximum decreases of the atrial rate and developed tension.
Previously a chemotactic factor similar to an inflammatory factor (leucoegresin) was produced in vitro from natural IgG of man and rabbit by a neutral SH-dependent protease from inflammatory tissue. The enzyme induced a similar chemotactic generation of IgG subclasses of man and rabbit. The generation of chemotactic substance was more pronounced from human IgG2 and IgG4 or rabbit fast-moving IgG than from human IgG1 and IgG3 or rabbit slow-moving IgG. The results suggested that the enzyme activity was influenced by some particular structural specificity of IgG molecules.
Cyclophosphamide-cytochrome P-450 difference spectrum in microsomes from the rat liver was of type 1. The shape of the difference spectrum indicates that cyclophosphamide is bound to microsomal hemeprotein (P-450). In the in vivo experiments, blood concentra-tions of cyclophosphamide after intraperitoneal administration to rats pretreated with phenobarbital or chloramphenicol were measured. It was found J that the blood levels of the active metabolites of cyclophosphamide (normustard-like substances) in rats pretreated with phenobarbital were higher than those in normal controls, and that those in rats pretreated with chloramphenicol were lower than those in normal controls. Moreover, the levels of microsomal cyto-chrome P-450 in rat liver treated with phenobarbital or with chloramphenicol were almost in parallel with the blood levels of normustard-like substances. The above data suggest that, in the chemotherapy with anti-cancer drugs, inductive or inhibitory effect of the drugs on microsomal drug-metabolizing enzymes should be taken into consideration.
Metabolic and endocrinologic effects of circulating maltose in diabetic states were studied. Six normal subjects, eight diabetic patients, and five mild ketoacidotic diabetic patients were given an intravenous infusion of 300 ml of 10% maltose over a 30-min period. The mean fasting blood glucose concentration in the ketoaci-dotic diabetic patients was 251±28 mg/100 ml, and this value was little affected by intravenous maltose administration, though an indefinite nadir of 242±18 mg/100 ml was attained at 120 min after the start of infusion. In contrast, maltose infusion produced a 53% increase in blood glucose over the basal level in the normal subjects. Maltose did not enhance insulin concentration of peripheral blood in the normal subjects despite such a significant increase in blood glucose. In diabetic and mild ketoacidotic diabetic patients, plasma insulin also remained unaltered after maltose infusion. In response to maltose, plasma FFA concentration was reduced by the following percentages at 30 min after infusion as compared with values in the basal state: -43% in normal subjects, -31% in diabetic patients, and -43% in mild ketoacidotic diabetic patients. Maltose infusion produced no change in blood acetone in diabetic patients. Similar metabolic effects of maltose were observed when 10% maltose solution was infused into alloxan diabetic rabbits at a rate of 0.2 ml/min over a 120-min period. These results indicate that intravenous maltose administration may be beneficial for the treatment of diabetes mellitus, since maltose is utilized by the patients in the insulin deficient state without any remarkable rise in blood glucose concentration.
Complex carbohydrate fraction (E-Fr) was extracted with 40% aqueous EDTA (pH 7.4) from the acetone-dried bone powders of rabbit femur. E-Fr was separated into five fractions, CPC-S Fr, 0.3 M Fr, 0.5 M Fr, 0.75 M Fr and 1.0 M Fr by the successive chromatography on a CM-Sephadex C-25 column and a CPC (cetylpyri-dinium chloride)-cellulose column. Subsequently, CPC-S Fr was purified by the chromatography on a DEAE-Sephadex A-50 column. The resulting major fraction (CPC-S-M) was identified as a sulfated glycoprotein-like substance carrying a small amount of chondroitin sulfate A. On the other hand, 0.75 M Fr and 1.0 M Fr were purified separately by the rechromatography on a CPC-cellulose column. The purified preparations of 0.75 M Fr and 1.0 M Fr were identified as a glycoprotein-bound chondroitin sulfate A and protein-free chondroitin sulfate A, respectively.
The sequence of antigen accumulation in the lung of mice infected intraperitoneally with PR8 strain of influenza virus was pursued by means of immunofluorescent (IF) staining. Influenza infection following intraperitoneal inoculation will be characterized by the fact that only when a large inoculum of virus was injected, around 50% of mice succumbed to generalized pneumonitis 6 days after infection. In such infections, virus growth in the lung reached a maximum at 3 days following virus inoculation, and at this stage, pathological features of mouse lung were comparable to those after intranasal instillation. However, initial spread of virus in the lung was found to be different from that after intranasal inoculation. IF was detected as early as 30 min in reticular cells locating along the lymphsinus of parabronchial lymph nodes, and this IF diminished at 24 hr. Since then, the infection spread through alveolar sac and IF was detectable in both type A and B alveolar cells. Ascending mode of infection through bronchioles was then detected from 24 hr and the intensity of IF in the epithelial cells along bronchial lining reached maximum at 120 hr.
The effects of dibutyryl cyclic AMP (D-cAMP) on the carbohydrate and lipid metabolism were studied in dogs. D-cAMP caused a marked elevation in the blood levels of glucose, lactate and pyruvate in association with a decrease in the level of non-esterified fatty acids. These findings indicate that D-cAMP causes an acceleration of glycogenolysis and a reduction of lipolysis. Although excess lactate and L/P did not show significant changes, it should be considered that there may be a possibility of lactic acidosis with the administration of D-cAMP under certain conditions such as tissue hypoxia or liver function disturbance.
In patients of male sterility, plasma levels of FSH, LH and testosterone were measured before and after ejaculation. The differences in plasma levels of such sex hormones identified respectively in the two states were generally insignificant, indicating no particular effect of ejaculation on plasma sex hormones even in such patients.