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Biomedical subjects

Naoki Itoh

Publications and source records attributed to Naoki Itoh.

At least 37 records · Page 2Linked to original sources

First report of three protozoan parasites (a haplosporidian, Marteilia sp. and Marteilioides sp.) from the Manila clam, Venerupis (=Ruditapes) philippinarum in Japan.

Recently, natural stocks of the Manila clam, Venerupis (=Ruditapes) philippinarum, have been drastically reduced in Japan. To clarify the reason for this decline in number, clams were sampled monthly from Yamaguchi and processed for histological observations, during which three protozoan parasites were discovered. Transmission electron microscopy revealed that these parasites were unidentified haplosporidian in the connective tissues, Marteilia sp. in the digestive gland and Marteilioides sp. in the oocytes. Histopathological observations suggest that Marteilia sp. and Marteilioides sp. were not pathogenic to the host. However, infection with a haplosporidian may have a negative impact on the clams. The prevalence of these parasites was low and further investigations should be undertaken to clarify their taxonomic status and establish any pathogenicity to clams.

Animals↗

Characterization of prostatic neuroendocrine cell line established from neuroendocrine carcinoma of transgenic mouse allograft model.

BACKGROUND: The role of neuroendocrine (NE) cells in prostate cancer remains unclear. A useful model is necessary to study the biology of NE cells. We herein describe the establishment and characterization of an immortalized cell line from an NE-10 allograft of murine prostatic NE carcinoma. METHODS: A novel cell line, designated NE-CS, was developed from an NE-10 allograft that was established from the ventral prostate of the LPB-T-antigen (Tag) transgenic mouse, line 10 (12T-10). We investigated the growth, karyotype, electron microscopic findings, expression of Tag and androgen receptor (AR), and tumorigenesis of the cells in athymic mice. RESULTS: The immortal cell line NE-CS was maintained in vitro for more than 2 years. The NE-CS cells had dendritic-like extensions with dense core granules in the cytoplasm and produced serotonin and somatostatin in conditioned medium. The cells expressed neither Tag nor AR. They showed androgen-independent growth in vitro and a hypotetraploid karyotype similar to the original NE-10 allograft. The NE-CS cells, which were subcutaneously inoculated into athymic mice, formed tumors with the NE phenotype. The tumors exhibited accelerated growth compared to the original NE-10 allograft. CONCLUSIONS: The established cell line has characteristics of NE differentiation and tumorigenic ability. This cell line may be a promising model to understand the molecular mechanisms associated with the acquisition of hormone refractory prostate cancer.

Animals↗

Prevalence of female sexual dysfunction symptoms and its relationship to quality of life: a Japanese female cohort study.

OBJECTIVES: To clarify the age prevalence of female sexual dysfunction and the factors that contribute to the varying frequency of sexual intercourse and satisfaction with sexual life in Japanese women. METHODS: Of 8956 participants (median age 57 years, range 17 to 88) in a Japanese female cohort study, 5042 (56.3%) responded. We evaluated 2095 women aged 30 to 69 years (median 48) who completed a questionnaire that queried about their sexual life. RESULTS: When women in their 30s were compared with those in their 60s, we found that the prevalence of the symptom of orgasmic disorder, sexual desire disorder, arousal disorder, and lubrication disorder had increased significantly from 15.2% to 32.2%, 27.7% to 57.9%, 29.7% to 57.9%, and 12.5% to 51.2%, respectively. Multivariate analysis showed that the rigidity of the partner's erection, orgasm, and arousal contributed significantly to sexual frequency and foreplay and orgasm to satisfaction with sexual life. CONCLUSIONS: The prevalence of female sexual dysfunction increased with age. The results of multivariate analysis indicated that favorable sexual function is important to maintain the opportunity for sexual intercourse in both men and women and that foreplay and orgasm are essential for satisfactory sexual life in women.

Adult↗

Ligands for peroxisome proliferator-activated receptor gamma have potent antitumor effect against human renal cell carcinoma.

OBJECTIVES: To examine whether peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed in human renal cell carcinoma (RCC) cells, and whether activation of PPARgamma by its ligands can have multiple antitumor effects on human RCC cells in vitro. METHODS: We examined the expression of PPARgamma in four human RCC cell lines by reverse transcriptase-polymerase chain reaction and immunocytochemical staining. The effects of two PPARgamma ligands, pioglitazone and 15-deoxy-Delta12,14-prostaglandin J2, on cell proliferation were investigated by 3-[4,5-dimethylthiazol-2-thiazoly]-2,5-diphenyltetrazolium bromide assay. The induction of apoptosis by the ligands was examined using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling method and Annexin V assay. Furthermore, we investigated whether these ligands suppressed the production of angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor, by enzyme-linked immunosorbent assay. RESULTS: PPARgamma and retinoid X receptor, which forms a heterodimer with PPARgamma, were expressed in all RCC cell lines. In addition, immunocytochemical studies showed expression of PPARgamma protein in the RCC cells. PPARgamma ligands inhibited the cell growth in all cells in a dose-dependent manner. These ligands also induced apoptosis. Furthermore, secretion of both vascular endothelial growth factor and basic fibroblast growth factor was inhibited by these ligands in a dose-dependent and time-dependent manner. CONCLUSIONS: Ligands for PPARgamma have multiple antitumor effects in human RCC cells in vitro. Activation of the PPARgamma pathway may be a new strategy for treatment of patients with RCC.

Carcinoma, Renal Cell↗

Bladder cancer discovered by ovarian metastasis: cytokeratin expression is useful when making differential diagnosis.

A 49-year-old woman underwent hysterectomy and bilateral adnexectomy after the diagnosis of a right ovarian tumor with paraaortic and pelvic lymph node metastases. The pathological diagnosis was undifferentiated carcinoma of the ovary. After the operation, a bladder tumor was discovered during the evaluation for microscopic hematuria. The bladder tumor was pathologically diagnosed as transitional cell carcinoma, pT1b, G3. Although the pathological findings of the bladder cancer and ovarian cancer were very similar, we could diagnose primary bladder cancer with ovary and lymph node metastases according to the immunohistochemical staining pattern of cytokeratins 7 and 20. Herein, the clinical usefulness of immunohistochemical staining using cytokeratins for making a differential diagnosis of the origin of a tumor in the pelvic cavity is demonstrated.

Biomarkers, Tumor↗

[Chemotherapy for prostate cancer].

The clinical significance of chemotherapy for patients with hormone refractory prostate cancer(HRPC) is still controversial. Some randomized-controlled trials represented that mitoxantrone combined with prednisone (or hydrocortisone) provided palliative benefit to patients with HRPC. These treatments are well tolerated by elderly patients. On the other hand, the high PSA response rates have been observed in trials with both estramustine and taxane, however, higher toxicity was also recognized. The most relevant endpoint is not only palliative efficacy but also survival in these trials. Recently, the improvement of survival with docetaxel-based chemotherapy was reported. Further studies with chemotherapeutic agents will be needed to provide patients of HRPC good quality of life and longer survival.

Androgen Antagonists↗

[Tumor size and regional lymph node metastasis in patients with M0 renal cell carcinoma: analysis in those having regional lymph node dissection].

We evaluated the relationship between regional lymph node metastasis and tumor size in patients with M0 renal cell carcinoma who received regional lymph node dissection. The study involved 234 of the 247 patients with localized renal cell carcinoma who underwent radical nephrectomy with lymph node dissection at our institute between 1985 and 1999. Patients were arbitrarily classified into 3 groups by the greatest diameter of the tumor on preoperative computed tomography (CT): 4.0 cm or less (group A), 4.1 to 7.0 cm (group B), and 7.1 cm or more (group C). The incidence of lymph node metastasis was assessed in each group. The current study showed that 11 (4.7%) of the 234 patients with lymph node dissection together with radical nephrectomy were lymph node positive. The incidences of lymph node metastasis were 4.0% in group A, 2.3% in group B, and 8.4% in group C (p = 0.79). Of these 11 patients with lymph node metastasis, 2 (18.2%) have so far survived for over 5 years following surgery. Although the role of regional lymph node dissection with radical nephrectomy might be limited and controversial in renal cell carcinoma, urological surgeons should always be aware of possible metastasis for any tumor size.

Adult↗

[Ejaculatory disorder by alpha-1 adrenoceptor antagonist in patients with benign prostatic hyperplasia; retrospective comparison between naftopidil and tamsulosin].

We cross-sectionally studied the incidence and impact on quality of life of ejaculatory disorders caused by alpha-1 adrenoceptor antagonists (tamsulosin or naftopidil) in patients with benign prostatic hyperplasia (BPH). By questionnaire, we queried 88 clinical BPH patients concerning ejaculatory disorders, who were treated with tamsulosin or naftopidil between February 1999 and August 2003. We investigated the difference in the incidence and types of disorders between the two drugs. Of the 88 patients, 63 (71.6%) had sexual activities during the treatment. The incidence of ejaculatory disorders was significantly higher in the tamsulosin group (30.0%) than in the naftopidil group (3.0%). Eighty percent of patients having the disorders noticed the absence or reduced volume of semen although they experienced orgasms. The median quality of life index concerning the disorder was rated as 4, "mostly dissatisfied." Our results indicated that ejaculatory disorders occurred more frequently in the tamsulosin group. We should inform patients about this adverse effect caused by alpha-1 adrenoceptor antagonists prior to treatment.

Adrenergic alpha-1 Receptor Antagonists↗

Modulation of phenotype of human prostatic stromal cells by transforming growth factor-betas.

BACKGROUND: We investigated the effects of transforming growth factor (TGF)-betas on morphological and receptor phenotypes, as well as proliferation of four currently established human prostatic myofibroblast cell lines and one commercially available prostatic stromal cell line. METHODS: The effects of TGF-betas on morphological changes and proliferation of the cells were studied by immunohistochemistry and bromodeoxyuridine assay, respectively. The expression of alpha 1-receptor subtypes was measured by real time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and the radioligand binding assay for the receptors was also performed. RESULTS: TGF-betas 1, 2, and 3 induced expression of desmin and myosin of cells of the established cell lines, and significantly inhibited their growth. The alpha 1a-receptor was expressed only in the commercially available cell line and alpha 1b and 1d, in all cell lines. TGF-beta 1 suppressed the expression of all three subtypes of the alpha 1-receptor. The binding sites of cells of all the cell lines were reduced by treatment with this growth factor. CONCLUSIONS: TGF-betas may induce human prostatic stromal cells to express the smooth muscle phenotype and inhibited their growth. However, the growth factor reduced the binding sites of the receptor and suppressed mRNA expression of its subtypes, suggesting that morphological and receptor phenotypes may be regulated via more than one pathway by TGF-beta(s).

Cell Division↗

Prophylactic antimicrobial agents in urologic laparoscopic surgery: 1-day versus 3-day treatments.

Although the incidence of surgical site infection (SSI) is generally low in laparoscopic urologic surgery, the standard protocol for prophylactic use of antimicrobial agents remains to be established. We retrospectively compared the incidence and severity of SSI after laparoscopic surgery between two different protocols for prophylactic use of antimicrobial agents. This study included 114 patients who underwent urologic laparoscopic surgery categorized as "clean" or "clean-contaminated" in Sapporo Medical University School Hospital between January 1996 and October 2002. As a prophylactic antimicrobial agent, one of the cephalosporins or penicillins was administered intravenously to all patients. For 46 consecutive patients between January 1996 and July 2000, an antimicrobial agent was given 30 min before operation and thereafter every 12 h on the same day and the next 2 days after operation (the 3-day group). For 68 consecutive patients from August 2000 to October 2002, an antimicrobial agent was given once 30 min before operation and was additionally given only in the evening or night of the day of operation (the 1-day group). The incidence of SSI was retrospectively investigated. There were two patients who developed SSI in each group (4.3% in the 3-day group and 2.9% in the 1-day group). The incidence of SSI was not significantly different between the two groups. The 1-day protocol has efficacy equal to that of the 3-day protocol in prophylaxis of SSI. The 1-day use of a prophylactic antimicrobial agent may be recommended for the clean or clean-contaminated urologic laparoscopic surgery described above.

Aged↗

Early developmental stages of a protozoan parasite, Marteilioides chungmuensis (Paramyxea), the causative agent of the ovary enlargement disease in the Pacific oyster, Crassostrea gigas.

A paramyxea, Marteilioides chungmuensis, causes the irregular enlargement of the ovary in the Pacific oyster, Crassostrea gigas in Korea and Japan. The knowledge about the life cycle of the parasite has been limited to the sporulation stages within the oocyte of oysters. In this study, we used the parasite-specific DNA probes and electron microscopy to experimentally infected oysters in a field and successfully clarified early developmental stages of the parasite. The parasite invaded the oysters through the epithelial tissues of the gills, mantle and labial palps. Extrasporogony repeatedly occurred in the connective tissues by binary fusion. The inner cell of the extrasporogonic stage migrated into the gonadal epithelium, invaded the oocyte to start sporulation.

Animals↗

Idiopathic stuttering priapism: recovery of detumescence mechanism with temporal use of antiandrogen.

We report a case of idiopathic stuttering priapism in a 56-year-old Japanese man. We treated his recurrent priapism in stepwise fashion by withdrawal of the alpha/beta-blocker he used for hypertension, administration of low doses of an antiandrogen and baclofen, and finally by increasing the dose of antiandrogen, which lowered his testosterone to the castration level and was effective in preventing priapism. After 6 months of antiandrogen treatment, his erectile function gradually recovered to the baseline level, and he had no recurrence of priapism during the following 6 months without any medication.

Baclofen↗

Antiproliferative and antiangiogenic activities of genistein in human renal cell carcinoma.

OBJECTIVES: To determine whether genistein, an isoflavone that is plentiful in soy beans, could inhibit the growth of human renal cell carcinoma (RCC) cells in vitro, induce apoptosis, and suppress neovascularization in vivo induced by human RCC cells. METHODS: We investigated the effect of genistein on cell proliferation in four human RCC cell lines, SMKT R-1, R-2, R-3, and R-4. The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assay was performed to examine whether genistein could induce apoptosis in SMKT R-1 cells. To evaluate the effect of genistein on in vivo angiogenesis, we used a new mouse dorsal air sac model in which we could evaluate it simply and quantitatively. Radioisotope-labeled red blood cells were injected into a tail vein in mice bearing a Millipore filter chamber containing genistein, and the vascular volume was examined by measuring the radioactivity of the mouse dorsal skin. RESULTS: Treatment with genistein for 48 hours inhibited cell proliferation in a dose-dependent manner and 100 microg/mL genistein inhibited it in a time-dependent manner. A dose of 50 microg/mL genistein clearly induced cell apoptosis. The vascular volume after implantation of the Millipore filter chamber containing RCC cells increased to threefold that without RCC cells. Genistein in the Millipore filter chamber significantly decreased the neovascularization induced by human RCC cells in vivo. CONCLUSIONS: The results of this study demonstrated that genistein inhibited cell proliferation, induced apoptosis, and suppressed in vivo angiogenesis in human RCC cells. Genistein may be a promising antitumorigenic and antiangiogenic agent for the treatment and prevention of RCC.

Angiogenesis Inhibitors↗

Systemic inflammatory response syndrome in open versus laparoscopic adrenalectomy.

OBJECTIVES: To compare the surgical invasiveness of laparoscopic adrenalectomy with that of open surgery when the invasiveness is evaluated by the incidence of systemic inflammatory response syndrome (SIRS). METHODS: Patients who underwent open adrenalectomy (35 patients) and those who underwent transperitoneal laparoscopic adrenalectomy (35 patients) were included in this study. We retrospectively investigated the incidence and duration of SIRS in the two groups. Of the 70 patients, 39 had primary aldosteronism and 31 had clinically nonfunctioning adrenal tumors. RESULTS: The incidence of SIRS was 51.4% (18 patients) in the open group and 31.4% (11 patients) in the laparoscopic group (P = 0.14, Fisher's exact probability test). The mean duration of SIRS was 1.9 days in the open group and 1.2 days in the laparoscopic group (P = 0.04, unpaired t test). Surgical site infection, which occurred in 2 patients in the open group (5.7%) and 3 patients (8.5%) in the laparoscopic group, was the only infectious complication. No patient had any severe or life-threatening complications. CONCLUSIONS: Laparoscopic adrenalectomy seems less invasive than open surgery, when the magnitude of the invasiveness is evaluated by the incidence of SIRS.

Adrenal Gland Neoplasms↗

Local recurrence after radical cystectomy for invasive bladder cancer: an analysis of predictive factors.

OBJECTIVES: To examine which clinicopathologic parameters predict clinically detectable local recurrence after radical cystectomy. Local recurrence after radical cystectomy for invasive bladder cancer was infrequently observed until 20 years ago because of the lack of adequate diagnostic tools. The recent development and use of pelvic computed tomography has allowed us to detect local recurrence more precisely. However, only a few studies have investigated the rate and pattern of local recurrence in the computed tomography era. METHODS: This retrospective review included 145 patients with muscle-invasive bladder cancer treated with radical cystectomy, regional pelvic lymph node dissection, and urinary diversion between January 1990 and December 2001. The development of local recurrence and/or distant metastasis was analyzed as the endpoint using univariate and multivariate analyses. RESULTS: Local recurrence developed in 27 (18.6%) of the 145 patients at a median of 8 months after cystectomy. Of the 27 patients, 8 had local recurrence alone and 19 had concurrent distant metastasis. Distant metastasis without local recurrence developed in 34 patients (23.4%). Univariate and multivariate analyses revealed that Stage pT3-T4 and pathologic pelvic lymph node involvement were statistically significant factors predicting clinical failure, local recurrence, and/or distant metastasis. However, a concomitant squamous cell carcinoma component in the specimen was the only independent predictor of local recurrence alone in both univariate and multivariate analyses. CONCLUSIONS: Only the finding of a concomitant squamous cell carcinoma component in the specimen was an independent predictor of local recurrence in patients treated with radical cystectomy.

Adult↗

Erectile function following external beam radiotherapy for clinically organ-confined or locally advanced prostate cancer.

BACKGROUND: External beam radiotherapy (XRT) has been a standard treatment for clinically localized prostate cancer. However, preservation of erectile function following XRT is controversial. In this study, the influence of XRT on erectile function of patients with clinically organ-confined or locally advanced prostate cancer was retrospectively evaluated. METHODS: The study included 34 of 84 patients with organ-confined or locally advanced prostate cancer who underwent XRT between 1995 and 2002. Erectile function following radiotherapy was assessed by a simple mailed questionnaire that was constructed for the study. To determine the predictive factors for erectile dysfunction following radiotherapy, data were analyzed by multivariate analysis with the Cox proportional hazards model. RESULTS: The modality of XRT was the only factor to independently predict erectile dysfunction following XRT. The maintenance rates of erectile function were 47.6% at 1 year and 19% at 3 years in patients who received the 3-dimensional conformal radiotherapy, which were significantly higher than in those who received conventional radiotherapy (P = 0.026). CONCLUSIONS: XRT significantly reduced the maintenance rate of erectile function during the follow-up period, with the rate being 19% at 3 years in patients who received 3-dimensional conformal radiation. The XRT modality was involved in the reduction of erectile function. These results suggest that erectile dysfunction is a possible adverse event following XRT.

Aged↗

Early and late complications of radical retropubic prostatectomy: experience in a single institution.

BACKGROUND: Radical retropubic prostatectomy is one of the first-line treatments for clinically organ-confined prostatic cancer. However, some studies have reported the morbidity of this procedure. We retrospectively assessed the incidence of complications of radical retropubic prostatectomy in our institution. METHODS: We reviewed 123 consecutive medical charts of prostate cancer patients who underwent radical retropubic prostatectomy between 1988 and 2001 at our institution. We evaluated intraoperative complications, early complications within 1 month postoperatively, and late complications, including anastomotic stricture and urinary incontinence. RESULTS: The median age of patients was 66 years (range, 53 to 74 years) and median follow-up duration was 44.0 months (range, 2 to 157 months). None of the patients died due to surgery-related causes. Intraoperative complications included rectal injuries in six patients (4.9%) and ureteral injury in one patient (0.8%). As for late complications, anastomotic strictures were observed in 16 patients (13.8%), and stress urinary incontinence that persisted for more than 12 months was observed in 13 patients. The estimated continence recovery rate at 12 months was 87.3%. Multivariate analysis did not reveal any predictive factor for anastomotic stricture. However, the blood loss volume and period of surgery were significant predictive factors of continence recovery. CONCLUSIONS: Radical retropubic prostatectomy was safely performed, though there were various intra- or postoperative complications that were adequately managed. Early recovery of continence was related to the blood loss volume and the surgery period. Adequate surgical experience and a meticulous technique to avoid excessive bleeding are important factors for an early recovery.

Aged↗

Membrane-anchored CD14 is important for induction of interleukin-8 by lipopolysaccharide and peptidoglycan in uroepithelial cells.

We investigated the induction of interleukin-8 (IL-8) by bacterial lipopolysaccharide (LPS) and peptidoglycan (PGN) in the bladder cancer cell lines T24, 5637, UM-UC-3, and HT1197. T24 and 5637 cells strongly induced IL-8 after stimulation with LPS or PGN in a dose- and time-dependent manner, whereas UM-UC-3 and HT1197 cells did so very weakly. The expression of CD14 at the mRNA, total cellular protein, and cell surface protein levels differed among these cell lines, but the expression levels of Toll-like receptors 2 and 4 (TLR2 and TLR4) were not significantly different. The CD14 expression levels were found to correlate with the inducibility of IL-8 by LPS or PGN. Treatment of T24 and 5637 cells with phosphatidylinositol-specific phospholipase C to eliminate CD14 from the cell surface dramatically suppressed the induction of IL-8. On the other hand, UM-UC-3 cells transfected with CD14 cDNA expressed membrane-anchored CD14 and showed more efficient induction of IL-8 by LPS stimulation than untransfected controls. These results suggest that the presence of the membrane-anchored, but not the soluble, form of CD14 is a strong factor in IL-8 induction in bladder epithelial cells in response to bacterial components. The presence of the membrane-anchored form of CD14 may thus be a determinant for the inflammatory response of uroepithelial cells.

Cell Line, Tumor↗