Dihydropyrimidinuria without clinical symptoms.
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Biomedical subjects
Publications and source records attributed to S Sumi.
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We studied the possible role of endogenous gastrin in the regenerating pancreas. Male Wistar rats underwent sham operation or 90% partial pancreatectomy (Px). Lansoprazole (30 mg/kg body wt), a proton pump inhibitor (PPI), was given p.o. for 3 weeks after surgery. Plasma glucose levels were higher in Px rats than in shams. Lansoprazole lowered plasma glucose levels in the Px rats. In addition, integrated insulin secretion during an oral glucose tolerance test (2 g/kg body wt) was significantly (p < 0.01) higher in lansoprazole-treated Px rats than in control Px rats, while lansoprazole did not affect insulin secretion in shams. Fasting serum gastrin levels were higher (p < 0.01) in lansoprazole-treated animals than in controls both in sham rats and in Px rats. Furthermore, lansoprazole increased the pancreas weight per body weight and elevated the insulin content of the pancreas in Px rats. These results suggest that endogenous hypergastrinemia has a trophic effect on endocrine pancreas during regenerating processes and that administration of PPI may be clinically beneficial to the remnant pancreas after pancreatectomy if the whole stomach is preserved.
The authors evaluated magnetic resonance (MR) angiography of the portal vein performed with a breath-hold, gadolinium-enhanced, magnetization-prepared rapid acquisition gradient-echo sequence in five volunteers and 24 patients. The main portal vein and its branches and the liver were depicted clearly in all images. The hepatic vein was clearly depicted in 21 of the 24 patients. MR angiography performed with this sequence allowed high-quality imaging of the portal and hepatic veins.
OBJECTIVE: Breath-hold MR urography using half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences was evaluated as a noninvasive alternative to excretory urography in healthy volunteers and in patients with disorders of the urinary tract. SUBJECTS AND METHODS: Twenty healthy volunteers and 45 patients with disorders of the urinary tract underwent HASTE MR urography on a 1.5-T MR imaging unit. Imaging time was 2 sec for single-thick-slice (20- to 60-mm slice thickness) technique and 10-18 sec for multislice technique. In the latter, images were postprocessed with maximum-intensity-projection technique and visualized in an arbitrary plane. Obstruction and its level were determined solely by excretory urography in eight patients, by excretory urography with other imaging techniques (CT, retrograde pyelography, or sonography) in 27 patients, and by sonography alone in the 20 normal volunteers, seven pregnant women, and three patients who were allergic to iodinated contrast media. We evaluated whether HASTE MR urograms showed obstruction, showed the level of obstruction, and showed the cause of obstruction. RESULTS: In all 20 healthy volunteers and all 45 patients, the upper, middle, and lower group of renal calices and the pelvis were clearly revealed by HASTE MR urography. In patients whose urinary tracts were seen on excretory urography (n = 31), the accuracy of HASTE MR urography in revealing urinary tract dilatation and level of obstruction completely correlated with that of excretory urography, although functional information about the obstructed collecting system was not obtained. However, MR urography revealed nonfunctioning urinary tracts that were invisible on excretory urography (n = 6). In patients with extrinsic obstruction (n = 27), MR urography also revealed the obstructing lesions. Small stones within the ureter were more clearly seen on single-shot or source images. With HASTE MR urography, hydronephrosis in pregnant women (n = 7) was clearly shown. CONCLUSION: HASTE MR urography can be used as an alternative to excretory urography to obtain high-quality images of the dilated urinary tract and adjacent abnormalities. HASTE MR urography allows rapid acquisition of images, thus overcoming the drawbacks of earlier MR urography techniques.
To study immunorecognition of free type and complex type prostate-specific antigen (PSA) by current commercial PSA assays, sera from 3 patients with stage D2 prostate cancer were separated by Sephacryl S-200 chromatography and determined by Delfia PSA, ACS-PSA and Eiken PA kits. Two antibodies used in the 3 kits are 2 monoclonal, 1 monoclonal and 1 polyclonal and 2 polyclonal antibodies, respectively. Following chromatography, two PSA peaks were obtained in all patients. One was about 100 kDa and the other about 30 kDa. The former was considered to be the complex type PSA (complex with alpha-1 antichymotrypsin) and the latter to be free type PSA. As to free type PSA, the ACS-PSA kit and Eiken PA kit quantitated PSA values approximately 5.1 and 2.5 times higher than the Delfia PSA kit. For complex type PSA, the quantity determined by ACS-PSA kit was approximately 1.3 times higher than that determined by the Delfia PSA kit, while the quantity determined by the Eiken PA kit was about one third of that determined by Delfia PSA kit. The ratio of complex type PSA to total PSA (free type PSA + complex type PSA) was 74.8 +/- 14.9% (mean +/- SD) when determined by Delfia PSA kit, 59.3 +/- 18.4% by ACS-PSA kit and 52.9 +/- 13.8% by Eiken PA kit. The range of this ratio determined by ACS-PSA kit was from 47.3% to 80.5% in the 3 patients. These findings suggest that there are qualitative differences in immunorecognition of free type PSA and complex type PSA among current commercial PSA assays and that there are quantitative differences in the ratio of the 2 forms of PSA in serum among prostatic cancer patients. The measurement and follow-up of both free type and complex type PSA might be important for diagnosis and monitoring of prostate cancer.
We studied the clinical significance of free-type prostate specific antigen (PSA) and bound-type PSA in serum of the patients with prostatic carcinoma and benign prostatic hypertrophy. The levels of PSA, gamma-seminoprotein and prostatic acid phosphatase (PAP) in 17 healthy adult males, 20 patients with benign prostatic hypertrophy and 23 patients with prostatic carcinoma were measured by ACS-PSA, Delfia and Eiken-PSA method. The levels of PSA in serum from prostatic carcinoma patients was significantly elevated as compared with that from benign prostatic hypertrophy. Linear regression analysis of the data showed that, although overall correlations were well, different assays gave different PSA concentrations. We have studied the forms of PSA in serum by gel filtration technique and measured PSA levels in each fractions using three methods. Moreover, the characteristics of ACS-PSA method was compared with that of Delfia and Eiken-PSA method. Two peaks of PSA were detected on the elution profiles from three prostatic carcinoma patients sera. Those were estimated complex-type PSA (90kDa) and free-type PSA (30kDa). The complex-type PSA fractions detected by ACS-PSA method were almost identical with that detected by Delfia-PSA method, while free-type PSA fractions detected by ACS-PSA method were greater quantity than those by Delfia and Eiken method. Many factors were contributory to the difference between the assay kits on serum complex-type PSA and free-type PSA levels. The present results suggest that there are some quantitative differences in the immunorecognition of complex-type PSA and free-type PSA between the assay kits.
Xanthine oxidase (xanthine dehydrogenase) is composed of two identical subunits of approximately 150,000 daltons. Each subunit contains four oxdation-reduction active cofactors/monomers. In vivo, the enzyme exists mostly as the dehydrogenase type (the NAD-dependent type). The cDNA has been cloned from human liver, and the amino acid sequence has been determined. As xanthine oxidase seems to produce superoxide in postischemic reperfusion, the relation between the superoxide and postischemic tissue injury has been discussed. It has also been reported that inhibition of xanthine oxidase by allopurinol may cause severe 6-mercaptopurine toxicity.
Hereditary xanthinuria is a rare autosomal recessive disorder, with xanthine oxidase deficiency. Patients often display renal symptoms because they excrete a large amounts of xanthine in urine. An high-fluid-intake, alow-purine-food, and alkalinization of urine are effective in the patients. Molybdenum cofactor is essential for xanthine oxidase, sulfite oxidase and aldehyde oxidase. Patients with molybdenum cofactor deficiency display severe neurological symptoms, such as severe convulsions. The patients increase urinary excretions of xanthine and sulfite. Treatments are ineffective for neurological symptoms.
The post-diagnostic changes in the free to total PSA ratio in the serum of patients with prostate carcinoma, after the initiation of endocrine treatment were examined. Two-week pretreatment with either chlormadinone acetate (100 mg/day) or flutamide (375 ng/day) was administered orally to 14 patients with newly diagnosed advanced prostate carcinoma (clinical stage was C in 2, Dl in 1 and D2 in 11). Then the LH-RH analogue was injected. Total and free PSA in the serum of these patients were measured every 4 weeks by the Ab bead PSA (Eiken) and the recently developed assay for free PSA by Eiken, respectively. The follow-up period ranged from 3 to 9 months with a median of 6 months. Levels of both total and free PSAs decreased significantly following the endocrine treatment, while free to total PSA ratio at 4 to 16 weeks after the start of LH-RH analogue was increased significantly compared to the pretreatment level (p < 0.05). These findings suggest that the rate of decrease of complex PSA during the first 4 months after the beginning of treatment may exceed that of free PSA in the serum of patients with advanced prostate carcinoma initially treated with endocrine therapy.
Deficiency of dihydropyrimidine dehydrogenase or dihydropyrimidinase, enzymes that catalyze the breakdown of pyrimidine chemotherapy agents such as 5-fluorouracil, may cause serious adverse reactions to these agents. We attempted to establish the reference range for urinary pyrimidines in adults to detect individuals with abnormal pyrimidine metabolism. We analyzed urinary pyrimidine levels in 1133 adults to establish a reference range for persons ages 20 years or older. Urinary dihydrouracil and uracil levels were determined by high-performance liquid chromatography with column switching. The reference range obtained was found to be 0-59.3 micromol/g creatinine for dihydrouracil and 0-129.8 micromol/g creatinine for uracil. In addition, an asymptomatic man with suspected dihydropyrimidinase deficiency was detected on the basis of dihydropyrimidinuria. Although only three cases of this disease have been found worldwide, including one infant reported previously by our group, it may not be so rare as has been thought. In this man, a 10 mg/kg oral uracil loading test yielded a peak blood dihydrouracil level of 192.1 micromol/liter and a peak uracil level of 67.8 micromol/liter. Eight h after loading, the uracil level was still 11.1 micromol/liter, about 17 times that in healthy subjects. Additional research on dihydropyrimininase deficiency may help to prevent adverse reactions to pyrimidine chemotherapy agents in susceptible individuals.
An automated screening system for purine and pyrimidine metabolism disorders using high-performance liquid chromatography (HPLC) with column switching is described. The system consists of a reversed-phase column, a cation-exchange column, a column switch, four sets of ultraviolet absorbance detectors, a microcomputer and other conventional equipment. As this system permits the simultaneous determination of urinary orotic acid, uracil, dihydrouracil, pseudouridine, xanthine, 2,8-dihydroxyadenine and succinyladenosine, it offers a useful method for the detection of orotic aciduria, dihydropyrimidine dehydrogenase deficiency, dihydropyrimidinuria, xanthinuria, adenine phosphoribosyltransferase deficiency and adenylosuccinase deficiency.
Differences between human renal cortex and human renal cell carcinoma (RCC) in asparagine (Asn)-linked sugar chain structures of gamma-glutamyltransferase (GGT) were investigated by using a serial lectin affinity chromatographic technique. The relative amounts of GGT which passed through the concanavalin A (Con A) column but bound to the phytohaemagglutinin E column, were significantly decreased in RCC, but there were significant increases in the relative amounts of GGT which bound weakly to the Con A column and passed through the pea lectin (PSA) column, and bound strongly to the Con A column and bound to the wheat germ agglutinin column in RCC compared with those of the normal renal cortex. A significant correlation was observed in RCC between nuclear grade and relative amount of GGT which bound weakly to the Con A column and passed through the PSA column. The findings indicate that Asn-linked sugar chain structures are altered in RCC and suggest that studies of qualitative differences of sugar chain structures of GGT might lead to a useful diagnostic tool for human RCC.
We report a high-performance liquid chromatographic method with column switching for urinary hypoxanthine and xanthine. Analyses were carried out with both a reversed-phase column and an anion-exchange column connected by a column switch and controlled automatically by a computerized system controller. The relationships between standard concentrations and peak heights were linear in a concentration range of 1 to 1000 nmol/ml. The recovery of hypoxanthine added to urine was 101.1%, and that of xanthine was 98.1%. With our method urinary hypoxanthine and xanthine can be measured accurately without any sample preparation other than filtration.
OBJECTIVE: To use mice to examine the effects of cyclosporine and tacrolimus (FK 506) on two forms of acute pancreatitis often seen after clinical organ transplantation. METHODS AND DESIGN: In the first experiment, male CD-1 mice received cyclosporine (10 mg/kg), tacrolimus (0.32 mg/kg), or saline solution (control) subcutaneously once a day for 10 days. On the 11th day, acute edematous pancreatitis was induced by ceruletide (cerulein). In the second experiment, female ICR mice were fed with a choline-deficient, ethionine-supplemented (CDE) diet for 72 hours to induce necrotizing pancreatitis. After 30 hours on the CDE diet, the mice received cyclosporine (10 mg/kg), tacrolimus (0.32 mg/kg), or saline solution (control) subcutaneously twice daily for 3 days. RESULTS: The pancreatic dry-to-wet weight ratios after ceruletide injections significantly decreased in mice treated with cyclosporine but did not with tacrolimus. Cyclosporine also significantly increased serum amylase levels, but tacrolimus did not. Cyclosporine or tacrolimus alone did not produce pancreatitis. In the CDE diet groups there was a significant difference in survival among the cyclosporine-treated, the tacrolimus-treated, and the control groups. CONCLUSIONS: Cyclosporine or tacrolimus given alone does not induce acute pancreatitis. In contrast, cyclosporine can adversely affect the course of acute edematous pancreatitis, and both immunosuppressants may worsen the survival of mice with acute hemorrhagic necrotizing pancreatitis. This study also demonstrated that the deteriorating effect of tacrolimus is less potent than that of cyclosporine.
Endothelin-1, a 21-residue peptide isolated from vascular endothelial cells, has a broad spectrum of actions. To clarify the involvement of endothelin-1 in acute pancreatitis, we examined the effects of endothelin-1 and its receptor antagonist BQ-123 on cerulein-induced pancreatitis in rats. Rats were infused intravenously with heparin-saline (control), endothelin-1 (100 pmol/kg/hr), cerulein (5 micrograms/kg/hr), or cerulein plus endothelin-1 for 3.5 hr. In another experiment, cerulein or cerulein plus BQ-123 (3 mg/kg/hr) was infused. Infusion of cerulein caused hyperamylasemia and pancreatic edema. Endothelin-1, when infused with cerulein, decreased the extent of pancreatic edema with a significant increase in the pancreatic dry- to wet-weight ratio. Histological changes induced by cerulein were markedly attenuated when endothelin-1 was given with cerulein. In contrast, endothelin-receptor blockade with BQ-123 further augmented pancreatic edema caused by cerulein. The extent of inflammatory cell infiltration was greater than BQ-123 was given with cerulein. Endothelin-1 or BQ-123 had no influence on hyperamylasemia. This study suggests that endothelin-1 has protective effects on experimental acute pancreatitis.
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The noncoding control region of the mitochondrial DNA of various gallinaceous birds was studied with regard to its restriction fragment length polymorphism (RFLP) and sequences of the first 400 bases. Tandem duplication of the 60-base unit was established as a trait unique to the genus Gallus, which is shared neither by pheasants nor by quails. Unlike its close ally Gallus varius (green junglefowl), the red junglefowl Gallus gallus is a genetically very diverse species; the 7.0% sequence divergence was seen between those from Thailand (G. g. gallus and G. g. spadiceus) and the other from the Indonesian island of Java (G. g. Bankiva). Furthermore, the divergence increased to 27.83% if each transversion is regarded as an equivalent of 10 transitions. On the other hand, a mere 0.5-3.0% difference (all transitions) separated various domestic breeds of the chicken from two G. g. gallus of Thailand, thus indicating a single domestication event in the area inhabited by this subspecies of the red junglefowl as the origin of all domestic breeds. Only transitions separated six diverse domesticated breeds. Nevertheless, a 2.75% difference was seen between RFLP type I breeds (White Leghorn and Nagoya) and a RFLP type VIII breed (Ayam Pelung). The above data suggested that although the mitochondrion of RFLP type V was the main contributor to domestication, hens of other RFLP types also contributed to this event.
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