Hidenobu Iwata

The Organic Matrix of Urinary Uric Acid Crystals

We have demonstrated that urinary uric acid crystals contain an organic matrix within the crystalline boundaries, morphologically similar to that of uric acid stones. Among several glycosaminoglycans in urine, heparan sulfate was almost exclusively identified in this matrix, as in that of uric acid stones. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed that several proteins in urine were incorporated in this matrix on a selective basis; two of which were albumin and Tamm-Horsfall mucoprotein. An affinity of uric acid or urate for selective urinary macromolecules in a liquid phase was supposed to be the origin of this matrix. But the proteins in the uric acid stone matrix were not separated by SDS-PAGE. Therefore we could not conclude whether the organic matrix of urinary uric acid crystals is similar to that of uric acid stones.

Crystal-Matrix Interrelations in Brushite and Uric Acid Calculi

Brushite and uric acid calculi were studied by means of scanning electron microscopy with the partial dissolution method and transmission electron microscopy. Brushite calculi consist of radially oriented columnar crystals which have sheet-like substructure. The organic matrix is identified chiefly at the outside of the crystals but partly included between the substructure. The concentric matrix bands are often dislocated between the neighbouring crystals. Uric acid calculi also consist of radially oriented columnar crystals, and a fine meshwork of the organic matrix is incorporated within the crystals. The concentric matrix layers of different density are angled according to the crystal lattice. These findings indicate that the organic matrix arose from a mucinous surface coat, at least in the radially striated calculi. The crystals continued to grow in this gel-state milieu, either thrusting the matrix aside or incorporating it within the crystals.

Solubility of Uric Acid and Supersaturation of Monosodium Urate: Why is Uric Acid So Highly Soluble in Urine?

The solubility of uric acid and the stability of supersaturation of monosodium urate (NaU) were studied in buffer solutions containing 150 mM sodium in the physiological urinary pH range at 37C. The solubility of uric acid increased with the rise in pH, and the total dissolved urate (undissociated uric acid + urate anion) concentration did not change during seven-day incubation in the pH range below 6.6. In this pH range, the calculated concentration of undissociated uric acid was constant (about six mg./dl.). Consequently, the increasing solubility of uric acid with the rise in pH depended solely on the increase of urate anion. As much as 220 mg./dl. of uric acid could be dissolved for 24 hours at pH 7.0. But following seven-day incubation the total dissolved urate concentration decreased to 16 mg./dl. due to NaU crystallization. The stability of NaU supersaturation depended not only on the concentration of sodium and urate anion but also on time and pH. When monopotassium urate crystals were incubated for seven days, the total dissolved urate concentration decreased according to NaU crystallization; the higher the pH, the more marked the decrease. However, at least some 80 mg./dl. of total dissolved urate was stable up to pH 8.2 within 24 hours. These findings can well explain why NaU crystals are seldom formed in the normal urine. Urinary stasis and/or pathological high urinary pH may cause NaU crystallization.

Primary signet-ring cell carcinoma of urinary bladder

Abstract The tenth reported case of primary signet-ring cell carcinoma of the urinary bladder is described. This adenocarcinoma of varying degrees of differentiation (predominantly, signet-ring cells and, partially, poorly differentiated cells and mucin-secreting columnar cells which were arranged in glandular pattern) involved almost the entire mucosa, invading the inuscularis of bladder wall in places, ejaculating ducts, and prostatic ducts.

Correlation between angiotensin-converting enzyme activity and histologic patterns in benign prostatic hypertrophy tissue.

Abstract Angiongensin converting enzyme (ACE) activities in 46 benign prostatic hypertrophy (BPH) tissues from 23 patients were compared with respect to histologic patterns, i.e., cystic, adenomatous and fibromuscular components. There was a good correlation between the enzyme activity and the percentage of cystic component in the tissue. On immunofluorescent study using antiserum against purified human kidney ACE, human prostatic ACE in tissues from BPH was mainly located in tubular epithelial cells and cystic lumens.

Possible role of hyaluronate in experimental renal stone formation in rabbits.

We produced renal stones in rabbits by modifying Itatanis method, ligation of the right ureter followed by ureteroneocystostomy 1 week later. Renal stones formed in all animals within 2 weeks after ureteroneocystostomy. We measured the components of glycosaminoglycan in the stone matrix, renal tissue and urine by 2-dimensional electrophoresis. Glycosaminoglycan of the stone matrix consisted solely of hyaluronate. Glycosaminoglycan of the control normal urine consisted of only chondroitin sulfate, although hyaluronate was contained in urine in the hydronephrotic and stone forming period. Glycosaminoglycan of the control normal kidney consisted mainly of hyaluronate and chondroitin sulfate, while hyaluronate was the main component of glycosaminoglycan in the stone forming kidney. From these results, it is clear that hyaluronate is the most important component of glycosaminoglycan in the early stone forming period.

Calcium phosphate crystal-associated proteins: α-2-HS-glycoprotein, prothrombin fragment 1 and osteopontin

Abstract To study the inhibitory effects of calcium phosphate‐associated proteins on calcium oxalate crystallization and urinary concentrations of proteins in people who form stones and healthy controls. From 60 L of urine from healthy men, calcium phosphate‐associated proteins (α‐2‐HS‐glycoprotein, prothrombin fragment 1 and osteopontin) were obtained. The effects of the proteins on calcium oxalate (CaOx) crystallization were studied with a mixed suspension mixed product removal system. To examine urinary concentrations of the proteins, urine samples were collected from 17 healthy subjects and 15 stone formers and analyzed using anion‐exchange chromatography and an enzyme immunoassay. Prothrombin fragment 1 (PTF1) and osteopontin (OPN) had strong inhibitory effects on CaOx crystallization, while α‐2‐HS‐glycoprotein had a mild inhibitory effect. Urinary concentrations of PTF1 and OPN were lower in stone formers than in healthy controls. Low urinary concentrations of PTF1 and OPN might be one of the reasons for stone formation.

Inverted papilloma of urinary bladder: Scanning and transmission electron microscopic observation

Abstract On the top of the inverted papilloma some pits with occasional outflow of mucoid material were observed with scanning electron microscope. The epithelial cells facing microcyst showed some special characteristics under transmission electron microscope.

Histological study of urinary bladder transplantation in rats.

Patients who require cystectomy are usually treated with an ileal conduit or intestinal neobladder for urinary control. In some of them, however, the bowel segment cannot be used because of previous abdominal surgery or radiation treatment. Bladder transplantation from cadavers may be beneficial to these patients, if possible. To obtain basic knowledge about bladder transplantation, we developed an animal model of whole bladder transplantation in rats. Male Lewis rats weighing 270-320 g were used as both donors and recipients. Of the 23 recipients, 12 (52.2%) survived 7 days or longer after surgery. At 1 week after transplantation, the bladder showed loss of transitional epithelium and remarkable cellular infiltration. In the bladder at 5 weeks after transplantation, the transitional epithelium regenerated markedly and submucosal cellular infiltration was much improved. Regeneration of some smooth muscle cells was also noted. At 6 months after transplantation, the nerve fibers were recognized in the bladder and the volume of the transplanted bladder was well preserved (1.0-1.3 ml). This article describes an animal model of whole bladder transplantation in the rat which we produced and the results of our study. Because a large number of pure-bred animals can easily be used, we believe our rat model is very useful for basic studies of bladder transplantation.

Production of angiotensin-converting enzyme in rat epididymis

Summary:  Unilateral ductuli efferentia testis of immature rat were severed in order to interrupt the continuity between testis and epididymis and angiotensin‐converting enzyme (ACE) activities were measured 5 weeks after the operation. The epididymal ACE on the operated side increased to nearly the same level as that on the contralateral side, but the testicular ACE activity on the operated side was markedly lower than that on the contralateral side.