Naoki Chida

URINARY EXCRETION OF EPIDERMAL GROWTH FACTOR IN CHILDREN WITH REFLUX NEPHROPATHY

PURPOSE We determined urinary levels of epidermal growth factor in children with reflux nephropathy to evaluate the clinical significance of urinary epidermal growth factor. MATERIALS AND METHODS We studied 59 boys and 41 girls 3 to 15 years old with reflux nephropathy, and 64 boys and 36 girls 3 to 15 years old who were healthy. Levels of urinary epidermal growth factor were determined by sandwich enzyme immunoassay using spot urine samples. We also determined the levels of serum creatinine, urinary alpha 1-microglobulin and urinary microalbumin. Absolute values of function of the left and right kidneys were assessed by 99mtechnetium dimercapto-succinic acid (DMSA) uptake. RESULTS Levels of urinary epidermal growth factor gradually decreased with age in healthy children. There were low levels of urinary epidermal growth factor in 20 of the 44 patients (45%) with unilateral low DMSA uptake and 18 of the 19 (95%) with low total DMSA uptake (right and left uptakes). Urinary epidermal growth factor significantly correlated with serum creatinine (R = -0.702, p < 0.0001), urinary alpha 1-microglobulin (R = -0.606, p < 0.0001), urinary microalbumin (R = -0.708, p < 0.0001) and total DMSA uptake (R = 0.744, p < 0.0001). CONCLUSIONS These results suggest that urinary epidermal growth factor may be a useful clinical tool to monitor functional nephron mass in children with reflux nephropathy.

Differentiation‐dependent enhanced expression of protein phosphatase 2Cβ in germ cells of mouse seminiferous tubules

The presence of five distinct isoforms of protein phosphatase 2Cβ (PP2Cβ1∼‐5) is known. In this study, we demonstrate that the mRNA levels of PP2Cβ‐3, ‐4 and ‐5 and PP2Cβ protein level increased during the course of the first wave of spermatogenesis in neonatal mouse testis. Northern blot and in situ hybridization analyses revealed that PP2Cβ‐3, ‐4 and ‐5 were expressed predominantly in pachytene spermatocytes and in more highly differentiated germ cells. The substrate specificity of PP2Cβ‐4 determined with artificial substrates differed from those of PP2Cβ‐3 and ‐5, suggesting that the difference in the structure of PP2Cβ‐3, ‐4 and ‐5 reflect their unique physiological functions in testicular germ cells.

SOLUBLE INTERLEUKIN-2 RECEPTOR IN CHILDREN WITH REFLUX NEPHROPATHY

PURPOSE Serum soluble interleukin-2 receptor level is a sensitive and quantitative marker of lymphocyte activation. We determined levels of serum soluble interleukin-2 receptor in children with reflux nephropathy to evaluate its clinical significance in the prediction for the progression of renal injuries. MATERIALS AND METHODS Serum soluble interleukin-2 receptor values were determined in 63 children with reflux nephropathy. The group consisted of 37 boys and 26 girls 10 to 18 years old. T cells (naive and memory), B cells and macrophages were evaluated immunohistochemically in the scarred kidneys of 4 other patients (3 boys and 1 girl 5 to 16 years old) who underwent nephrectomy due to severe reflux nephropathy with little function seen on (99m)technetium-dimercapto-succinic acid (DMSA) renal scan. Levels of serum soluble interleukin-2 receptor were measured by an enzyme-linked immunosorbent assay. We simultaneously determined serum levels of creatinine and beta2-microglobulin, and urinary levels of alpha1-microglobulin and microalbumin. Individual functions of the right and left kidneys were estimated by renal dimercaptosuccinic acid uptake. RESULTS Levels of serum soluble interleukin-2 receptor in the patients who had low total uptake of DMSA (right uptake plus left uptake) were significantly higher than those from patients with normal total uptake. Levels of serum soluble interleukin-2 receptor correlated significantly with levels of creatinine (r=0.616, p <0.0001) and beta2-microglobulin (r=0.803, p <0.0001), and levels of urinary alpha1-microglobulin (r=0.753, p <0.0001) and microalbumin (r=0.673, p <0.0001). A significant negative correlation was observed between levels of serum soluble interleukin-2 receptor and total DMSA uptake values (right uptake plus left uptake r=-0.678, p <0.0001). In the scarred kidneys leukocyte infiltrates were markedly increased in fibrosed spaces. The predominant cell type in these lesions was memory T cells. CONCLUSIONS These results suggest that elevated levels of serum soluble interleukin-2 receptor are likely to reflect activated T cells in the kidneys of patients with reflux nephropathy and may be a useful predictor of progression of renal injury in these children.

Enhanced UV sensitivity of yeast cells induced by overexpression of Mg2+-dependent protein phosphatase α (type 2C α)

The UV sensitivity of wild-type Saccharomyces cerevisiae cells was increased 2-fold when rat Mg(2+)-dependent protein phosphatase alpha (protein phosphatase type 2C alpha) was overexpressed in the cells. The overexpression of this enzyme rendered the rad 18 mutant (defective in postreplication repair) more UV-sensitive than was observed in the wild-type cells. However, this increase in UV sensitivity disappeared when the host cells had a rad 1 mutation (defective in excision repair). These results suggest that the Mg(2+)-dependent protein phosphatase overexpressed in the yeast cells inhibited their excision repair system.

Crossed Ureteral Ectopia with an Ectopic Blind-Ending Ureter

A rare case of multiple urological anomalies is presented. The chief complaint of the patient, a 12-year-old girl, was urinary incontinence. Radiologic and endoscopic examinations revealed that the patient had a normal left kidney and ureter, a left ectopic blind-ending ureter that opened near the neck of the bladder, and right complete double ureters with an ectopic orifice that opened on the left of the external urethral meatus. This orifice was responsible for her urinary incontinence. Right ureteroneocystostomy was performed and the incontinence was cured. An attempt was made to explain the embryological origin of the anomalies observed in this case. We postulated that during development, on the left, there were three ureteral buds on the mesonephric duct. The first bud was at the normal position and drained the left kidney in a normal manner. The second bud was cranial from the normal position on the mesonephric duct and was associated with growth in an abnormal direction. This bud made contact with the upper portion of the right metanephric mass. The last bud grew between the two aforementioned buds. This bud was not draped by the metanephric mass and became the blind-ending ureter. On the right, one ureteral bud was located on the mesonephric duct and it made contact with a metanephric mass that became the right kidney. The upper part of the right kidney was drained by the ureter that had originally been located on the left mesonephric duct. This condition should be termed crossed ureteral ectopia rather than crossed renal ectopia, since the ureter was the structure that crossed.