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Uropepsinogen in human urine: its protein nature, activation and enzymatic properties of activated enzyme.

Uropepsinogen (UPG) in human urine was highly purified by chromatography on columns of DEAE-lignocellulose, elastin-celite, etc. The purified UPG was composed of two electrophoretically distinguishable components (UPG I and UPG II), and they were isolated in the pure state, respectively. UPG I and UPG II were the same in molecular weight (3.9 X 10(4)) and in N-terminal (leucine) and C-terminal (alanine) amino acid residues. Also, they were quite similar in amino acid composition. They were activated to uropepsin (UP I and UP II, molecular weight, 3.3 X 10(4), respectively), but the activated enzymes were the same in the various properties examined, suggesting that the difference between UPG I and UPG II is due to only a minor change in the peptide segment, perhaps by deamidation. The activation of UPG I and UPG II occurred at acid pHs, the best pH being at 2.0. Both the proenzymes previously incubated with pepstatin at pH 6.8, however, were not activated even in the following incubation at acid sides. The results obtained are discussed in regard to the origin of the proenzyme and its properties before and after activation.

Amino Acid Sequence↗

The kallikrein-kinin system in the kidney.

To understand the role of the kallikrein-kinin system in the kidney all components of the system and their localization need to be considered. About half the kallikrein in urine occurs as the proenzyme which arises in the distal tubule. Kinins are formed in the distal tubule and collecting duct from urokinnogen which is found throughout the tubule. Urine contains about twice as much lysyl-brandykinin as bradykinin. A third kinin, methionyl-lysyl-bradykinin, also can occur in urine. It is probably produced by uropepsin as the kinin is largely formed in acidified urine and its formation is inhibited by pepstatin. The significance of the three kinins is unknown. Kinins are normally slowly (few hours) destroyed in urine. The importance of kallikrein, urokinogen and kininases in regulating the level of kinins needs to be determined.

Adult↗

[Primary preventive medicine and laboratory medicine].

Nutrition plays an important role in the primary preventive medicine. In 1999, we have introduced the Dietary Reference Intakes (DRI) established by the National Academy of Sciences of U.S. into Recommended Dietary Allowances (RDAs) for the Japanese population. Where, reference intervals for the concentration of nutrient in blood are required in setting an Adequate Intakes (AI). For vitamins, also the AI is experimentally determined based on the reference intervals of healthy people, and the assessment of the nutritional status by laboratory investigations is an important part of preventive medicine. In 1997, we founded the Japan Committee for Vitamin Laboratory Standards and standardized whole blood vitamin B1 levels using HPLC method. Reference intervals for vitamin A, vitamin C and vitamin E might be presented in future report. We annually examined 15,000 participants in national nutrition survey. We proposed a use of results of this research for setting AI of vitamins. Genetic investigation should be introduced in future primary preventive medicine, and stress markers such as "biopyrrin" for oxidative stress, uropepsin, and urinary 17KS-S seems to be very important for medical examination.

Biomarkers↗

Systemic lupus erythematosus; results of treatment with triamcinolone.

Twenty-nine patients with systemic lupus erythematosus were treated with a new synthetic unsaturated prednisolone derivative, triamcinolone, for as long as 11 months. This hormone is 1.3 times as powerful as prednisone and 4.4 times more potent than hydrocortisone as an anti-inflammatory agent. The average dose for beginning therapy in cases of mild systemic lupus erythematosus was 20.6 mg. a day. The average maintenance dose used to control mild exacerbations of the disease was 26.0 mg. a day. There was no evidence of sodium retention or potassium loss. Sixteen patients had upper gastrointestinal x-ray studies before and during therapy with triamcinolone. There was no evidence of peptic ulceration except in one patient who was receiving 96 mg. a day. Nine patients had gastric analysis with histamine before and during therapy. No significant changes were noted in results of these tests, even in the patient who had an ulcer. No abnormal increase in uropepsin was noted in cases in which this factor was tested. The pattern of clinical improvement closely paralleled that obtained by previous treatment with older steroids. There was a disappearance of all the clinical and laboratory abnormalities produced by the disease, with the exception of long standing renal involvement. A major difference between triamcinolone and other steroids was a tendency to progressive gradual loss of weight, partly owing to fluid loss. Cushingoid appearance produced by other steroid therapy did not disappear. The cutaneous side effects, particularly Cushingoid appearance, hirsutism and striae were more pronounced than with older steroids. The most serious side effect was muscle weakness which appeared in six patients, all women, in from four to thirty-two weeks after starting triamcinolone. The profound muscle weakness, most pronounced in the quadriceps group, gradually cleared after several weeks of therapy with another steroid. Fourteen patients had received prior steroid therapy with all the older anti-inflammatory hormones and seven of them were better controlled and felt better with triamcinolone.

Anti-Inflammatory Agents↗

[Cellular and humoral immunity in duodenal peptic ulcer with gastrin cell hyperplasia].

A total of 61 patients with frequently relapsing duodenal ulcer were examined. Of these, 18 patients were in the acute phase and 43 experienced remission. Using 1 mm2 of the mucosa, measurements were made of the counts of duodenal and pyloric G-cells (by immunomorphologic assay), of the absolute and relative counts of T and B lymphocytes, the content of IgA, IgM and IgG, histamine and serotonin (by fluorometry) in the blood, and of the concentration of uropepsin in the urine. In the stages of exacerbation and remission, the patients suffering from duodenal ulcer with hyperplasia of G-cells manifested, as compared with the analogous patients without hyperplasia, a decrease of the absolute and relative counts of T cells, especially of those of B cells, combined with a rise of the content of IgM and IgG during exacerbation, followed by its returning to normal in the phase of remission. Over one year part of the duodenal ulcer patients with hyperplasia of G-cells received preventive treatment with ranitidine, which resulted in a tendency towards the lowering of the count of pyloric G-cells and the rise of the absolute and relative counts of T cells.

Adolescent↗

[Trypsin inhibitors in human urine (author's transl)].

By using ammonium sulfate, Arg-Sepharose and gel filtration, an urinary trypsin inhibitor (UTI) with molecular weight of 67,000 (UTI7) was isolated from normal human urine. The yield of UTI7 was about 3,200 U per liter of urine. When urine was acidified, an uropepsin-like substance was activated which caused molecular weight change of UTI7. New UTIs had molecular weight of 45,000 and 22,000 (UTI4-5 and UTI-2-2), respectively. These inhibitors showed a strong effect on trypsin, alpha--chymotrypsin and lesser extent on plasmin and elastase, but had no effect on esterolytic activity on thrombin and the first components of complement Cls an Clr.

Electrophoresis, Polyacrylamide Gel↗

[Secondary prevention of gastric cancer in a risk group of persons without gastric acid. 2nd communication (author's transl)].

More than 6,000 predominant unselected persons were examined by tubeless gastric acid test using the "Desmoidpille" and by simultaneous determination of uropepsin according to West et al. About 1,000 probands demonstrating a lacking acid secretion were recognized as risk group and taken into supervision over several years since 1972. In this risk group 20 cases of gastric cancer were detected, 9 of them already by first investigation. 5 gastric cancers were found during the follow-up as true early gastric cancers. In 5,200 probands without risk signs (normal acid test) only 6 cases of gastric cancer were observed during time of follow-up. So it is a high risk group indeed, we have selected. Regarding the casuistry of 7 persons, younger than 70 years of age, with gastric cancer detected during follow-up, 4 of them survived, such a dispensaire included in a general geriatric care seems useful to practice.

Aged↗

[Metabolic function characteristics and respiratory pathology of premature infants].

A total of 143 premature children of the first 3 months of life (the body weight upon birth 1200-2500 g) staying at a specialized hospital, and 28 children (the body weight upon birth 1100-2500 g) under 3 years staying at a pulmonological sanatorium were examined. Studies on enzymatic functions (uropepsin, glutathione, protease and lipase activity in the blood serum) revealed a decrease in adaptation processes in premature children with acute pneumonia, and during reconvalescence in children with hypotrophy. In premature neonates on formula feeding with a mixture of "Malyutka", the content of total lipids, cholesterol and phospholipids was lower than in children on natural feeding. The content of free fatty acids and acetone tended towards an increase during formula feeding. Pneumonia incidence in premature children was 4 times higher in the first year of life and 2 1/2-2 times higher in the second and third years of life, as compared to full-term babies. The respiratory diseases in premature children were followed by the asthmatic syndrome. The results obtained may be used for the development of dietetic management of premature children with pneumonia and hypotrophy.

Body Weight↗