A novel mutation in the SLCO2A1 gene, encoding a prostaglandin transporter, induces chronic enteropathy.

Chronic enteropathy associated with SLCO2A1 gene (CEAS) is caused by loss-of-function mutations in SLCO2A1, which encodes a prostaglandin (PG) transporter. In this study, we report a sibling case of CEAS with a novel pathogenic variant of the SLCO2A1 gene. Compound heterozygous variants in SLCO2A1 were identified in an 8-year-old boy and 12-year-old girl, and multiple chronic nonspecific ulcers were observed in the patients using capsule endoscopy. The splice site mutation (c.940 + 1G>A) of the paternal allele was previously reported to be pathogenic, whereas the missense variant (c.1688T>C) of the maternal allele was novel and had not yet been reported. The affected residue (p.Leu563Pro) is located in the 11th transmembrane domain (helix 11) of SLCO2A1. Because SLCO2A1 mediates the uptake and clearance of PGs, the urinary PG metabolites were measured by liquid chromatography coupled to tandem mass spectrometry. The urinary tetranor-prostaglandin E metabolite levels in the patients were significantly higher than those in unaffected individuals. We established cell lines with doxycycline-inducible expression of wild type SLCO2A1 (WT-SLCO2A1) and the L563P mutant. Immunofluorescence staining showed that WT-SLCO2A1 and the L563P mutant were dominantly expressed on the plasma membranes of these cells. Cells expressing WT-SLCO2A1 exhibited time- and dose-dependent uptake of PGE2, while the mutant did not show any uptake activity. Residue L563 is very close to the putative substrate-binding site in SLCO2A1, R561 in helix 11. However, in a molecular model of SLCO2A1, the side chain of L563 projected outside of helix 11, indicating that L563 is likely not directly involved in substrate binding. Instead, the substitution of Pro may twist the helix and impair the transporter function. In summary, we identified a novel pathogenic variant of SLCO2A1 that caused loss-of-function and induced CEAS.

Diagnostic accuracy of urine-based kits for detection of Helicobacter pylori antibody in children.

BACKGROUND: Rapid urine-HpAb is reported to be a reliable test of Helicobacter pylori infection in adults, but there are no data on the application of the test in children. The aim of this study was to evaluate the accuracy of a urine-based enzyme-linked immunosorbent assay (urine-HpELISA) and immunochromatography (rapid urine-HpAb) kit for anti-H. pylori immunoglobulin G antibody in children. We compared its sensitivity and specificity in reference to the (13) C-urea-breath test (UBT) and H. pylori stool antigen test (HpSA). METHODS: In total, 101 Japanese children without significant upper-abdominal symptoms were included (mean age, 7.1 years; range 2-15 years). Their sensitivity and specificity were evaluated in reference to the UBT and HpSA. RESULTS: Thirty-seven children were judged H. pylori-positive and 64 negative by the UBT and HpSA. No discrepancy in the results was observed between UBT and HpSA. Urine-HpELISA showed 91.9% sensitivity and 96.9% specificity with an accuracy of 95.0%. Rapid urine-HpAb showed 78.4% sensitivity and 100% specificity with an accuracy of 92.1%. Seven false negative results for rapid urine-HpAb were from children aged younger than 10 years, and their antibody titers of urine-HpELISA were lower than true positives. CONCLUSIONS: For the diagnosis of H. pylori infection in Japanese children, both tests are non-invasive, inexpensive, reliable and easy-to-perform methods giving satisfactory accuracy, although the sensitivity of the rapid urine-HpAb kit was inferior to that of the urine-HpELISA kit, especially in children aged younger than 10 years, showing relatively low titer of H. pylori antibody.

Evaluation of urine sucrose concentration for detection of gastric ulcers in horses.

OBJECTIVE: To evaluate the use of sucrose permeability testing to detect ulcers in the gastric squamous mucosa of horses. ANIMALS: 13 adult horses ranging from 5 to 19 years of age. PROCEDURE: Following induction of gastric ulcers by intermittent feed deprivation, horses underwent sucrose permeability testing (administration of sucrose by nasogastric intubation followed by collection of urine at 2 and 4 hours after intubation) and gastric endoscopy. Squamous ulcers were assigned a severity score (range, 0 to 3) by use of an established scoring system. Horses were subsequently administered omeprazole for 21 days, and sucrose testing and endoscopy were repeated. Pair-wise comparisons of urine sucrose concentration were made between horses with induced ulcers before and after omeprazole treatment. Urine sucrose concentrations also were compared on the basis of ulcer severity score. RESULTS: Urine sucrose concentrations and ulcer severity scores were significantly higher in horses with induced ulcers before omeprazole treatment than after treatment. Urine sucrose concentrations were significantly higher for horses with ulcer severity scores > 1. Use of a cut-point value of 0.7 mg/mL revealed that the apparent sensitivity and specificity of sucrose permeability testing to detect ulcers with severity scores > 1 was 83% and 90%, respectively. Results were similar after adjusting sucrose concentrations for urine osmolality. CONCLUSIONS AND CLINICAL RELEVANCE: Urine sucrose concentration appears to be a reliable but imperfect indicator of gastric squamous ulcers in horses. Sucrose permeability testing may provide a simple, noninvasive test to detect and monitor gastric ulcers in horses.

Sucrose permeability as a means of detecting diseases of the upper digestive tract.

The healthy gastric epithelium will not allow easy permeation of a disaccharide-sized molecule such as sucrose. However, during gastric damage, intact sucrose can pass the gastric epithelium and ultimately appear in the urine. We examined the relationship between total urinary sucrose excretion and various diseases. We used 149 patients (105 had upper gastrointestinal disease, 12 had gastric cancer and 32 were normal). Subjects were given a solution containing 100 g sucrose in 450 c.c. water. All urine was collected for 7.5 h. The urinary sucrose concentration was determined by anion exchange high-performance liquid chromatography. Total urinary sucrose excretion was significantly higher in patients with gastric ulcer and those with gastric cancer than in endoscopically normal controls. In the 34 patients with gastric ulcer, the total sucrose excretion was closely correlated with ulcer size. Ulcer location did not affect urinary sucrose excretion. A strong correlation was also observed between sucrose excretion and lesion size in the 12 patients with gastric cancer. The sucrose permeability test may be a relatively sensitive method to detect gastric disease.

The clinical significance of u-FCC, an antigen of anti-fucosylceramide antibody found in urine, in patients with gastric and colorectal carcinoma.

BACKGROUND: It has already been shown that the production of fucosylceramide, an aberrant glycolipid, is associated with neoplastic changes in human tissues. The authors of this study designed a sandwich radioimmunoassay (RIA) using a mouse monoclonal anti-fucosylceramide antibody, PC47H, designated as PC/PC RIA, and measured the level of u-FCC, an antigen of PC47H, in the urine of cancer patients. METHODS: The cohort comprised 41 patients with gastric carcinoma, 35 with colorectal carcinoma, 34 with other malignancies, 14 with cholelithiasis, 18 with gastric ulcer, and 110 healthy individuals. The u-FCC was quantified by PC/PC RIA. The cutoff value of u-FCC was obtained from the 110 healthy individuals, and the rates of positivity for gastric and colorectal carcinoma patients were evaluated. RESULTS: The rates of u-FCC positivity were 63% for patients with gastric carcinoma and 69% for colorectal carcinoma patients. The rate was only 1% (1/110) for the healthy individuals. The u-FCC value did not correlate with the values of either CA 19-9 or carcinoembryonic antigen (CEA). In a combination assay of u-FCC with CA 19-9 and CEA, the positivity rates were 84% for gastric carcinoma patients and 85% for colorectal carcinoma patients. CONCLUSIONS: Gastric and colorectal carcinoma patients have significantly high levels of u-FCC in their urine compared with normal individuals.

[Level of certain carbohydrate components in blood serum and urine of patients stomach and duodenal ulcer patients in the late post-vagotomy period]. / Soderzhanie nekotorykh uglevodnykh komponentov v syvorotke krovi i moche bol'nykh v otdalennye sroki posle vagotomii pri iazvennoi bolezni zheludka i dvenadtsatiperstnoi kishki.

Estimation of protein-bound hexoses, fucose and sialic acids in the blood and urine of 64 patients with gastroduodenal ulcers within later periods after various types of gastric vagotomy showed that the denervation inhibited the protective barrier of gastric and duodenal mucosal membrane. Protective functions of gastroduodenal mucosal membrane were most distinctly inhibited after selective proximal vagotomy which may be responsible for higher amounts of recurrences of ulcerous disease after this type of vagotomy than other types of denervation.

[The determination of the concentration of antithrombin III in the urine]. / Opredelenie kontsentratsii antitrombina III v moche.

The authors developed the special enzyme immunoassay technique for the detection of the urinary antitrombin III (AT-III) levels. Sensitivity of the method was 7.8 ng/ml. The study lasted for 2 hrs. The levels of AT-III were studied in the circadian human urine in health, in physiological and nephropathy-complicated pregnancy, as well as in patients with gastroduodenal ulcer-induced bleeding. There was a 34.1-fold increase in the urinary AT-III levels in pregnant females with Stages II-III nephropathy and a 17.3-fold increase in those who sustained the resection of the stomach, which could be explained by proteinuria and abnormal resorption of AT-III in the proximal tubules of the kidney.

[Elimination of glycosaminoglycans in duodenal peptic ulcer and problems of its pathogenesis]. / Vydelenie glikozaminoglikanov pri iazvennoi bolezni dvenadtsatiperstnoi kishki i nekotorye voprosy ee patogeneza.

Changes in the excretion and composition of proteoglycans specific for duodenal ulcer were studied in 50 patients with duodenal ulcer, 30 patients with gastric ulcer, 30 patients with chronic endogenous gastroduodenitis and in 35 healthy persons. In all the examinees proteoglycans were isolated from daily urine, their carbohydrate components--glycosaminoglycans (GAG)--were separated and divided into fractions (keratan sulfate, hyaluronic acid, heparan sulfate, chondroitin sulfate-4, chondroitin sulfate-6, dermatan sulfate, and heparin) by column chromatography on unmodified cellulose. It has been established that only peptic ulcer is characterized by disorders in GAG excretion differing in the period of exacerbation and remission. Changes in the composition of proteoglycans excreted with urine resulted probably from a deficiency of chondroitin sulfate-6 in patients with chronic duodenal ulcer. The deficiency was more marked during exacerbation but did not disappear in the period of remission of duodenal ulcer either.

[Various characteristics of the urinary excretion of glycosaminoglycans in patients with peptic ulcer, chronic duodenal ulcer and in their relatives]. / Nekotorye osobennosti vydeleniia glikozaminoglikanov u bol'nykh iazvennoi bolezn'iu, s khronicheskoi duodenal'noi iazvoi i ikh rodstvennikov.

The authors describe the results of studying secretion of glycosaminoglycans (GAG) with urine in 82 patients with peptic ulcer, 30 relatives and in 30 normal subjects with nonaggravated heredity. Patients with chronic duodenal ulcer during exacerbation and their normal relatives showed an essential reduction in the magnitude of the above indicator (1.6- and 1.8-fold, respectively, P less than 0.001) at the expense of a decrease in secretion of chondroitinsulfates (CDS) (2.4- and 2.1-fold, respectively, P less than 0.001). In peptic ulcer of the stomach, such a phenomenon was not recorded. During a disease remission there was an increase in GAG secretion with urine, linked with hyperheparinuria (13.1-fold, P less than 0.001). The data obtained indicate that the genetically determined impairment of CDS synthesis may be among one of the mechanisms by which hereditary aggravation in peptic ulcer of the duodenum is mediated. Hyperproduction of heparin during a disease remission is likely to play the role of one of the components of the defense-adaptation reaction responsible for ulcer healing.

[Urinary glycosaminoglycans in peptic ulcer, chronic gastritis, and normal subjects]. / Glikozaminoglikany v moche bol'nykh iazvennoi bolezn'iu, khronicheskim gastritom i zdorovykh liudei.

Excretion of glycosaminoglycans with urine in patients with duodenal ulcer was lowered due to a distinct decrease in amount of chondroitin sulphates. If the ulcer was localized in stomach and in chronic gastritis the glycosaminoglycan excretion was near the normal level. During the acute period of duodenal ulcer chondroitin sulphate deficiency was compensated by an increased production of hyaluronic acid, while at the period of clinical remission a stimulation of heparin production was noted.

[L-DOPA test for evaluating in vivo catecholamine biosynthesis in normal persons and persons with different diseases]. / Proba s vvedeniem L-DOFA dlia otsenki in vivo biosinteza katekholaminov u cheloveka v norme i patologii.

Administration of 1-DOPA into healthy persons increased its excretion with urine and elevated the adrenaline secretion. The increase of catecholamines excretion was not observed in aged patients with hypertension; the data obtained suggest that the synthesis of catecholamines with utilization of DOPA was inhibited. In patients with ulcerous disease excretion of 1-DOPA was not increased after its administration, but secretion of catecholamines was decreased during the day time. Under ulcerous disease 1-DOPA appears to be used in process unrelated to synthesis of catecholamines.