Biomedical subjects

Takehiko Ogawa

Publications and source records attributed to Takehiko Ogawa.

At least 19 recordsLinked to original sources

PubMed2006

Production of functional spermatids from mouse germline stem cells in ectopically reconstituted seminiferous tubules.

Testicular germ cell transplantation into the seminiferous tubules is at present the only way to induce spermatogenesis from a given source of spermatogonial stem cells. Here we show an alternative method that harnesses the self-organizing ability of testicular somatic cells. The testicular cells of embryonic or neonatal mice or rats and of newborn pigs were dissociated into single cells. Each of them reorganized into a tubular structure following implantation into the subcutis of immunodeficient mice. When mouse germline stem (GS) cells derived from spermatogonial stem cells and expanded in culture were intermingled with testicular cells of rodents, they were integrated in the reconstituted tubules and differentiated beyond meiosis into spermatids. Normal offspring were produced by the microinjection of those spermatids into oocytes. This method could be applicable to various mammalian species and useful for producing functional gametes from GS cells in a xenoectopic environment.

Animals↗

PubMed2006

[Micropenis].

Explore the source record for details and available documents.

Cholestenone 5 alpha-Reductase↗

PubMed2006

Testosterone administration promotes regeneration of chemically impaired spermatogenesis in rats.

AIM: It has been proposed that gonadotropin-releasing hormone (GnRH) analog administered after testicular damage stimulates the recovery of spermatogenesis. However, GnRH analogs suppress the function of sex accessory organs. In this study, we investigated whether testosterone also stimulates the regeneration of rat spermatogenesis after exposure to busulfan. METHODS: Male Fisher rats were divided into three groups of five each and all rats were treated with busulfan, 25 mg/kg, intraperitoneally at week 0. Group A served as the control. The other two groups received testosterone enanthate, 8 mg/kg, subcutaneous injections at 3 week intervals two times before (group B) or three times after (group C) busulfan. States of spermatogenesis were evaluated by histology and by the number of spermatid nuclei per testis at week 25. RESULTS: The mean percentage of 'recovered' seminiferous tubules plus or minus standard deviation was 10.3 +/- 7.8% in group A and 2.1 +/- 1.2% in group B. In both groups, more than 80% of the tubules remained degenerated. However, testes of group C rats showed an improvement of up to 37.1 +/- 20.5% (P < 0.05). The significant recovery of spermatogenesis was also demonstrated in group C by counting the number of spermatid nuclei per testis ([78.8 +/- 57.5] x 106). However, the count was only (7.6 +/- 13.5) x 106 and (0.52 +/- 1.0) x 106 in group A and B, respectively. CONCLUSIONS: Testosterone administration after severe testicular damage enhanced the regeneration of spermatogenesis in rats. We assumed that supplementary doses of testosterone would be more practical for clinical application than GnRH analogs, because exogenous testosterone maintains androgenicity.

Animals↗

PubMed2006

[A case of salvage combination chemotherapy of gemcitabine plus nedaplatin for squamous cell carcinoma of the ureter].

A 46-year-old man complained of lower abdominal pain, and his abdominal and pelvic computed tomographic scan revealed left hydronephrosis and a huge tumor (9 X 9 cm) in the left distal ureter involving the left iliac vessel that was considered unresectable. Histological diagnosis showed squamous cell carcinoma, and histoculture drug response assay (HDRA) suggested the effectiveness of gemcitabine and nedaplatin. A cycle of adjuvant chemotherapy consisting of MEC (methotrexate 30 mg/ m2: day 1 and 15, epirubicin 50 mg/m2: day 1, and cisplatin 50 mg/m2: day 2 and 3) was performed as a first line chemotherapy, but the size of the ureteral tumor did not change. He was treated with 3 cycles of systematic combination chemotherapy consisting of gemcitabine (1,000 mg/m2: day 1 and 8) and nedaplatin (80 mg/m2: day 1). After 2 courses of chemotherapy, the tumor size was reduced by 50% (PR; RECIST guidelines) and the tumor markers (SCC, CYFRA, NSE, CEA, and CA19-9) dropped to within the normal range. There were no serious adverse events except for grade 3 neutropenia which spontaneously recovered. However, because the tumor size was not reduced after the third cycle of chemotherapy, we applied external beam radiation to the primary lesion and the metastatic retroperitoneal lymph node site. No evidence of residual tumor progression has been found for 6 months after radiation therapy. We concluded that GN chemotherapy may be useful for patients with squamous cell carcinoma of the ureter.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

[Propiverine hydrochloride improved correlatively subjective QOL and objective findings in Japanese patients with urinary frequency and/or incontinence].

To investigate how urinary frequency and incontinence affect the patient's subjective quality of life (QOL) and whether an improvement in objective findings by medical treatment affects his/her subjective QOL, a voiding diary using the King's Health Questionnaire (KHQ) and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) was delivered to patients with urinary frequency and/or incontinence before and after treatment with propiverine hydrochloride for 8 weeks. Sixty-eight patients completed the diary and the questionnaires. Objective symptoms decreased significantly with respect to the mean frequency of urination and to the mean incidence of urinary incontinence. The KHQ and ICIQ-SF scores improved significantly with respect to all domains except personal relationships in the KHQ. In the KHQ, furthermore, a significant correlation was found between decreased incidence of urinary incontinence and improvement in role limitations and between decreased incidence of urinary incontinence and improvement in emotional problems. In the ICIQ-SF, a significant correlation was found between decreased incidence of urinary frequency and subjective improvement in quantity of leakage, between decreased incidence of urinary frequency and improvement in subjective QOL scores, between decreased incidence of urinary frequency and improvement in the total ICIQ-SF score, and between decreased incidence of urinary incontinence and improvement in subjective QOL scores. Thirty-two episodes of adverse reactions were observed. None of them were serious. These results suggest that an improvement in objective symptoms with propiverine hydrochloride favorably improves subjective QOL of the patient, and provide further evidence about the safety and efficacy of propiverine hydrochloride.

Adult↗

PubMed2006

[A case of transitional cell carcinoma with squamous differentiation which developed squamous cell carcinoma in situ in the clinical course].

In August 2000, a 62-year-old woman presented to another municipal hospital with macroscopic Transurethral resection of bladder tumor (TUR-Bt) was performed. The pathological hematuria. diagnosis was transitional cell carcinoma (TCC), G2 > squamous cell carcinoma (SCC). TUR-Bt repeated in July 2003 indicated recurrence. The pathological diagnosis was TCC, G2. She was referred to our hospital in August 2003 because she desired bladder preservation. After cystoscopy and random biopsy, pathological diagnosis was TCC with squamous differentiation, G1-G2, pTis. She received 7 weekly intravesical bacillus Calmette-Guerin (BCG) instillations. In April 2004, TUR-Bt was repeated and multiple recurrences were found. The pathological diagnosis was TCC with squamous differentiation, G1-G2, pTa. She received 10 weekly intravesical Pirarubicin hydrochroride instillations. In August cystoscopy and random biopsy were performed for evaluation of the intavesical instillation treatment. Pathological diagnosis was atypical squamous cells. In November, cystoscopy revealed recurrence of a bladder tumor. After admission, a small papillary tumor and multiple flat lesion biopsies demonstrated SCC without obvious invasion. The patient underwent cystectomy. There were widespread areas of full thickness squamous atypia. Most of the bladder did not show appearance of typical TCC, but the final pathological diagnosis was TCC because the case developed from TCC and could not be diagnosed as pure SCC. The diagnosis of SCC in situ of bladder is difficult, and this may contribute to its rarity.

Administration, Intravesical↗

PubMed2005

Treatment of androgen-independent, hormone-refractory prostate cancer with docetaxel in Japanese patients.

BACKGROUND: Although patients with prostate cancer with metastatic lesions initially respond to androgen ablation therapy, most patients ultimately develop a hormone-refractory state. Effective treatment for men with hormone-refractory prostate cancer (HRPC) has not been established. We performed a clinical study of docetaxel in HRPC patients, and evaluated its efficacy. METHODS: Nine patients with HRPC were administered 55 mg/m2 docetaxel, every 3 weeks, simultaneously with hormonal therapy, with a luteinizing hormone-releasing hormone analog, and daily oral dexamethasone. Change in serum prostate-specific antigen (PSA) was determined as the primary endpoint. RESULTS: The mean age of the patients was 64 years (range, 49 to 76 years). Median follow-up time was 8.5 months (range, 5.3 to 16.7 months). In eight patients whose pretreatment serum PSA was elevated, six patients (75.0%) had a PSA decline of more than 50%, and four (50.0%) had a PSA decline of more than 75%. Median time to progression for all patients was 7.9 months (range, 0.0 to 11.6 months; 95% confidence interval [CI], 0.0 to 26.3). The median overall survival was 8.5 months (range, 5.3 to 16.7 months; 95% CI, 8.1 to 13.8). Four of six patients (66.7%) with pain before treatment obtained pain relief and were able to discontinue analgesic agents. This regimen was well tolerated. Grade 3 or 4 neutropenia or leukocytopenia without fever was seen in three patients (33.3%). Only one patient required administration of granulocyte-colony stimulating factor because of neutropenia. No other grade 3 or 4 toxicity was observed. CONCLUSION: Docetaxel was an active agent in Japanese HRPC patients, and was well tolerated in this population. To establish its efficacy and safety in Japanese HRPC patients, a large-scale study in Japan is warranted.

Adenocarcinoma↗

PubMed2005

The niche for spermatogonial stem cells in the mammalian testis.

The theory of the "stem cell niche" was originally proposed for the hematopoietic system, and the existence of the niche as an actual entity was proved in the Drosophila germ cell system. Historically, mammalian spermatogenesis has been studied extensively as a prime example of a stem cell system, and studies have established a stem-progenitor hierarchical order of spermatogonia. In the niche on the basal lamina of seminiferous tubules, spermatogonial stem cells (SSCs) are secluded from the outside world and divide constantly to self-renew and differentiate. During the last 10 years, the development and exploitation of the germ cell transplantation method has expanded our understanding of the nature of SSCs and their niches. The ability to maintain and expand SSCs in vitro, which recently became possible, has further reinforced this research area as a mecca of stem cell biology. Nonetheless, the mammalian germ stem cell and its niche remain to be defined more strictly and precisely. We are still on a journey in search of the real stem cell and its true niche.

Animals↗

PubMed2005

[Two cases of testicular tumors with high alpha-fetoprotein levels: a case report].

Two patients with testicular tumors whose serum alpha-fetoprotein (AFP) persisted to show an abnormally high concentration are reported. Case 1 : A 42-year-old male who had been suffering from chronic hepatitis, underwent left high orchiectomy for a left testicular tumor in 1998. Diagnosis was an authentic stage I seminoma. In 2002, chemotherapy was performed for a metastatic seminoma revealed as a solitary mass in the mediastinum by radiographic studies, and histologically confirmed to be a metastatic seminoma. Although lymph nodes were gradually reduced in size, the serum AFP and transaminase levels remained at an abnormally high concentration. The subfraction profile with lens culinaris hemagglutinin (LCA) revealed elevation of only peak 1 which implied that the chronic hepatitis was due to liver dysfunction. After a 10-month follow-up the levels of both AFP and transaminase decreased, and the patient was disease-free. Case 2: In 2002, a 30-year-old male underwent left high orchiectomy for a left testicular tumor, and histological examination revealed seminoma, immature and mature teratoma, embryonal carcinoma. The serum AFP was elevated to 45 ng/ml. Diagnosis was authentic stage I. After 2 courses of chemotherapy, the serum AFP remained at an abnormally high concentration. However, there were no new lesions. The serum AFP level was not elevated in any of the family members. The subfraction profile with LCA revealed elevation of only peak 1, which implied that there were no viable lesions. After a 24-month follow-up AFP was about 20 ng/ml and the patient was disease-free.

Adult↗

PubMed2004

Infrared reflection absorption spectroscopy of the sulfuric acid anion adsorbed on Pd(S)-[n(111) x (111)] electrodes.

Adsorption of the sulfuric acid anion (HSO4- or SO42-) has been studied on Pd(S)-[n(111) x (111)] electrodes (n = 2, 3, 5, 9, 20, infinity) using in situ infrared reflection absorption spectroscopy (IRAS). A single band is observed around 1200 cm(-1) on all the electrodes. The band is assigned to the SO stretching vibration of the sulfuric acid anion adsorbed with three- or onefold geometry. This result differs from the case of Pt-stepped surfaces on which two IRAS bands are observed around 1200 and 1100 cm(-1). The maximum coverage of the sulfuric acid anion is enhanced with the increase of the terrace width. The surfaces with n more than 3 have similar IRAS band shifts (dv/dE). Pd-stepped surfaces, for which the terrace is wide enough for the anion adsorption, adsorb the anion on the terrace rather than the step.

Journal Article↗

PubMed2004

Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta.

Spermatogenesis is a complex process that involves cooperation of germ cells and testicular somatic cells. Various genetic disorders lead to impaired spermatogenesis, defective sperm function and male infertility. Here we show that Cnot7(-/-) males are sterile owing to oligo-astheno-teratozoospermia, suggesting that Cnot7, a CCR4-associated transcriptional cofactor, is essential for spermatogenesis. Maturation of spermatids is unsynchronized and impaired in seminiferous tubules of Cnot7(-/-) mice. Transplantation of spermatogonial stem cells from male Cnot7(-/-) mice to seminiferous tubules of Kit mutant mice (Kit(W/W-v)) restores spermatogenesis, suggesting that the function of testicular somatic cells is damaged in the Cnot7(-/-) condition. The testicular phenotypes of Cnot7(-/-) mice are similar to those of mice deficient in retinoid X receptor beta (Rxrb). We further show that Cnot7 binds the AF-1 domain of Rxrb and that Rxrb malfunctions in the absence of Cnot7. Therefore, Cnot7 seems to function as a coregulator of Rxrb in testicular somatic cells and is thus involved in spermatogenesis.

Animals↗

PubMed2004

Derivation and morphological characterization of mouse spermatogonial stem cell lines.

Spermatogonial stem cells (SSCs), having yet to possess decisive markers, can only be detected retrospectively by transplantation assay. It was reported recently that mouse gonocytes collected from DBA/2 and ICR neonates propagated in vitro. This cultured germ cell, named the germline stem cell (GS cell), produced functional sperm to make progeny when transplanted into recipient mouse testes. Here we show that GS cell lines can be established not only from neonatal testes but also from the testis of adult mice. We also confirmed that GS cells once transplanted into a host testis can be recovered to resume in vitro expansion, indicating that they are convertible mutually with SSCs in adult testes. Confocal laser microscopic examination showed GS cells resemble undifferentiated spermatogonia in the adult testis. This unique cell line could be useful for research in germ cell biology and applicable as a new tool for the genetic engineering of animals.

Animals↗

PubMed2004

Abnormal sperm morphology caused by defects in Sertoli cells of Cnot7 knockout mice.

Cnot7 is a co-factor of transcription regulation, expressed in a variety of tissues including the lung, liver, thyroid gland, and testis. Our previous study (Nakamura et al., 2004) showed that deletion of the Cnot7 gene in mice caused almost no abnormal phenotypes except for male infertility, due to oligo-astheno-teratozoospermia. This study also showed that Cnot7-/- mouse germ cells transplanted as donors could colonize in recipient wild mouse testes to develop normal spermatogenesis by spermatogonial transplantation assay, suggesting that the abnormal spermatogenesis observed in the Cnot7-/- testes was induced by the impaired testicular microenvironment rather than a germ cell defect. In the present study, we have carried out reciprocal germ cell transplantation in which wild type germ cells were transplanted as donors into the recipient Cnot7-/- testes to evaluate the recipient microenvironment for supporting the spermatogenesis of donor cells. We noticed that donor cell colonization was less efficient in Cnot7-/- than in Cnot7+/- testes, and that the donor derived spermatids in the recipient Cnot7-/- testes showed severe deformities. These results support our previous report that Sertoli cell defects in the Cnot7-/- testes could induce oligo-astheno-teratozoospermia.

Animals↗

PubMed2003

Identification and characterization of stem cells in prepubertal spermatogenesis in mice.

The stem cell properties of gonocytes and prospermatogonia at prepubertal stages are still largely unknown: it is not clear whether gonocytes and prospermatogonia are a special cell type or similar to adult undifferentiated spermatogonia. To characterize these cells, we have established transgenic mice carrying EGFP (enhanced green fluorescence protein) cDNA under control of an Oct4 18-kb genomic fragment containing the minimal promoter and proximal and distal enhancers; Oct4 is reported to be expressed in undifferentiated spermatogonia at prepubertal stages. Generation of transgenic mice enabled us to purify gonocytes and prospermatogonia from the somatic cells of the testis. Transplantation studies of testicular cells so far have been done with a mixture of germ cells and somatic cells. This is the first report that establishes how to purify germ cells from total testicular cells, enabling evaluation of cell-autonomous repopulating activity of a subpopulation of prospermatogonia. We show that prospermatogonia differ markedly from adult spermatogonia in both the size of the KIT-negative population and cell cycle characteristics. The GFP(+) KIT(-) fraction of prospermatogonia has much higher repopulating activity than does the GFP(+)KIT(+) population in the adult environment. Interestingly, the GFP(+)KIT(+) population still exhibits repopulating activity, unlike adult KIT-positive spermatogonia. We also show that ALCAM, activated leukocyte cell adhesion molecule, is expressed transiently in gonocytes. Sertoli cells and myoid cells also express ALCAM at the same stage, suggesting that ALCAM may contribute to gonocyte-Sertoli cell adhesion and migration of gonoyctes toward the basement membrane.

Activated-Leukocyte Cell Adhesion Molecule↗

PubMed2003

Increment of murine spermatogonial cell number by gonadotropin-releasing hormone analogue is independent of stem cell factor c-kit signal.

Recent studies have demonstrated that GnRH-analogues can stimulate regeneration of spermatogenesis of rats when administered after testicular damages. Although the mechanism of this phenomenon has not been elucidated yet, stem cell factor (SCF) produced by Sertoli cells was proposed to mediate the effects of GnRH-analogues on spermatogonial proliferation and/or survival. In the present study, we quantitatively evaluated the proliferation of spermatogonia and addressed whether SCF mediates the effect of GnRH-analogue on spermatogonial proliferation, using a novel approach combining spermatogonial transplantation and laser confocal microscopic observation. In the first experiment, using wild-type mice as recipients for spermatogonial transplantation, the number of donor spermatogonia per 100 Sertoli cells in each spermatogenic colony was significantly higher in the experimental group of mice treated with leuprorelin, a GnRH-agonist, than that of the control group at 4 and 5 wk after transplantation. In the second experiment, Steel/Steeldickie (Sl/Sld) mutant mice, which lack expression of membrane bound form SCF, were used as recipients. As seen in the first experiment, the number of undifferentiated spermatogonia was significantly higher in leuprorelin-treated than in the control group. Since undifferentiated spermatogonia do not express the receptor of SCF, the present study clearly demonstrates that neither membrane-bound nor secreted forms of SCF are involved in the mechanism of GnRH-analogue's effect on spermatogonial proliferation and/or survival.

Animals↗

PubMed2003

Expansion of murine spermatogonial stem cells through serial transplantation.

Mammalian male germ cells might be generally thought to have infinite proliferative potential based on their life-long production of huge numbers of sperm. However, there has been little substantial evidence that supports this assumption. In the present study, we performed serial transplantation of spermatogonial stem cells to investigate if they expand by self-renewing division following transplantation. The transgenic mouse carrying the Green fluorescent protein gene was used as the donor cell source that facilitated identification and recollection of colonized donor germ cells in the recipient testes. The established colonies of germ cells in the recipient testes were collected and transplanted to new recipients. This serial transplantation of spermatogonial stem cells repopulated the recipient testes, which were successfully performed sequentially up to four times from one recipient to the next. The incubation periods between two sequential transplantations ranged from 55 to 373 days. During these passages, the spermatogonial stem cells showed constant activity to form spermatogenic colonies in the recipient testis. They continued to increase in number for more than a year following transplantation. Colonization efficiency of spermatogonial stem cells was determined to be 4.25% by using Sl/Sl(d) mice as recipients that propagated only undifferentiated type A spermatogonia in their testes. Based on the colonization efficiency, one colony-forming activity was assessed to equate to about 20 spermatogonial stem cells. The spermatogonial stem cells were estimated to expand over 50-fold in 100 days in this experiment.

Animals↗

PubMed2003

Semen cryopreservation for patients with malignant or non-malignant disease: our experience for 10 years.

PURPOSE: We report our experience in 10 years of sperm cryopreservation to reveal the present state of the cryopreservation project. MATERIALS AND METHODS: 42 germ cell tumor, 110 non-germ cell tumor and 2 non-malignant disease patients who visited our clinic for semen cryopreservation were retrospectively analyzed. RESULTS: Only 7 (20%) out of 35 unilateral testicular tumor patients who had received no chemotherapy met the WHO criteria for sperm concentration and motility. However, there were no patients with azoospermia. Three testicular tumor patients with previous chemotherapy and 4 retroperitoneal germ cell tumor patients had poor sperm concentrations and motilities. Twenty (52%) out of 38 non-germ cell tumor patients without previous chemotherapy met the WHO criteria. In contrast, only 9 patients (13%) met the WHO criteria among 72 patients with previous chemotherapy. Twenty-nine patients (40%) with chemotherapy were azoospermia. Totally, 74 (96%) of 77 tumor patients' semen without chemotherapy and 34 (45%) of 75 with chemotherapy were cryopreserved. Sperm from a patient with testicular torsion were cryopreserved. CONCLUSION: Most cancer patients without previous chemotherapy, regardless of underlying disease, had abundant motile sperm. However, half of the patients who had received chemotherapy did not have suitable sperm for freezing. It is important to inform young cancer patients of the cryopreservation project immediately after the diagnosis is made.

Adolescent↗

PubMed2003

[Sjogren's syndrome with bilateral hydronephrosis caused by pseudolymphoma of bilateral renal pelves: a case report].

We report a case of bilateral hydronephrosis caused by pseudolymphoma of bilateral renal pelves. A 52-year-old woman with Sjogren's syndrome and bronchial asthma was found to have bilateral hydronephrosis. Abdominal plain computerized tomography showed an irregular thickening of the bilateral renal pelves with moderate hydronephrosis. The gallium scintigraphy revealed intense tracer uptake in bilateral renal pelves. Open biopsy of the right renal pelvis was performed under the diagnosis of malignant lymphoma. The pathologic diagnosis was pseudolymphoma of the renal pelvis. Steroid therapy dramatically improved pseudolymphoma and hydronephrosis within a month. There were no signs of recurrence.

Female↗