Search PubMed⌕ Search

Biomedical subjects

Z Tsutsumi

Publications and source records attributed to Z Tsutsumi.

At least 19 recordsLinked to original sources
PubMed2001

Functioning adrenal black adenoma with pulmonary and cutaneous cryptococcosis: a case report and review of English literature.

A 53-year-old woman experienced progressive general weakness and lumbago in the 2 years prior to a physical examination which disclosed cushingoid manifestations and a skin ulcer on the back of her right knee joint. Her plasma cortisol concentration ranged from 24.7 to 31.1 microg/dl, with an ACTH level <5 pg/ml. Urinary excretions of 17-hydroxycorticosteroid (17-OHCS) and 17-ketosteroid (17-KS) were 20.5 mg/day and 5.1 mg/day, respectively, and urinary cortisol was also increased (421 microg/day). Cortisol was not suppressed after the administration of 8 mg dexamethasone. Abdominal ultrasound sonography, computed tomography (CT) scan, and magnetic resonance imaging (MRI) studies demonstrated a left adrenal tumor and further, a chest X-ray examination showed a cavitary lesion containing a fungus ball-like mass in the left lower lung field. The serum cryptococcal antigen titer was positive at 1:128 and a bronchoalveolar lavage fluid culture yielded a growth of Cryptococcus neoformans. A biopsy specimen of the skin ulcer also suggested cryptococcosis. As a result, a left adrenectomy was performed, and the excised specimen was shown to be an adenoma consisting of compact cells with abundant pigmentation (black adenoma). A diagnosis of functioning black adenoma of the adrenal gland, complicated with pulmonary and cutaneous cryptococcosis was made.

Adrenal Gland Neoplasms↗
PubMed2001

An atypical case of primary renal tubular hypokalaemic metabolic alkalosis with chronic tophaceous gout.

A 55-year-old woman was referred to our ward for further evaluation of marked hyperuricaemia and suspected tophi. On physical examination, huge subcutaneous nodules were observed on the knee joints as well as a small nodule on the lateral side of the left sole. Blood chemistry showed marked hyperuricaemia (0.85 mmol/l), hypokalaemia (2.7 mmol/l) and a mild degree of renal insufficiency. Arterial blood gas analysis showed signs of metabolic alkalosis. Daily urinary uric acid excretion on a purine non-restricted diet was 8.9 mmol/day. Uric acid clearance and fractional uric acid clearance were 0.8 ml/min and 2.6%, respectively. Plasma renin activity was 21.8 ng/ml/h, and plasma angiotensin II and aldosterone concentrations were 61 and 121 pg/ml, respectively. However, pressor response to an intravenous administration of angiotensin II was normal. The urinary calcium to creatinine molar ratio was 0.069, and serum magnesium concentration was normal to supranormal. A biopsy of the subcutaneous nodule showed a typical appearance of tophus. Based on these findings, the patient was diagnosed with an atypical case of renal tubular hypokalaemic metabolic alkalosis, with marked hyperuricaemia and tophi as the initial manifestations. So far, only four cases of Bartter's syndrome with gout and/or hyperuricaemia have been described in Japan. This rare case is presented and its mechanism of hyperuricaemia discussed.

Arthritis, Gouty↗
PubMed2001

Human xanthine dehydrogenase cDNA sequence and protein in an atypical case of type I xanthinuria in comparison with normal subjects.

To investigate the properties of xanthine dehydrogenase/xanthine oxidase (XDH/XO) deficiency in a patient with atypical type I xanthinuria, as indicated by oxypurine data, a cDNA sequence encoding XDH, XDH/XO immunoblot analysis and a competitive PCR assay were performed, and the results were compared with those of normal subjects. The xanthine dehydrogenase cDNA sequence of the patient was consistent with the controls, while immunologically reactive 150 kD XDH/XO protein was not present in the xanthinuric duodenal mucosa, unlike the control duodenal mucosa. In addition, a decrease in XDH/XO messenger RNA was found by competitive PCR. These results suggest that atypical type I xanthinuria is due to a decrease in messenger RNA of XDH/XO. Furthermore, it was considered that this decrease could explain the normal plasma level and near normal urinary excretion of hypoxanthine seen in this case of xanthinuria, though XDH/XO activity and protein were not detected spectrophotometrically and immunologically, respectively.

Base Sequence↗
PubMed2001

Effect of furosemide on renal excretion of oxypurinol and purine bases.

To examine whether furosemide affects the plasma concentration and urinary excretion of purine bases and oxypurinol, we administered allopurinol (300 mg) orally to 6 healthy subjects and then administered furosemide (20 mg) intravenously 10 hours later. Furosemide (20 mg) decreased the urinary excretion of uric acid by 40% (P < .01), oxypurinol by 39% (P < .05), and xanthine by 43% (P < .05) and the fractional clearance of uric acid by 45% (P < .01) and oxypurinol by 34% (P < .05) when measured 1 to 2 hours after administration. Moreover, furosemide increased the plasma concentration of uric acid by 6% at 1.5 hours after administration. These results indicate that furosemide may decrease the urinary excretion of uric acid and oxypurinol by acting on their common renal transport pathway(s). In addition, it is suggested that the effect of furosemide on oxypurinol is clinically important, since the hypouricemic effect of allopurinol may become more potent as a result.

Administration, Oral↗
PubMed2001

Increased visceral fat accumulation further aggravates the risks of insulin resistance in gout.

We performed the present study to determine the degree of visceral fat accumulation and incidence of visceral fat obesity in 138 gout patients who were classified as overexcretion type (n = 53) and underexcretion type (n = 85) by their levels of uric acid clearance and urinary uric acid excretion. We also investigated the relationship between visceral fat accumulation and insulin resistance expressed by the homeostasis model assessment (HOMA) index. Visceral fat area (VFA)/surface body area (SBA) was significantly increased in patients with gout as compared with control subjects (79.7 +/- 30.8 cm(2)/m(2) v 65.1 +/- 24.1 cm(2)/m(2), P <.001). It was also shown that VFA/SBA in the gout overexcretion group was significantly increased as compared with the gout underexcretion group (88.3 +/- 32.8 cm(2)/m(2) v 74.3 +/- 28.3 cm(2)/m(2), P <.01). Although the incidence of visceral fat obesity (VFO) was not different between gout patients and control subjects, the incidence of VFO was significantly higher in the gout overexcretion type than the gout underexcretion type (19 of 53 v 11 of 85, P <.01). Further, there was a significant relationship between visceral fat area and HOMA index. Gout patients possess some factors that are included in the insulin resistance syndrome, irrespective of the presence of VFO, and the insulin resistance risk factors observed in gout become more prominent when it is complicated with VFO. Our results suggest that gout patients, especially the overexcretion type who have greater levels of visceral fat accumulation, may be more vulnerable to atherosclerotic diseases.

Adult↗
PubMed2001

Decreased activities of lipoprotein lipase and hepatic triglyceride lipase in patients with gout.

Postheparin plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities were measured in 30 male primary gout patients as well as in control subjects. The activities of these lipolytic enzymes were significantly decreased in the patients as compared with the controls (gout v control; LPL, 5.4 +/- 0.4 v 7.9 +/- 0.9 U; HTGL, 14.6 +/- 2.0 v 17.9 +/- 3.4 U) when matched with serum triglyceride concentration. Further, LPL activity was negatively correlated with serum- and very-low-density lipoprotein (VLDL)-triglyceride in gout patients, while that of HTGL was negatively correlated with low-density lipoprotein (LDL)-triglyceride in both gout patients and control subjects. These results suggest that decreased activities of LPL and HTGL may contribute, in part, to the increased concentrations of serum-, VLDL-, and LDL-triglyceride seen in gout patients, leading to a higher risk for coronary atherosclerotic diseases in gout.

Adult↗
PubMed2001

Effect of norepinephrine on the urinary excretion of purine bases and oxypurinol.

To examine whether norepinephrine affects the plasma concentrations and urinary excretion of purine bases and oxypurinol, we orally administered allopurinol (300 mg) to 5 healthy subjects and 9 hours later intravenously administered norepinephrine (12 to 20 microg/kg body weight), which causes a more than 10 mm Hg increase in diastolic pressure for 2 hours. Norepinephrine decreased the urinary excretion of uric acid by 33% (P <.01), oxypurinol by 32% (P <.01), and xanthine by 51% (P <.01), as well as the fractional clearance of uric acid by 32% (P <.01), oxypurinol by 24% (P <.05), and xanthine by 21% (P <.05) when measured 1 to 2 hours after administration. These results indicate that norepinephrine decreases the urinary excretion of uric acid, oxypurinol, and xanthine, probably via hemodynamic change. It is also suggested that the hypouricemic effect of allopurinol may be more potent than that expected in gout patients with enhanced sympathetic tone, such as in salt-sensitive hypertension.

Adult↗
PubMed2001

Widespread cellular distribution of aldehyde oxidase in human tissues found by immunohistochemistry staining.

Aldehyde oxidase (EC 1.2.3.1) is a xenobiotic metabolizing enzyme that catalyzes a variety of organic aldehydes and N-heterocyclic compounds. However, its precise pathophysiological function in humans, other than its xenobiotic metabolism, remains unknown. In order to gain a better understanding of the role of this enzyme, it is important to know its exact localization in human tissues. In this study, we investigated the distribution of aldehyde oxidase at the cellular level in a variety of human tissues by immunohistochemistry. The enzyme was found to be widespread in respiratory, digestive, urogenital, and endocrine tissues, though we also observed a cell-specific localization in the various tissues studied. In the respiratory system, it was particularly abundant in epithelial cells from the trachea and bronchium, as well as alveolar cells. In the digestive system, aldehyde oxidase was observed in surface epithelia of the small and large intestines, in addition to hepatic cells. Furthermore, the proximal, distal, and collecting tubules of the kidney were immunostained with various intensities, while glomerulus tissues were not. In epididymus and prostate tissues, staining was observed in the ductuli epididymidis and glandular epithelia. Moreover, the adrenal gland, cortex, and notably the zona reticularis, showed strong immunostaining. This prevalent tissue distribution of aldehyde oxidase in humans suggests some additional pathophysiological functions besides xenobiotic metabolism. Accordingly, some possible roles are discussed.

Aldehyde Oxidase↗
PubMed2001

Spot urine uric acid to creatinine ratio used in the estimation of uric acid excretion in primary gout.

OBJECTIVE: Uric acid overexcretion in patients with gout is frequently assessed by the measurement of 24 hour urinary uric acid excretion, which is cumbersome with ambulatory patients, and requires accurate timing and complete collection of the specimen. We assessed whether uric acid to creatinine ratio (Uua/Ucr) in spot urine is useful for the estimation of uric acid overexcretion in patients with gout. METHODS: One hundred thirty male patients with gout and 33 non-gout male control subjects were studied. Early morning urine and/or a portion of 24 h collected urine (24 h urine) were used as spot urine samples. Uric acid overexcreters were defined as those with a 24 h urinary uric acid excretion > or = 1000 mg/day, while uric acid underexcreters were defined as those with uric acid clearance < 6 ml/min. RESULTS: There was a significant relationship between 24 h urinary uric acid excretion and early morning urine Uua/Ucr in patients with gout, while no such relationship was observed in controls. No significant difference in Uua/Ucr was observed between patients with gout and controls, or in Uua/Ucr between gout uric acid overexcreters and underexcreters in early morning urine. A significant difference in this value was observed between the 2 groups in the 24 h urine specimens. Although the diagnostic accuracy of gout uric acid overexcretion was 87.2% using early morning urine and 89.6% using 24 h urine, the sensitivity of gout uric acid overexcretion was only 25.0% when using early morning urine and 25.0% when using 24 h urine, when the cutoff value of Uua/Ucr was 0.63 and 0.64, respectively. CONCLUSION: Uua/Ucr using spot urine, especially early morning urine, is not an accurate indicator of uric acid overexcretion in patients with gout.

Chemistry, Clinical↗
PubMed2001

Effect of fenofibrate on plasma concentration and urinary excretion of purine bases and oxypurinol.

OBJECTIVE: To investigate whether fenofibrate increases the clearance of purine bases (hypoxanthine, xanthine, uric acid) and oxypurinol. METHODS: We administered fenofibrate (150 mg) 3 times a day for 3 days, and then allopurinol (300 mg) 4 h after the last administration of fenofibrate, to 5 healthy subjects. Ten hours later, a clearance study was done. RESULTS: Following 3 day administration of fenofibrate, fractional clearance of xanthine, uric acid, and oxypurinol increased by 41% (p < 0.05), 101% (p < 0.01), and 51% (p < 0.01), respectively, compared to baseline values, while the respective plasma concentrations decreased by 46% (p < 0.05), 46% (p < 0.05), and 19% (p < 0.05). CONCLUSION: Our results suggest that fenofibrate, fenofibric acid, or fenofibrate derivatives can increase fractional clearance of xanthine, uric acid, and oxypurinol by acting on their common renal pathways. It is suggested that the hypouricemic effect of combination therapy using allopurinol and fenofibrate may be less than additive.

Adult↗
PubMed2000

Effect of branched-chain amino acids on the plasma concentration of uridine does not occur via the action of glucagon or insulin.

To examine whether branched-chain amino acids affect the plasma concentration of uridine, we administered branched-chain amino acids (L-isoleucine, 2.85 g, L-leucine 5.71 g, and L-valine, 3.43 g) orally to 6 healthy subjects. Plasma uridine and glucose decreased by 44% and 12%, respectively, together with an increase in plasma isoleucine, leucine, and valine 90 minutes after administration. However, branched-chain amino acids did not affect the plasma concentration and urinary excretion of purine bases (hypoxanthine, xanthine, and uric acid) and uridine or the plasma concentration of insulin, glucagon, and cyclic adenosine monophosphate (cAMP). Since small amounts of regular insulin, which were found to decrease plasma glucose more than the amino acids, did not decrease the plasma concentration of uridine, these results suggest that plasma uridine was decreased by a direct effect of the branched-chain amino acids on the cellular uptake and/or release of uridine.

Adult↗
PubMed2000

Effect of furosemide on the plasma concentration and urinary excretion of purine bases, adenosine, and uridine.

To examine whether furosemide affects the plasma concentration and urinary excretion of purine bases, adenosine, and uridine, we administered 20 mg furosemide intravenously to 6 healthy subjects. Furosemide decreased the plasma concentration of hypoxanthine by 39% and increased plasma renin activity (PRA) and the plasma concentration of protein by 3.4-fold and 9%, respectively, at 90 minutes after administration. Furthermore, it decreased the urinary excretion of hypoxanthine, xanthine, and uric acid by 47%, 49%, and 49%, respectively, and the fractional clearance of xanthine and uric acid by 44% and 47%, respectively, during the 1-hour period between 60 and 120 minutes after administration. However, furosemide did not affect the plasma concentration or urinary excretion of adenosine and uridine. In addition, in an in vitro incubation study of erythrocytes, furosemide (10 microg/mL) did not affect the concentration of hypoxanthine in the incubation medium or the activity of erythrocyte purine nucleoside phosphorylase and 5'-nucleotidase. These results imply that xanthine may share a renal transport pathway with uric acid. Further, it is suggested that the furosemide-induced decrease in hypoxanthine may be ascribable to a decrease in adenosine triphosphate (ATP) degradation related to the inhibition of chloride transport in the body.

Adenosine↗
PubMed2000

Effect of TEI-6720, a xanthine oxidase inhibitor, on the nucleoside transport in the lung cancer cell line A549.

To examine the effect of 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid (TEI-6720), an inhibitor of xanthine oxidase, on purine metabolism in the lung cancer cell line A549, the activities of adenosine deaminase, purine nucleoside phosphorylase, adenine phosphoribosyltransferase, hypoxanthine guanine phosphoribosyltransferase, xanthine oxidase, and guanase together with pyrimidine nucleoside phosphorylase were measured with or without the addition of TEI-6720, and the extracellular concentrations of hypoxanthine, xanthine, inosine, uracil, and uridine were measured after the addition of inosine or uridine to the incubation medium with or without TEI-6720. Moreover, the Na-independent nucleoside transport was determined in A549 cells with or without TEI-6720. TEI-6720 inhibited the activity of xanthine oxidase in A549 cells, but did not affect other enzymes. During incubation, TEI-6720 not only prevented a decrease in the inosine concentration in inosine-containing medium, but also a decrease in the uridine concentration in uridine-containing medium. Furthermore, the Na-independent transport of uridine was inhibited by TEI-6720 with a K(i) value of 4.1 micromol/l. These results indicate that TEI-6720 is an inhibitor of the Na-independent nucleoside transport of uridine and inosine, as well as xanthine oxidase.

Allopurinol↗
PubMed2000

Effect of urine storage on urinary uric acid concentrations.

Accurate determination of serum and urinary uric acid concentrations is essential for the diagnosis and classification of gout according to uric acid metabolism derangement. Urine and/or serum samples are often kept at either 4 degrees C or -20 degrees C until assayed, when a large number of samples are handled simultaneously. Our preliminary study indicated a significant decrease in urinary uric acid concentration after preservation, regardless of the storage temperature. Uric acid crystals were often observed in these cases which showed a marked decrease in urinary uric acid concentration after storage. In the present study, we sought the factor(s) that might cause this decrease in urinary uric acid concentration, as well as measures to overcome the problem. High urinary uric acid concentration and low pH proved to play major roles in the decrease in urinary uric acid concentration after storage. In contrast, dilution of the urine samples before storage resulted in no significant change in urinary uric acid concentration. Based on these results, we recommend diluting urine before storage for determination of uric acid concentration and avoiding underestimation.

Gout↗
PubMed2000

Effect of losartan potassium, an angiotensin II receptor antagonist, on renal excretion of oxypurinol and purine bases.

OBJECTIVE: To examine whether losartan affects the plasma concentrations and urinary excretion of purine bases and oxypurinol. METHODS: We administered allopurinol (300 mg) and then 9 h later losartan potassium (100 mg) to 5 healthy subjects. RESULTS: The urinary excretion of uric acid increased by 3.9- and 2.6-fold, and that of oxypurinol by 2- and 1.8-fold, at 1 to 2 h and at 2 to 3 h, respectively, after administration of losartan potassium. The fractional clearance of uric acid was increased by 4.3- and 3.2-fold, oxypurinol by 2.3- and 2.1-fold, and xanthine by 1.32- and 1.26-fold, at 1 to 2 h and at 2 to 3 h, respectively, after administration of losartan potassium. The plasma concentrations of uric acid decreased by 8% and 16%, oxypurinol by 7% and 11%, and xanthine by 42% and 45%, at 1.5 and 2.5 h, respectively, after oral administration. CONCLUSION: These results suggest that losartan potassium could increase urinary excretion of uric acid, xanthine, and oxypurinol by acting on their common renal transport pathways, since it was found that uric acid may share a renal transport pathway with oxypurinol and xanthine. It is also suggested that the effect of losartan potassium on oxypurinol and uric acid is clinically important, since the hypouricemic effect of a combination therapy using allopurinol and losartan potassium may be less than additive, while the uricosuric effect of losartan potassium may increase the frequency of calculi in the urinary tract.

Adult↗