Asymmetric synthesis with a chiral catalyst generated from asymmetric autocatalysis.

A new and efficient one-pot system of asymmetric catalysis is presented in which a chiral catalyst (5-pyrimidyl alkanol) self-improves its ee by asymmetric autocatalysis and then acts as a highly enantioselective chiral catalyst for other asymmetric synthesis (addition of dialkylzincs to aldehydes) to provide products (sec-alcohols) with very high ee (up to 99%).[reaction: see text]

[A case of congenital hydronephrosis suffering from rupture of the renal pelvis due to trauma].

A 19-year-old male patient was admitted with the chief complaint of left abdominal pain. After receiving a mild punch in the abdomen during boxing exercises, he had severe abdominal pain and was brought to an emergency room. Since abdominal CT scanning revealed the retention of massive fluid in the retroperitoneum, hydronephrotic rupture due to the trauma was diagnosed and nephrectomy was performed. The removed kidney was filled as a result of urinary retention, and congenital hydronephrosis accompanied by the ureteropelvic junction obstruction was macroscopically and pathohistologically diagnosed. Postoperative course was favorable and the patient was discharged on the 10th hospital day.

Asymmetric autocatalysis of a pyrimidyl alkanol induced by chiral monosubstituted [2.2]paracyclophanes.

[figure: see text] Monosubstituted[2.2]paracyclophanes 3a-c with planar chirality were found to act as chiral initiators in an enantioselective addition of diisopropylzinc to 2-alkynylpyrimidine-5-carbaldehyde 1 to afford 2-alkynylpyrimidyl alkanol 2 with up to 97% ee.

[A case of ureterovesical malacoplakia that manifested hydronephrosis].

A 70-year-old woman visited a nearby physician with a chief complaint of fever and was admitted to a hospital with a diagnosis of acute pyelonephritis. After discharge, pyuria persisted and examination revealed an intravesical solid tumor. The patient was referred to this department for close examination and treatment. The right kidney was hydronephrotic. The intravesical tumor that was resected was solid yellowish-white and ranged from the neck of the uterus to both ureteral orifices. In addition, a grain-sized tumoral lesion, was found in the lower part of the ureter and was also resected. There was sclerotic thickening localized to the right intramural ureter, which had a slightly edematous interior. This was considered to be the cause of the hydronephrosis and a ureteral stent was put in place. Pathological diagnosis was given as malacoplakia. With this case, placement of a ureteral stent was chosen based on the findings of a minimal ureteral lesion, a narrow area of scarring in the intramural ureter as a probable cause of hydronephrosis, and a judgement of mild obstruction. A stent is less invasive for patients, but consideration should be given to urinary infection due to long-term placement recurrence of malacoplakia due to the increased risk of infection, and trouble with periodical exchanging of catheters due to aggravated scarring. Absence of pyuria or signs of recurrence after seven months' placement suggests that use of the stent was the best method.

Telomerase activity in human renal cell carcinoma.

PURPOSE: Telomerase activity has been detected in a wide variety of human tumors. The present study evaluated telomerase activity in association with the acquisition of renal cell carcinoma (RCC). METHODS: Telomerase activity was examined in 30 RCC and the adjacent normal kidney tissue, obtained as surgical specimens. The activity was assayed by polymerase chain reaction-based telomeric repeat amplification protocol assay. RESULTS: Among the 30 RCC, 18 (60%) displayed telomerase activity, whereas none of the normal tissue samples exhibited it. Subdivision of the tumors according to telomerase activity did not reveal any obvious difference in distribution with regard to tumor size, stage, histocytological subtype, or DNA-ploidy. However, a statistically significant relationship was found between the frequency of telomerase-positive activity and both serum immunosuppressive acidic protein level in the patient and tumor grade (P<0.05). There was no significant difference in the recurrent-free survival and the disease-specific survival between patients with positive telomerase activity and patients with negative activity. CONCLUSION: The present results indicate that telomerase activity might be related to the progression of RCC and thus a marker of malignant potential.

Long-term follow-up of the Indiana pouch: efficacy of the pouch construction using the absorbable gastrointestinal staples.

The Indiana pouch procedure was used on 34 bladder cancer patients. The Heinecke-Mikulicz reconfiguration was carried out, involving the conventional hand-sewn and the absorbable GIA stapled methods with the continence mechanism of a staple-tapered efferent limb. The tunnelled tenial anti-refluxing implantation of ureters was performed. The stapled pouch construction saved approximately 1 h of operating time and reduced by 18% the overall loss of blood. There were 3 complications (wound infection/dehiscence in two, leakage from the enteric anastomosis in one, and acute renal failure in one) within 30 days postoperatively. As a late complication, ureter implantation stricture was experienced in two and pouch stone formation in five. No significant difference in the incidence of stone formation was evident between the hand-sewn and the stapled pouches, nor was any difference of pouch volume and catheterization interval. All patients had acceptable continence. These data demonstrated that the Indiana pouch is a reliable procedure with an acceptable complication rate. The pouch construction using the stapled method, which simplified the procedure, is more convenient than the one using the hand-sewn technique.

[Metastatic renal tumor originating from esophageal carcinoma: a case report].

We report a case of renal metastasis from esophageal carcinoma. The patient was a 74-year-old man, who had undergone an operation for esophageal carcinoma thirteen months previously. He was admitted to our clinic for examination of a right renal mass. Computed tomography (CT) revealed an irregular low density area in the right kidney and angiography showed a hypovascular tumor. Partial nephrectomy was performed. Histological examination revealed squamous cell carcinoma and the diagnosis was metastasis of esophageal carcinoma. Metastatic renal tumors are rarely encountered clinically and, to our knowledge, the present case is only the 16th clinical report of the renal metastasis of esophageal carcinoma in Japan. However, metastasis to the kidney is relatively common at autopsy. It is the fifth most common site of metastasis following the lungs, liver, bones and adrenals. Consequently, patients with malignancy should be followed up while keeping renal metastasis in mind.

Inhibition of tumor growth and angiogenesis by vitamin D3 agents in murine renal cell carcinoma.

PURPOSE: To investigate the effect of active vitamin D3(VD) agents on tumor growth and metastasis. MATERIALS AND METHODS: BALB/c mice were inoculated with murine renal cancer Renca and graded doses of 1,25-dehydrovitamin D3 or 1- hydrovitamin D3 were given intraperitoneally every other day beginning on day 1, 3, or 7 and ending on day 9, 11, or 15. Direct cytocidal activity and angiogenic activity were evaluated by 48-hour MTT assay and by the colorimetric method, respectively. RESULTS: Both VD agents inhibited tumor growth and prolonged the life span of Renca-bearing mice in a dose-dependent manner and both suppressed tumor growth in athymic mice and euthymic mice with eliminated NK activity. Marginal body-weight loss without appreciable hypercalcemia was observed in mice given VD agents. When treatment was delayed on day 7, the VD agents failed to inhibit tumor growth. The MTT assay showed no direct cytotoxicity of VD agents on Renca. Tumor angiogenesis was inhibited to 46 to 30% of the control level by VD agents. Furthermore, VD agents reduced pulmonary and hepatic foci in the metastatic models. CONCLUSIONS: These results suggest that VD agents may be effective as a treatment for renal cell carcinoma, especially when micrometastases are involved.

[Primary squamous cell carcinoma of the prostate: a case report].

The patient was a 77-year-old man who visited our clinic with a chief complaint of dysuria. Digital rectal examination suggested prostatic carcinoma, but prostatic tumor marker levels were within normal limits. Transrectal needle biopsy was performed and histology was squamous cell carcinoma. Radical prostatectomy and pelvic lymph node dissection were performed with the diagnosis of T3N0M0 primary squamous cell carcinoma of the prostate. The 127 gm. tumor was moderately differentiated pT3N2M0 squamous cell carcinoma. Metastasis to the bilateral internal iliac arterial lymph nodes was confirmed histologically. Therefore, four courses of chemotherapy were performed using methotrexate, cisplatin, and pepleomycin. However, local recurrence was observed 11 months postoperatively and multiple pulmonary metastasis was developed at 13 months. The patient died of the disease 14 months after the operation. In Japan, seven cases of primary squamous cell carcinoma of the prostate have been reported, but none of these patients were treated by radical prostatectomy when the diagnosis was established by preoperative biopsy. In this case, changes in the squamous cell carcinoma antigen level in the blood corresponded to the effect of postoperative chemotherapy.

Surgical treatment of renal cell carcinoma extending into the vena cava.

BACKGROUND: Renal cell carcinoma has a tendency to invade the vasculature and the prognostic implications of intravena caval tumor thrombectomy remains controversial. We reviewed our clinical experience with RCC patients who underwent tumor thrombectomy and radical nephrectomy. METHODS: Surgery was carried out in 13 renal cell carcinoma patients with inferior vena cava extension over the past seven years. Diagnosis of intracaval tumor extension and thrombus formation was made by imaging techniques including ultrasonography and computed tomography. Cavography and magnetic resonance imaging were also performed in some cases. RESULTS: The level of the tumor thrombus was infrahepatic (V2a) in nine cases and retrohepatic (V2b) in four. Ultrasound and magnetic resonance imaging were extremely useful in defining the extent of the thrombus in addition to detecting its presence. The caval thrombi were reached simply by ligation and division of the short hepatic veins in the V2a cases, but liver mobilization was required in the V2b cases. There were no operative deaths. Two patients who had metastases on surgery died of the disease eight and 13 months after surgery. Four of the 11 patients in whom no evidence of metastasis was found on surgery also died of the disease between nine and 16 months postoperatively. The remaining seven patients are still alive at periods of 6-74 months after surgery, with or without residual tumors. The nature of the intracaval tumor thrombi seems to affect the overall prognosis for survival. Elevated levels of acute phase reactants and immunosuppressive acidic protein were associated with short survival times. CONCLUSIONS: Our experience suggests that aggressive surgery should be considered in selected patients with non-metastatic renal cell carcinoma extending into the vena cava.

[Clinical study of renal cell carcinoma invading adjacent organs].

We studied 15 patients with renal cell carcinoma invading adjacent organs (stage T4) between January 1980 and December 1991. Such invasion was four times more frequent in males than in females. The patients were between 41 and 78 years old, with a mean age of 63.9 years. The tumor was on the right side in 4 cases, and on the left side in 11 cases. Six patients (40%) presented with flank pain. The pancreas was the organ involved most frequently. Eleven patients had regional lymph node involvement or distant metastasis. Most patients had an increased erythrocyte sedimentation rate (ESR), elevated alpha-2 globulin levels, and positivity for c-reactive protein (CRP). In 6 patients, nephrectomy was extended to the abdominal or retroperitoneal structures that seemed to be invaded by tumor. Patients with T2 or T3 tumor had a significantly longer overall survival than patients with a T4 tumor. However, there was no significant difference in survival between T2/T3 tumors and T4 tumors in nephrectomized patients. Two patients who survived longer than 3 years showed no abnormalities of ESR, alpha-2 globulin and CRP. They also had no nodal or distant metastases, and had a good initial performance status. These findings suggest that extended local resection can improve the survival and quality of life for selected patients with T4 tumors.

[A case of renal liposarcoma].

A-48-year-old male was admitted to our hospital with a right renal tumor. He received radical nephrectomy immediately. Histological examination of surgical specimen revealed renal liposarcoma, which consisted of mixed type of pleomorphic and well differentiated subtypes. Multiple tumorous lesions were scattered in the renal parenchyma. He has been alive without disease for 2 years and 7 months after surgery. Only 23 cases of renal liposarcoma have been reported in Japan.

[Clinical experience of autologous blood transfusion in patients undergoing nephrectomy with renal cell carcinoma].

We studied the possibility of performing radical nephrectomy with only predeposit autologous blood transfusion in the treatment of patients with renal cell carcinoma. A total of 15 patients who ranged in age from 32 to 69 years and had a hemoglobin concentration of over 12 g/dl on admission underwent radical nephrectomy with preoperative autologous blood donation. Five patients did not need transfusions. Seven patients were transfused only autologous blood. The other 3 required some homologous blood in addition to their own banked blood. In our series, patients were able to donate 600 ml of blood during the last week before surgery and their hemoglobin concentration did not decrease by over 2 g/dl except in the case of two patients with advanced disease. Therefore, it was concluded that an adequate autologous blood volume for nephrectomy was 600 ml and that 80% of renal cell carcinoma surgery could be performed without homologous blood transfusion. For patients requiring resection of renal cell carcinoma, autologous transfusion is recommended as safe and convenient.

[Epidermal growth factor in the urine of patients with renal cell carcinoma and bladder tumor].

We evaluated the concentrations of immunoreactive epidermal growth factor (EGF) in urine samples from 14 patients with renal cell carcinoma, 16 patients with bladder tumor and 43 non-malignant controls by using radioimmunoassay. In the non-malignant controls, urinary EGF excretion significantly decreased with age (r = -0.46, p less than 0.01), and females excreted significantly more EGF than males [16.3 +/- 7.6 and 9.9 +/- 6.0 (mean +/- SD) ng/mg.creatinine; p less than 0.05]. There was no significant difference between urinary EGF excretion in the patients with renal cell carcinoma and non-malignant controls matched for sex and age (15.9 +/- 12.0 and 14.5 +/- 7.9 ng/mg.creatinine). The difference in excretion of EGF between the patients with bladder tumor and non-malignant controls also was not significant (9.9 +/- 5.6 and 11.7 +/- 7.0 ng/mg.creatinine). These findings indicate, that urine EGF has little usefulness as a tumor marker for renal cell carcinoma and bladder tumor.

[Effect of biological response modifiers on a spontaneous murine renal cell carcinoma regression of metastases caused by the streptococcal preparation OK-432].

The effect of the streptococcal preparation OK-432, which is one of the biological response modifiers, was examined in BALB/c mice using a transplantable murine renal cell carcinoma (Renca) of spontaneous origin, and an analysis of effector cells was performed. The tumor grew progressively and metastasized consistently to the abdominal lymph nodes and then to distant organs following the inoculation of Renca cells in the left renal subcapsular site in BALB/c mice, and the survival time of the mice was under 42 days. In this tumor model, i.p. administration of OK-432 after tumor inoculation significantly extended the survival time and significantly inhibited the formation of the inoculated tumor itself. Removal of the left kidney on the 7th day after tumor inoculation neither extended the survival time nor augmented the effect of OK-432. Splenic cells obtained on the 7th day after tumor inoculation from Renca-bearing mice treated with OK-432 were capable of lysing syngeneic Renca cells, NK-sensitive allogenic YAC-1 cells, and LAK-sensitive EL-4 cells in a 4-hour 51Cr-release assay in vitro. Those obtained from healthy mice treated with OK-432 also showed cytotoxic activity against Renca cells. The cytotoxicity of splenic cells from Renca-bearing mice treated with OK-432 was lost almost completely for both Renca and YAC-1 cells after in vitro treatment with anti-asialo GM1 antibody, and was partially lost after in vitro treatment with anti-Thy-1,2 antibody. Additionally, in vivo i.p. administration of anti-asialo GM1 antibody significantly counteracted the effect of OK-432 on survival. These findings demonstrated that Renca cells were NK-sensitive and that the i.p. administration of OK-432 was beneficial for the prevention of the spontaneous metastasis of Renca carcinoma. As the effectors, NK cells played a dominant role and activated T cells were also involved.

[Studies on metabolism and disposition of sizofiran (SPG), an anti-tumor polysaccharide. III. Degradation and excretion of SPG in rats].

Degradation and excretion of Sizofiran (SPG), an anti-tumor polysaccharide, were studied in rats after a single or multiple administration. After a single intravenous injection of [14C]SPG (3 mg/kg), SPG distributed in the liver was degraded at very slow rate to SPG-like substances (SPGLS) having lower molecular weight than that of SPG, while SPG in the spleen and mesenteric lymph node was metabolized at much slower rate than that in the liver. In the experiment with multiple subcutaneous administration, SPG was also found to be present mainly as SPGLS in the liver, but almost as an unchanged SPG in the spleen. SPG was excreted in the urine mainly as metabolites with a molecular weight of less than 10000. These results indicate that degradation of SPG to lower molecular weight-SPGLS is a prerequisite for efficient urinary excretion and the degradation occurs mainly in the liver.

[Antitumor activity of UFT against murine renal cell carcinoma: a study on the suppression tumor metastases].

Experimental chemotherapy with UFT was performed against murine renal cell carcinoma (Renca) of spontaneous origin in BALB/c mice and the antitumor activity of UFT was compared with that of 5-FU. By oral administration started from the day after inoculation of Renca cells under the capsule of a kidney, the growth of tumor and formation of the spontaneous metastases to the lymph nodes, lung, spleen, and abdominal wall were inhibited significantly. The UFT or 5-FU treatment started on the 8th day after tumor inoculation also extended the survival time of the tumor-bearing mice and the anti-tumor effect of UFT was more marked than 5-FU. However, UFT treatment started on the 15th day did not prolong the survival time of Renca-bearing mice. From these results, UFT therapy seems to be beneficial for prevention of metastases after nephrectomy in the patients with renal cell carcinoma.

[Serum rifampicin concentrations by means of different assay methods and their critical estimation].

Determination of serum rifampicin (RFP) after dose of the drug is often requested not only for the clinical criteria on its use, but also for the check of its adverse reactions. In comparative examination on each clinical use of 2 kinds of RFP commercial products: Rifadin and Aptesin, the authors had a chance of simultaneous determination of serum RFP by means of 3 different assay methods: solvent extraction method (SE), biological activity method (BA) and liquid-chromatography method (LC). Ten healthy male volunteers and 19 hospital patients (14 males and 5 females) with lung tuberculosis cooperated for this investigations. RFP blood samples were taken serially after oral administration of 450 mg RFP, at 1, 2, 3, 4, 6, 8, 12 and 24 hours in the volunteers, and at 2 and 4 hours in the patients. The serum RFP concentrations determined by the present methods showed generally a good correlation between each other, but there was a considerable difference in their quantity. The highest determinations were presented by the SE, which was devised as total assay method determining desacetyl RFP and 3-formyl rifamycin SV besides free RFP. The lowest determinations were brought about by the LC, which was devised fundamentally for the assay of free RFP. Thus the difference between both determinations by SE and LC was caused by RFP metabolites. This explanation was further proved by the fact that the difference rate, namely (SE-LC)/SE, increased clearly with the lapse of time, and could be used as an index of serial pattern of RFP metabolism. The serum determinations by BA appeared to be useful to monitor clinical efficacy of the drug, but seemed to be out of the absolute estimation. Incidentally the determination by BA was always ranked between both determinations by SE and LC figures. The detailed analysis of two examinations at ten-day intervals in the same volunteers revealed that the RFP determinations by SE appeared to show much better reproducibility than those by BA and LC. By the present assay methods, nearly no difference was demonstrated in the blood level of 2 RFP products. Some attensions were called to the practical estimation of the serum RFP concentrations: Clear individual differences were found in the serum RFP concentrations after dose of the drug, and appeared to become clearer in the stage of its continuous administrations. Above all, it was noteworthy that the individual difference in the first dose of RFP was found to be decided by the grade of absorption within 2 hours after the dose.(ABSTRACT TRUNCATED AT 400 WORDS)

[Clinical efficacy of recombinant interleukin-2 for renal cell carcinoma and the effect of blood transfusion upon the immune response of these patients].

We studied the efficacy and safety of recombinant interleukin-2 (rIL-2: S-6820) for the treatment of renal cell carcinoma as well as the effect of blood transfusion upon the immune response of these patients. Among 14 cases of renal cell carcinoma treated by i.v. infusion of rIL-2, a partial response (PR) was achieved in one patient, 10 patients had no change, and in 3 had the disease progressed. The overall efficacy rate was 7.1%. However, the rate increased to 12.5% in cases with pulmonary metastases and to 14.3% in cases without any blood transfusion within a year before treatment with rIL-2. No severe side effects were observed, except for central nervous system disturbance in one case. During the rIL-2 therapy, LAK activity was suppressed in the transfused patients. On the other hand, NK activity was augmented in transfused patients to the same degree as in non-transfused cases. No significant changes of lymphocyte count and the subsets of peripheral blood lymphocytes were observed in either group treated with rIL-2. Anemia and radical nephrectomy did not affect the immune response in these patient. Thus, it appeared that blood transfusion altered the immune response in patients treated with rIL-2. However, it could not be concluded that transfusion definitely had an adverse effect on the clinical efficacy of rIL-2 for renal cell carcinoma.