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Biomedical subjects

T Umekawa

Publications and source records attributed to T Umekawa.

At least 91 records · Page 5Linked to original sources

Usefulness of mazindol in combined diet therapy consisting of a low-calorie diet and Optifast in severely obese women.

We conducted a double-blind test to examine whether or not the addition of mazindol, an appetite suppressor, to combined diet therapy [low-calorie diet + Optifast: 4600-3928kj(1100-940 kcal)/day] enhances the weight-reduction effect and reduces dropout from treatment in women with severe obesity. All of the patients were enrolled in the combined diet therapy and exercise [1255kj(300 kcal/day)] for 7 months. At the end of the first month, the patients were given, at random, three tablets of either 0.5 mg mazindol (18 women) or placebo (18 women) per day, in three doses for three months, in addition to the diet and exercise therapies. At 7 months, the key for the double-blind test was opened by the controller. Four of the 18 patients in the placebo group dropped out of the programme at 2 months after drug treatment, because they could not endure the intense hunger. Therefore, data for these 4 patients were excluded from evaluation. However, none of the patients treated with mazindol + combined diet therapy dropped out. The body weight and body-fat ratio showed marked reduction (p < 0.01 vs. premedication weight). The percent weight loss and percent reduction in body-fat ratio in the mazindol group was significantly (p < 0.01) greater than those found in the placebo group, which also showed a significant decrease in body weight and body-fat ratio (p < 0.01 vs. pre-medication weight) during the same period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Calprotectin-like protein is related to soluble organic matrix in calcium oxalate urinary stone.

Soluble organic matrix was extracted with 0.1 M EDTA from calcium oxalate monohydrate urinary stone (CaOx), purified by SDS-polyacrylamide gel electrophoresis and transferred to polyvinylidene difluoride membranes for the NH2-terminal amino acid sequence analysis. A protein at 30 kDa showed complete homology with calprotectin (20 amino acids in the NH2-terminal), so we termed this a calprotectin-like protein. Calprotectin which was extracted from human granulocytes had inhibitory activity in calcium oxalate monohydrate crystal growth in vitro. This study suggested that, calprotectin-like protein detected in CaOx is thought to be a potent inhibitor of crystal growth and may therefore be important in the etiology of CaOx formation.

Amino Acid Sequence↗

[Clinical statistics on patients operated at the Department of Urology, Kaizuka Municipal Hospital during ten years (from 1983 to 1993)].

A statistic survey was made on the patients undergoing operations between July, 1983 and June, 1993. The total number of patients was 1780, comprising 1469 males and 311 females. The most frequent organ was the prostate with 526 cases (29.6%), followed by 415 (23.3%) penile and scrotum cases, and 290 (16.3%) bladder cases. Major operations were transurethral resection of prostate (418 cases) and bladder tumor (191 cases).

Adult↗

Mechanism of anti-obesity action of benidipine hydrochloride in mice.

Benidipine hydrochloride, a dihydropyridine calcium antagonist, decreases body weight and also has a hypotensive effect. The mechanism of its inhibitory effect on body weight is unclear, although this agent increases blood flow in brown adipose tissue, which functions as a main thermogenic organ. The hypothesis that benidipine hydrochloride activates brown adipose tissue to induce body weight loss was tested on mice made obese by pretreatment with monosodium-L-glutamate (MSG). When benidipine hydrochloride was incorporated in the diet (1.0 mg per gram of food) for 4 weeks, binding of guanosine-5'-diphosphate in brown adipose tissue mitochondria was significantly increased. Body weight and body fat decreased in both MSG obese mice and in lean controls. Results support the hypothesis and suggest the possibility that benidipine hydrochloride may be useful for treating obese hypertensive patients.

Adipose Tissue, Brown↗

Relationship between basal metabolic rate, thermogenic response to caffeine, and body weight loss following combined low calorie and exercise treatment in obese women.

To clarify whether there were any differences in basal metabolic rate (BMR) and thermogenic response to caffeine in individual obese women, and if so, whether such differences affected weight loss, the basal and resting metabolic rates at 30 min after a caffeine loading test (4 mg/kg ideal body weight, per os) were measured in 136 obese women and ten lean age-matched controls. The obese subjects were then asked to follow a combined low calorie diet and exercise regimen. There were no differences in the BMR and thermogenic responses to caffeine between the obese and lean groups. However, the BMR and the thermogenic responses to caffeine varied widely in obese subjects. After two months of treatment, body weight and percentage body fat in obese women were significantly (P < 0.001) reduced. There were significant correlations between the BMR and body weight loss (r = 0.3621, P < 0.001), between BMR/lean body mass and body weight loss (r = 0.3196, P < 0.001) and between the thermogenic response to caffeine and body weight loss (r = 0.6943, P < 0.001). When the criterion of a BMR less than 3.10 kJ/min (less than two standard deviations below the mean of the age-matched lean control) was used to define an obese group with reduced BMR, there were 30 obese subjects in this group, and their body weight was significantly decreased by treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Platelets-induced stimulation of endothelin-1 production and inhibition by phosphoramidon.

The effects of platelets on endothelin-1 (ET-1) production were examined by using cultured bovine pulmonary artery endothelial cells (ECs). Platelets (6 x 10(6) to 2 x 10(9) platelets/ml) prepared from rat peripheral arterial blood markedly stimulated immunoreactive (IR)-ET release from ECs into the culture medium, in a time-and platelet number-dependent manner. High-performance liquid chromatography analysis of the culture supernatant following exposure to platelets revealed one major IR-ET component corresponding to the elution position of synthetic ET-1. Northern blot analysis showed that platelets enhanced prepro ET-1 mRNA expression in the ECs. Increased IR-ET release was observed with the supernatant obtained after incubation of platelets, and this increment was significantly inhibited by transforming growth factor-beta 1 neutralizing antibody. Phosphoramidon, an ET converting enzyme inhibitor, significantly decreased the amount of IR-ET accumulating in the culture medium of ECs, incubated with or without platelets, and the decreasing effect of phosphoramidon in the presence of platelets was greater than that in their absence. A similar effectiveness of phosphoramidon was seen when transforming growth factor-beta 1 was used instead of platelets. Thus, platelets appear to stimulate the endothelial production of ET-1 in vitro, probably through a release of transforming growth factor-beta 1. We also suggest that the inhibition of ET converting enzyme by phosphoramidon is more effective in the augmented condition of ET-1 production than in the basal condition.

Animals↗

Structure and expression of the mRNA encoding urinary stone protein (osteopontin).

The chemical nature of urinary stone protein is poorly understood. We have sequenced a cDNA of urinary calcium oxalate stone protein extracted with EDTA. cDNA sequences showed complete identity between urinary stone protein and human osteopontin. Osteopontin protein was detected by staining with Stains-All, which specifically stains phosphoproteins, and by digestion with the highly specific protease thrombin, demonstrating that urinary calcium oxalate stones consist of osteopontin protein. We used a technique of in situ hybridization to detect osteopontin mRNA in the kidney. In control rats, distal tubular cells were sporadically positive, and proximal tubular cells and glomeruli were negative for osteopontin mRNA. A rat model of stone formation was induced with glyoxylic acid. In stone-forming rats, staining of distal tubular cells was remarkably increased, but proximal tubular cells and glomeruli were still negative. Immunostaining for the osteopontin protein also revealed that epithelial cells of distal tubules were weakly positive in control rats and significantly increased in stone-forming rats, although proximal tubular cells and glomeruli were negative. Northern blot analysis showed a significant increase of osteopontin mRNA in stone-forming rats in proportion to the dosage and the duration of the stone-inducing drugs. These results show that osteopontin in the kidney is presumably involved in urinary stone formation as the stone matrix.

Animals↗

Sequencing of a urinary stone protein, identical to alpha-one antitrypsin, which lacks 22 amino acids.

We have extracted and purified proteins from calcium containing urinary stones with 4 M guanidine chloride and sequenced the amino acids of the proteins. The protein of approximately 49kDa was defined as human alpha-one antitrypsin (AT, from 23rd to 42nd amino acids of NH2-terminal) by amino acid sequence analysis. The ratio of the amount of AT to total proteins was 34.9% analyzed by densitometer. AT is presumably involved in stone formation as a coprecipitating substance because equilibrium dialysis revealed that AT has no affinity for calcium.

Amino Acid Sequence↗

Studies on changes in parameters of the coagulation and fibrinolysis in association with extracorporeal shock wave lithotripsy.

Tissue damage by extracorporeal shock wave lithotripsy (ESWL) is assumed to be attributable to ischemic changes in the treated region surrounding the particular vessel which is first ruptured by shock waves. Such changes cannot take place without being accompanied by acceleration of coagulation and fibrinolysis. In the literature on renal damage by ESWL, no parameters of the coagulation and fibrinolysis of blood were used. The present study was designed to investigate renal damage by shock waves through the quantification of sequential changes in the following parameters between before and after ESWL: thrombin antithrombin III complex (TAT), alpha 2-plasmin inhibitor-plasmin complex (PIC), fibrin and fibrinogen degradation products (FDP) and D-dimer (D-D). In ESWL for renal stones, a significant acceleration of TAT occurred on the 1st postoperative day, followed by acceleration of PIC on the 3rd postoperative day. A transient acceleration was observed for FDP and D-D after operation. The levels of these parameters, however, returned to normal by the 1st postoperative week. In ESWL for ureteral stones, unlike for renal stones, none of the parameters showed statistically significant acceleration. In the construction of percutaneous nephrostomy (PNS) cases for ureteral stones before ESWL, none of the parameters showed significant acceleration either. Changes in these parameters of coagulation and fibrinolysis due to ESWL for renal stones were greater than those of construction of PNS or ESWL for ureteral stones. The reason for the difference of the alteration in these parameters between renal stones and ureteral stones were more abundant vessels in the kidney than the ureter. All these changes in the parameters, however, disappeared within almost 1 week.

Antifibrinolytic Agents↗

Continuous evaluation for retroperitoneal hematoma following extracorporeal shock wave lithotripsy.

In this paper we report on a patient with extensive retroperitoneal hematoma due to extracorporeal shock wave lithotripsy (ESWL) for a renal stone. The patient had a negative history of previous primary renal disease or risk factors for retroperitoneal hemorrhage after ESWL. The hematoma was treated conservatively and it was completely absorbed 9 months after ESWL as evaluated by computed tomography. Gd-DTPA-enhanced dynamic magnetic resonance imaging (dynamic MRI) was performed immediately after formation of the hematoma. The decrease in renal blood flow in the affected kidney could be observed in this patient by dynamic MRI and its time intensity curve.

Adult↗

Glucose metabolism in renal stone patients.

The calciuric response and the changes of plasma glucose and insulin produced by a 75-gram oral glucose tolerance test were determined in 27 male patients with idiopathic calcium renal stones (6 with dietary hypercalciuria, 5 with nondietary hypercalciuria and 16 with normocalciuria) and 22 healthy male subjects. The subjects were classified as obese (> or = 120% ideal weight) and nonobese. The incidence of an abnormal response to glucose loading was similar in the stone patients and the healthy subjects. In addition, the plasma glucose and insulin levels after oral glucose load did not differ between the stone patients and control subjects and were affected by the individual degree of obesity. Urinary calcium excretion increased significantly after glucose ingestion in both the stone patients and the control subjects. Urinary calcium excretion was greater in the stone patients than in the control subjects due to the presence of patients with nondietary hypercalciuria, and the increment in urinary calcium excretion in the dietary hypercalciuric and normocalciuric stone patients was indistinguishable from that in the control subjects. The degree of obesity did not affect the increment in urinary calcium excretion. These results suggest that overconsumption of refined carbohydrates such as sugar-sweetened soft drinks, soda and cakes may be a risk factor for stone formation, especially in the patients with nondietary hypercalciuria.

Adult↗

[Evaluation of preoperative diagnosis of primary hyperparathyroidism--special reference to normocalcemic cases].

Since the opening of our clinic 117 years before, we have treated 62 cases of primary hyperparathyroidism (PHPT), among which there were 6 cases (1 male, 5 females) whose calcium levels fell within the normal range. However, in all these cases the serum ionized calcium (Ca++) levels and the serum ionized calcium/calcium ratio (Ca++/Ca ratio) were high. Moreover, in comparing them with hypercalcemic patients (56 cases), the serum Ca++ levels were significantly lower, but the (Ca++/Ca ratio) was significantly higher. Also, the excised weight of 606.1 +/- 520.3 mg was significantly smaller than that of hypercalcemic patients, which was 1,967.9 +/- 2,086.3 mg. Preoperative locations showed significantly lower levels in comparison with hypercalcemic patients by all methods including computed tomography (CT), ultrasonography, scintigraphy, and magnetic resonance imaging (MRI). In normocalcemic patients following parathyroidectomy, although the decrease in serum calcium levels was not significant, the serum Ca++ levels and the Ca++/Ca ratio decreased significantly, so that not only are they useful parameters for preoperative diagnosis of PHPT, but they are also considered necessary and indispensable for observation of the post-operative course and judging therapeutic effects including the operation. Based on our study we concluded that in multiple and recurrent stone formers with normal range of serum Ca levels, regardless of the presence or absence of local diagnosis, if the serum Ca++ level and Ca++/Ca ratio are high, existence of primary hyperparathyroidism must be suspected, and adequate treatments should be instituted promptly.

Calcium↗

[Effect of verapamil on urinary calcium and oxalate excretion in renal stone formers].

The effect of the calcium antagonist verapamil on urinary calcium and oxalate excretion was examined and compared with that of trichlormethiazide to evaluate whether verapamil is useful in the prevention of calcium oxalate renal stones. Twenty-four-hour urine of 16 renal stone formers was measured at the outpatient clinic before and after administration of 120 mg/day verapamil for a mean duration of 2.7 months (range, 2 weeks to 6 months). The 24-hour urine was analyzed for creatinine, calcium, oxalic acid, magnesium and citric acid and the results compared with those in 20 renal stone formers who were administered trichlormethiazide. Verapamil was found to significantly reduce the urinary oxalate excretion of the 5 hyperoxaluric (> or = 50 mg/day) patients but no significant effect on urinary calcium, magnesium or citric acid was observed. Conversely, trichlormethiazide significantly decreased urinary calcium excretion in the hypercalciuric (> or = 250 mg/day) patients. Calcium oxalate risk index of hypercalciuric and hyperoxaluric patients was significantly reduced after the administration of verapamil. These findings suggest that verapamil is effective in reducing urinary oxalate excretion in the hyperoxaluric patients.

Calcium↗

Molecular cloning and sequencing of cDNA encoding urinary stone protein, which is identical to osteopontin.

We have sequenced a cDNA of urinary stone protein. cDNA sequences show complete homology between urinary stone protein and human osteopontin (bone sialoprotein) (nucleotides 265-886 and 1183-1424). Osteopontin is a recently discovered bone matrix protein which has been implicated in mediating mineral formation within bone extracellular matrix. This result shows that osteopontin is presumably involved in stone formation as stone matrix.

Base Sequence↗

A new method for determination of urinary citrate.

We have developed a new assay technique using high-performance liquid chromatography. The assay was performed at a flow rate of 0.7 ml/min, a temperature of 60 degrees C and an ultraviolet absorption of 214 nm. Comparison of the results of the new assay with the results obtained for identical samples using the conventional fluorometric method demonstrated a very high correlation coefficient of 0.931.

Adult↗

A simple method for measurement of phosphoramidon-sensitive endothelin converting enzyme activity.

We have developed a rapid and convenient assay for measurement of the action of endothelin (ET) converting enzyme (ECE) using the scintillation proximity assay (SPA) principle. On incubation of [125I]big ET-1 at 37 degrees C for 0.5-6 hr with an enzyme preparation, the reaction was terminated by the addition of an ET-1-specific antibody formulated in a buffer designed to shift the pH to alkaline. The antibody was allowed to come to equilibrium for 1 hr at room temperature and the amount of ET-1 produced, detected in a single step by the addition of protein A SPA beads. Using this assay, ECE activities of enzyme preparations obtained from porcine cultured endothelial cells and rat lung were clearly detected. These activities were inhibited by phosphoramidon in a concentration-dependent manner. The SPA based assay is homogeneous requiring no separation steps and takes a half day to complete. This method is therefore suitable for the high throughput screening of potential ECE inhibitors.

Animals↗

Influence of morphologic factors on calcium-containing stone formation.

Pathogenesis of urolithiasis cannot be explained only by metabolic disorder. In the present study, morphologic differences of the renal pelvic-caliceal system (PCS) were examined on both the stone and normal sides in calcium-containing stone formers. The results indicated that as compared to the normal side, the urine flow in the PCS was stagnant or not straight on the stone side even in the same individual, showing unfavorable conditions for stone formation. It is therefore considered that morphologic disorders of the urinary tract may be one of the causes for stone formation.

Adult↗