Masanobu Maekawa

Side Effects of Extracorporeal Shock-Wave Exposure in Patients Treated by Extracorporeal Shock-Wave Lithotripsy for Upper Urinary Tract Stone

The side effects of shock-wave exposure on patients treated by extracorporeal shock-wave lithotripsy were analyzed by measuring chemical substances including cell-escaped enzymes in the blood and urine. Free hemoglobin, glutamic oxaloacetic transaminase (GOT) and lactate dehydrogenase (LDH) increased as a function of shock-wave count. Total bilirubin, GOT and LDH reached a peak on the 1st postoperative day and decreased to pretreatment values by the 4th day. Creatine phosphokinase and myoglobin also significantly increased on the 1st postoperative day but returned to pretreatment levels by the 4th day. The urinary ratio of N-acetyl-beta-d-glucosaminase to creatinine significantly increased after treatment and was still high on the 4th day. These results suggest that significant hemolysis and myolysis developed owing to shock-wave exposure, and that the kidney was damaged to some extent. Therefore, these side effects must be taken into account in determining the dose and frequency of treatment.

Purification and NH2-terminal amino acid sequences of human and rat kidney fatty acid ω-hydroxylases

A cytochrome P-450 (P-450), designated P-450HK omega, has been isolated and purified from human kidney microsomes to a specific content of 13 nmoles of P-450/mg of protein. P-450HK omega showed an apparent molecular weight of 52,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Absolute spectra of the oxidized form indicated that this P-450 was largely in the low-spin state and partly in the high-spin state. It catalyzed the omega- and (omega-1)-hydroxylation of fatty acids such as laurate, myristate, and palmitate, with no activity toward prostaglandin A1, benzphetamine, 7-ethoxycoumarin, or 7-ethoxyresorufin. The first 35 NH2-terminal amino acid sequence of P-450HK omega had about 70% homology with those of rabbit kidney fatty acid omega-hydroxylases of the P-450 IVA gene subfamily, P-450ka-1, P-450ka-2, and P-450kd, except for four undetermined residues. Moreover, Western blot and immuno-inhibition studies showed that P-450HK omega reacted with an antibody against the rabbit kidney fatty acid omega-hydroxylase. The results suggest that P-450HK omega is a member of the same P-450 gene family (IVA subfamily) as the rabbit enzymes. In addition, the terminal sequence of P-450HK omega also showed 54% homology with that of P-450k-2, a fatty acid omega-hydroxylase from rat kidney microsomes. To our knowledge, this is the first time that a P-450 specific for fatty acid omega-hydroxylase activity has been isolated to homogeneity from human tissues.

Effects of high energy shock wave exposure on renal function during extracorporeal shock wave lithotripsy for kidney stones

In order to study the effects of high energy shock wave exposure on the kidney in extracorporeal shock wave lithotripsy (ESWL) using Dornier HM3, renal hemodynamics and renal function before and after ESWL were analyzed by 99mTc-DTPA renoscintigraphy. Various urinary enzyme activities (LDH, GOT, GPT, NAG, gamma-GTP) and low molecular protein concentrations (alpha 1-microglobulin, beta 2-microglobulin) before and after ESWL were also compared. In the early phase of the renoscinitgram obtained in the 1st min after injection of 99mTc-DTPA, the time required to reach maximum radioactivity was significantly prolonged after ESWL in both the affected and contralateral kidney. This indicated that renal blood flow decreased in both the affected and contralateral kidney immediately after ESWL. An analysis of the 30-min renoscintigram showed that urinary clearance was delayed in the affected kidney in spite of no overt obstruction due to stone fragments. As for urinary enzyme activities and low molecular protein concentrations, they were standardized by urinary creatinine concentration measured at the same time. Urinary LDH, GOT, GPT and NAG activities remarkably increased on the day of ESWL followed by a decrease close to pretreatment levels on the 4th day, though these levels were still significantly higher than pretreatment levels. Urinary gamma-GPT activity was significantly higher than the pretreatment level only on the day of ESWL. Urinary alpha 1-microglobulin and beta 2-microglobulin concentrations significantly increased on the day of ESWL and were still high on the 4th day.(ABSTRACT TRUNCATED AT 250 WORDS)

Examination of Aggravating Factors of Urinary Excretion of N-Acetyl-Beta-D-Glucosaminidase after Extracorporeal Shock Wave Lithotripsy

We measured urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion before and after extracorporeal shock wave lithotripsy (ESWL) with a view to study the underlying factors which aggravate renal impairment immediately after ESWL. The factors associated with the significant elevation of urinary NAG after ESWL included female sex, a previous history of ESWL, and urinary tract infection (UTI). By studying the backgrounds of these factors, we found that both the female group and the group with a previous history of ESWL contained significantly more patients with UTI. These findings indicate that UTI may be one of the risk factors which aggravate renal damage immediately after ESWL, and that careful management is necessary in the ESWL treatment of urinary tract stones with UTI.

Specific and rapid assay of urinary oxalic acid using high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method was developed to determine the levels of oxalic acid in the urine. This acid was extracted from urine with tri-n-butyl phosphate and converted into the fluorescent derivative by esterification with 9-anthryldiazomethane (ADAM). The reaction mixture containing the oxalic acid derivative can be directly chromatographed on HPLC using octadecylsilane reverse-phase column monitoring with a fluorophotometric detector. A linear relationship was observed in the range from 1 to 100 micrograms/ml of standard oxalic acid dissolved in saline. Disease-free Japanese adults excrete 23.8 +/- 9.0 mg (mean +/- SD) of oxalic acid per day. This method should prove valuable for routine measurements of urinary oxalic acid as it is accurate, simple, and specific.

Molecular understanding of cellular adhesion on artificial surfaces

This study was conducted to clarify cellular adhesion mechanisms of blood cells (platelets [PLT] and white blood cells [WBC]) and vascular endothelial cells at the molecular level. This study indicated that the adhesion of three cellular systems to proteins such as fibronectin and fibrinogen proceeds via the RGD (Arg-Gly-Asp) ligand-receptor interaction, in which the RGD tripeptidyl sequence is the minimal amino acid sequence common to adhesive proteins. This was evident from the dose-dependent inhibitory effect of RGD-containing peptide on cellular adhesion. Additional supporting evidence was the presence of PLT and WBC receptors, which molecularly recognize RGD, verified by fluorescein-labelled RGD-containing peptide. The adhesion of vascular endothelial cells was also predominantly controlled by the ligand-receptor mechanism, and participation of complement activation on WBC adhesion was demonstrated as well. The adhesion of WBCs on surface hydroxyl group-bearing polymers proceeded via the CR3 receptor-C3b ligand interaction, in which activated complement factor C3b is chemically fixed upon complement activation. Thus, the molecular understanding of cellular adhesion mechanisms provide the basis of biocompatibility for implantation and extracorporeal circulation, as well as molecular design of artificial and bioartificial organs.

Correlation of tumor necrosis factor and prostaglandin E2 production of monocytes in bladder cancer patients

Patients with advanced malignant neoplasms have a variety of abnormal monocyte and lymphocyte functions. The authors examined tumor necrosis factor (TNF) and prostaglandin E2 (PGE2) production of monocytes in 48 patients with bladder cancer and 16 control subjects. Monocytes were isolated from peripheral blood mononuclear cells by adherence to plastic tissue. They were cultured with lipopolysac‐charide for 24 hours, and the culture supernatant was obtained. The TNF was measured by enzyme immunoassay using anti‐recombinant human TNF antibody, and PGE2 was measured by radioimmunoassay. As a result, in high‐stage bladder cancer patients, there was a significant inverse correlation between TNF and PGE2 production of monocytes. However, there was no significant correlation in control subjects and low stage patients. Accordingly, some patients with high‐stage bladder cancer had higher TNF production but lower PGE2 production of monocytes, and vice versa.

Serum Levels of Acetate and TCA Cycle Intermediates during Hemodialysis in Relation to Symptoms

In order to study the metabolism of acetate transferred from dialysate, the plasma concentrations of organic acids including the tricarboxylic acid cycle (TCA cycle) intermediates were measured during hemodialysis in a comparative study between acetate dialysate and bicarbonate dialysate in 17 patients on maintenance hemodialysis treatment. Continuous measurements of serum concentrations of these organic acids during hemodialysis were performed using the filtrate obtained through an ultrafiltrate sampling device. The organic acids were measured by isotachophoresis. Serum acetate, malate and citrate concentration increased with time in acetate dialysis compared with bicarbonate dialysis. Correlations were found between these organic acids. Isocitrate became detectable when the serum acetate concentration was over 7 mmol/l which was correlated to the acetate concentration, and was accompanied by the development of symptoms. The above results suggest that an acetate overload on the patients during acetate dialysis affects acetate metabolism through the TCA cycle resulting in an accumulation of organic acids in the serum and the development of symptoms.

Stone fragility-measurement of stone mineral content by dual photon absorptiometry

We measured the mineral content of urinary tract stones by dual photon absorptiometry, which is widely used for the analysis of bone mineral content, and compared the values of the stones by dual photon absorptiometry (DPA values) with the results of an in vitro fracture study as well as those of an in vivo extracorporeal shock wave lithotripsy treatment study. The results of a preliminary experiment showed that the DPA values of 20 urinary tract stones reflected actual stone mineral content. As a result of the in vitro fracture study, the DPA value calculated by volume of a struvite stone, which was the most easily disintegrated, was the lowest (0.53 g/cm3). The DPA values of calcium oxalate monohydrate and apatite stones, which poorly disintegrated, were the highest (0.98, 1.01 g/cm3). The DPA value of calcium oxalate dihydrate, which moderately disintegrated, was 0.86 g/cm3. By the in vivo extracorporeal shock wave lithotripsy treatment study, the total DPA values of stones measured before extracorporeal shock wave lithotripsy treatment in 12 patients were 0.73 +/- 0.34 g in successful cases and 1.92 +/- 0.43 g in unsuccessful cases with a significant difference between the two (p less than 0.05). These results showed that the measurement of stone mineral content by dual photon absorptiometry was useful in predicting the fragility of stones against shock waves before performing extracorporeal shock wave lithotripsy treatment for patients with urinary tract stones.

Granulocytic sarcoma of testis preceding acute myelocytic leukemia.

A unique case of granulocytic sarcoma of the testis as a first manifestation of acute myelocytic leukemia preceding hematologic pathology is reported. The testicular specimen was identified by immunoperoxidase staining to be composed of immature granulocytes. Acute myelocytic leukemia of which the first manifestation is a primary testicular tumor is extremely rare, and the related literature is reviewed.