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Iwao Fukui

Publications and source records attributed to Iwao Fukui.

At least 19 recordsLinked to original sources
PubMed2006

Activation of GIRK channels by muscarinic receptors and group II metabotropic glutamate receptors suppresses Golgi cell activity in the cochlear nucleus of mice.

Granule cells and parallel fiber circuits in the dorsal cochlear nucleus (DCN) play a role in integration of multimodal sensory with auditory inputs. The activity of granule cells is regulated through inhibitory connections made by Golgi cells. Golgi cells in turn probably receive parallel fiber inputs and regulate activity of the DCN. We have investigated the electrophysiological properties of Golgi cells using the whole cell patch-clamp method in slices made from transgenic mice that express green fluorescent protein driven by the promotor of metabotropic glutamate receptor subtype 2. Stimulation of auditory nerve fibers (ANFs) and of parallel fibers evoked glutamatergic excitatory postsynaptic currents (EPSC) through AMPA receptors. The strengths and latencies of these inputs differed, however. ANF stimulation evoked EPSCs after 4.7 +/- 0.4 ms, whereas parallel fiber stimulation evoked EPSCs after 1.4 +/- 0.2 ms that were on average 2.5 times as large. The multiple peaks and prolonged activity suggest the presence of polysynaptic connections between ANFs and Golgi cells. Agonists for group II metabotropic glutamate receptors (mGluRs) and for muscarinic receptors induced membrane hyperpolarization and suppressed the firing of Golgi cells by activating G-protein-coupled inward rectifier K(+) (GIRK) channels. These results strongly suggest that Golgi cells were regulated through the combined activities of glutamatergic and cholinergic synapses, which presumably regulated the temporal firing patterns of granule cells and through them the activity of principal cells of the DCN.

Action Potentials↗
PubMed2006

Optimal sampling sites for repeat prostate biopsy: a recursive partitioning analysis of three-dimensional 26-core systematic biopsy.

OBJECTIVES: To explore an optimal combination of sampling sites to detect prostate cancer in a repeat biopsy setting. METHODS: A transrectal ultrasound-guided systematic three-dimensional 26-core biopsy (3D26PBx), a combination of transrectal 12 and transperineal 14 core biopsies, was performed in 235 Japanese men with prior negative biopsy. Using recursive partitioning, we evaluated cancer detection of all possible combinations of sampling sites and selected the combination that provides the highest cancer detection rate at a given number of biopsy cores. RESULTS: Prostate cancer was detected in 87 of the 235 (37%) men. The 3D26PBx improved cancer detection by 89% relative to the conventional transrectal sextant biopsy. Neither Gleason score nor percentage of Gleason 4/5 cancers differed between cancers with and without positive cores within the transrectal sextant-sampling sites. A three-dimensional combination of transrectal and transperineal approaches outperformed either transrectal or transperineal approach alone. Recursive partitioning revealed that a three-dimensional 16-core (transrectal eight cores plus transperineal eight cores) biopsy could detect all the cancers with the minimum number of cores. CONCLUSIONS: We propose a three-dimensional combination of transrectal eight cores taken from the far lateral peripheral zone and the parasagittal base, and transperineal eight cores taken from the anterior and posterior apex and the transition zone as an optimal set of sampling sites for repeat biopsy.

Aged↗
PubMed2006

Phase I/II study of a combined gemcitabine, etoposide, and cisplatin chemotherapy regimen for metastatic urothelial carcinoma.

BACKGROUND: The authors attempted to determine the maximum tolerated dose (MTD) of gemcitabine in combination with etoposide and cisplatin as a chemotherapy regimen and investigated the safety and antitumor activity with the recommended doses of gemcitabine with etoposide and cisplatin for patients with metastatic urothelial carcinoma. METHODS: Patients age 75 years or younger with measurable lesions, creatinine clearance>or=50 mL per minute, and adequate bone marrow and hepatic function were studied. Etoposide and cisplatin were given on Days 1 through 3 at fixed doses of 75 mg/m2 and 25 mg/m2, respectively, and gemcitabine was given on Days 1, 8, and 15. In the Phase I component, gemcitabine was administered at increasing doses from 600 mg/m2. Cycles were repeated every 28 days unless progressive disease was encountered. RESULTS: In Phase I, with the initially fixed doses of etoposide and cisplatin, the MTD of gemcitabine could not be determined because of the occurrence of dose-limiting toxicity at Level 1 in all 3 patients. When the doses of etoposide and cisplatin were modified to 60 mg/m2 and 20 mg/m2, respectively, the MTD of gemcitabine was 1000 mg/m2. Next, 19 additional patients were entered into Phase II with the recommended gemcitabine dose of 800 mg/m2, and 20 patients in all were treated at this dose level. The main toxicity was bone marrow suppression, with Grade 3 or 4 neutropenia and thrombocytopenia recognized in 20 patients (100%) and 14 patients (70%), respectively, although no toxic deaths occurred. In total, all 31 patients at all dose levels had an assessable response, with 6 complete responses and 15 partial responses observed, for an overall response rate of 67.7%. Patients who had visceral metastasis had a significantly worse response rate than patients who had lymph node metastasis alone (50.0% vs. 78.9%; P=.042). The response rate (66.7%) for 21 patients who received prior chemotherapy was not different from that for 10 chemotherapy-naive patients. The median survival for all patients was 13.1 months, and 4 patients survived for >2 years with no evidence of disease. Patients younger than age 65 years had significantly better survival than patients age 65 years or older (P=.026). CONCLUSIONS: Although bone marrow toxicity was considerable, combination chemotherapy with gemcitabine, etoposide, and cisplatin appeared to be very active in patients with urothelial carcinoma and may be especially promising for younger patients, although further study is warranted.

Aged↗
PubMed2006

Improvement of phase information at low sound frequency in nucleus magnocellularis of the chicken.

Nucleus magnocellularis (NM) is one of the subnuclei of the avian cochlear nucleus and has a role of extracting the temporal information of sound from the auditory nerve fibers (ANFs). Neurons in NM are varied along the tonotopic axis in synaptic transmission and membrane excitability and are high-fidelity relay neurons at the high to middle characteristic frequency (CF) regions. Here we have compared the firing properties between ANFs and NM neurons in vivo and found that at high but not near threshold intensities, spike firings are more phase-locked in NM than in ANFs in the CF region <500 Hz. Moreover, NM shows reduced occurrence of multiple spikes within one cycle of sound stimuli and higher vector strength than ANF. The improved phase-locked firing nature of NM is discussed in relation to the in vitro findings of small EPSCs in the low CF neurons (Fukui and Ohmori 2004). It is concluded that NM neurons are not simple relay neurons in the low CF region but are coincidence detectors of monoaural synaptic inputs that improve the synchronization of spike firing to auditory inputs.

Acoustic Stimulation↗
PubMed2006

Successful therapy of a malignant phyllodes tumor of the prostate after postoperative local failure.

A 19-year-old student who had presented with acute urinary retention was referred to our hospital with biopsy diagnosis of proliferating mesenchymal tumor of the prostate. Magnetic resonance imaging showed enlarged prostatic masses. Suspecting prostate sarcoma, we performed a nerve-sparing radical prostatectomy. Histologic diagnosis of the tumor was prostatic malignant phyllodes tumor. Five months after the operation, bilateral obturator lymph node metastases appeared, which were treated with etoposide, ifosfamide, and cisplatin chemotherapy. After a good response was achieved with four cycles of the chemotherapy, pelvic irradiation was added. Since then, there has been no evidence of recurrence for more than 4 years.

Adult↗
PubMed2006

Three-dimensional combination of transrectal and transperineal biopsies for efficient detection of stage T1c prostate cancer.

BACKGROUND: Although an increasing number of men present with stage T1c prostate cancer, the optimal biopsy strategy for detecting stage T1c disease still remains to be defined. The aim of this study was to explore an efficient first-time biopsy scheme for detecting stage T1c and T2 prostate cancer. METHODS: A transrectal ultrasound-guided systematic three-dimensional 26-core (3D26) biopsy comprising 12 transrectal and 14 transperineal sampling sites was performed in 321 men with median prostate-specific antigen (PSA) level of 6.0 ng/ml in the first-time biopsy setting. By analyzing site-specific cancer detection rates, we determined the best combination of transperineal and transrectal sampling sites. RESULTS: Prostate cancer was detected in 109 of the 321 men (34%) with a major complication rate of 0.6%. 3D26 biopsy significantly improved cancer detectability by 60% relative to the conventional transrectal sextant (TR6) biopsy. Improvement was significant in 263 men with normal digital rectal examination (DRE) (85%, P = 0.0004) but not in 58 men with abnormal DRE (22%, P = 0.18). The mean Gleason score of the 41 cancers without a positive core within the TR6 sites was marginally lower than that of 68 cancers with a positive core within the TR6 sites (P = 0.04). Recursive partitioning revealed that a three-dimensional 14-core (transrectal 8-core plus transperineal 6-core) and a three-dimensional 8-core (transrectal 4-core plus transperineal 4-core) biopsies could detect more than 95% of stage T1c and T2 cancers with a minimum number of cores, respectively. CONCLUSION: We propose a three-dimensional 14-core and a three-dimensional 8-core biopsy as efficient first-time biopsy schemes to detect stage T1c and T2 prostate cancer, respectively.

Adenocarcinoma↗
PubMed2006

Possibility of recovery of estrogen sensitivity following high-dose glucocorticoid therapy in a patient with hormone-refractory prostate cancer.

A 74-year-old man underwent irradiation therapy (RT) to the prostate bed because of prostate-specific antigen (PSA) failure after retropubic radical prostatectomy (RRP). Six months after the RT, a solitary bone metastasis developed in the third thoracic vertebra, and hormonal therapy (HT) was initiated. Three years later, following the loss of response to all hormonal agents, including oral estrogen and glucocorticoid therapy, paraplegia developed, due to a spinal metastasis. RT and high-dose glucocorticoid therapy were given for the spinal metastasis. Diethylstilbestrol diphosphate (DES-DP) was given continuously during this treatment, except for a 1-month period when the patient had pneumonia. After the RT and high-dose glucocorticoid therapy, his serum PSA decreased, from 308 to 36.99 ng/ml. In accordance with the 1-month discontinuation, and then resumption of DES-DP, the serum PSA levels went up and down. So we suspected that the tumor had recovered sensitivity to DES-DP with the high-dose glucocorticoid therapy. With a further decrease of serum PSA to 2.12 ng/ml, he has been alive for more than 3 years to date since the diagnosis of hormone-refractory prostate cancer (HRPCA). To our knowledge, there have been no reports showing such a marked recovery of hormone-sensitivity in HRPCA. No optimal therapy has yet been established for HRPCA; therefore, high-dose glucocorticoid therapy in combination with DES-DP warrants further study.

Adenocarcinoma↗
PubMed2006

[A case of inflammatory myofibroblastic tumor of the urinary bladder finally diagnosed by anaplastic lymphoma kinase (ALK) immunostaining].

A 52-year-old house wife presented with pain on urination. Cystoscopy and magnetic resonance imaging revealed solid and sessile tumor of 3 cm in diameter invading the bladder wall. Pathological examination of the transurethral resection specimen showed proliferation of spindle cells and epithelial cells. Since both types of cells were positive for cytokeratin immunostaining, sarcomatoid carcinoma was highly suspected. She underwent anterior pelvic exenteration and construction of continent reservoir (Penn Pouch). Since the tumor cells showed spindle cell proliferation alone without epithelial growth and positive staining for anaplastic lymphoma kinase, we corrected the final diagnosis as an inflammatory myofibroblastic tumor of the urinary bladder. She has been doing well without recurrence for 1 year.

Anaplastic Lymphoma Kinase↗
PubMed2005

Effectiveness of adjuvant intermittent endocrine therapy following neoadjuvant endocrine therapy and external beam radiation therapy in men with locally advanced prostate cancer.

PURPOSE: To clarify the optimal duration and methods for adjuvant endocrine therapy after external beam radiation therapy (EBRT) in patients with locally advanced prostate cancer. MATERIALS AND METHODS: Between 2001 and 2003, 215 patients with locally advanced prostate cancer were enrolled in the study. Patients were registered as primary candidates of the study and were treated with 6 months of LHRH agonist, with short-term of antiandrogen treatment for flare-up prevention. Patients with PSA levels below 10 ng/ml after the 6-month endocrine treatment were randomly divided into two arms. Then, a total dose of 72 Gy was given to the prostate. After 14 months of the protocol treatment, patients were treated with continuous androgen ablation (arm 1) or intermittent androgen ablation (arm 2). RESULTS: A total of 188 cases (87%) remained in the protocol. The median PSA level at entry was 25.3 ng/ml. The Gleason score was 2-6 in 32 cases (16%), 7 in 94 cases (48%), and 8-10 in 68 cases (35%). The median PSA level showed a remarkable decrease to 1.1, 0.2, and 0.1 ng/ml, after 6, 8, and 14 months of the protocol treatment, respectively. Of the 157 cases treated with EBRT, 153 cases (97.5%) had no biochemical failure in the mean follow-up of 17.3 months. CONCLUSIONS: The present study may reveal the possibilities of intermittent endocrine therapy after EBRT. However, the follow-up interval is short and little can be said about the results observed so far, exception of acute tolerance and patient acceptance of the protocol.

Adenocarcinoma↗
PubMed2005

Tonotopic specialization of auditory coincidence detection in nucleus laminaris of the chick.

The interaural time difference (ITD) is a cue for localizing a sound source along the horizontal plane and is first determined in the nucleus laminaris (NL) in birds. Neurons in NL are tonotopically organized, such that ITDs are processed separately at each characteristic frequency (CF). Here, we investigated the excitability and coincidence detection of neurons along the tonotopic axis in NL, using a chick brainstem slice preparation. Systematic changes with CF were observed in morphological and electrophysiological properties of NL neurons. These properties included the length of dendrites, the input capacitance, the conductance of hyperpolarization-activated current, and the EPSC time course. In contrast to these gradients, the conductance of low-threshold K+ current and the expression of Kv1.2 channel protein were maximal in the central (middle-CF) region of NL. As a result, the middle-CF neuron had the smallest input resistance and membrane time constant, and consequently the fastest EPSP, and exhibited the most accurate coincidence detection. The specialization of middle-CF neurons as coincidence detectors may account for the high resolution of sound-source localization in the middle-frequency range observed in avians.

Action Potentials↗
PubMed2005

Successful treatment of chemo-refractory pulmonary metastases of renal pelvic cancer by second-line chemotherapy including gemcitabine followed by salvage surgery.

A 51-year-old woman developed multiple pulmonary metastases after receiving nephroureterectomy and two cycles of adjuvant chemotherapy for the treatment of renal pelvic transitional cell carcinoma. All metastases disappeared after four cycles of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy followed by radiotherapy; however, 8 months later two pulmonary metastases recurred. The patient was entered into a phase I study of combination chemotherapy with gemcitabine, etoposide and cisplatin, designed for chemorefractory urothelial cancer. The lung masses showed significant reduction after two cycles of this chemotherapy; following salvage surgery, the patient has been well with no evidence of recurrence for more than 3 years.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Tonotopic gradients of membrane and synaptic properties for neurons of the chicken nucleus magnocellularis.

Nucleus magnocellularis (NM) is a division of the avian cochlear nucleus that extracts the timing of auditory signals. We compared the membrane excitability and synaptic transmission along the tonotopic axis of NM. Neurons expressed a Kv1.1 potassium channel mRNA and protein predominantly in the high characteristic frequency (CF) region of NM. In contrast, the expression of Kv1.2 mRNA did not change tonotopically. Neurons also showed tonotopic gradients in resting potential, spike threshold, amplitude, and membrane rectification. All neurons were sensitive to 100 nm dendrotoxin, but the effects were most significant in the high CF neurons. The EPSC recorded by minimal stimulation of auditory nerve fibers (ANFs) was 13 times larger in high CF neurons than in low CF neurons. Moreover, EPSCs were generated in an all-or-none manner in the high CF neurons when stimulus intensity was increased, whereas EPSCs were graded in the low CF neurons, indicating multiple axonal inputs. ANF synaptic terminals were visualized by DiI. ANF formed enfolding end-bulbs of Held around the cell body in the high and middle CF region but not in the low CF region. These observations indicate coordinated gradients of neuronal properties both presynaptically and postsynaptically along the tonotopic axis. Such specializations may be suitable for extracting and preserving the timing information of auditory signals over a wide range of acoustic frequencies.

Action Potentials↗
PubMed2004

[The result of VIP chemotherapy as an induction therapy in 6 patients with non-seminomatous extragonadal germ cell tumor].

We treated 6 patients with non-seminomatous extragonadal germ cell tumor (NSEGCT) by VP-16 + ifosfamide + cisplatin (VIP) chemotherapy as an induction therapy to investigate the effectiveness and safety. Primary lesions were located at the mediastinum in 4 patients and the retroperitoneum in 2 patients. As a rule, all patients were treated with VIP chemotherapy of 4 courses with or without second-line treatment such as chemotherapy, residual tumor resection and/or radiation. Following the induction therapy (VIP), 4 of 6 patients (67%) achieved complete or partial responses. After salvage therapy, 4 patients (67%) achieved complete responses and two other patients also achieved partial responses. However, only 2 of the 5 patients who had been follow-up for more than 2 years have remained disease free. The effects of VIP chemotherapy on non-seminomatous extragonadal germ cell tumor appeared to be similar to those of the conventional chemotherapies though the number of patients was small in the current study. It appears to be necessary to design more effective regimen.

Adult↗
PubMed2003

Developmental changes in membrane excitability and morphology of neurons in the nucleus angularis of the chicken.

In order to understand how sound intensity information is extracted and processed in the auditory nuclei, we investigated the neuronal excitability in the nucleus angularis (NA) of the chicken (P0-5) and the chicken embryo (E16-21). In embryos, neurons fired basically in three patterns in response to current injections: the onset pattern (19 %), the tonic pattern (52 %) and the pause pattern (29 %). After hatching, neurons fired either in the tonic pattern (83 %) or in the onset pattern (17 %). In both pre- and post-hatch periods, multiple firing neurons (tonic and pause) increased the maximum rate of rise of the action potential 2.6-fold, the fall 3.9-fold, and the maximum firing frequency 4-fold, and shifted the threshold potential to be more negative. After hatching, the firing frequency of tonic neurons reached a maximum at about 650 Hz. Application of TEA (1 mM) reduced the firing frequency, broadened action potentials and reduced the maximum rate of fall, but the threshold current was not changed. Dendrotoxin-I (DTX, 100 nM) reduced the threshold current. Application of DTX induced the onset neuron to fire repetitively. Branching patterns of auditory nerve fibres (ANFs) in NA were visualized by labelling with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Di-I) placed within the cochlea. Di-I placed near the apex of the cochlea labelled the ventral part of the NA, and Di-I placed in the base labelled the dorso-lateral part. Tonic neurons labelled with biocytin extended dendrites in parallel with the projection of ANFs in the nucleus after hatching. ANF activity of a limited range of characteristic sound frequencies is thought to be extracted by tonic neurons and encoded into firing frequencies proportional to the strength of the input.

Action Potentials↗
PubMed2003

[A case of locally advanced prostate cancer with low serum testosterone associated with intake of an androgenic medicine].

A 74-year-old man was referred to our clinic for the work-up of digitally hard and irregularly surfaced prostate and elevated serum prostate-specific antigen (PSA). His serum PSA was elevated to 41 ng/ml, but testosterone and LH level were decreased to 23.5 ng/dl and 0.5 mIU/ml, respectively. He had a history of taking an androgenic medicine containing methyl-testosterone 2 to 3 times a week for 2 year and 6 months. Transrectal sextant prostatic biopsy revealed moderately differentiated adenocarcinoma (Gleason score: 3 + 4) in 6 of 6 specimens and CT scan of the abdomen showed an enlarged obturator lymph-node (15 mm), resulting in the diagnosis of stage D1 (T3aN1M0) prostate cancer. Since serum testosterone level seemed to recover around the normal level after discontinuation of the exogenous androgen, we treated him with combination androgen blockade with LHRH agonist and bicaltamide, although his testosterone level was very low. Indeed, serum PSA decreased to 0.09 ng/ml and the right obturator node was markedly reduced by the hormone treatment. After the neoadjuvant therapy of 6 months duration, radical prostatectomy and limited pelvic lymph node dissection was carried out. Histologically, viable cancer cells were not found in any of resected lymph nodes, but they remained in bilateral lobes of the prostate (pT2bN0). The histological effect of the neoadjuvant hormone therapy according to General rule for Clinical and Pathological Studies on Prostate Cancer (3rd ed.) was grade 2. The patient has been well with undetectable PSA and no evidence of clinical failure for more than 12 months, though serum testosterone level recovered to near normal (288 ng/dl) 8 months after the cessation of the hormone treatment following the operation. Combination androgen blockade or non-steroidal anti-androgen agent appears to be effective for the treatment of prostatic cancer patients who takes exogenous androgenic medicine, even with a suppressed low serum testosterone level.

Adenocarcinoma↗
PubMed2002

[Carcinoma in situ of the penis rapidly progressing after carbon dioxide laser treatment].

Laser treatment is considered to be effective in treating carcinoma in situ of the penis. We, however, report a case with carcinoma in situ of the penis which developed invasive carcinoma and inguinal lymphnode metastases only 6 months after the laser treatment. A 74-year-old man with pseudophimosis presented with redness of the glans penis. A physical examination revealed thick erythema, 12 millimeters in diameter, around the external urethral meatus. Histologically, biopsy revealed squamous cell carcinoma in situ. No metastasis was suspected by physical examination and imaging studies. Although the lesion appeared to slightly extend into the urethra, it was primarily treated with the CO2 laser. Six months after the treatment, however, local recurrence was confirmed by the touch smear cytology, resulting in the partial amputation of the penis. The histopathological examination revealed subepithelial and marked lymphatic invasion of the tumor and positive margin in the urethral stump (squamous cell carcinoma in situ). Further, since bilateral superficial inguinal lymphnode swelling appeared, total amputation of the penis with perineal urethrotomy and pelvic/inguinal lymphnode dissection was performed subsequently. The metastases to bilateral inguinal lymphnodes were confirmed histologically. The patient received adjuvant chemotherapy and has been alive and well without evidence of disease 40 months after the initial treatment.

Aged↗
PubMed2002

[Multiple synchronous primary malignant tumors of fibrosarcoma and squamous cell carcinoma in the urinary bladder: a case report].

A 65-year-old housewife presented with a diagnosis of malignant spindle cell tumor of the bladder which had been diagnosed by work up for chance hematuria. Urine cytology revealed a small number of squamous epithelial cells showing dyskeratosis but no spindle cells. Computed tomography and magnetic resonance images showed a markedly enhanced mass, 4 cm in diameter, on the anterior wall of the urinary bladder, which appeared to be adhesive to the pubic bone. However, no metastasis was found. Under the suspicion of sarcoma of the urinary bladder, we performed anterior pelvic exenteration with construction of an ileal conduit. Although the anterior wall of the urinary bladder was mildly adhesive to the pubic bone, the surgical margin was negative for malignant cells. The tumor corresponded to a fibrosarcoma that infiltrated the adipose tissue surrounding the urinary bladder. The entire mucosa of the bladder showed diffuse squamous metaplasia, and well differentiated squamous cell carcinoma with pearl formation was found in part. These two malignant tumors were clearly apart from each other, resulting in the histologic diagnosis of synchronous multiple malignant tumors of the bladder. The patient developed a local relapse and pulmonary metastasis of fibrosarcoma one month postoperatively and died two month later without any response to chemotherapy (CYVADIC) and radiotherapy. The current case seems to be the first one in Japan (third in the world) of a patient with multiple synchronous primary malignant tumors, carcinoma and sarcoma, airsing in the urinary bladder.

Aged↗