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Biomedical subjects

S Akimoto

Publications and source records attributed to S Akimoto.

At least 199 records · Page 11Linked to original sources

DNA strand scission by hemin-thiolate complexes as models of cytochrome P-450.

Hemin-thiolate complexes, as chemical models for cytochrome P-450 monooxygenases, have been shown to cause strand scission of DNA. Circular super-coiled DNA was degraded to open-circular and linear forms by these complexes in 30 min at pH 7.8 under aerobic conditions, the degradation depending on the structure of the thiol ligand and the ratio of thiol ligand to hemin concentration. The relationship between the structure of the thiol ligand and DNA strand cleaving activity was examined. Complete cleavage of DNA was observed by complexes containing TGE and ME at 400-600 moles excess of thiol ligand to hemin, those containing Cys, CysMe, and CysEt at 50-200 moles excess, and those containing MPG, GSH, penta- and nona-peptides at 5-20 moles excess. Complexes containing NACys and MEA caused no cleavage of DNA. Inhibition experiments suggested the involvement of active oxygen species in the cleavage.

Cysteine↗

Properties of progestin-binding protein in benign hypertrophic human prostate.

RU 27987 is a new ligand for progesterone receptor and binds in high affinity to nuclei of target tissues of progesterone. Using this compound, progestin-binding components in the benign hypertrophic human prostate were studied, and compared with those examined with R 5020, a conventional ligand, in the study of progesterone receptor. In cytosols, the binding affinity of RU 27987 was higher than that of R 5020, and the number of maximum binding sites for RU 27987 seemed to be large but correlated well with those of R 5020. The binder for RU 27987 sedimented at 8.6 S, and the binding was specific to progestational steroids, indicating that binding properties of this binder in the cytosols are identical to those for R 5020. Although there was no binding with R 5020 in the nuclear extract, a small amount of specific binding with RU 27987 was detected. However, the cytosol bound with RU 27987 was not retained in DNA Sepharose and no specific binder for RU 27987 in the nuclear extract was observed in a sucrose density gradient centrifugation. From these observations, it was assumed that the nuclear binding observed was attributable to contamination of the cytosolic binder. The results obtained in the present study suggest that the progestin-binding component in the benign prostatic hypertrophy is not the progesterone receptor but a high affinity binder for progestins whose physiological role is not clear at present.

Alpha-Globulins↗

[Prostatic acid phosphatase and prostatic specific antigen measured by immunoenzyme assay].

Prostatic acid phosphatase (PAP) and prostatic specific antigen (PA) were determined with a Cetus test kit (California, USA) for prostatic cancer and others. Abnormal values of PAP in untreated prostatic cancer were found in 0, 0, 50, 50, 0, 73% of stage A1, A2, CpN0, CNX, D1 and D2 cases, respectively, and those of PA were found in 25, 0, 50, 100, 100, 100% of the same stages, respectively. Grade was not related to the level of PAP or PA. Prostatic hypertrophy showed increased values of PAP and PA in 11.1% and 7.4%, respectively. The levels of PAP were not correlated to those of PA. Endocrine treatment decreased the elevated values of PAP and PA in 60% of the cases. Most of the PAP and PA levels in the cases controlled under endocrine therapy were within normal values, but after relapse most showed elevated levels.

Acid Phosphatase↗

[Intraarterial bolus infusion followed by rapid removal of anticancer agents with hemocarboperfusion under local hyperthermia in advanced hepatic cancer].

Reported herein is a new multidisciplinary treatment modality for unresectable hepatic cancer in which local hyperthermia and intraarterial infusion of bolus anticancer agent are simultaneously undertaken while anticancer agent leaking from the hepatic bed into the general circulation is rapidly removed by charcoal hemoperfusion. Local hyperthermia induced by exposure to 13.56-MHz radiofrequency waves was conducted between one and one and a half hours once or twice a week. During the hyperthermia treatment, a bolus of either 1 mg/kg Mitomycin C or 2 mg/kg Adriamycin was injected into the hepatic artery via a Vascular Access Port, the catheter portion of which had been surgically inserted into the hepatic artery and the reservoir of which had been implanted subcutaneously. In general, a regular dose of 6 mg of Mitomycin C was injected into the Vascular Access Port during the following hyperthermia procedures. In seven of nine patients (78%) treated with this method, a marked reduction in tumor size of more than 50% was observed on computed tomograms. A light to moderate degree of side effects such as leukocytopenia, thrombocytopenia, liver dysfunction or hair loss were noticed after the bolus infusion, but were not so serious as to threaten the patients' lives.

Adult↗

[Treatment of prostatic cancer with an LH-RH analog].

LH-RH analog (Buserelin) was administered in 10 cases of untreated prostatic cancer in our hospitals. All 10 cases had stage D2 disease. Five cases were of moderately differentiated carcinoma and 5 cases were of poorly differentiated carcinoma. The levels of luteinizing hormone and follicle stimulating hormone in blood plasma tended in decrease four weeks after treatment except for one case. The levels of testosterone in blood plasma reached the castrated level four weeks after administration except for the above one case. In adjacent effect by National Prostatic Cancer Project Criteria, the LH-RH proved to be effective in 6 of the 10 cases. The flush of face appeared in two cases, but it disappeared spontaneously. One case had a slight temporal macrohematuria one week after treatment.

Aged↗

Cleavage of DNA by model complexes of cytochrome P-450.

Thiolate-hemin complexes as chemical models for cytochrome P-450 have been shown to cause cleavage of DNA. The cleavage of DNA to open-circular and linear forms depended on the structure of thiol ligand and the thiol ligand:hemin ratio at pH 7.8. Complete cleavage of DNA was observed by complexes containing thioglycolate ethylester and mercaptoethanol at 400-600 moles excess of thiol ligand to hemin, those containing cysteine, cysteine methylester and cysteine ethylester at 50-200 moles excess, and those containing mercaptopropionylglycine, glutathione, glutathione dimethylester, penta- and nonapeptides at 5-100 moles excess. Inhibition experiments suggested the involvement of active oxygen species in the cleavage of DNA.

Cytochrome P-450 Enzyme System↗

[Staging pelvic lymphadenectomy for the prostatic cancer].

Staging pelvic lymphadenectomy was performed on 21 patients with the prostatic cancer of stage A, B and C from January in 1981 to April in 1985. Twelve cases (57%) showed lymph node metastasis. Gleason's scores of the cases with lymph node metastasis proved lower than those of the cases without lymph node metastasis (p less than 0.05). There were no differences in grade between primary tumors and lymph node metastases. The percentage of metastasis to the external iliac, internal iliac and obturator lymph nodes was 55%, 83% and 82%, respectively. Two patients suffered from the delayed healing of the wound and the edema of the lower extremities, respectively, but the other patients had no complication.

Aged↗

[Congenital subclavian steal syndrome: a case of right aortic arch with atretic aberrant left subclavian artery].

Surgical experience of a rare case of congenital subclavian steal syndrome is reported. A 53 year old man was admitted to our hospital complaining of black out attack and headache. Non invasive and angiographic studies revealed the subclavian steal associated with right aortic arch and atretic aberrant left subclavian artery. Through the supraclavicular incision, the direct anastomosis of the left common carotid and subclavian artery was performed. Postoperative angiograms showed a perfect reconstruction of the left subclavian artery and the disappearance of the subclavian steal and about on third amount of the complaints are still remained. Concerning a review of the literatures, several problems are discussed.

Aorta, Thoracic↗

[A case of synchronous contralateral renal cell carcinoma and ureteral transitional cell carcinoma].

A case of synchronous contralateral renal cell carcinoma and ureteral transitional cell carcinoma is reported. A 56-year-old man, who had been incidentally found to have an abnormal mass in the upper pole of the right kidney on ultrasound sonography, was admitted on January 8, 1985. CT scanning and renal arteriography revealed right renal malignancy. Right radical nephrectomy was performed and histological examination showed adenocarcinoma, granular cell type of the right kidney. He was discharged on February 3, 1985. Two months postoperatively, he was rehospitalized for macroscopic hematuria. Left retrograde pyelogram showed obstruction at middle ureter and cytology of urine from left ureter was positive. So a left ureteral tumor was suspected, and partial resection of left ureter and ureteroureterostomy were performed. Histological examination revealed ureteral transitional cell carcinoma. He is now doing well at 6 months following the lat surgery, without any evidence of recurrence.

Carcinoma, Renal Cell↗

Expression of srnB gene of F plasmid by altered RNA polymerase in Escherichia coli.

Degradation of otherwise stable rRNA and tRNA takes place in the presence of rifampin, dependent on the F plasmid srnB gene. We have reported that a protein newly synthesized in the presence of rifampin might be a product of the srnB gene required for stable RNA degradation (Ito, R. and Ohnishi, Y. (1983) Biochim. Biophys. Acta 739, 27-34). Here we have further studied the mechanism of srnB expression. Among eighteen mutants with altered RNA polymerase, two (TJ2470 (rpoC4) and TJ302 (rpoC56)) showed RNA degradation at high temperature (42 degrees C) when the srnB gene was present. Labeling proteins at 42 degrees C in strain TJ2470 indicated that a protein of molecular weight 12 000 was a product of the srnB gene, and that expression of the srnB gene provoked RNA degradation. Using plasmid pTK4, in which the srnB gene is inserted downstream of the promoter of lacZ, lac promoter-dependent expression of the srnB gene, with production of the putative protein product, also induced RNA degradation at 42 degrees C, with no requirement for added rifampin or altered RNA polymerase. RNA degradation in these conditions was quite similar to that in the case of the addition of rifampin; e.g., it showed some responses to Mg2+, temperature and RNAase I content of the cells. Expression of the srnB gene dependent on lac promoter was also observed in minicells. Thus, it is inferred that the srnB gene is probably repressed under normal conditions with its own promoter; its expression initiates RNA turnover.

Bacterial Proteins↗

NGF-dependent and -independent growth of neurites from sympathetic ganglion cells of the aged human in a serum-free culture.

Small pieces of tissue isolated from abdominal sympathetic ganglia in aged male patients were cultured in a chemically defined, serum-free medium. The growth of neurites from pieces of ganglia in cultures with and without 50 ng/ml mouse 2.5S nerve growth factor (NGF) was compared. The NGF stimulated significantly greater regeneration of neurites, causing the growth of long fibers from the ganglion pieces. Many short neurites grew, even in the absence of the NGF, but these were generally short, except for long neurites generated in several nerve cells. A method was devised for the evaluation of NGF-dependent growth of neurites in the culture. The rate of the NGF-dependent growth of neurites, which was calculated by the difference in the total lengths of the NGF-dependent neurites between 2- and 4-day-old cultures, was approximately 160 micron/day. The results indicate that although the growth of neurites from some sympathetic nerve cells of the aged human become independent of the NGF, most of the nerve cells remain dependent on the NGF, even in the stage of senescence.

Culture Techniques↗

Cloning and expression of the pnd gene of R16: determination of transcriptional direction and evolutionary analysis.

The gene promoting nucleic-acid degradation (pnd) of IncB plasmid R16 was cloned into the vector plasmid pACYC177. The pnd gene was found to be located on a 0.55-kilobase (kb) AluI-PstI fragment by constructing subclones carrying various portions of the initially cloned fragment. The direction of transcription of the pnd gene was determined by inserting the gene in both orientations into the lacZ' gene of the plasmid pUR222. In the recombinant plasmid pCM2, transcription of the pnd gene was controlled by the lac promoter region. Addition of cAMP at 42 C resulted in rapid degradation of stable RNA in cells harboring pCM2. In contrast, no RNA degradation was observed in cells harboring pCM14, which has the same insert as pCM2 but in the opposite orientation. The equivalent gene, pnd of IncI alpha plasmid R483, has previously been cloned, and a detailed restriction map of the region has been constructed (Akimoto, S., and Ohnishi, Y. 1982. Microbiol. Immunol. 26: 779-793). We constructed a detailed restriction map of the pnd region of R16 and compared it with that of R483. Restriction analyses revealed a similar structure in these two pnd regions. The results suggest that the pnd genes of R16 and R483 have a common evolutional origin.

Biological Evolution↗

Binding of mibolerone to androgen receptor of benign hypertrophic human prostate. Comparison with R1881.

The binding nature of mibolerone in cytosols and nuclear extracts from hypertrophic human prostate was examined in comparison with that of R 1881. The binding of mibolerone in the cytosol and nuclear extract was single and of high affinity when evaluated by the method of Scatchard (1949). Binding of mibolerone with testosterone-binding globulin was not detected. The sedimentation coefficients of the binder for mibolerone in the cytosol and nuclear extract were 10.6 S and 3.6 S, respectively. When triamcinolone acetonide was induced in the binding medium, inhibition of mibolerone binding in the cytosol by testosterone and dihydrotestosterone was potentiated and this may imply that the binding observed in the presence of triamcinolone acetonide was responsible for the binding of the androgen receptor. In the nuclear extract, the binding was attributable mainly to the androgen receptor irrespective of the presence or absence of triamcinolone acetonide. These properties of the binding observed in the hypertrophic human prostate were almost same as those of the binding with R 1881. Although maximum binding sites measured using mibolerone were correlated with those using R 1881 in the cytosols as well as in the nuclear extracts, the values obtained with mibolerone were slightly greater than those with R 1881. Thus, mibolerone seems to be a suitable ligand for measuring the androgen receptor, but when compared with R 1881 no special merits in using mibolerone were detected.

Cell Nucleus↗

[Effect of recombinant alpha-interferon on advanced renal cell carcinoma].

The present study was undertaken to assess the efficacy of single agent chemotherapy with alpha A-interferon or alpha 2-interferon for metastatic renal cell carcinoma. alpha A and alpha 2-Interferon were administered i.m. at a primary dose of 3 X 10(6) units/day to 13 patients. Two patients (15%) showed partial response; 1 patient (8%), minor response; 5 patients (38%), no change; 6 patients (46%), progressive disease. These preliminary observations indicate that these interferons are active antitumor agents in patients with renal cell carcinoma.

Adenocarcinoma↗

[Surgical treatment of fusiform thoracoabdominal aortic aneurysm with Marfan's syndrome. A report on reconstruction of 4 major abdominal visceral branches].

A fusiform thoracoabdominal aortic aneurysm involving celiac, superior mesenteric and renal arteries was successfully replaced in a 53-year-old female with Marfan's syndrome who also had annuloaortic ectasia, dissecting aneurysm of descending aorta and bilateral subclavian arterial aneurysms. Exposure of the aneurysm was obtained with a thoracoabdominal incision by reflecting the abdominal viscera to the right. First the limbs of a 24 X 12mm dacron bifurcated prosthesis were attached to common iliac arteries in an end-to-side fashion. Then renal arteries were anastomosed end-to-end to the branches previously attached to the body of the prosthesis. With the temporary bypass from left subclavian to left limb of the dacron graft, reconstruction of the celiac and superior mesenteric arteries was performed by direct suture of orifices to the opening made in the graft. Proximal anastomosis between descending aorta and the graft was made in an end-to-end fashion. The dissecting lesion of the proximal descending aorta was wrapped by dacron mesh. The immediate postoperative course was uneventful except transient hepatitis and pneumonia. The patient was discharged 49 days after operation. One month later, however, she died suddenly. Autopsy could not reveal the exact cause of death. Retrograde revascularization combined with Crawford's method was useful in shortening the occlusion time.

Aorta, Abdominal↗