Morihiro Watanabe

Therapeutic Outcome of Primary Aldosteronism: Adrenalectomy Versus Enucleation of Aldosterone-Producing Adenoma

Our followup study of 48 patients with primary aldosteronism concerns the results of 2 different operative methods. After preoperative localization of the unilateral solitary tumor 22 patients underwent unilateral adrenalectomy and 26 underwent enucleation of aldosterone-producing adenoma. Both operative methods improved hypertension, hypokalemia, the low urinary sodium-to-potassium ratio, suppressed plasma renin activity, high plasma aldosterone concentration, high urinary aldosterone excretion and high urinary kallikrein excretion in similar orders of magnitude for 5 years. Levels of plasma cortisol and plasma adrenocorticotropic hormone following respective operations were also identical. Five years postoperatively, ambulation and furosemide administration under low sodium diet stimuli remarkably enhanced plasma renin activity and plasma aldosterone concentration in the aldosterone-producing adenoma enucleation group (p < 0.001), almost similar to that of normal subjects but increment magnitudes were slight (p < 0.05 to < 0.01) in the adrenalectomy group. Preoperatively, angiotensin II infusion failed to increase plasma aldosterone concentration in patients with primary aldosteronism. After respective operations, responses of plasma aldosterone concentration to angiotensin II infusion and of plasma cortisol to adrenocorticotropic hormone administration in the aldosterone-producing adenoma enucleation group were more sensitive than those in the adrenalectomy group. There was no remission of recurrent hyperaldosteronism in either group throughout the study. These results suggest that angiotensin II induces aldosterone release by an activation of tumor uninvolved cortical cells and that the enucleation of aldosterone-producing adenoma is more preferable than unilateral adrenalectomy.

Electropermeabilization in bladder cancer chemotherapy.

Abstract Purpose: Electropermeabilization has been used for the introduction of genes into cells. Using this technique, we introduced the cytotoxic drug bleomycin (BLM) into cells and examined whether the technique might be useful for the treatment of bladder cancer. Materials and methods: For electropermeabilization in vitro, we used YTS-1 cells, a human transitional cell carcinoma line. Aliquots of cell suspension were mixed with a solution of BLM and immediately exposed to electric pulses. A high-power pulse generator was used to supply square-shaped pulses of 1250 V/cm (100 μs, eight pulses). After a 2-h post-shock incubation, cells were washed and incubated for one further hour. Then the concentration of BLM in the cells was measured using a bioassay. For electropermeabilization of tissue, we used normal male Wistar rats. The bladder was exposed and 10 mg/kg BLM was injected into the caudal vein. A series of eight pulses with a time constant of 100 μs at an electric field intensity of 1000 V/cm was applied. The bladder, liver and lungs were extracted 1 h later and prepared for quantification of the BLM concentration using the bioassay. Results: Electrotreated cells contained significantly higher concentrations of BLM than nonelectrotreated cells. The concentration of BLM 1 h after electrotreatment in bladder tissue was 2.7 times higher than that in nonelectrotreated bladder tissue. Conclusion: The electropermeabilization technique has the potential to serve as a new and effective modality for the treatment of bladder cancer.

Left Preureteral Vena Cava (Retrocaval or Circumcaval Ureter) Associated with Partial Situs Inversus

We present a rare case of left preureteral vena cava associated with partial situs inversus. A 68-year-old woman was referred to our clinic for further study of left hydronephrosis on computerized tomography. The abdominal viscera were in mirror image and the heart was levocardia. The middle portion of the left ureter was dorsal to the left inferior vena cava. The left ureter was reanastomosed ventral to the inferior vena cava. To our knowledge, coexistence of preureteral vena cava and partial situs inversus has not been reported previously in the literature.

Analysis of protooncogene c-erbB-2 in benign and malignant human prostate.

In this report, we characterized the c-erbB-2 gene and its product in prostatic cancer cells. Three prostatic cancer cell lines (PC3, DU145 and TSU-Pr1), one primary prostatic cancer and four benign prostatic hyperplasias (BPH) were studied. In reverse transcribed polymerase chain reaction, c-erbB-2 mRNA was demonstrated in all three cell lines and prostatic cancer tissues as well as BPH. The c-erbB-2 protein was expressed higher in prostatic cancer cells and tissues as compared with benign tissue by enzyme immunoassay, but it was not statistically significant. Immunohistochemical study, with the monoclonal antibody SV2-61γ that recognizes the extracellular domain of c-erbB-2, showed that all the prostatic tissues and cells had reactivity. Antigenicity was mainly in the cytoplasm. Analysis of genomic DNA failed to disclose gene amplifications or rearrangements of c-erbB-2 in both prostatic cancer and BPH. The sequence of amplified c-erbB-2, which corresponds to transmembrane domain, disclosed wild type in all prostatic cancer cells. These results demonstrate that although the number is limited, c-erbB-2 gene and protein are expressed in prostatic cancers and benign prostates. In the previous studies on c-erbB-2 expression in prostatic tissue, mainly conducted by immunohistochemistry, its frequency varies among each study, ranging from less than 0% to 100%. Therefore, to evaluate the c-erbB-2 in prostatic tissue precisely, it is also necessary to detect mRNA of c-erbB-2 as demonstrated in our study.

Suppression of sympathetic nervous system attenuates the development of two-kidney, one-clip goldblatt hypertension

PURPOSE This study tried to assess the possible contribution of the sympathetic nervous system to the onset of two-kidney, one-clip (2K-1C) Goldblatt hypertension. MATERIALS AND METHODS The effect of chlorisondamine administration with or without subsequent splanchnicotomy on the development of hypertension was examined in 2K-1C rats with special reference to norepinephrine synthesis. RESULTS The 2K-1C rats were treated either with chlorisondamine or chlorisondamine plus subsequent splanchnicotomy, so that the development of hypertension was effectively arrested for 4 weeks. An apparently high rate of release of norepinephrine in 2K-1C rats was reduced by treatment with chlorisondamine plus splanchnicotomy. A similar trend was also seen in plasma norepinephrine concentration and norepinephrine clearance, to a lesser extent. There were significant positive relationships between percent change of systolic blood pressure and apparent rate of release of norepinephrine, plasma norepinephrine concentration and norepinephrine clearance in 2K-1C rats and 2K-1C + chlorisondamine + splanchnicotomy rats. There were no significant relationships in these parameters in sham-treated rats. CONCLUSION Increased sympathetic innervation appears to participate in the development of 2K-1C Goldblatt hypertension.

Dihydroxyphenylglycol in Pheochromocytoma: Its Diagnostic Use for Norepinephrine Dominant Tumor

PURPOSE To discern whether the 3,4-dihydroxyphenylglycol produced in adrenal medulla is associated with altered urinary excretion, we compared the tissue and urinary levels of this catecholamine metabolite, epinephrine and norepinephrine in 23 patients with pheochromocytoma and 26 subjects with renal cell carcinoma. MATERIALS AND METHODS Tissue and urine concentrations of dihydroxyphenylglycol, epinephrine and norepinephrine were determined by catechol-O-methyl-transferase-based radioenzymatic method and high performance liquid chromatography with electrochemical detection. RESULTS Contents of dihydroxyphenylglycol, epinephrine and norepinephrine in pheochromocytomas were higher than those in normal adrenal medullae. Removal of pheochromocytomas lowered urinary excretion of these catecholamines and dihydroxyphenylglycol. Norepinephrine content correlated closely with dihydroxyphenylglycol content in normal adrenal medullae and pheochromocytomas but not with epinephrine content in either tissue. Contents of norepinephrine and dihydroxyphenylglycol correlated significantly with urinary norepinephrine excretion and dihydroxyphenylglycol excretion in patients with pheochromocytoma but not in subjects with renal cell carcinoma. The norepinephrine-to-dihydroxyphenylglycol ratio in a 24-hour preoperative urine collection from patients with pheochromocytoma was higher than that from subjects with renal cell carcinoma, which was almost similar to that of epinephrine dominant pheochromocytomas. CONCLUSIONS Our study suggests that dihydroxyphenylglycol in urine in subjects with renal cell carcinoma is predominantly of a neuronal origin and urinary dihydroxyphenylglycol in patients with pheochromocytoma is of tumor origin. A high level of norepinephrine-to-dihydroxyphenylglycol ratio in urine can be used to determine the diagnosis of the norepinephrine dominant type pheochromocytoma. Measurement of at least a few markers is preferable for precise biochemical diagnosis of pheochromocytoma.

REMARKABLY SUPPRESSED MANGANESE SUPEROXIDE DISMUTASE ACTIVITY IN MALIGNANT PHEOCHROMOCYTOMA

There are almost no special histopathological characteristics or criteria that exactly define a malignant pheochromocytoma. Tissue concentrations of catecholamine metabolites and superoxide dismutase activity have been proposed as possible candidates for discriminating between benign and malignant pheochromocytomas. Tissue concentrations of dihydroxyphenylalanine, metanephrine, normetanephrine, vanillylmandelic acid, and 3-methoxy-4-hydroxyphenylethylglycol were determined in 29 normal adrenal medullas, 13 benign pheochromocytomas and 6 malignant pheochromocytomas, respectively. The copper-zinc superoxide dismutase and manganese superoxide dismutase activities in remnants of these tissues were determined by interruption of nitric formation from hydroxylamines. Catecholamine metabolites and copper-zinc superoxide dismutase activity in benign and malignant pheochromocytomas were identical. Manganese superoxide dismutase activity in malignant pheochromocytoma was the lowest among the groups examined. These data suggest that the assay of catecholamine metabolites in removed specimens is not a reliable method for making a differential diagnosis of benign or malignant pheochromocytoma. However, a low level of manganese superoxide dismutase activity in malignant pheochromocytoma may be a marker for malignancy of this neoplasm.

The effect of oestradiol-17β on connective tissue protein in rat prostate

The concentrations of collagen, non-collagenous protein and elastin in ventral and dorsolateral prostates in oestradiol-17β-treated rats were higher than in vehicle-treated rats. Thein vivo incorporation rates of3H-proline into these connective tissue proteins in ventral and dorsolateral prostates were reduced following oestradiol-17β-treatment. The degradation rate of3H-proline incorporated into each connective tissue protein was lowest in oestradiol-17β-treated animals.These findings indicate that the accumulation of collagen, non-collagenous protein and elastin in prostates of oestradiol-17β-treated rats can be largely accounted for by the suppressed degradation of biosynthesis of these connective tissue proteins.

Increased vascular collagen and noncollagenous protein synthesis contributes to sustain chronic phase of two-kidney, one-clip renovascular hypertension

PURPOSE Although the enhanced renin-angiotensin (R-A) system responsible for two-kidney, one-clip (2K-1C) hypertension is well known, there may be a shift with time so that this, hemodynamic factor plays a less important role and increased vascular resistance is predominant in sustaining hypertension. While increased vascular protein synthesis has been demonstrated in genetically hypertensive rats, we evaluated the possible relationship between vascular protein synthesis and 2K-1C hypertension with special reference to the R-A system. MATERIALS AND METHODS Two-kidney one-clip rats were treated with splanchnicotomy, beta-aminopropionitrile (collagen inhibitor), or captopril (angiotensin converting enzyme inhibitor) in the acute or chronic hypertensive phase. 3H-proline was injected into rats, and incorporation rates of 3H-proline into vascular collagen, noncollagenous protein and elastin were counted. The plasma level of the R-A system was assayed. RESULTS In the acute phase of 2K-1C hypertensive rats whose R-A system was enhanced, captopril treatment further enhanced plasma renin activity and plasma angiotensin I and suppressed plasma angiotensin II while reducing blood pressure. Synthesis of the vascular proteins was almost identical. In the chronic phase of 2K-1C hypertensive rats whose R-A system was within normal limits, increased incorporation rates of 3H-proline into noncollagenous protein or collagen of mesenteric arteries were decreased by splanchnicotomy or beta-aminopropionitrile and hypertension was lowered. Captopril failed to reduce protein synthesis. CONCLUSIONS An enhanced R-A system participates in the pathogenesis of the acute phase of 2K-1C hypertension while increased noncollagenous protein and collagen syntheses of small arteries appear to play some role in the etiology of the chronic phase of hypertension.

Successful renal autotransplantation with Y-prosthetic aortic replacement in a patient with complete occlusion of abdominal aorta and renal artery.

Occlusion of the abdominal aorta represents the end stage of an atherosclerotic process and often is associated with stenosis of renal artery inducing renal failure and hypertension. Surgical and medical treatments are indicated to preserve and restore renal function in patients with these conditions. We report herein the first successful renal autotransplantation combined with aortic replacement by Y prosthesis in a patient with complete occlusion of abdominal aorta and bilateral renal arteries, resulting in limb-threatening ischemia and progressive renal failure.