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Biomedical subjects

S Akimoto

Publications and source records attributed to S Akimoto.

At least 109 records · Page 6Linked to original sources

[Clinical evaluation of TANDEM PSA in Japanese cases and comparison with other methods].

Clinical evaluation of TANDEM PSA which is the most frequently used prostate specific antigen (PSA) assay method in the world and a comparison with other methods were performed in Japanese cases in a cooperative research fashion. The minimum detectable level of the method was found to be 0.50 ng of PSA in one ml of serum and 1.9 ng/ml was regarded as the upper normal value in Japanese males. The distribution of serum PSA showed a significant difference between the benign prostate hypertrophy (BPH) cases and patients with stage C or D prostate cancer. The sero-diagnosis prostate cancer at an early stage with the TANDEM PSA was difficult. The correlation to other methods of PSA detection was very high. Furthermore, the clinical use of the method in following-up the clinical course of prostate cancer patients was very useful. These findings suggested that the PSA detection using TANDEM PSA is applicable even in Japanese cases although the upper cut-off level is decreased.

Aged↗

[Treatment of sclero-corneomalacia after cataract surgery].

We treated sclero-corneomalacia in an 84-year-old woman, which occurred 7 months after cataract surgery on her left eye. Since medical therapy could not prevent progress of the sclero-corneal lesion and perforation of the eyeball was likely, we performed implantation of preservable sclera and keratoepithelioplasty. The patient has an uneventful postoperative course without recurrence and good visual acuity was preserved. To minimize the post-operative inflammation and early reform of the ocular surface, implantation of preservable sclera and keratoepithelioplasty is an effective procedure.

Aged↗

A truncated beta-catenin disrupts the interaction between E-cadherin and alpha-catenin: a cause of loss of intercellular adhesiveness in human cancer cell lines.

Cadherin cell adhesion molecules play an essential role in creating tight intercellular association and are considered to work as an invasion suppressor system of cancer cells. They form a molecular complex with catenins, a group of cytoplasmic proteins including alpha- and beta-catenins. While alpha-catenin has been demonstrated to be crucial for cadherin function, the role of beta-catenin is not yet fully understood. In this study, we analyzed the cadherin-catenin system in two human cell lines, HSC-39 and its putative subline HSC-40A, derived from a signet ring cell carcinoma of stomach. These cells grow as loose aggregates or single cells, suggesting that their cadherin system is not functional. In these cell lines, an identical 321-base pair in-frame mRNA deletion of beta-catenin was identified; this led to a 107-amino-acid deletion in the NH2-terminal region of the protein. Southern blot analysis disclosed a homozygous deletion in part of the beta-catenin gene. On the other hand, these cells expressed E-cadherin, alpha-catenin, and plakoglobin of normal size. Immunoprecipitation analyses showed that E-cadherin was coprecipitated with the mutated beta-catenin but not with alpha-catenin, and antibodies against beta-catenin did not copurify alpha-catenin. However, the recombinant fusion protein containing wild-type beta-catenin precipitated alpha-catenin from these cells. These results suggest that the dysfunction of E-cadherin in these cell lines is due primarily to its failure to interact with alpha-catenin, and that this defect results from the mutation in beta-catenin. Thus, it is most likely that the association between E-cadherin and alpha-catenin is mediated by beta-catenin, and that this process is blocked by NH2-terminal deletion in beta-catenin. These findings indicate that genetic abnormality of beta-catenin is one of the mechanisms responsible for loosening of cell-cell contact, and may be involved in enhancement of tumor invasion in human cancers.

Animals↗

c-erbB-2 gene product associates with catenins in human cancer cells.

Phosphorylation of beta-catenin, an intracytoplasmic cadherin-binding protein, causes disruption of the cadherin-mediated cell adhesion system in cancer cells. A 185-kDa phosphorylated protein, identified as the c-erbB-2 gene product, was co-immunoprecipitated with the E-cadherin-catenin complex. Association of the c-erbB-2 gene product with the cadherin-catenin complex was proven to be mediated through beta-catenin and plakoglobin using an in vitro protein-protein precipitation system. These results indicate that the c-erbB-2 gene product associates with catenins and may regulate the cell adhesion and invasive growth of cancer.

Cadherins↗

Complete sequence of the Bacteroides fragilis YCH46 neuraminidase-encoding gene.

The nucleotide sequence of the Bacteroides fragilis neuraminidase-encoding gene (nanH) and its flanking regions was determined. The B. fragilis nanH open reading frame (ORF) of 1632 nucleotides encoded a neuroaminidase of 544 amino acid residues with a calculated molecular mass of 59.51 kDa. The amino acid sequence at the N-terminus of the deduced protein exhibited the common features of procaryotic signal sequences. The Asp box sequence, Ser-X-Asp-X-Gly-X-Thr-Trp, which is conserved among bacterial neuraminidases, was found at five positions in the deduced amino acid sequence. A single transcription start point was identified 88 nucleotides upstream of the nanH ORF. Northern blot analysis using an internal nanH probe revealed a single mRNA species with a length of 1.8 kb that could encode just the neuraminidase.

Amino Acid Sequence↗

Cloning and expression of the Bacteroides fragilis YCH46 neuraminidase gene in Escherichia coli and Bacteroides uniformis.

A neuraminidase-encoding gene nanH of Bacteroides fragilis strain YCH46 was cloned into the cosmid vector pHC79. The nanH gene was subcloned from the cosmid and was located within a 2.2-kb XhoI-KpnI fragment. Southern hybridization experiments demonstrated that the gene was present as a single copy on the bacterial chromosome. Neuraminidase activity expressed in the initial Escherichia coli clone was approximately 3600-fold lower than that expressed in B. fragilis YCH46. However, when nanH was transferred from E. coli to B. uniformis by mobilization of a shuttle plasmid, the transconjugant expressed 1100-fold higher activity than the E. coli donor did. These results suggest that modes of nanH expression in E. coli and Bacteroides are heterologous.

Bacteroides↗

Natural course of human benign prostatic hyperplasia with relation to urinary disturbance.

To examine the natural course of human benign prostatic hyperplasia (BPH), cases in health care examination with or without slight urinary symptoms were examined by echography. In comparison with these cases, the size of the prostate was examined in patients who received prostatectomy. Prostatic sizes of health care cases varied widely along with increasing age, but could be divided into two groups: increasing or no-change. According to serial determinations of prostatic sizes in the increasing group, the annual growth rate of the prostate was calculated as 1.65 +/- 1.13 and 0.85 +/- 0.44 g in men < 65 years old and in men > or = 65 years old, respectively. Distribution of prostatic sizes as a function of age in health care cases was similar to that in operated patients, showing that the size was not correlated with urinary symptoms or surgical indication. Since uroflow rates decreased along with increasing age in the no-change group of operated patients, aging was a factor in deterioration of uroflow. Between the increasing and the no-change groups in health care cases, differences were found in total cholesterol and neutral fat in serum, in addition to gamma-seminoprotein; the latter may be due to differences in the size of the prostate. In conclusion, natural course of the prostatic hyperplasia is separated into two groups, increasing and no-change. Occurrence of urinary symptoms does not simply relate to an increase in prostatic weight but, at least in part, to the aging process.

Adult↗

Effect of naftopidil on urethral obstruction in benign prostatic hyperplasia: assessment by urodynamic studies.

Thirty-two patients with voiding dysfunction attributable to symptomatic benign prostatic hyperplasia were treated with naftopidil, an alpha 1-blocker, at doses of 25-75 mg/day for 4-6 weeks. The efficacy of the drug was assessed from the changes in urinary symptoms and urodynamic data. Total symptom scores were significantly reduced after treatment (P < 0.001). Average flow rate and maximum flow rate were significantly increased (P < 0.001 and P < 0.001, respectively), and residual urine volume, residual urine rate (ratio of residual urine volume/sum of voided volume and residual urine volume), and maximum urethral closure pressure were significantly (P < 0.05, P < 0.01, and P < 0.05, respectively) reduced, and at bladder capacity, the first desire to void was significantly (P < 0.05) increased. The pressure/flow study demonstrated no changes in intravesical pressure at maximum flow, but a significant (P < 0.05) reduction in minimum urethral resistance. A mild side effect (dizziness) was noted in one patient (3.3%), which soon disappeared after the dose was decreased. The efficacy was good or excellent in 21 of 30 patients (70.0%). The drug was evaluated to be promising in the treatment of bladder outlet obstruction due to benign prostatic hyperplasia.

Adrenergic alpha-Antagonists↗

Chemotherapy for endocrine-therapy-refractory prostate cancer.

The effects of various chemotherapy regimens on endocrine-therapy-refractory prostate cancer were examined in 64 patients. Chemotherapy was started from the first evidence of relapse. The regimens of the initial chemotherapy were as follows: cisplatin (CDDP, 4 cases) and ifosfamide (4 cases) were given as single agents and vincristine, ifosfamide, and peplomycin (VIP, 8 cases); cyclophosphamide, doxorubicin, and CDDP (CAP, 14 cases); ifosfamide, doxorubicin, and CDDP (IAP, 24 cases); and etoposide, doxorubicin, and CDDP (EAP, 10 cases) were given as combinations. On the basis of the results, the patients were divided into two groups: single agents plus VIP and other combinations. In the CAP, IAP, and EAP groups, the cause-specific survival was similar, and the survival of these groups was longer than that of the single agents plus VIP group. Since patients with a long duration between the start of endocrine therapy and the start of chemotherapy were contained in the CAP, IAP, and EAP groups, comparison was performed without these cases. No difference was found between the two groups, suggesting that no superior regimen was found. The short-term effect was evaluated on the basis of the changes observed in prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) levels at 3 months after the start of chemotherapy, and patients showing a complete response, partial response, or no change on any of the regimens exhibited longer survival than did those with progressive disease. Since the PSA doubling time estimated before the chemotherapy correlated with the change in the PSA values due to the chemotherapy, the rate of proliferation of the tumor influenced the effect of the chemotherapy. Thus, this finding suggests that slowly growing cancers show a better response to chemotherapy than do rapidly proliferating ones.

Acid Phosphatase↗

Relationship between diurnal rhythm of serum testosterone and two prostatic markers (PSA and PAP) in untreated prostate cancer.

OBJECTIVE: To clarify the relation between diurnal rhythm of serum levels of testosterone and two prostatic markers, prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP). METHODS: Blood was obtained every four hours during a thirty-two-hour period from fourteen men with untreated prostate cancer. RESULTS: Serum levels of PSA and PAP showed circadian rhythm in 4 and 5 patients, respectively. About half of the remaining patients, the highest or nearly highest peaks of serum levels of PSA or PAP were observed in the afternoon rather than the morning. In 3 patients, circadian rhythms were not observed in serum levels of PAP, but the fluctuation patterns were the same as those of testosterone and showed synchronous movement. In 7 patients, serum testosterone levels were followed by the same fluctuation pattern for either PSA or PAP after some time delay. Little change in serum levels of PSA was seen throughout the thirty-two-hour period despite large fluctuations of testosterone and PAP levels in 5 patients. CONCLUSIONS: Close relation between the fluctuation in serum levels of PSA and PAP, and that in serum levels of testosterone during diurnal periods could be considered. However, the relationship between serum testosterone levels and those of PSA and PAP was ambiguous because of both the difference in the time delay of PSA and PAP in relation to testosterone and the small fluctuation in PSA despite obvious fluctuations in testosterone and PAP in some cases.

Acid Phosphatase↗

Frequent loss of alpha catenin expression in scirrhous carcinomas with scattered cell growth.

To investigate the mechanisms of disruption of cell-cell contact in scirrhous carcinoma cells, the expression of both E-cadherin and alpha catenin, which is an intracellular cadherin-binding molecule, were determined in scirrhous-type adenocarcinomas of the stomach and breast using immunohistochemical and immunoblotting techniques. The losses of E-cadherin expression in gastric and breast scirrhous adenocarcinomas were 18.1% and 0%, respectively, and those of alpha catenin expression were 54.6% and 75%, respectively. Frequent loss of alpha catenin expression occurred in scirrhous carcinomas with scattered cell growth in the stomach and the breast and showed no organ specificity. In addition, all the infiltrating lobular carcinomas, which also infiltrate the stroma as single cells, showed no E-cadherin or alpha catenin expression. These findings suggest that down-regulation of either alpha catenin or E-cadherin plays a critical role in the disruption of cell adhesion in carcinomas with scattered cell growth.

Adenocarcinoma, Scirrhous↗

State of adenomatous polyposis coli gene and ras oncogenes in Japanese prostate cancer.

Genetic alterations of ras oncogenes (K-, H- and N-ras) and adenomatous polyposis coli (APC) gene in tissues of prostate cancer from Japanese patients were examined using PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) analysis and direct sequencing. Tissues from 8 cases of untreated stage B prostate cancer surgically removed and from 10 cases of endocrine therapy-resistant metastatic disease obtained at autopsy were used in the present study. In four out of 18 cases (22%), ras point mutations were found, two in either codon 12 or 61 of K-ras and two in either 13 or 61 of H-ras. These point mutations were detected in one of the stage B cases (13%) and in three of the autopsy cases (30%). All these cases were poorly differentiated adenocarcinoma. In autopsy cases showing ras mutation in cancerous prostate, the same alteration was observed in metastatic tissues. No APC gene mutation was detected in any sample, although polymorphism was found in some cases. These results indicate that ras oncogene mutations are related to the progression of prostate cancer, whereas APC gene alteration is not involved in tumorigenesis and development of this cancer.

Adenocarcinoma↗

Diurnal rhythm of serum gamma-seminoprotein in patients with untreated prostate cancer: comparison of the original and revised assay kits.

To compare levels of gamma-seminoprotein (gamma-Sm) assayed by original and revised assay systems, blood was obtained every 4 h over a 32-h period from 8 untreated prostate cancer patients. Serum levels of prostate specific antigen (PSA) were also examined. In 6 patients, the coefficient of variation (CV) of the serum levels assayed by the revised assay was significantly different from that of the intra-assay samples. In contrast, the CV of the gamma-Sm serum levels assayed by the original assay differed significantly from that of the intra-assay samples in only 2 patients. The fluctuations in gamma-Sm assayed by the revised assay were, at least in part, similar to those of the PSA serum levels in all patients. The mean CV of the gamma-Sm serum levels assayed by the revised assay was significantly larger than that for levels measured by the original assay. After treatment, the rate of decrease in gamma-Sm serum levels determined by the original assay differed from that in the serum levels of PSA and prostatic acid phosphatase. These results indicate that the original assay for gamma-Sm do not detect diurnal differences in serum gamma-Sm levels, even at levels below 20 ng/ml. These observations indicate that the analysis of data obtained using the original gamma-Sm kit should be interpreted with caution.

Acid Phosphatase↗

Radiation therapy for prostate cancer confined to pelvis.

To evaluate the usefulness of external beam radiotherapy for patients with prostate cancer confined to the pelvis, long-term results and prognostic factors were analyzed. During the period 1975-1989, 44 cases were treated with staging pelvic lymphadenectomy followed by monotherapy using external beam irradiation by Linac X-ray and/or fast neutrons and observed without any treatment until relapse was evident. All patients were followed until death or for a mean of 78.6 mo (range: 36-113 mo) for patients still alive. Four cases died of prostate cancer at 26, 28, 54, and 83 mo from the start of radiation. Eleven cases died of other causes (10-72 mo, mean 36.4 mo). Fourteen cases (31.8%) manifested clinical relapse of cancer; 4 had local relapse, 7 developed bone metastases, and 3 relapsed at lymph nodes. After relapse, endocrine therapy was effective in most cases. The five-year disease-free survival rates of pN0 (32 cases) and pN1 (8 cases) patients were 79.8% and 52.5%, respectively, but that of pN2 (4 cases) was worse. Cause-specific survival was similar between patients with pN0 and pN1 disease, the rate at 5 yr being 92.5% in the former and 100% in the latter. Those with high levels of serum prostate specific antigen (PSA) before treatment and advanced local disease (clinical stage C) showed unfavorable prognoses. The number of argyrophilic nucleolar organizer regions (AgNORs) might be a predictive factor in patients treated with irradiation. In conclusion, prostate cancer patients with stage A2-C, diagnosed as pN0-1 by staging pelvic lymphadenectomy, were successfully treated with external beam radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[The role of repeat transurethral resection in stage A1 carcinoma of the prostate].

In order to evaluate the significance of repeat transurethral resection (TUR) in differentiating stage A1 prostatic adenocarcinoma from those with stage A2, we performed repeat TUR in 34 patients with an initial diagnosis of stage A1 prostatic adenocarcinoma. It was found that residual adenocarcinoma was present in five cases (14.7%), but the diagnosis was changed from stage A1 to stage A2 in only one case (2.9%). In one patient with final diagnosis of stage A1 carcinoma, bone metastases were detected seven months after the repeat TUR. It was concluded that repeat TUR for stage A1 prostatic adenocarcinoma did not yield clinically significant information.

Adenocarcinoma↗

[The course and limitation of medical treatment for benign prostatic hyperplasia].

To clarify the effects and limitation of medical treatment for benign prostatic hyperplasia (BPH), 2,476 patients with BPH were analyzed in terms of symptoms, objective findings, treatment modality and whether surgery was required during the course of medical treatment. As initial therapy, 1,320 cases (53.3%) were treated with medicine and 783 cases (31.6%) underwent surgery. In the group of patients initially treated with medicine, 264 cases (20.0%) required surgery and most operations were performed within six months from the start of medical treatment. Those who required surgery had a larger prostate and more residual urine than those who continued medical treatment. This tendency was also observed in the patients treated with antiandrogen. Therefore, medical therapy might be inappropriate to treat the patients with more than 50 ml of residual urine or significantly large prostate such as goose egg sized or larger. In conclusion, medical treatment possessed potential usefulness for the management of BPH, however, there seemed to be limitation of the effects of medical treatment.

Adult↗

[Measurement of serum prostatic acid phosphatase (PAP) by Delfia PAP Kit using europium and clinical evaluation in patients with prostate cancer].

Fundamental and clinical studies of serum prostatic acid phosphatase (PAP) detected by a Delfia PAP kit were performed. The system is a time-resolved fluoroimmunoassay using europium as a tracer. The lower limit of detection was 0.2 ng/ml. Sera from 54 patients with prostate cancer, 20 with benign prostatic hypertrophy, 20 with urological malignancies other than prostate cancer and 140 adult males over 46 years old were determined. From the mean + 2 S.D. of serum PAP values obtained on the adult males, 1.5 ng/ml was considered as the upper normal level of adult males. By calculating the efficiency and ROC curve using the PAP values of prostate cancer and benign prostatic cancer, 2.5 ng/ml was decided as a cut-off value of this kit. The positive rates of adult males, prostate cancer, benign prostatic cancer and urological malignancies other than prostate cancer were 0.7%, 65%, 20% and 10%, respectively. The sensitivity of stage A2, B2, C and D1 + D2 was, 0%, 0%, 64% and 83%, respectively. The efficiency of the Delfia PAP kit was 52% and that of the Markit M PA kit was 71%. The correlation between the values assayed with the Delfia PAP kit and the Dinabot PAP kit was very high; the value obtained with the Delfia PAP kit was about 80% of that obtained with the Dinabot PAP kit.

Acid Phosphatase↗

A prospective randomized trial for treating stages B2 and C prostate cancer: radical surgery or irradiation with neoadjuvant endocrine therapy.

A randomized clinical trial of neoadjuvant endocrine therapy followed by either surgery or irradiation and a resumption of endocrine therapy for stages B2 and C prostate cancer has been in progress since 1989. A hundred patients entered the trial between 1989 and 1993, and 95 cases were evaluated. Forty-six patients received surgery and 49 were treated with irradiation. Neoadjuvant endocrine therapy for two months resulted in prostate shrinkage and prostate specific antigen lowering. Except for two patients, one dying of a progression of disease and the other of another concurrent cancer, all are alive with an average follow-up term of 25 (range 3-53) months. The good prognostic results obtained from both treatment groups at present seem to be due in part to the neoadjuvant endocrine therapy; but in order to reach a final conclusion further comparisons need to be made.

Aged↗