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.

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]

Ferensimycins A and B. Two polyether antibiotics. Taxonomy, fermentation, isolation, characterization and structural studies.

Ferensimycin A* (I), C34H59O10Na, mp 133 approximately 135 degrees C, and ferensimycin B** (II), C35H61O10Na, mp 143 approximately 145 degrees C, were isolated as their sodium salts from the fermentation broth of Streptomyces sp. No. 5057, a strain similar to Streptomyces myxogenes Shomura et al. The physicochemical data of I and II showed that they are both closely related congeners of lysocellin (III). Ferensimycins A and B exhibit activity against Gram-positive bacteria and are effective in the treatment of coccidiosis of fowl.

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.

[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.

[Studies on metabolism and disposition of sizofiran (SPG), an anti-tumor polysaccharide. II. Effects on hepatic drug-metabolizing enzyme system in rats].

The effect of a single or multiple administration of sizofiran (SPG), an anti-tumor polysaccharide, on a hepatic drug-metabolizing enzyme system was studied in rats. When SPG was given intravenously at a single dose of 0.5 or 10 mg/kg, no alteration was observed in activities of aminopyrine (AP) N-demethylase and aniline hydroxylase, and in cytochrome P-450 (P-450) content in the livers of rats 48 h after dosing. However, only AP demethylase activity decreased by 34% after the administration of 200 mg/kg. Similarly, no change in the hepatic enzyme activities and P-450 content was observed for up to 180 d after a single dose of 10 mg/kg. Subcutaneous treatment of animals with either 10 or 40 mg/kg dose for 3 and 6 months resulted in no alteration in the enzyme activities and P-450 content. These results may indicate that the therapeutically effective dose of SPG has no effect on a hepatic drug-metabolizing enzyme system in rats.

[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)

[A case of bilateral testicular tumor of germ cell origin].

A 28-year-old man visited our clinic with a complaint of painless swelling of left scrotal contents. An initial right semicastration for embryonal carcinoma and seminoma had been performed 10 years earlier. Left semicastration was performed, and its histopathological finding was pure seminoma. A total of 96 cases of bilateral testicular tumors of germ cell origin reported in Japan are summarized and discussed concerning incidence, age, histology, interval, prognosis and mechanism of the tumorigenesis.

[Immunohistochemical demonstration of carcinoembryonic antigen (CEA) and ABO (H) blood group antigens on tissue sections of urinary bladder tumors].

The carcinoembryonic antigen (CEA) and ABO (H) blood group antigens of 47 bladder tumors were investigated by immunohistochemistry (CEA by peroxidase-antiperoxidase method and blood group antigens by Avidin-biotin-peroxidase complex method) and the results were compared with the histopathological diagnosis. Twenty five percent of the bladder tumors had CEA-positive tumor cells. They were found in 11.1% of pT1 cases, in 12.5% of pT2 cases, 70.0% of pT3 cases and 50.0% of pT4 cases and were also found in 13.3% of grade I cases, in 50.0% of grade II cases and in 40.0% of grade III cases. On the other hand, positive blood group antigen cells were found in 85.2% of pT1 cases, 50.0% of pT2 cases, 20.0% of pT3 cases and 50.0% of the pT4 cases and also in 80.0% of the grade I cases, 41.1% of the grade II cases, and 20.0% of the grade III cases. A statistical difference was seen between the low stage (pT1) and high stage cases (pT2-pT4) and between the low grade (G-I) and high grade cases (G-II, III) (P less than 0.01) for both CEA and the blood group antigens which were statistically related (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Rhabdomyosarcoma of the prostate: report of a case and review of the literature].

Rhabdomyosarcoma of the prostate is a rare tumor and its prognosis is extremely poor. However, the survival rate has been gradually improved by using combined chemotherapy. A 17-year-old man with the chief complaint of dysuria was referred to our hospital on April 7, 1986. Prostatic needle biopsy was performed and pathological diagnosis was rhabdomyosarcoma of the prostate. The patient was given preoperative combined chemotherapy consisting of actinomycin D and cyclophosphamide. Total cystoprostaurethrectomy and ileal conduit were performed on April 30, 1986. He underwent postoperative combined chemotherapy (vincristine, actinomycin D, cyclophosphamide). He is well 13 months after his initial symptoms and is clinically free of tumor 12 months postoperatively. Forty-two cases of rhabdomyosarcoma of the prostate including our case were collected from the Japanese literature and reviewed with respect to the multimodal treatment and prognosis.

[Two cases of metastatic renal tumor].

Two cases of metastatic renal tumor are reported, one in a 78-year-old male who had undergone total gastrectomy for gastric carcinoma, and the other in a 45-year-old female who had undergone hysterectomy for cervical carcinoma of the uterus. The chief complaint was flank pain and nephrectomy was performed in both cases. Histopathological examination of the removed specimen revealed metastatic renal tumor the primary site of which was probably the stomach in the first case and cervix uteri in the second case. The literature on metastatic renal tumors in Japan is reviewed.

[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.

[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.

[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.

[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.

[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.

[Clinical experience of norfloxacin in urinary tract infection].

Norfloxacin (NFLX) was administered to outpatients and inpatients with urinary tract infections at our department. Clinical efficacy and safety were evaluated in 50 patients by the criteria for evaluation of clinical efficacy of antimicrobial agents on urinary tract infection. Overall clinical efficacy for 17 cases with acute simple cystitis was excellent in 13 cases, moderate in 4 cases with an effectiveness rate of 100%. The overall clinical efficacy for 33 cases with chronic complicated UTI was excellent in 18 cases, moderate in 6 cases and poor in 9 cases with an effectiveness rate of 73%. The eradication rate of 21 strains from acute simple cystitis patients was 100%. Forty four out of 60 strains from chronic complicated UTI patients were eradicated and the eradication rate was 73%. Neither subjective nor objective adverse reactions were observed in 50 patients. Abnormal changes in laboratory tests were found in 8 patients, but were probably not related to NFLX administration. Judging from these results, NFLX is considered to be an effective and safe antibacterial for the treatment of UTI.

[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.

[Effect of selective intra-arterial infusion of OK-432 against renal cell cancers].

In 8 cases of operable renal cancer, selective intraarterial infusion of the streptococcal preparation, OK-432 was performed and its cytocidal effects on the surgical specimens, which were removed on the 8th day after infusion, were investigated histopathologically with immunological parameters of the peripheral blood. The histopathological study revealed a high grade of sinus histiocytosis of the renal pedicle lymph nodes, but the anti-tumor effect on renal tumors was not so marked in any of the 8 cases. OK-Ia-positive lymphoid cells of peripheral blood were increased significantly and Con-A stimulation index of blastogenesis was lowered without any change in the PHA stimulation index after the OK-432 infusion. No serious complications of the selective intraarterial infusion were experienced except for high fever (less than 38 degrees C). In conclusion, OK-432 selective intraarterial infusion was an effective method for improving regional and systemic immunoactivity, but the cytocidal effect against tumor cells could not be confirmed histopathologically.

[The efficacy of recombinant interleukin 2 in local treatment of superficial bladder tumors].

The present study was undertaken to assess the efficacy of recombinant Interleukin 2 (rIL-2: S-6820) in treatment of superficial bladder tumors. Three intratumor injections at a dose of 5 x 10(5) units/day via urethra, were performed every other day under endoscopic control in 12 patients with superficial bladder cancer. On the 15th day after completion of the series of injections, the tumor had disappeared in one patient and 50% regression over was observed in two other patients. Therefore, the response rate to the rIL-2 treatment in our study was 25.0%. Each tumor which responded to the therapy, was single, small and low grade. In the peripheral blood of the 12 patients, an increase in IL-2 receptor-positive lymphocytes and augmentation of natural killer activity were detected after the rIL-2 intratumor injection. There were no serious side effects except for moderate fever in our study.