Search PubMed⌕ Search

Biomedical subjects

Akihiko Okuyama

Publications and source records attributed to Akihiko Okuyama.

At least 19 recordsLinked to original sources
PubMed2006

Carbamylated erythropoietin protects the kidneys from ischemia-reperfusion injury without stimulating erythropoiesis.

Several studies have shown that erythropoietin (EPO) can protect the kidneys from ischemia-reperfusion injury and can raise the hemoglobin (Hb) concentration. Recently, the EPO molecule modified by carbamylation (CEPO) has been identified and was demonstrated to be able to protect several organs without increasing the Hb concentration. We hypothesized that treatment with CEPO would protect the kidneys from tubular apoptosis and inhibit subsequent tubulointerstitial injury without erythropoiesis. The therapeutic effect of CEPO was evaluated using a rat ischemia-reperfusion injury model. Saline-treated kidneys exhibited increased tubular apoptosis with interstitial expression of alpha-smooth muscle actin (alpha-SMA), while EPO treatment inhibited tubular apoptosis and alpha-SMA expression to some extent. On the other hand, CEPO-treated kidneys showed minimal tubular apoptosis with limited expression of alpha-SMA. Moreover, CEPO significantly promoted tubular epithelial cell proliferation without erythropoiesis. In conclusion, we identified a new therapeutic approach using CEPO to protect kidneys from ischemia-reperfusion injury.

Animals↗
PubMed2006

Isolation of germ cells from leukemia and lymphoma cells in a human in vitro model: potential clinical application for restoring human fertility after anticancer therapy.

More than 70% of patients survive childhood cancer, but chemotherapy and radiation therapy may cause irreversible impairment of spermatogenesis. To treat infertility secondary to anticancer treatment for childhood cancer, we have developed a procedure to isolate germ cells from leukemic mice by fluorescence-activated cell sorting with two surface markers, and transplantation of isolated germ cells successfully restored fertility without inducing leukemia. In the present study, we analyzed human germ cells and human malignant cells, including five leukemia cell lines and three lymphoma cell lines, by fluorescence-activated cell sorting with antibodies against MHC class I and CD45. Testicular specimens were obtained from a patient who underwent surgery for testicular rupture. In the high forward scatter and low side scatter region, no malignant cells were found in the MHC class I-negative and CD45-negative fraction (the germ cell fraction), with the exception of K562 cells. A total of 39.2% of the germ cells were found in the germ cell fraction. A total of 1.45% of K562 cells were found in the germ cell fraction. Treatment with IFNgamma induced the expression of MHC class I on K562 cells but not on germ cells and made it possible to isolate germ cells from K562 cells. In conclusion, we isolated human germ cells from malignant cells with two surface markers after treatment with IFNgamma. Immunophenotyping for each patient will be necessary before isolation and induction of surface marker will be clinically applicable.

Cell Line, Tumor↗
PubMed2006

Evaluation of renal arteries in living renal donors: comparison between MDCT angiography and gadolinium-enhanced 3D MR angiography.

PURPOSE: The purpose of this study was to clarify and compare the accuracy of contrast-enhanced computed tomography (CT) angiography using multidetector-row helical CT (MDCT angiography) and gadolinium-enhanced MR angiography using three-dimensional Fourier transformation gradient-echo sequence (3D MR angiography) for preoperative evaluation of renal arteries in living renal donors. MATERIALS AND METHODS: A total of 42 living renal donor candidates underwent both MDCT angiography and 3D MR angiography before digital subtraction angiography (DSA). Each MDCT angiogram and 3D MR angiogram was prospectively interpreted, and the findings were compared with the DSA results. RESULTS: MDCT angiography identified all of the 12 supernumerary arteries detected by DSA, whereas 3D MR angiography identified only 8. MDCT angiography identified all of the 19 proximal arterial branches detected by DSA, whereas 3D MR angiography identified only 16. CONCLUSION: A more accurate depiction of renal arteries in living renal donors can be achieved with MDCT angiography than with 3D MR angiography.

Adult↗
PubMed2006

High-dose-rate brachytherapy without external beam irradiation for locally advanced prostate cancer.

BACKGROUND AND PURPOSE: High-dose-rate brachytherapy (HDR-BT) had been used only in combination with external beam irradiation (EBI) until our previously reported first trial of HDR-BT alone without EBI. The purpose of the current report is to evaluate the feasibility, toxicity and efficacy of this regimen, with more patient accrual and longer follow-up. MATERIAL AND METHODS: From 1995 through 2004, 111 patients with localized prostate cancer were treated with HDR-BT without EBI. Fifteen patients were considered as low-risk, 28 as intermediate-risk, and 68 as high-risk. The prescribed dose was 48 Gy/8 fractions/5 days or 54 Gy/9 fractions/5 days. Median follow-up time was 27 months (range 5-119). RESULTS: All the patients completed the treatment regimen. The 3- and 5-year PSA failure-free rates were 83% and 70%, and the local control rates 100% and 97%. The maximum toxicities observed were Grade 3 by CTCAE v3.0 (6 acute, 1 chronic). CONCLUSIONS: HDR-BT without EBI was feasible and its toxicity acceptable. Short-term tumor control was promising, even for locally advanced cases. More patient accrual and longer follow-up are needed to confirm the efficacy of this novel approach.

Aged↗
PubMed2006

Hepatocyte growth factor has protective effects on crystal-cell interaction and crystal deposits.

OBJECTIVES: To investigate whether hepatocyte growth factor (HGF) has a protective role against crystal-cell interaction and crystal deposits in a stone-forming rat model kidney. Crystal-cell interaction is an important step during the early stages of stone formation. High oxalate levels induce cell injuries and increase adhesion of calcium oxalate monohydrate (COM) crystals to renal tubular cells. HGF was initially identified as the most potent growth factor for hepatocytes and is well known as a mesenchyme-derived pleiotropic factor for various types of cells. HGF has mitogenic, morphogenic, and anti-apoptotic effects on renal tubular cells. METHODS: Madin-Darby canine kidney cells were exposed to potassium oxalate or COM crystals in the presence or absence of HGF. We measured lactate dehydrogenase activity in the medium and analyzed apoptosis by FACScan. COM crystal formation was induced by administration of 0.5% ethylene glycol in the drinking water and forced feeding of 0.5 microg of 1alpha-OH-D3 every other day to male Sprague-Dawley rats. Plasmid vector encoding HGF was transferred to stone-forming rats on day 1, and the kidneys were excised on day 8. RESULTS: Exposure of Madin-Darby canine kidney cells to both potassium oxalate (KOX) and COM crystals resulted in an increase in lactate dehydrogenase release and the proportion of apoptotic cells, but these effects were reduced by HGF. HGF had inhibitory activity against the adhesion of COM crystals to Madin-Darby canine kidney cells. HGF gene transfer significantly reduced crystal deposits on the renal tubules in stone-forming rats. CONCLUSIONS: These findings suggest that HGF might play an important role in stone formation.

Animals↗
PubMed2006

The expression of thymidine phosphorylase is a prognostic predictor for the intravesical recurrence of superficial bladder cancer.

BACKGROUND: Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor, has been implicated in the angiogenesis of bladder cancer. The aim of this study is to investigate the association between TP expression and the clinicopathologic findings, and the prognostic value. METHODS: TP immunohistochemical staining was performed in specimens from 71 patients (50 men and 21 women) with superficial bladder cancer (pTa or pT1). Thirty-nine patients had received intravesical instillation of tetrahydropyranyladriamycin (THP) after transurethral resection (TUR) and the other 32 had not. For immunohistochemistry, paraffin-embedded specimens were stained with mouse monoclonal antibody against TP. When more than 10% of tumor cells were positively stained, staining was defined as positive. The correlations between TP immunostaining and clinicopathological features were analyzed. Multivariate analysis, using the Cox proportional hazard model, was performed to determine the risk factors for intravesical recurrence. RESULTS: Specimens from 29 of the 71 patients (19 men and 10 women) were positive for TP. The expression of TP was not correlated with age, sex, histological grade, multiplicity, or morphology. Also, TP expression was not associated with whether the cases were primary or recurrent. Multivariate analysis demonstrated that the decreased expression of TP and the use of THP instillation could be independent predictors of a higher rate of intravesical recurrence-free bladder cancer. CONCLUSION: The present study suggests that immunohistochemical TP staining is useful for predicting the intravesical recurrence of superficial bladder cancer after Transurethral resection of bladder tumor (TUR-Bt).

Administration, Intravesical↗
PubMed2006

Brain processing of audiovisual sexual stimuli inducing penile erection: a positron emission tomography study.

PURPOSE: Penile erection is dependent on commands from the central nervous system. Although basic studies of animals and neuroimaging studies of humans have been conducted to identify key brain regions associated with sexual arousal, to our knowledge no reliable studies of the first excitation phase of sexual arousal leading to penile erection have been reported. MATERIALS AND METHODS: We used H(2)(15)O-positron emission tomography to analyze regional cerebral blood flow just before penile erection in heterosexual volunteers. The subjects viewed 3 different types of audiovisual materials-sexually explicit clips, nonsexual neutral clips and dynamic mosaic image control clips-presented in random order, and penile rigidity was monitored in real time with a RigiScan(R) Plus device. Positron emission tomography scanning was initiated simultaneously when each clip was started, and images obtained when the subjects showed appropriate penile response were analyzed and compared. RESULTS: The advanced audiovisual cortices and cerebellar vermis in the right hemisphere were activated for sexually explicit-dynamic mosaic image control clip contrast, and only the right middle frontal gyrus was activated for sexually explicit- nonsexual neutral clip contrast. Several primary visual and audio regions were activated for dynamic mosaic image control-sexually explicit clip contrast and nonsexual neutral-sexually explicit clip contrast. CONCLUSIONS: We speculate that advanced audiovisual activity with imagination, not primary visual and audio activity, occurs when men experience sexual arousal inducing penile erection. Furthermore, the cerebellar vermis may be a key region for induction of penile erection in humans.

Acoustic Stimulation↗
PubMed2006

The endoscopic surgical skill qualification system in urological laparoscopy: a novel system in Japan.

PURPOSE: The Japanese Urological Association, and Japanese Society of Endourology and ESWL have established the Endoscopic Surgical Skill Qualification System in urological laparoscopy. The system consists of a urological section as well as gynecology and general surgery sections. We present details of the Endoscopic Surgical Skill Qualification System and year 1 results. MATERIALS AND METHODS: Endoscopic Surgical Skill Qualification System requirements test the ability to complete common laparoscopic surgeries in each field. In urology applicants are required to complete adrenalectomies or nephrectomies appropriately and safely. Applicants should have 2 years of experience with laparoscopic practice, in addition to having completed a 6-year formal urological training program. Also, each surgeon must have performed more than 20 laparoscopic surgeries. According to assessment guidelines applicant skills are assessed by 2 referees who view unedited videotapes showing the entire laparoscopic procedure. To establish these referees 6 expert referees were first selected and 23 were then chosen from 36 referee applicants. Each referee had completed more than 100 laparoscopic surgeries and was chosen after video assessments by the 6 initial expert referees. RESULTS: Of 5,600 certified urologists in Japan 205 applied to this system in its first year, including 6 expert referees and 36 referee applicants. After video assessments by the referees 136 applicants were certified as having appropriate skills, resulting in a 66% pass rate. CONCLUSIONS: The Endoscopic Surgical Skill Qualification System has just started but it has drawn a lot of attention from the public. We hope that this qualification system will help prevent complications of urological laparoscopic surgeries and promote safer surgical procedures.

Clinical Competence↗
PubMed2006

Salvage microdissection testicular sperm extraction after failed conventional testicular sperm extraction in patients with nonobstructive azoospermia.

PURPOSE: TESE is considered the best procedure for identifying a tubule for spermatozoa retrieval. This technique improves the SRR to around 50%. However, it has been unclear whether it is useful in patients in whom conventional TESE has failed. We compared the outcome of microdissection TESE in patients in whom conventional TESE failed to that in patients who did not undergo conventional TESE. We also evaluated relations between the outcome of salvage microdissection TESE and the characteristics of previous conventional TESE. MATERIALS AND METHODS: A total of 46 patients with nonobstructive azoospermia in whom salvage microdissection TESE was performed after failed conventional TESE were included. Patient characteristics and the SRR were compared between these patients and 134 in whom conventional TESE had not been performed previously. The previous TESE procedure, testicular histology and interval between TESEs were also evaluated. RESULTS: Patient characteristics did not differ significantly between the groups. The microdissection TESE SRR also did not differ significantly between the groups (45.7% vs 44.0%). The possibility of successful spermatozoa retrieval by salvage microdissection TESE remained regardless of the previous failure of any other TESE procedure and regardless of testicular histology. The salvage microdissection TESE SRR was not related to the interval between TESEs. CONCLUSIONS: Because salvage microdissection TESE is effective in patients in whom conventional TESE has failed, this option should be made available to them with the understanding that extended followup after salvage microdissection TESE is necessary due to the risk of hypogonadism.

Adult↗
PubMed2006

Laparoscopic adrenalectomy for primary hyperaldosteronism: clinical experience with 60 cases.

PURPOSE: To assess the long-term outcome of patients with primary hyperaldosteronism who underwent laparoscopic adrenalectomy and to study hormone dynamics and differences between postoperative and preoperative blood pressure. PATIENTS AND METHODS: From December 1992 to February 2005, 60 patients with primary hyperaldosteronism underwent laparoscopic adrenalectomy at our institution. Their clinical and biochemical parameters were reviewed retrospectively. In 45 patients, it was possible to follow the hormone dynamics and blood pressure to compare the preoperative values with those >or=2 months after the operation. RESULTS: The average operating time was 261.7 minutes (range 95-835 minutes), and the average blood loss was 204.2 mL (range 10-3740 mL). The average time to ambulation was 1.7 days (range 1-7 days). Five patients (8.3%) had intraoperative hemorrhage that necessitated blood transfusion. Serum aldosterone in all 45 patients who were followed up was normalized postoperatively. At >or=2 months postoperatively, only 12 of the 45 patients (26.7%) needed antihypertensive drug(s). CONCLUSIONS: Laparoscopic adrenalectomy is a safe and effective way to treat primary hyperaldosteronism. Many of the patients in whom hypertension persisted postoperatively were men or elderly.

Adenoma↗
PubMed2006

Expression profiles and single-nucleotide polymorphism analysis of human HANP1/H1T2 encoding a histone H1-like protein.

Recently we cloned the Hanp1 cDNA that encodes a histone H1-like haploid germ cell-specific nuclear protein in the mouse. Homozygous Hanp1 mutant male mice were infertile, while females were fertile. Although a substantial number of sperm were recovered from the epididymis, their shape and function were abnormal. Hanp1 protein is essential for nuclear formation in functional spermatozoa, and is specifically involved in the replacement of histones with protamines during spermiogenesis. To investigate the roles of human HANP1 (h-HANP1) and its relation to male infertility, we isolated h-HANP1 cDNA from a human cDNA plasmid library using mouse Hanp1 cDNA as a probe. h-HANP1 is expressed in the testes and its genomic construct also intronless as mouse Hanp1. We found that the h-HANP1 coding region have 5 single-nucleotide polymorphisms in Japanese men.

Amino Acid Sequence↗
PubMed2006

Incidence of positive C4d deposition in long-term survival cases over 10 yr after renal transplantation.

BACKGROUND: The incidence of positive C4d deposition in peritubular capillaries (PTC) in long-term survival cases remains controversial. Some incidences of positive C4d deposition in PTC in cases of long-term survival less than 10 yr have been reported. We retrospectively examined the incidence of positive C4d deposition in long-term survival cases over 10 yr after renal transplantation and the histological and clinical characteristics of the positive C4d staining cases. METHODS: We examined 14 protocol biopsy cases performed at Osaka University Hospital between March 2004 and March 2005. The average interval between the operation and the day of biopsy was 15.4 yr. Histological diagnosis was made in accordance with the Banff 97 classification. Paraffin-embedded tissue was stained with polyclonal anti-C4d antibody. Detection of donor-specific antibody (DSA) was determined by flow cytometric assay. The cases were divided according to C4d positivity. RESULTS: Three of 14 cases (21.4%) were C4d positive and belonged to the C4d+/DSA+ group, while 11 cases were of the C4d-/DSA- group. There were no significant differences between the two groups in serum creatinine (sCr) or proteinuria at the time of biopsy. A trend towards decreasing rate of the inverse of sCr (1/sCr) in the C4d+/DSA+ group was noted. In the C4d+/DSA+ group, three transplant glomerulopathy (TGP) were identified. On the other hand, TGP were identified in six of 11 cases of the C4d-/DSA- group. We investigated the relevance of typical chronic rejection (CR) features and the positivity of C4d. No significant differences were observed between the CR features and C4d depositions in PTC (p = 0.26). CONCLUSION: In long-term survival cases with positive C4d, a trend towards decreasing rate of 1/sCr was revealed, but their histological characteristic features was not recognized.

Adult↗
PubMed2006

ABO-incompatible kidney transplantation with anti-CD20 monoclonal antibodies, intravenous immunoglobulin and plasmapheresis without splenectomy: a case report.

A 24-yr-old man was admitted to our hospital for ABO-incompatible kidney transplantation. His blood type was O, and the donor's (his father's) blood type was B. The recipient had pancytopenia, splenomegaly, splenorenal shunts and esophageal varices due to congenital hepatic fibrosis. Therefore, if splenorectomy was performed, the blood pressure of the portal vein and the growth of esophageal varices were predicted. Eventually, in return for splenectomy, anti-CD20 monoclonal antibodies (rituximab), intravenous immunoglobulin and plasmapheresis was performed for additional immunosuppression. Because of progression of pancytopenia, we had to decrease the dose of mycophenolate mofetil and gave up on using deoxyspagalin. Nevertheless the serum creatinine level decreased and remained in the 1.6 to 1.8 mg/dl range.

ABO Blood-Group System↗
PubMed2006

Urinary macromolecules and renal tubular cell protection from oxalate injury: comparison of normal subjects and recurrent stone formers.

AIM: To determine whether urinary macromolecules (UMM), which are the high molecular weight substances in urine, can provide protection against the oxalate-associated injury to the renal tubular cells. METHODS: UMM were extracted from 24-h urine of 12 healthy adult male volunteers and 13 recurrent-stone-former male patients. Urine parameters in relation to urolithiasis were measured, including the level of glycosaminoglycans (GAG) in the UMM. Madin-Darby canine kidney (MDCK) cells were used to evaluate the protective activity of UMM from oxalate-induced cytotoxicity by LDH release measurement and methyl-thiazolyl tertrazolium (MTT) assay. RESULTS: Considering urinary parameters, citrate was significantly higher in urine from normal subjects than stone-former subjects; the other parameters show no differences between the groups. Total UMM and the level of GAG in the UMM were also significantly higher in the normal subject group. Compared with normal subject and stone-former subject UMM, after cells were treated with the UMM and then exposed to oxalate solution, LDH release was significantly higher in stone-former group. In the MTT assay, we found that more viable cells were observed after treatment with UMM compared to control in both groups. Moreover, UMM from the normal subjects showed higher protective activity against oxalate-related cytotoxicity than UMM from the stone-former subjects. CONCLUSION: UMM protected renal epithelial cells from oxalate-related injury. This protective activity was found to be higher in normal subject UMM than stone-former UMM. Among other factors, a higher concentration of GAG and citrate in normal subject UMM might affect some parts in this finding.

Adult↗
PubMed2006

Testicular epidermoid cyst in Klinefelter's syndrome.

A 38-year-old Japanese man was referred to our outpatient clinic for treatment of infertility. Semen analysis showed azoospermia. Chromosome analysis revealed a 47XXY karyotype, and non-mosaic Klinefelter's syndrome (KFS) was diagnosed. Upon physical examination, the patient's right testicular volume was 30 mL and the left testicular volume was 3 mL. Laboratory tests showed normal levels of lactate dehydrogenase, alpha-fetoprotein, and human chorionic gonadotropin beta-subunit. The plasma luteinizing hormone and follicle-stimulating hormone levels were increased to 15.7 mIU/mL and 45.9 mIU/mL, respectively. The plasma testosterone was decreased to 0.25 ng/mL. Magnetic resonance imaging showed a right testicular mass of low-signal intensity on the T1-weighted image and of high-signal intensity on the T2-weighted image. Therefore, the final diagnosis was KFS with a right testicular tumor. Thus, a right high orchiectomy was performed. Histological examination revealed an epidermoid cyst of the right testis. Epidermoid cysts in cases of KFS are rare. To our knowledge, only seven cases, including ours, have been reported in the literature.

Adult↗
PubMed2006

Fibronectin inhibits endocytosis of calcium oxalate crystals by renal tubular cells.

BACKGROUND: Fibronectin (FN; 230 kDa) is a multifunctional alpha2-glycoprotein distributed throughout the extracellular matrix and body fluids. We recently reported that FN has a protective effect against injury of renal tubular cells by exposure to oxalate and calcium oxalate (CaOX) crystals and inhibits the adhesion of CaOX crystals to renal tubular cells. In the study presented here, we investigated whether FN has inhibitory effect on crystal endocytosis by renal tubular cells. METHODS: The inhibitory effect of FN on endocytosis of CaOX crystals by MDCK cells was examined by using a radioactivity uptake assay. Also, crystal endocytosis by cells was morphologically assessed by means of transmission electron microscopy (TEM). RESULTS: FN had inhibitory effects on CaOX crystal endocytosis by MDCK cells. The morphological TEM study showed that few crystals were taken into cells when FN was added compared to the number of crystals when FN was not added. CONCLUSION: We found that FN had the inhibitory effects on the interaction between crystals and renal tubular cells, including the adhesion or endocytosis of crystals by cells.

Animals↗
PubMed2006

A case of renal cell carcinoma with multiple lung metastases refractory to interferon-alpha showing complete remission by interleukin-2 monotherapy.

We report a case in which a regimen of interleukin-2 (IL-2) achieved pathologically complete remission against renal cell carcinoma with multiple lung metastases. A 63-year-old man was admitted to the Osaka University Hospital with a right renal tumor and multiple lung metastases. Right radical nephrectomy was performed and the histological diagnosis was clear cell carcinoma, G3 > G2, INFbeta, pT3a, pN0. Postoperatively, despite treatment with interferon-alpha, the lung metastases progressed. Consequently, intravenous administration of IL-2 was started at a dose of 70 x 10(4) JRU/day five times per week. After 16 weeks of IL-2 therapy, most of the multiple lung metastases completely vanished and the largest metastatic lung mass was reduced in size. Resection of this residual lung mass was performed and pathological examination revealed no viable cancer cells.

Adenocarcinoma, Clear Cell↗