Osamu Miyake

Renal cell carcinoma in dialysis patients: a single center experience.

Aim: Renal cell carcinoma (RCC) is a life‐threatening complication of end‐stage renal disease with an unclear pathogenesis. We evaluated RCC developing in patients undergoing dialysis.

FIBRONECTIN AS A POTENT INHIBITOR OF CALCIUM OXALATE UROLITHIASIS

PURPOSE Fibronectin (230 kD.) is a multifunctional alpha2-glycoprotein distributed throughout the extracellular matrix and body fluids. Many investigators have demonstrated that fibronectin, because of its cell adhesive action, is related to biological processes such as morphogenesis, wound healing and metastasis. Recent studies have shown that a variety of molecules, including fibronectin, inhibit endocytosis of calcium oxalate crystals in vitro. We investigated other roles of fibronectin in calcium oxalate stone formation. MATERIALS AND METHODS Immunoblotting of the crystal surface binding substance obtained from pooled healthy male urine samples was used to analyze whether fibronectin was adsorbed onto the surface of calcium oxalate crystals. To clarify the relationship between fibronectin and calcium oxalate crystals, we performed 6 experiments. Experiment 1 was immunohistochemical examination of fibronectin expression in stone forming rat model kidneys, and experiment 2 examined the fibronectin content of stone forming rat kidney models with the enzyme-linked immunosorbent assay. Experiment 3 was designed to determine fibronectin content of Madin-Darby canine kidney (MDCK) cells stimulated by addition of calcium oxalate crystals and experiment 4 identified the inhibitory effect of fibronectin on calcium oxalate crystal growth by the seed crystal method. For experiment 5 we used an aggregometer system to clarify the inhibitory effect of fibronectin on calcium oxalate crystal aggregation and experiment 6 examined the inhibitory effect of fibronectin on the adhesion of calcium oxalate crystals to MDCK cells. RESULTS In the crystal surface binding substance immunoreactive bands at 230 kD., which correspond to the molecular weight of fibronectin, were detected by Western blot analysis. In stone forming rat kidneys strong expression of fibronectin was found on the renal tubules to which the crystals were attached. The fibronectin content of these kidneys was significantly greater than that of kidneys without calcium oxalate crystals. The fibronectin content of MDCK cells tended to increase in proportion to the concentration of calcium oxalate crystals added to the culture medium. The growth inhibition assay showed that the inhibitory effect of fibronectin on calcium oxalate crystal growth was small in relation to the quantity of fibronectin excreted. However, fibronectin had inhibitory effects on calcium oxalate crystal aggregation and adhesion of the crystals to MDCK cells. CONCLUSIONS Fibronectin secretion can be stimulated by calcium oxalate crystals, and this protein, which is excreted from the tubular cells, may inhibit calcium oxalate crystal aggregation and attachment to cells.

Secondary Involvement of Genitourinary Organs in Malignant Lymphoma

We examined 322 patients who had died of malignant lymphoma at our institute between 1958 and 1985 in order to study secondary involvement of genitourinary organs (GUO). Secondary involvement of GUO was more common in non-Hodgkin lymphoma (NHL) than in Hodgkins disease. The most commonly affected GUO was the kidney, which was secondarily involved in 121 out of 322 patients (37.6%). The adrenal gland was the second most commonly affected organ: 58 cases (18%) were affected by the disease and 40 of them were associated with renal involvement. Third and fourth were the urinary bladder (8.4%) and the testis (5.9%). Secondary involvement of the bladder in NHL was often accompanied with that of other GUO. Next, the relationship between metastases and histological characteristics in NHL was investigated. However, no significant correlation proved to exist between histological grade and metastases to the GUO.

HIGH URINARY EXCRETION LEVEL OF CITRATE AND MAGNESIUM IN CHILDREN : POTENTIAL ETIOLOGY FOR THE REDUCED INCIDENCE OF PEDIATRIC UROLITHIASIS

Abstract It is well known that the incidence of calcium oxalate (CaOX) urolithiasis is much lower in children than in adults [2, 21]. One purpose of this study was to compare the inhibitory activity on CaOX crystal growth and nucleation of urine from children (ufC) with that of urine from adults (ufA). Another was to measure low molecular weight urinary substances related to CaOX lithiasis, including citrate and magnesium, which have been identified as stone inhibitors. The excretion volume per body weight of uric acid, phosphorus, magnesium and citrate was all significantly higher in 24-h ufC than in 24-h ufA, but that of calcium and oxalate was not. The growth inhibitory activities against CaOX crystals of ufC and ufA were measured in a whole urine system. The diameter of the crystals produced in this system was smaller for ufC (3.68 μm) than for ufA (4.66 μm). We also examined the metastable limit for CaOX with fresh spot urine, which was 3.15 mmol/l in ufC and 0.41 mmol/l in ufA. These results indicate that ufC has a more powerful inhibitory effect on CaOX crystal growth and nucleation than ufA. We also found that the excretion rate of citrate and magnesium in ufC was much higher than in ufA. We suggest that these two stone inhibitors are very likely to elevate the inhibitory activity of ufC against CaOX crystal growth and nucleation. The lower incidence of CaOX lithiasis in children might thus be partly attributed to citrate and magnesium.

Possible causes for the low prevalence of pediatric urolithiasis

OBJECTIVES To determine why the incidence of pediatric urolithiasis is less than that of adult urolithiasis, we investigated the difference in inhibition of calcium oxalate (CaOX) crystallization between pediatric and adult urinary macromolecules (UMMs). METHODS Urinary parameters in relation to urolithiasis, the inhibition of CaOX crystallization of original urine and urine from which UMMs (greater than 3 kDa) had been removed, and the inhibition of CaOX crystal growth and aggregation of UMMs alone were measured. These inhibitory activities were compared between children and adults. RESULTS In the original urine, the inhibition of CaOX crystallization was significantly stronger for children than for adults, but was the same in urine from which the UMMs had been removed. The inhibition of CaOX crystal growth by UMMs alone showed no significant differences between children and adults; their inhibition of CaOX crystal aggregation was significantly stronger for children than for adults. Much more glycosaminoglycan (GAG) was included in pediatric UMMs than in adult UMMs, although there was no difference in UMM concentration between urine from children and urine from adults. CONCLUSIONS The lower incidence of CaOX lithiasis in children may be attributed, among other factors, to the stronger inhibition of CaOX crystal aggregation by pediatric UMMs, which in turn might be affected by the higher concentration of GAGs in childrens urine.

Laparoscopic diagnosis and treatment of nonpalpable testis

Abstract Objective: Laparoscopy has become one of the important diagnostic modalities of nonpalpable testis and has been developed and applied in the treatment of this disease. In the present study, we investigated the usefulness of laparoscopy in the diagnosis and treatment of nonpalpable testis.

Strong inhibition of crystal-cell attachment by pediatric urinary macromolecules: a close relationship with high urinary citrate secretion.

OBJECTIVES To investigate other reasons for the low incidence of pediatric urolithiasis, we evaluated the difference in the crystal-cell adhesion inhibitory activity of urinary macromolecules (UMMs) between children and adults. We also evaluated whether citrates influence the above inhibitory activity, because citrates are important in pediatric urine. METHODS Urine samples were collected from children and healthy male adults during a 24-hour period, and urinary components with a molecular weight of 3 kDa or greater were extracted as UMMs to compare their inhibitory activity during the adhesion of calcium oxalate monohydrate crystals to cultured Madin-Darby canine kidney cells between children and adults. Subsequently, various concentrations of citrates were added to adult UMMs to evaluate the changes in the crystal-cell adhesion inhibitory activity of UMMs. RESULTS Pediatric UMMs more strongly inhibited the adhesion of calcium oxalate monohydrate crystals to cultured Madin-Darby canine kidney cells at a concentration of 0.1 mg/mL compared with adult UMMs. In addition, pediatric UMMs contained higher proportions of fibronectin and glycosaminoglycans, both of which exhibit crystal-cell adhesion inhibitory activity. When citrates were added to adult UMMs, the crystal-cell adhesion inhibitory activity of UMMs was increased in a dose-dependent manner. However, citrates alone did not result in any differences in the inhibitory activity at any of the three different concentrations. CONCLUSIONS We speculate that the incidence of pediatric urolithiasis is low because pediatric UMMs more potently inhibit the adhesion of calcium oxalate crystals to renal tubular cells or because the higher proportion of citrates in pediatric urine enhances the crystal-cell adhesion inhibitory activity of UMMs in a dose-dependent manner.

Comparison of Fibronectin Content in Urinary Macromolecules between Normal Subjects and Recurrent Stone Formers

Objectives: Fibronectin (FN: 230 kD) is a multifunctional α2–glycoprotein distributed throughout the extracellular matrix and body fluids. Recent studies have shown that a variety of molecules, including FN, inhibit the endocytosis of calcium oxalate (CaOx) crystals in vitro. We recently reported that FN was oversecreted from the renal tubular cells as a result of the stimulation of CaOx crystals, and inhibited the aggregation of CaOx crystals and the adhesion of CaOx crystals to the renal tubular cells. In the present study, we investigated the difference of FN content in urinary macromolecules (UMMs) between normal subjects and recurrent stone formers. Materials and Methods: Urinary parameters in relation to urolithiasis of normal subjects and recurrent stone formers were measured. Proteins in extracted UMMs from urine of normal subjects and recurrent stone formers were measured with a BioRad protein assay, GAGs in each UMMs with a modified DMB assay and the FN content with the ELISA method. Results: In urinary parameters, citrate was significantly higher in urine from normal subjects (female) than normal subjects (male) or recurrent stone formers, and the other parameters showed no differences between each group. The protein concentrations in UMMs showed no differences between each group. Normal subjects (male and female) showed a significantly higher concentration of GAGs than recurrent stone formers (with and without silent stone). Compared with normal subjects and recurrent stone formers without silent stones, higher FN levels were found in recurrent stone formers with silent stones. Normal subjects showed a significantly higher concentration of FN than recurrent stone formers without silent stones. No difference in FN level was shown between normal subjects (male) and normal subjects (female). Conclusion: Recurrent stone formers with silent stones showed a significantly higher concentration of FN in UMMs than normal subjects. This finding suggests that FN might be oversecreted from the renal tubular cells as a result of the stimulation of CaOx stones in vivo. Recurrent stone formers without silent stones showed a significantly lower concentration of FN in UMMs than normal subjects. From this finding it is suggested that FN might play a role as a potent inhibitor of CaOx urolithiasis in a clinical setting.

Characterization of protein components of human urinary crystal surface binding substance

We previously extracted crystal surface binding substance (CSBS) from human urine and showed that it appeared to constitute a substantial proportion of urinary macromolecular inhibitors of calcium oxalate crystallization. CSBS was isolated from human urine and fractionated by three consecutive chromatography procedures in order to characterize protein inhibitors of calcium oxalate crystallization. Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and NH2-terminal amino acid sequencing revealed that inhibitory fractions eluted from a final, hydroxyapatite column contained prothrombin and osteopontin. Hydroxyapatite column fractions also contained other, unidentified protein inhibitors of calcium oxalate crystallization. CSBS contained also human serum albumin, α1-acid glycoprotein, α2-microglobulin, α2-HS glycoprotein, retinol-binding protein, transferrin, and Tamm-Horsfall protein, but these proteins seemed to play no direct role in inhibitory activity.

Infected urachal cyst ruptured during medical palliation.

Since most cases of urachal cyst are asymptomatic, they are frequently detected after complication by infection. Ruptured urachal cysts are frequently detected after complication by severe infections such as sepsis. We report on a 31‐year‐old man who was diagnosed preoperatively as having an infected urachal cyst and the decision was made to follow the patient because primary excision was scheduled to be performed a few days later. Symptoms were transiently relieved, but the cyst ruptured during medical palliation. We treated this case with a two‐stage surgical procedure.