Takuo Koide

Heparan sulfate in the stone matrix and its inhibitory effect on calcium oxalate crystallization

SummaryThe nature of the soluble stone matrix and its possible role in urinary stone formation was studied. For this purpose we performed two-dimensional cellulose acetate membrane electrophoresis of the glycosaminoglycans (GAGs) which were contained in the soluble stone matrix, substances adsorbed onto calcium oxalate crystals in vitro (crystal surface binding substances, CSBS) and urinary macromolecules (UMMs). The main GAG in the soluble stone matrix and CSBS was found to be heparan sulfate, whereas the UMMs contained various GAGs usually seen in urine. An inhibition assay showed the soluble stone matrix to have the strongest inhibitory activity among these macromolecular substances when inhibitory activity was expressed in terms of uronic acid concentration. It is suggested that the main GAG in the soluble stone matrix consists of heparan sulfate, which has a strong inhibitory activity on calcium oxalate crystal growth and aggregation and constitutes part of the CSBS.

Incidentally diagnosed renal cell carcinoma.

We analyzed the incidence, sex and age distribution, diagnostic methods and survival rate of incidentally detected renal cell carcinomas (RCCs) and compared these factors with those of symptomatic RCCs. Of 141 patients with RCC treated between 1980 and 1989, 44 cases (31.4%) were incidentally detected. Thirty-one of these 44 cases were diagnosed by abdominal ultrasonography. The age of the incidental cases was significantly higher than that of the symptomatic ones (p = 0.045), particularly in male patients (p = 0.049). The tumor size in incidental cases was smaller and tumor stage earlier (p less than 0.0001). Moreover, the grade of malignancy was significantly lower, and clear cell type tumors were more frequently detected in the incidental cases. No difference was observed between the survival rates of incidental and symptomatic cases with stage 1 or 2 tumors. Of the incidental cases with stage 1 or 2, however, no patient with a tumor 3 cm or less in diameter has died. In conclusion, abdominal ultrasonography is a useful tool to detect RCC at an early stage, and patients with a relatively small tumor tend to have a good prognosis.

THE INHIBITORY EFFECT OF KAMPOU EXTRACTS ON IN VITRO CALCIUM OXALATE CRYSTALLIZATION AND IN VIVO STONE FORMATION IN AN ANIMAL MODEL

Kampou medicine is a traditional Japanese therapeutic system which originated in China and was used to treat various diseases for hundreds of years until it was superseded by Western medicine. In recent years, there has been a resurgence of interest in Kampou medicine among many physicians. Unfortunately, however, little evaluation has been performed using objective scientific methods until now, and the pharmacodynamics of Kampou medicine are still unclear. Generally speaking, Kampou medicine has been shown to have fewer side‐effects than Western medicine based on the experience gained from its long usage. We first selected 16 Kampou extracts for screening as possible calcium oxalate stone prophylactic agents in vitro. This resulted in the selection of two kinds of Kampou extracts, Takusya and Kagosou, as potential Kampou extracts for stone prophylaxis. Next, these two Kampou extracts were tested in vivo for their effects on stone formation in an animal model. Takusya showed significant stone prophylaxis, while Kagosou did not. Lastly, Chorei‐to, which contains Takusya and has been approved for prescription as a Kampou medicine for urolithiasis patients in Japan, was examined in vivo at two different concentrations. As a result, a low dose of Chorei‐to which corresponded to the human daily dose per unit of body weight exhibited apparent stone prophylaxis, despite the disadvantage of decreasing citrate excretion. In contrast, high doses of Chorei‐to did not exhibit stone prophylaxis in viva These results suggest that Chorei‐to has conflicting effects on stone prevention as a whole, but the Takusya extract in Chorei‐to seems to play a major role in stone prophylaxis and the remaining four Kampou extracts seemed to interfere with the prophylactic effect of Takusya on calcium oxalate stone formation.

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.

Urinary crystal surface binding substances on calcium oxalate crystals

SummaryIn order to study the effect of urinary crystal surface binding substances (CSBS), we extracted the naturally existing CSBS from urine from healthy individuals by conducting homogeneous crystallization of calcium oxalate. CSBS proved not to be promoters but rather strong inhibitors of calcium oxalate crystal growth and aggregation. It is suggested that CSBS exhibited their inhibitory effect by masking the growing sites and aggregating sites on the crystal surface. As for the characteristics of CSBS, we found around 10 peaks of molecular weight, and all of them contained both peptides and saccharides. The findings suggest that CSBS are composed of various kinds of glycoproteins and proteoglycans.

Immunohistochemical study of nodular hyperplastic parathyroid glands in patients with secondary hyperparathyroidism

Thirty-seven nodular hyperplastic parathyroid glands obtained by subtotal parathyroidectomy from 11 haemodialysed patients with secondary hyperparathyroidism were examined both pathologically and immunohistochemically. Four consecutive sections of the largest section-surface of each gland were subject to 4 different stains (haematoxyline-eosin, Grimelius, and the immunohistochemical stains for parathyroid hormone and chromogranin A) for comparison of each nodule. It was found that the major part of each nodule consisted of a single cell type with a single pattern of cells. These reacted uniformly to each stain. The mechanism involved in the storage and secretion of the secretory granule appeared to be regulated at the nodule and not at the cell level. The results suggest that the nodules may come from a monoclonal proliferation of a single parathyroid cell. Our present light microscopic immunohistochemical study, failed to demonstrate completely identical immunoreactive positivity of each nodule or each parathyroid cell to PTH. Chromogranin A or secretory protein-I did not indicate the coexistence of PTH and SP-I in the same secretory granule, which was in good agreement with the electron microscopic immunocytochemical study of Arps using bovine parathyroid glands. Our present study, however, provides good evidence that chromogranin A positivity is demonstrable in the human parathyroid gland outside the adrenal medulla and sympathetic nerves.

Clinical Manifestations of Calcium Oxalate Monohydrate and Dihydrate Urolithiasis

We studied retrospectively 155 patients with calcium oxalate urolithiasis. The patients were divided into 3 groups: 1) those with calcium oxalate monohydrate, 2) those with calcium oxalate dihydrate and 3) those with mixed calcium oxalate monohydrate and dihydrate. Various differences were noted between patients with calcium oxalate monohydrate and those with calcium oxalate dihydrate, with respect to stone characteristics, spontaneous passage of stones, stone recurrence and multiple occurrence. Most important, we noted that patients with calcium oxalate dihydrate had more stone recurrences than patients with calcium oxalate monohydrate.

Pituitary-gonadal function in schoolboys with varicocele and indications of varicocelectomy.

Pituitary-gonadal functions were investigated by LH-RH test, HCG test and bilateral testicular biopsies in 5 boys with unilateral varicocele at various pubertal stages and the results were compared with those in the normal boys at puberty. The ages of the patients ranged from 12 to 18 years. With the progress of pubertal stage, both the basal value and response of serum FSH to LH-RH became higher as compared with normal boys. The basal value and response of serum LH showed no significant difference except for one case where higher values and no significant differences in the basal value and response of plasma testosterone to HCG stimulation were observed. The disturbance of spermatogenesis in the affected testis becomes prominent with the progress of puberty, while changes in the testis of opposite side were mild.

A Simple hCG Stimulation Test for Normal and Hypogonadal Males

A simple human chorionic gonadotropin (hCG) test to measure Leydig cell function is described. Plasma testosterone was measured on two occasions, once before intramuscular injection of 10,000 IU of hCG and again four days later. Preliminary tests in 10 adult males showed a maximal increase in plasma testosterone between the third and fifth day that was confirmed in a further 20 normal subjects when measured once on the fourth day. Except for 2 patients with hypospermatogenesis, 24 showed a good response and the mean increase was comparable with that in normal males. Nineteen patients with Klinefelters syndrome usually had lower basal levels and showed a poor response, with the exception of six patients in whom there were moderate but definite increases. Twelve patients with hypogonadotropic hypogonadism had basal testosterone concentrations below 1 ng/ml and eight responded poorly to hCG stimulation. However, four patients showed a moderate but definite response.