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Biomedical subjects

S Akimoto

Publications and source records attributed to S Akimoto.

At least 181 records · Page 10Linked to original sources

[Treatment of prostatic cancer with slow-release formulation of luteinizing hormone releasing hormone (LH-RH) analog].

A slow-release formulation of the luteinizing hormone releasing hormone (LH-RH)analog(TAP-144-SR) was administered in 6 cases of prostatic cancer. Five were untreated cases, 3 of moderately-differentiated and 2 of poorly-differentiated cancers (four D2 and one C, NX), the other (D2) was under control by another LH-RH analog. The plasma level of luteinizing hormone and follicle stimulating hormone fell below normal, and the plasma testosterone was less than 1 ng/ml by four weeks after start of treatment. According to the National Prostatic Cancer Project Criteria, 2 of the untreated cases showed a partial response and 3 of the untreated ones showed a stable response, one of which underwent transurethral resection later. The pretreated case still continued controlled more than 4 months. No side effect was noticed.

Acid Phosphatase↗

[Treatment of prostatic cancer].

Since more than half of stage A-C prostatic cancers show pelvic lymph node metastasis (D1, pN1-3), a staging operation is required at the start of treatment. Most pN0 and pN1 (stage A2BC) cases have been treated with radiation, and good results have been obtained. Endocrine therapy, consisting of orchiectomy and immediate administration of a large dose, followed by an intermediate dose of estrogen or antiandrogen, was applied to pN2-4 and D2 cancer cases. Five-year survival was approximately 40%, and side effects were less marked than those reported in western countries. Factors affecting prognosis during endocrine therapy were grade, acid phosphatase response, and tissue androphilic protein. For D2 with risk factors, chemoendocrine therapy was applied, but no improvement in survival was observed.

Androgen Antagonists↗

[Trends in patterns of care for prostatic cancer in Japan: statistics of 9 institutions for 5 years].

Five hundred and sixty-five patients with prostatic cancer, who first visited 9 institutions in Japan between 1981 and 1985, were analyzed. The peak of age distribution was in the seventies. As clinical symptoms, disturbance on micturition was the most frequent and pain caused by metastasis was a complaint in approximately one tenth of the cases. Alkaline phosphatase measurement, prostatic biopsy, intravenous pyelography, bone scintigraphy, cystourethrography, and measurements of serum prostatic acid phosphatase and serum acid phosphatase were performed on more than 80% of the patients. The clinical stage was stage A1 in 6.2%, A2 in 3.7%, B in 14.9%, C in 20.7%, D1 in 7.4%, and D2 in 43.7%. According to the histological grade, well, moderately and poorly differentiated adenocarcinoma were observed in 20.4, 33.3 and 32.7%, respectively. Increased ratio of high grade to low grade was noticed in the lower age group as well as in the advanced stage. In this series, endocrine therapy was still accepted in most of the patients. Almost all were treated with hormonal medication and half of them had undergone bilateral orchiectomy. Surgery, radiation, chemotherapy or multidisciplinary therapy were attempted judging from the clinical stage and histological grade. However, old age restricted the therapeutic modality. Actuarial survival rate at 5 years for stage A1, A2, B, C, D1 and D2 was 89.2, 66.1, 72.7, 51.0, 47.5 and 28.0%, respectively. In the patients with stage D2, the 5-year actuarial rate of poorly differentiated adenocarcinoma was lower than that of well or moderately differentiated adenocarcinoma, even though more intensive therapy was given to the former.

Adenocarcinoma↗

[Prostatic carcinoma. I: Androgen dependency of prostatic carcinoma].

Endocrine therapy, which consists of orchiectomy followed by administration of large doses of estrogen, then a reduced amount of estrogen, has been applied as the main treatment for stage D2 prostatic cancer. Alternatively, anti-androgen is used for elderly patients or those with cardiovascular disorders. Survival rate with endocrine therapy at 5 and 10 years was 35% and 16%, respectively. Therefore, in Japan, a better survival is shown than that reported in western countries using much smaller doses of estrogen. Most of the side effects caused by estrogen are not serious. Side effects caused by anti-androgen are few except for loss of libido. At the start of treatment, more than 80% of patients showed a response, but gradually relapse occurred and only 20% were well controlled 5 years after the start. Factors influencing the survival were pathological grade, response to endocrine therapy judged by the level of prostatic acid phosphatase 4 weeks after the start, and R1881 (methyltrienolone)-binding protein observed histochemically. The latter protein was also correlated with the grade and response to endocrine therapy. Relapse after endocrine therapy might be attributable to adaptation or mutation progressing to androgen-independent cells. Using SC 115, an androgen-dependent mouse tumor, these two types of relapse were demonstrated. Gradual progression to undifferentiated cancer was noticed between pretreatment biopsy and autopsy. Relapse in human prostatic cancer may thus be partly due to genetic change to a resistant clone.

Androgen Antagonists↗

Modalities of chemotherapy and endocrine therapy for growth inhibition of androgen-stimulated mouse carcinoma (Shionogi carcinoma 115).

Effects of chemotherapy and endocrine therapy applied individually or in combination on growth of an androgen-stimulated mouse tumor, Shionogi carcinoma 115 (SC 115), were examined. In the present study cyclophosphamide and castration were used as chemo- and endocrine therapy, respectively, and simultaneous combination of these two treatments was found to be the most effective in inhibiting tumor growth. When comparing the effect of castration alone with that of injection of cyclophosphamide alone, the former retarded the tumor growth more efficiently, but relapse occurred in both instances. Injection of cyclophosphamide to the relapsed tumor after castration caused a marked effect when compared with the effect of the drug on the untreated or the chemotherapy-relapsed tumors. Castration caused a retardation of growth in the chemotherapy-relapsed tumor, but the survival period was shorter than that observed in the mice that received castration followed by injection of cyclophosphamide. From these results, it was concluded that castration followed by chemotherapy was the preferred order among sequential treatments for the SC 115; however, the optimal treatment was produced by simultaneous combination of chemotherapy plus castration.

Androgens↗

Nucleotide sequence of the pnd gene in plasmid R483 and role of the pnd gene product in plasmolysis.

The pnd gene of R plasmid R483, like the srnB gene of the F plasmid, increases the degradation of stable RNA in Escherichia coli. The nucleotide sequence of the pnd locus was determined and compared with that of the srnB locus. The genes have open reading frames that are 54% homologous, and both have an upstream inverted repeat sequence. The pnd gene expression seems to decrease the osmotic barrier of the cytoplasmic membrane, since no plasmolytic vacuoles were formed in the cells carrying the gene when the cells were exposed to hypertonic sucrose solution. This result suggests that RNase I in the periplasm passes through the altered membrane to degrade stable RNA in the cytoplasm.

Base Sequence↗

Androgen receptor, testosterone uptake and karyotype in androgen-dependent mouse tumor (SC 115) and its androgen-independent subline (CS 2).

Content of androgen receptor, retention of injected testosterone and karyotype of SC 115, androgen-dependent tumor, were compared with those of CS 2, an androgen-independent subline derived from SC 115. Although Bmax was less than that of SC 115, androgen receptor was present in the cytosol and the nuclear extract from CS 2. To examine the ability for androgen retention, a large amount of testosterone was injected into tumor-bearing mice, and the amount of androgen in the crude nuclear and postnuclear fractions of tumors was compared. In both fractions, retention of injected androgen was higher in the SC 115 than in the CS 2. Since most of the injected testosterone was not metabolized in the tissues and the injection of testosterone 5 alpha-reductase inhibitor showed no significant influence on the growth rate of the SC 115, intracellular active androgen was assumed to be testosterone in these tumor cells. As the CS 2 was tetraploid, the androgen independency of the CS 2 seems to be related to chromosomal changes.

Animals↗

[Prostatic specific antigen in the serum in prostatic cancer].

Prostatic specific antigen (PA) level was determined with a Wako test kit (Japan) for prostatic cancer and others. The incidence of abnormal values of PA in untreated prostatic cancer, was 50, 50, 80, and 100% for stage A1, C (pN0, NX), D1 and D2 cancers, respectively. Grade was not related to the level of PA. Prostatic hypertrophy, prostatitis and urinary stone showed a false positive rate of 52, 18 and 0%, respectively. The level of PA was not correlated to those of prostatic acid phosphatase (RIA). In 31% of the cases, the elevated PA decreased 4 weeks after start of endocrine treatment. Elevated PA in low grade cancer was not normalized as much as that in high and moderate grade cancers. The positive rate of PA in the serum of reactivated patients was significantly higher than that of the patients with cancer under good control by endocrine treatment.

Acid Phosphatase↗

[Vascular endoscopy using a flexible fiberscope with a thin external diameter; experimental and clinical studies].

The purpose of this study is to evaluate capability of a fiberscope with a thin external diameter (2. 5mm, Olympus PF25-L) in observing the inner surface of blood vessels in animals and humans. Vascular endoscopy was firstly performed in three living dogs. The inner surface of canine abdominal aorta was not be fully inspected because of retrograde blood flow from the renal and lumbal arteries, but by blocking the proximal and distal blood flow using Fogarty catheters that of canine iliac artery including a flap of intima of 1mm diameter could be successfully observed. As clinical application of this endoscope the inspection of intravascular structures of Dardik's Biografts obliterated after peripheral bypass surgery were performed. In every case, bellows-like inner surface of this graft and several shapes of stenosis could be clearly recognized. Thus this endoscope presented the good optical quality, but due to lack of an angulating system visualization of anastomotic site was not achieved in most cases. No patient incurred complications of any sort. We conclude that vascular endoscopy using this type of endoscope can be performed safely, and provide useful information to the field of peripheral vascular surgery, but for the widespread clinical use of this vascular endoscopy, efforts should be made to improve the endoscope system itself and the method of effective interruption of blood flow.

Adult↗

Plasmid genes increase membrane permeability in Escherichia coli.

The membrane permeability to o-nitrophenyl beta-D-galactoside is increased in the presence of rifampicin in Escherichia coli cells carrying srnB+ or pnd+ plasmids, but not in the cells carrying srnB- or pnd- mutant plasmids. The same permeability alteration was also observed at 42 degrees C when a rpoC4- mutant strain was used as a host strain in the absence of rifampicin. These results and the blockage of the effects by action of chloramphenicol suggest that the increase of permeability to o-nitrophenyl galactoside was caused by the expression of srnB+ or pnd+ gene, respectively. srnB+ gene expression leads to massive RNA degradation, probably through the activation of the rna+ gene product. In an rna- strain carrying the srnB+ plasmid, the extent of RNA degradation was reduced, whereas the permeability to o-nitrophenyl galactoside was increased to the same level as in the rna+ strain. Also, the increase in permeability to o-nitrophenyl galactoside was observed at 30 degrees C, although high-temperature incubation (42 degrees C) was necessary for the induction of RNA degradation. These results suggest that the alteration in permeability is a more direct effect of the expression of srnB+ or pnd+ gene and that the RNA degradation is a secondary phenomenon caused by the alteration in the membrane.

Bacterial Proteins↗