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BphC derived from Pseudomonas sp. strain KKS102 is an extradiol-cleaving catecholic dioxygenase. This enzyme contains a non-heme iron atom and plays an important role in degrading biphenyl/polychlorinated biphenyls (PCBs) in the microbe. To elucidate detailed structures of BphC reaction intermediates, crystal structures of the substrate-free form, the BphC–substrate complex, and the BphC–substrate–NO (nitric oxide) complex were determined. These crystal structures revealed (1) the binding site of the O 2 molecule in the coordination sphere and (2) conformational changes of His194 during the catalytic reaction. On the basis of these findings, we propose a catalytic mechanism for the extradiol-cleaving catecholic dioxygenase in which His194 seems to play three distinct roles. At the early stage of the catalytic reaction, His194 appears to act as a catalytic base, which likely deprotonates the hydroxyl group of the substrate. At the next stage, the protonated His194 seems to stabilize a negative charge on the O 2 molecule located in the hydrophobic O 2 -binding cavity. Finally, protonated His194 seems to function as a proton donor, whose existence has been proposed.

Purpose We retrospectively evaluated the outcome of Hautmann neobladder reconstruction in terms of complications, lower urinary tract symptoms, and sexual function in a large group of patients who underwent radical cystectomy. Methods We reviewed the medical records of 118 patients (105 men and 13 women) who underwent radical cystectomy and Hautmann neobladder construction at the Gifu University Hospital or one of its affiliate hospitals between Jan 1993 and Dec 1999. The 118 patients were asked to complete a questionnaire regarding lower urinary tract symptoms and sexual activity, and the data was compiled. Results The mean follow-up period was 50.4 months (range, 6.8-88.2). Early complications comprised wound infection (in 17.8% of patients) and ileus (in 10.1% of patients). Late complications comprised ileus, pyelonephritis, stone, and stricture of the pouch-urethral anastomosis, each of which occurred in 3.4% of patients. Eighty-one (73 men and 8 women, 72.9%) of 90 surviving patients replied to the questionnaire. Seventy-seven (95.1%) of these patients reported spontaneous micturition, whereas 4 (4.9%) patients required intermittent self-catheterization. The mean total I-PSS was 11.6 points. Twenty-five percent of patients experienced interrupted voiding almost always; 38% of patients did not experience this at all. Approximately 26% of patients experienced weak urinary streams; 36% did not. Daytime continence was achieved in 97.3% of patients; nighttime incontinence was present in 61.3%. Preoperatively, 79.7% of the men were capable of sexual intercourse. Postoperatively, 63.6% of men who underwent radical cystectomy with the nerve-sparing procedure were capable of sexual intercourse, whereas only 14.8% of men who underwent radical cystectomy without the nerve-sparing procedure were. Conclusions Morbidity rates were acceptable and functional outcome was excellent in this rather large group of patients who underwent Hautmann neobladder construction. Some problems have not been fully overcome, however, i.e., nocturnal incontinence and sexual dysfunction.

Three human hyaluronan synthase genes ( HAS1 , HAS2 , and HAS3 ) have been cloned, but the functional differences between these HAS genes remains obscure. The purpose of this study was to examine which of the HAS genes are selectively regulated in epidermis. We examined the relation of changes between hyaluronan production and HAS gene expression when cytokines were added to cultured human keratinocytes. Interferon-γ increased hyaluronan production whereas transforming growth factor β decreased it. Both cytokines affected preferentially high-molecular-mass (> 10 6 Da) hyaluronan production. Consistent with the change in hyaluronan synthesis, we found that interferon-γ markedly upregulated HAS3 mRNA whereas transforming growth factor β downregulated HAS3 transcript levels. The expression of HAS1 mRNA was not significantly affected by either cytokine, and HAS2 mRNA expression was undetectable under either basal or cytokine-stimulated conditions by northern blot using total RNA. Furthermore, in situ mRNA hybridization showed that mouse epidermal keratinocytes abundantly expressed HAS3 mRNA from the basal to the granular cell layers, suggesting that HAS3 functions in epidermis. These findings suggest that HAS3 gene expression plays a crucial role in the regulation of hyaluronan synthesis in the epidermis.

DNA repair systems protect cells from genomic instability and carcinogenesis. Therefore, assays for measuring DNA repair activity are valuable, not only for clinical diagnoses of DNA repair deficiency disorders but also for basic research and anticancer drug development. Two commonly used assays are UDS (unscheduled DNA synthesis, requiring a precise measurement of an extremely small amount of repair DNA synthesis) and RRS (recovery of RNA synthesis after DNA damage). Both UDS and RRS are major endpoints for assessing the activity of nucleotide excision repair (NER), the most versatile DNA repair process. Conventional UDS and RRS assays are laborious and time-consuming, as they measure the incorporation of radiolabeled nucleosides associated with NER. Here we describe a comprehensive protocol for monitoring nonradioactive UDS and RRS by studying the incorporation of alkyne-conjugated nucleoside analogs followed by a fluorescent azide-coupling click-chemistry reaction. The system is also suitable for quick measurement of cell sensitivity to DNA-damaging reagents and for lentivirus-based complementation assays, which can be used to systematically determine the pathogenic genes associated with DNA repair deficiency disorders. A typical UDS or RRS assay using primary fibroblasts, including a virus complementation test, takes 1 week to complete.

The original definition of atypical antipsychotic drugs (APD) was drugs that are effective against positive symptoms in schizophrenia with no or little extrapyramidal symptoms (EPS). However, atypical APD have been reported to be more effective for cognitive dysfunction and negative symptoms in schizophrenia than typical APD, which expands the definition of 'atypicality'. This article provides a critical review of the pharmacology of atypical APD, especially from the viewpoint of receptor binding profiles and neurotransmitter regulations as well as neuroprotection and neurogenesis. A variety of serotonin (5-HT) receptors, such as 5-HT2A / 2C , 5-HT1A , 5-HT6 and 5-HT7 receptors, may contribute to the mechanisms of action of 'atypicality'. The dopaminergic modulations, including a low affinity for dopamine D2 receptors and a partial D2 receptor agonistic action, and glutamatergic regulations may also be involved in the pharmacological backgrounds of 'atypicality'. Atypical APD, but not typical APD, may facilitate cortical neuroprotection and hippocampal neurogenesis, which might be a part of the action mechanisms of atypical APD. The facilitation of cortical neuroprotection and hippocampal neurogenesis induced by atypical APD might be mediated by an increase in the Ser9 phosphorylation of glycogen synthase kinase-3β (GSK-3β). The stimulation of 5-HT1A receptors and/or the blockade of 5-HT2 receptors, which is characteristic of atypical APD, might increase Ser9 phosphorylation of GSK-3β. Moreover, atypical APD increase brain-derived neurotrophic factor (BDNF) levels. BDNF increases Ser9 phosphorylation of GSK-3β and has neuroprotective and neurogenic effects, as in the case of atypical APD. These findings suggest that GSK-3β might play a role in the action mechanisms of atypical APD, in both the 5-HT-dependent and BDNF-dependent mechanisms.

The aim of this study was to investigate risk factors affecting 5- and 10-year survival in autotransplantation of third molars with complete root formation at dental clinics. Participating dentists were requested to provide information on transplantations performed between 1 January 1990 and 31 December 2009. After data screening and elimination, 183 teeth in 171 men aged 20-72 years (mean, 44.8 years) and 205 teeth in 189 women aged 20-74 years (mean, 42.0 years) were included in the study. A single-factor analysis using the log-rank test revealed that the following factors had a significant influence (p

OBJECTIVE This prospective and randomized clinical study was initiated to compare the efficacy and safety of combined androgen blockade with combination with UFT in patients with untreated prostate cancer. METHODS A total of 142 patients were entered in this study between April 1990 and December 1992. All patients received bilateral orchiectomy and 200 mg/day of diethylstilbestrol diphosphate. Of these patients, 70 patients were administered an additional 400 mg/day of UFT after randomization. Either treatment was continued for at least 1 year or until objective progression occurred if the initial response was equal to or better than no change. The endpoints of this study were progression-free survival, cancer-specific survival and change of QOL scores. RESULTS A total of 136 patients were evaluable and 131 patients (96.3%) could be followed up with a median follow-up period of 1469 days. Both groups showed similar initial treatment response at 12 weeks, adverse effect and change of quality of life score during the first year after initiation of the treatment. There was a significantly longer progression-free survival and better but not significant cancer-specific survival in the endocrine chemotherapy group. The patients with earlier stage and initial serum prostate-specific antigen values

Background: Recently, a dopamine hypothesis of depression was put forward, and several studies have demonstrated that direct and indirect dopamine agonists have antidepressant effects. Methods: Using Clinical Global Impressions, we evaluated the efficacy of 4-week treatment of pergolide as an antidepressant adjuvant involving 20 unipolar depressed patients who were refractory to standard treatment with antidepressants. Results: One patients (5%) were very much improved, seven (35%) much improved, four (20%) minimally improved, six (30%) no change or worse, and two (10%) not assessed. There was no significant difference in any clinical factors between the pergolide responder and non-responder group. Limitations: This study was a non-blind open trial, and pergolide was added to tricyclic and heterocyclic antidepressants. Conclusion: Pergolide may be useful as an antidepressant adjuvant, suggesting a potential role for dopamine-2 stimulation in the antidepressant response.

The effects of 3-week treatment with a typical antipsychotic drug chlorpromazine and three atypical antipsychotic drugs (risperidone, olanzapine and perospirone) on the binding to dopamine D2 and serotonin 5-HT2A receptors were examined in the rat stratum and frontal cortex, respectively. Subchronic treatment with chlorpromazine (10 mg/kg) and perospirone (1 mg/kg) significantly increased D2 receptors, while no increase was observed with lower dose of chlorpromazine (5 mg/kg), perospirone (0.1 mg/kg), risperidone (0.25, 0.5 mg/kg) or olanzapine (1, 2 mg/kg). On the other hand, 3-week administration of chlorpromazine (5, 10 mg/kg) and olanzapine (1, 2 mg/kg) significantly decreased 5-HT2A receptors, but risperidone (0.25, 0.5 mg/kg) or perospirone (0.1, 1 mg/kg) had no effect. The measurement of in vivo drug occupation for D2 and 5-HT2A receptors using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) suggested that high occupation of 5-HT2A receptors with lower D2 receptor occupancy might be involved in the absence of up-regulation of D2 receptors after subchronic treatment with some atypical antipsychotic drugs.

This paper proposes a scheme for fast and reliable handover that uses dynamic rerouting controlled by a call setup control station (CCS) operating in mobile asynchronous transfer mode (ATM) networks. The CCS selects appropriate rerouted path and crossover switch (COS), and remotely controls the new path's setup. This omits crossover switch discovery process, and makes fast handover possible. The CCS can select the appropriate rerouted path because it directly and with little delay collects information about the state of links such as traffic loads, quality-of-service (QoS) parameters, and disconnection or restoration of links advertised from every ATM switch in its domain. This reduces blocking and congestion, and makes reliable handover possible. The CCS accepts a handover request message for either backward or forward handover, and can remotely control the new path's setup in the same manner for either handover. The scheme provides forward handover when the radio propagation conditions deteriorate unpredictably. This paper also shows sequences of call origination, connection pre-establishment, and route-change in our proposed scheme, and illustrates operation of the CCS and the ATM switches.

In vivo occupation of dopamine D1, D2 and serotonin (5-HT)2A receptors by a novel antipsychotic drug, SM-9018 (perospirone hydrochloride; cis-N- [4- [4- (1,2-benzisothiazol-3-yl)- 1-piperazinyl]butyl]cyclohexane-1,2-dicarboximide monohydrochloride) and its major metabolite (ID-15036; N-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]butyl]-1-hydroxy-1 , 2-cyclohexanedicarboximide) was measured in rat brain using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), an irreversible antagonist, at these receptor sites. SM-9018 and its metabolite, ID-15036, dose-dependently reversed EEDQ-induced 5-HT2A and D2 receptor inactivation, but not D1 receptor inactivation. At lower doses (0.1 mg/kg i.p.), SM-9018 showed a preferential occupation of the 5-HT2A receptors, with only a small effect on the D2 receptors; while at higher doses (1.0 and 5.0 mg/kg i.p.), it was nearly equipotent in its occupation of both the D2 (77.8%) and the 5-HT2A receptors (78.6%). On the other hand, ID-15036 was more potent in occupying the 5-HT2A than the D2 receptors even at higher doses (1.0 and 5.0 mg/kg i.p.). We previously reported that atypical antipsychotic drugs, such as clozapine, were characterized by a high occupancy of the 5-HT2A receptors, with a low or minimum occupancy of the D2 receptors in vivo. The present study suggests that SM-9018 and its metabolite ID-15036 show a preferential tendency to occupy 5-HT2A receptors, and that the clozapine-like atypical properties of SM-9018 may be due to some pharmacological action of both the SM-9018 itself and its metabolite, ID-15063.

Perospirone is an atypical antipsychotic agent originated and clinically used in Japan. Based on an in vitro study, it is reported that perospirone is mainly metabolized to ID-15036 by cytochrome P450 (CYP) 3A4. In this study, the authors investigated the effects of itraconazole, which is a specific inhibitor of CYP3A4, or tandospirone, which is mainly metabolized by CYP3A4 and is expected to competitively inhibit the activity of this enzyme, on single oral dose pharmacokinetics of perospirone. After pretreatment with 200 mg daily of itraconazole or 10 mg daily of tandospirone for 5 days, 9 healthy male subjects received 8 mg of perospirone. Plasma concentrations of perospirone and ID-15036 up to 10 hours after perospirone dosing were measured by high-performance liquid chromatography (HPLC). The metabolism of perospirone was significantly inhibited by treatment with itraconazole but not by tandospirone. The present study suggests that CYP3A4 is significantly involved in metabolism of perospirone in humans.

The main reasons for loss of autotransplanted teeth are different from those involved in natural teeth loss. The aim of this study was to investigate which procedures were employed to treat spaces vacated when autotransplanted teeth were lost. Participating dentists were requested to provide information on transplantations they had undertaken. A total of 614 teeth in 552 patients (37 dentists) ranging in age from 17 to 79 years (mean age: 44.1 years) were examined. A total of 102 transplanted teeth were lost during the observation period. Procedures for treatment of spaces vacated were not influenced by main reason for transplanted tooth loss. The procedure used to treat depended on the original prosthodontic treatment of the transplanted teeth. For single crowns, the spaces were left empty (33.9%) or replaced by bridge work (30.5%), implants (20.3%), or dentures (10.2%). For single crowns in the upper and lower second molar regions, the spaces were usually left empty (upper 100%, lower 71.4%), while for those in the upper and lower first molar regions, the spaces were often replaced by bridge work (upper 41.7%, lower 50.0%). For bridge abutments, spaces were replaced by dentures (42.9%), implants (33.3%), or left empty (14.3%), and in the lower second molar region, they were mostly replaced by implants (5 cases, 41.7%). For most denture abutment cases, the spaces were replaced by dentures (88.9%). During the survival period of the transplanted teeth, the masticatory burden on the other teeth is reduced and the adjacent teeth are supported by the transplanted tooth. Even if transplanted teeth are eventually lost, traditional procedures can be performed to fill the vacated space.

Hepatocellular carcinoma (HCC) and inflammatory pseudotumor of the liver (IPL) are often difficult to differentiate before surgery. To date, colocalization of IPL and HCC has not been reported. We experienced a case of necrotic HCC surrounded by IPL-like tissue. The raised levels of alpha-fetoprotein and PIVKA-II declined to within the normal ranges after resection of the tumor. The IPL-like nodule most likely developed as a process of an inflammatory reaction such as abscess formation after the spontaneous destruction of the HCC. Our case is a warning that the presence of a 'pseudotumor' does not rule out the possible simultaneous presence of carcinoma.

Yasushi Yoshioka, Yoshito Takahashi \ Ken Matsuoka, Kenzo Nakamura, Jun Koizumi, Mineo Kojima and Yasunori Machida 1 Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, 464-01 Japan 2 Laboratory of Biochemistry, Faculty of Agriculture, Nagoya University, Chikusa-ku, Nagoya, 464-01 Japan 3 Department of Applied Biology, Shinshu University, Tsuneta 3-15-1, Ueda, Nagano, 386 Japan

Cockayne syndrome (CS) is a genetic disorder characterized by developmental abnormalities and photodermatosis resulting from the lack of transcription-coupled nucleotide excision repair, which is responsible for the removal of photodamage from actively transcribed genes. To date, all identified causative mutations for CS have been in the two known CS-associated genes, ERCC8 (CSA) and ERCC6 (CSB). For the rare combined xeroderma pigmentosum (XP) and CS phenotype, all identified mutations are in three of the XP-associated genes, ERCC3 (XPB), ERCC2 (XPD), and ERCC5 (XPG). In a previous report, we identified several CS cases who did not have mutations in any of these genes. In this paper, we describe three CS individuals deficient in ERCC1 or ERCC4 (XPF). Remarkably, one of these individuals with XP complementation group F (XP-F) had clinical features of three different DNA-repair disorders--CS, XP, and Fanconi anemia (FA). Our results, together with those from Bogliolo et al., who describe XPF alterations resulting in FA alone, indicate a multifunctional role for XPF.

Prostatic stromal tumor of uncertain malignant potential (STUMP) is a rare neoplasm characterized by an atypical, unique stromal proliferation of the prostate. Two patients consulted our hospital with the complaint of urinary retardation. We performed holmium laser enucleation of the prostate since by digital rectal examination, magnetic resonance imaging and needle biopsy suggested benign prostatic hyperplasia. The pathologic examination of the surgical specimens revealed prostatic STUMP. Urologic and radiologic examinations have revealed no abnormalities after more than 2 years of follow-up.

We studied a relationship between in vitro sensitivity of the tumors to anti-cancerous drugs and histopathological effectiveness of an intra-arterial infusion chemotherapy in 15 patients with bladder cancers. The in vitro sensitivity test was performed by measuring intra-cellular ATP contents (ATP assay). The intra-arterial chemotherapy were performed by injecting methotrexate (MTX), adriamycin (ADM) and eisplatin (CDDP) from the internal iliac artery. When the intra-cellular ATP contents of the tumor cells treated with an anti-cancerous drug decreased to less than 50% of the untreated tumor cells, the tumor was evaluated as sensitive to the drug. The effectiveness of the chemotherapy were histopathologically evaluated by a pathologist according to the response criteria for bladder cancer treatment. When the histopathological responses of higher than grade 2 were observed in the tumor, the chemotherapy was evaluated as effective. In 8 of 9 tumors sensitive to ADM, chemotherapy were effective histopathologically and in all 6 tumors resistant to ADM, histopathological response of the chemotherapies were poor. The overall coincidence ratio between sensitivity to ADM and the histopathological effectiveness of the chemotherapy was 93%, showing statistically significant correlation. In 7 of 12 tumors sensitive to CDDP, the chemotherapies were effective and in 2 of 3 tumors resistant to CDDP, the chemotherapies were ineffective. Although the overall coincidence ratio between the sensitivities to CDDP and chemotherapeutic effectiveness was 60%, there was no significant correlation between them. In 7 of 8 tumors sensitive to both of ADM and CDDP, the chemotherapies were effective and in 6 of 7 tumors resistant to at least one of them, the chemotherapies were ineffective. (ABSTRACT TRUNCATED AT 250 WORDS)

Out of 110 strains of Staphylococcus aureus isolated from 1985 to 1990, isolation rate of methicillin-resistant S. aureus (MRSA) was investigated. Nineteen strains of 59 S. aureus from outpatients and 20 strains of 51 S. aureus from inpatients were determined as MRSA. Isolation frequency of MRSA from inpatients was increasing in the recent two years. Coagulase type, enterotoxin type and production of toxic shock syndrome toxin-1 (TSST-1) were examined in 22 strains of MRSA. Coagulase type II (86%), enterotoxin type C (68%) and TSST-1 positive strain was most dominant. Susceptibility of MRSA to 4 antimicrobial agents were measured, MRSA were sensitive to vancomycin (VCM), arbekacin (ABK) and minocycline, but resistant to flomoxef. Thirty-four patients from whom MRSA was isolated including 20 patients from urine, 13 from pus and 1 from blood, were analyzed clinically. Pyuria was not recognized in some cases in whom MRSA was isolated from their urine. Concomitant polymicrobial infection was frequently noted in those patients with MRSA in their urinary tract. These facts show that the pathogenic role of MRSA in the urinary tract infection was not significant. On the other hand, when MRSA was isolated from pus or blood, serious infections could be caused by MRSA, especially in compromised host. Regarding the treatment in these cases, administration of VCM or ABK was though to be necessary.

This study was conducted by the Japanese Society of Chemotherapy and is the first nationwide study on bacterial pathogens isolated from patients with urinary tract infections at 28 hospitals throughout Japan between January 2008 and June 2008. A total of 688 bacterial strains were isolated from adult patients with urinary tract infections. The strains investigated in this study are as follows: Enterococcus faecalis (n = 140), Escherichia coli (n = 255), Klebsiella pneumoniae (n = 93), Proteus mirabilis (n = 42), Serratia marcescens (n = 44), and Pseudomonas aeruginosa (n = 114). The minimum inhibitory concentrations of 39 antibacterial agents used for these strains were determined according to the Clinical and Laboratory Standards Institute (CLSI) manual. All Enterococcus faecalis strains were susceptible to ampicillin and vancomycin. Although a majority of the E. faecalis strains were susceptible to linezolid, 11 strains (7.8%) were found to be intermediately resistant. The proportions of fluoroquinolone-resistant Enterococcus faecalis, Escherichia coli, Proteus mirabilis, and S. marcescens strains were 35.7%, 29.3%, 18.3%, and 15.2%, respectively. The proportions of E. coli, P. mirabilis, K. pneumoniae, and S. marcescens strains producing extended-spectrum β-lactamase were 5.1%, 11.9%, 0%, and 0%, respectively. The proportions of Pseudomonas aeruginosa strains resistant to carbapenems, aminoglycosides, and fluoroquinolones were 9.2%, 4.4%, and 34.8%, respectively, and among them, 2 strains (1.8%) were found to be multidrug resistant. These data present important information for the proper treatment of urinary tract infections and will serve as a useful reference for periodic surveillance studies in the future.

Guided tissue regeneration (GTR) 法による治癒形態に対するプラークによる炎症の影響を評価するためイヌを用いて以下のような実験を行った。イヌの根面に対照群ではフラップ手術, 実験群ではGTR法を施し, 術後プラークコントロールを行わずに24週間経過後に実験部位の標本を作製し, 病理組織学的に検索した。その結果, 対照群では多量のプラークの沈着, アタッチメントの喪失を伴う深い歯周ポケットの形成, 広範囲に渡る炎症性細胞浸潤, 歯槽骨の吸収を生じていた。実験群では-歯銀辺縁部に限局した炎症性細胞浸潤を認めたが, ルートプレーニングされた根面には白亜質, 歯槽骨の新生を伴う新付着治癒が観察され, 全く炎症性細胞浸潤は認められなかった。以上のことよりGTR法後の治癒で獲i得した新付着はプラークに対する強い防御機構を有していることが示唆された。

We prospectively studied the usefulness of chlormadinone acetate (CMA) as an alternative therapy for prostate cancer relapse after combined androgen blockade (CAB) therapy. Sixteen patients with relapsed prostate cancer after treatment with CAB, including surgical or medical castration and nonsteroidal antiandrogens, 80 mg bicalutamide daily or 375 mg flutamide daily, were enrolled. After discontinuing the antiandrogen for evaluating the patient for the antiandrogen withdrawal syndrome, we administered 100 mg CMA daily as alternative antiandrogen and estimated its effect. Four patients showed aor = 50% decline in prostate-specific antigen (PSA) levels and another 4 patients showed a50% decline in PSA levels but residual 8 patients showed no decline in PSA levels. In 8 patients with a decline in PSA levels, the median duration of alternative CMA therapy was 11.4 months. Patients with a PSA level of1 ng/ml at the start of CMA therapy showed the tendency of decline in PSA levels. In contrast, patients with a nadir PSA level ofor = 0.2 ng/ml during pretreatment showed no effectiveness of the alternative CMA therapy. The alternative CMA therapy may be useful in a part of patients with prostate cancer relapse after CAB therapy.

本研究は, 23歳から54歳で, 初期治療終了後の再評価時に6mm以上のポケットを有し, 歯周外科治療を必要とした患者16名を用いそれぞれ8名の垂直性骨欠損部にGTRとFOPを応用した。GTR法は, フラップ手術に準じ, 粘膜骨膜弁を剥離, 翻転後, スケーリング・ルートプレーニングを行い, 骨欠損部へGore-Tex® periodontal materialを試適, 縫合固定し, 歯齦弁を元に戻して縫合した。なお, Gore-Tex® periodontal materialは術後4～6週で除去した。臨床診査は, 術後3, 6及び12ヵ月目に行った。その結果, ポケットの深さの減少量は, GTR群で有意に大であり, 12ヵ月目では, GTR群5.1±1.6mm, FOP群で2.4±1.5mmであった。アタッチメントの獲得量もGTR群で有意に大であり, 12ヵ月目で, GTR群で2.8±1.6mm, FOP群で0.3±0.8mmであった。以上の結果より, 垂直性骨欠損に対するGTR法は有効な手術法であることが証明された。

組織再生誘導法により歯根膜由来細胞が, 根表面に集積することによって生ずる治癒形態を検索した。実験には24頭のイヌを用い, 下顎頬側粘膜骨膜弁を形成後, 琺白境界部から根端側に約4mm歯槽骨を除去した。実験群に関しては膜を応用し, 対照群には膜を応用せずに弁を元に戻し縫合した。観察期間は1, 2, 3, 4, 6, 12週とし, 病理組織学的に検索した。その結果, 実験群では全期間を通して白亜質芽細胞が根表面に付着あるいは近接して認められ, コラーゲン線維を埋入した新生白亜質が認められた。一方, 対照群では全期間を通して根面に付着あるいは近接して線維芽細胞が認められた。しかし, 新付着形成は認められず, 根面と平行に走向するコラーゲン線維束からなる結合組織性付着が観察された。以上の結果から, 本研究では歯根膜および歯槽骨由来細胞が根表面で白亜質芽細胞に分化し, 新付着を獲得する能力をもっていることが示された。

Müllerian duct cysts occupying the pelvic/abdominal region are rare. We describe a müllerian duct cyst extending into the lower abdomen in a 47-year-old man complaining of urinary retention. We removed the cyst through a suprapubic retrovesical approach. No malignancy was found in the surgical specimen.

We retrospectively reviewed the discrepancy in Gleason score between needle biopsy and radical prostatectomy specimens. Specimens from 153 patients who underwent radical retropubic prostatectomy at Gifu University Hospital and 9 community-based institutions between January 2001 and December 2005, were studied. Gleason score was determined by the general pathologist at each institution. The coincidence rate of Gleason score between biopsy and prostatectomy specimens was 49.7%. In contrast, 37.4% of biopsy specimens were undergraded. In biopsy specimens given a Gleason score of 5 or less, the Gleason score was coincident or undergraded compared with prostatectomy specimens. In biopsy specimens given a Gleason score of 6, the coincidence rate was 39.6%. In 56% in biopsy specimens of cancers with a Gleason score of 6 the Gleason score was undergraded compared with the prostatectomy specimen. In this group, extra-prostatic extention was found significantly more often than in other groups (p = 0.04). In patients, who underwent extended biopsy, or had a more positive biopsy core (or = 25%), the coincidence rate was significantly greater (p = 0.03). We should be aware of the limitations of Gleason scores based on biopsy specimens, and give treatment opinions careful consideration.

An anterior urethral valve is uncommon compared to a posterior urethral valve as a cause of lower obstructive uropathy. Furthermore, an anterior urethral valve in the fossa navicularis is extremely rare. We describe the case in a 6-year-old boy who presented with a split urinary stream. Endoscopy revealed an anterior urethral valve in the fossa navicularis, and we successfully incised the valve with a hook knife. We should consider the possibility of an anterior urethral valve in any child with an abnormal urinary stream.

We evaluated the results and advantages of laparoscopic examination in 28 patients with 32 nonpalpable testes. Between April 1991 and May 2006, 28 patients, 12 months to 12 years old, with 32 nonpalpable testes underwent diagnostic laparoscopy under general anesthesia before surgical management of the testes. If the blind end of the vas deferens and/or spermatic vessels was observed, the diagnosis of vanishing testis was made, and no further examination or treatment was performed. If intra-abdominal testis was observed, laparoscopic orchiectomy or open orchiopexy was performed. If the internal spermatic vessels and vas deferens entered into the internal inguinal ring, the diagnosis of intra-canalicular testis was made so that the inguinal canal was opened for surgical interventions. Of the 32 nonpalpable testes 10 were on the right side and 22 were on the left side (4 patients had bilateral undescended testes). There were 7 (21.8%) vanishing, 5 (15.6%) intra-abdominal and 20 (62.5%) intra-canalicular testes. There were no complications related to laparoscopy. Laparoscopy can be safely performed to assess the location of the non-palpable testes. Another advantage of the laparoscopic examination is that orchiopexy or orchiectomy can be immediately performed after the examination to avoid a second surgery.

The incidence of sunlight-induced skin changes (photoaged skin, skin carcinogenesis) increases with increasing age and it is thought to be associated with an accumulation of mutations in skin cells. These mutations are mainly caused by UV exposure. The reactive oxygen species produced in UV-exposed skin can cause various kinds of DNA damages e.g., 8-oxoguanine, which are primarily repaired by the base excision repair (BER) system. In addition, UV can directly cause DNA damages; cyclobutane pyrimidine dimers (CPD) and pyrimidine-pyrimidone (6-4) photoproducts (6-4PP), both of which can be repaired by the nucleotide excision repair (NER) system. There have been several reports showing an age-related reduction in the DNA repair capacity in the NER, BER, and other repair systems, which contributes to the phenotypes of aging. To clarify the mechanism of skin aging, we examined the NER of skin fibroblasts from healthy donors of different ages. In a host cell reactivation assay, the cells from elderly donors exhibited a significant decline in the ability to restore transfected reporter DNA damaged by UV. In contrast, the ability to remove CPD and 6-4PP declined little with age, as assessed by an enzyme-linked immunosorbent assay. The mRNA expression of DNA repair synthesis-related genes was markedly decreased in the cells from elderly subjects as compared with those from young subjects. These results imply that the age-sensitive step took place after the damage excision in the NER, and that there is an impairment of the latter step of the NER in aging. Based on our data, as well as other reports, the reduced post-UV DNA repair capacity in aging resulting in an accumulation of UV-induced DNA damage is thus considered to be associated with the phenotypes of photoaged skin.

We report a case of huge renal arteriovenous malformation treated with superselective endovascular embolization in two treatments using N-butyl-2-cyanoacrylate (Hystoacryl).

We performed 50 laparoscopic adrenalectomies during the period from 1998 through 2003. We report our experience and the outcomes of this procedure, which has become a standard surgery for adrenal tumors. In most cases, the transperitoneal approach was used. In 48 cases, laparoscopic adrenalectomy was performed successfully. However, in two cases, the operation was converted to an open procedure because of bleeding. As our experience with laparoscopic adrenalectomy increased, operation time decreased. Laparoscopic adrenalectomy should be used more widely in the future.

A 56-year-old Japanese man consulted a urologist because of urethral bleeding. He had been undergoing hemodialysis for the past 15 years due to polycystic kidney disease. Computed tomography revealed an irregular cyst wall in the left kidney. Since a neoplasm could not be ruled out, we removed the left kidney, by laparoscopic radical nephrectomy after obtaining the patient's consent. Histopathologic diagnosis was renal cell carcinoma. Fourteen months after the operation, urethral bleeding recurred. Further examination of the bladder and the urethra revealed no significant abnormalities. The patient insisted on right nephrectomy. Therefore, laparoscopic radical nephrectomy was performed. Histopathologic diagnosis was also renal cell carcinoma. Renal cell carcinoma in patients with end-stage renal disease is fairly common and is associated with acquired cystic kidney disease. However, renal cell carcinoma associated with polycystic kidney disease is extremely rare.

A 33-year-old female patient was admitted to our department with bladder tumor. It was detected by a magnetic resonance imaging (MRI) in an examination for hysteromyoma. She had neither hypertention, gross hematuria nor the classic symptoms of cathecholamine excess during micturition. The diameter of the tumor was 33 mm. Cystoscopic examination showed a submucosal tumor in the left anterior wall of the bladder. Percutaneous needle biopsy was performed. Biopsy specimens revealed as a pheochromocytoma. 131 I-MIBG scintigraphy showed abnormal accumulation in the bladder, and no abnormal accumulation in the other lesion. Endocrinologic examination disclosed increased levels of serum and urinary noradrenalin. On May 18, 2005, partial cystectomy was performed. The catecholamine levels normalized after partial cystectomy. The patient has been followed up for 9 months and shown no recurrence.

Previously, renal arterial aneurysms were thought to be extremely uncommon. However, these lesions are now being detected more frequently as incidental findings on computed tomography (CT) and magnetic resonance imaging (MRI). The incidence of ruptured renal artery aneurysms is very low. A 58-year-old man presented to a physician complaining of left flank pain and was diagnosed as having a left kidney stone. Abdominal CT scan demonstrated a mass in the left renal pelvis. The mass measured 40mm in diameter and showed calcification. The patient was referred to our hospital 5 days after the first attack. Left renal mass was diagnosed as renal aneurysm based on clinical signs and perirenal findings on CT. Emergent endvascular embolization was performed. The postoperative course was uneventful. Hypertension improved after embolization.

Objectives To compare the efficacy of two alpha(1)-adrenoceptor antagonists, alpha(1A)-adrenoceptor-selective tamsulosin hydrochloride and alpha(1D)-adrenoceptor-selective naftopidil, in the treatment of lower urinary tract symptoms (LUTS) with benign prostatic hyperplasia (BPH). Patients and methods Thirty-four patients (mean age 72.4 years, sd 4.3, range 66-79) with LUTS (International Prostate Symptom Score, IPSS >8) secondary to BPH were enrolled in a randomized crossover study. Seventeen patients were initially prescribed naftopidil 50 mg for 4 weeks, followed by tamsulosin 0.2 mg for 4 weeks (group A); another 17 were initially prescribed tamsulosin 0.2 mg, followed by naftopidil 50 mg (group B). Patients changed to the alternative treatment after a 1-week washout period. Efficacy criteria were improvement in LUTS (IPSS), quality of life (QoL), uroflowmetry, and pressure-flow study (PFS) values based on the treatment with each agent. Results At baseline there were no significant differences between the groups in IPSS, QoL, uroflowmetry values or PFS values, except for the volume at maximum desire to void. After treatment with each agent, the IPSS and QoL were significantly improved and the reduction in bladder outlet obstruction confirmed by PFS. Naftopidil was significantly more effective than tamsulosin in relieving nocturia. The increases from baseline (before treatment) to the endpoint (after treatment with each agent) in the volume at first desire and maximum desire to void were significantly higher with naftopidil than with tamsulosin. Involuntary contractions disappeared in two patients with relief of nocturia with naftopidil, but not with tamsulosin. The decrease in other symptoms of the IPSS, QoL, increase in uroflowmetry values and changes in other PFS values were similar for both agents. Conclusions The two agents provided similar efficacy in the treatment of LUTS with BPH. However, naftopidil was better than tamsulosin for nocturia. The disappearance of involuntary contraction and the greater increase in first-desire volume with naftopidil may be associated with the relief of nocturia. The alpha(1D)-adrenoceptor antagonist is effective in alleviating both voiding and storage symptoms. The alpha(1D)-adrenoceptor antagonist may be more effective than the alpha(1A)-adrenoceptor antagonist in LUTS with BPH.

The purpose of the present paper was to evaluate clinical factors responsible for recurrence and prognosis of superficial bladder cancer.We reviewed date from 800 patients who were initially treated between 1991 and 2000. Recurrent and prognostic factors were examined with univariate and multivariate analysis. Kaplan-Meier Method and log rank test were used for comparing the significance of recurrence free curve and survival curve. Cox's proportional hazard model was used for univariate and multivariate analysis. A 5% level of significance was used for all statistical testing.Of 800 cases 282 patients (35.2%) had recurrence and 27 patients (3.4%) were died in during follow up. Progression was defined as the development of muscle invasion or metastasis, progression were noted on 10 metastasis cases and 16 muscle invasion cases. Univariate analysis revealed that tumor numbers, shape, size, stage and grade were significant recurrent and prognostic factors. Multivariate analysis revealed that tumor numbers (P0.0001), shape (P = 0.066) and size (P = 0.0178) were significant recurrent factors, and tumor shape (P = 0.0422), size (P = 0.0140) and stage (P = 0.0330) were significant prognostic factors. Of 272 recurrent cases, univariate analysis revealed that tumor shape, stage and grade were significant prognostic factors, and multivariate analysis revealed that tumor shape (P = 0.0164) and stage (P = 0.0017) were significant prognostic factors.We conclude that tumor numbers, shape and size are predictive value in recurrence and tumor shape, size and stage are predictive value in prognosis, and when recurrent case, tumor shape and stage are predictive value.

Purpose: The purpose of this retrospective study was to clarify the character of incidental prostate cancer, stages T1a and T1b. Methods: We analysed 101 cases of incidental prostate cancer. Incidental prostate cancer was diagnosed on the basis of normal digital rectal examination findings, a serum prostate-specific antigen (PSA) level of less than 4.0 ng/mL, and no abnormal computed tomography or ultrasonography findings. All patients were treated at Gifu University Hospital or an affiliated hospital during the period January 1992 through December 2001. Results: There were 64 stage T1a cancers and 37 stage T1b cancers. The mean age of patients was 71.3 years (range 51–87 years). The mean serum PSA level was 1.63 ng/mL (range 0.2–4.0 ng/mL). Thirty-five stage T1a patients (56.5%) and thirty-two stage T1b patients (86.5%) underwent some type of treatment. Total prostatectomy was performed in eight stage T1a cases and fifteen stage T1b cases. Pathological diagnoses were as follows: pTx (n = 1), pT0 (n = 5) and pT2 (n = 2) for stage T1a cancers, and pT0 (n = 6), pT2 (n = 8) and pT3 (n = 1) for stage T1b cancers. Only one stage T1b cancer recurred. Conclusion: The outcome of patients with incidental prostate cancer was satisfactory; disease recurred in only one case of stage T1b cancer and there were no cases of PSA failure, although the pathological diagnosis in nine of the fifteen stage T1b cases (60.0%) treated with total prostatectomy was pT2 or pT3. Careful monitoring was indicated for stage T1a cancer, and some treatment was necessary for stage T1b cancer.

We report the results of renal transcatheter arterial embolization (renal-TAE) in two patients with autosomal dominant polycystic kidney disease (ADPKD) treated with hemodialysis (HD). A 73-year-old man and a 65-year-old woman on HD visited our department complaining of abdominal fullness, abdominal pain and appetite loss. Abdominal computerized tomography (CT) revealed polycystic kidneys. Both patients underwent renal-TAE. Approximately 1 month later, the symptoms had improved and CT showed decreased cyst volume. These results suggest that renal-TAE is a useful therapy for patients with ADPKD.

We report a case of bladder cancer recurrence in fossa navicularis of urethra 17 months after cystourethrectomy for bladder cancer. A 75-year-old man had undergone cystourethrectomy preserving between fossa navicularis and external meatus, and ileal conduit urinary diversion for advanced bladder cancer on June 24, 2002. Histopathological findings showed urothelial carcinoma, G2G3, pT1N0. The patient had been followed regularly for 17 months without evidence of recurrence until he suffered the onset of hemorrhagic urethral discharge. Endoscopic examination of the residual urethra showed multiple, papillary sessile tumors which almost filled the fossa navicularis. He was admitted to our hospital on December 15, 2003. The urethral wash cytology revealed urothelial carcinoma. Since computed tomography, magnetic resonance imaging, and bone scintigraphy showed no evidence of lymph node and distant metastasis, partial penectomy was performed. Histopathological findings showed urothelial carcinoma pTa, G2G3, which was identical to primary tumor. Tumor had not invaded the corpus cavernosum. Careful follow-up of the patients with preservation of fossa navicularis is important.

CYP11B2, the gene encoding aldosterone synthase, has several frequent polymorphisms. In particular, the Lys173Arg (K173R) polymorphism is in complete genetic linkage disequilibrium with the -344T/C polymorphism in the promoter of CYP11B2 that involves a binding site for the steroidogenic factor-1 transcription factor. These polymorphisms have been associated with cardiovascular parameters, including hypertension, but not directly with gene expression.The objective of this study was to correlate CYP11B2 genotype with gene expression in adrenal tissue.We measured mRNA levels of CYP11B2 [presented as a ratio against glyceraldehyde-3-phosphate dehydrogenase (B2/G)] and CYP11B1 in relation to the K173R polymorphism.We studied 28 subjects with aldosterone-producing adenomas (APA) and 18 subjects with normal adrenals.The main outcome measure was CYP11B2 expression levels.Preoperative treatment with spironolactone or beta-blocker in five APA patients was associated with higher B2/G. The B2/G and B2/B1 ratios were much higher even in the remaining 23 APA patients than in subjects with normal adrenals. The B2/G and B2/B1 ratios in normal adrenals and APA were higher in the KK genotype than in the RR genotype. In patients with APA, urinary aldosterone excretion was higher in those with the KK genotype than in those with the KR genotype. Measurement of cDNA band intensities from normal and APA samples of the KR genotype revealed that the R173 allele was transcribed at levels 46.6 +/- 12.2% (mean +/- sd; n = 7) and 49.1 +/- 20.8% (n = 6), respectively, those of the K173 allele.A CYP11B2 haplotype including -344T and K173 is associated with higher gene expression than the -344C/R173 haplotype, supporting reported associations of -344T with higher aldosterone production and blood pressure.

Most antipsychotics were thought to induce antipsychotic action at an excess of 70% striatal dopamine D2 receptor occupancy, while the clinical dose of clozapine was reported to show less than 60% occupancy. High-dose clozapine could occupy as high as 80% of striatal dopamine D2 receptor in monkey PET studies. Although the time course of dopamine D2 receptor occupancy is an important property of antipsychotics, that by clozapine has not been investigated in a clinical setting. We measured the time course of extrastriatal dopamine D2 receptor occupancy with different doses of clozapine and evaluated whether the measured occupancies fitted the binding theory. Three consecutive PET scans with [11C]FLB 457 were performed for two patients with schizophrenia, chronically taking 600 mg/day and 200 mg/day of clozapine, respectively. Series of occupancies were also measured in combination with fluvoxamine or paroxetine in one patient. Dopamine D2 receptor occupancies were also simulated using individual clozapine plasma data and previously determined in vivo ED50 value. The occupancy of one patient with high plasma concentration (1207 ng/ml at peak time) was around 75% at peak and around 60% after 26 h. Another patient with medium plasma concentration (649 ng/ml at peak time) showed less than 50% occupancy at peak, decreasing to 15% after 25 h. The measured occupancy values fitted well with the simulated occupancy values. At high plasma concentration, clozapine can induce high extrastriatal dopamine D2 receptor occupancy in the human brain, and this finding fitted well with the theoretical estimation.

Four hundred sixty-two clinical isolates of Neisseria gonorrhoeae recovered from 1999 through 2002 in central Japan were examined for MICs of antimicrobial agents. The majority was sensitive to ceftriaxone and spectinomycin, but a remarkable increase in isolates with decreased susceptibility to penicillin, tetracycline, oral cephalosporins, and fluoroquinolones was observed from 2001 through 2002.

Aim Ventricular fibrosis is promoted by many effectors that chronically activate phospholipase D (PLD), and induces cardiac dysfunction and heart failure in cardiovascular diseases. Since ethanolamine is a product of PLD, we hypothesised that an administration of an analogue of ethanolamine, N -methylethanolamine (MEA), decreases PLD activity through a negative feedback mechanism, suppresses collagen accumulation, and thus prevents organ dysfunction. Methods and results In human fibroblasts 1-butanol inhibited collagen synthesis and enhanced collagenase production, but iso-butanol did not. These indicate crucial roles of PLD in collagen synthesis and degradation. In fibroblasts, MEA dose-dependently decreased PLD activity, inhibited collagen synthesis and enhanced collagenase production. In a hypertensive heart failure model using Dahl–Iwai salt-sensitive rats, PLD activity increased with progressive ventricular fibrosis, leading to myocardial stiffening and overt heart failure. Long-term administration of MEA did not significantly decrease blood pressure, however, but decreased PLD activity and collagen content with inhibited gene expression of collagens, leading to the prevention of myocardial stiffening and haemodynamic deterioration. MEA also attenuated ventricular hypertrophy, another detrimental structural alteration. Conclusion MEA may exert therapeutic effects on cardiac disorders due to ventricular fibrosis through suppression of PLD activity and modulation of the fibrosis pathway even without relief from mechanical stress.

We report a case of urinary retention complicated with acute transverse myelitis caused by Mycoplasma pneumoniae. A 16-year-old man visited a clinic because of urinary retention, fever, muscle weakness and sensory disturbance of lower extremities. He was referred to our hospital for further examination. He was diagnosed with acute transverse myelitis due to M. pneumoniae infection based on cerebrospinal fluid examination, serum titer of antibody to M. pneumoniae and magnetic resonance imaging. He was treated with corticosteroids for acute myelitis. A urethral catheter was indwellt for urinary retention. His muscle strength and sensory of lower extremities improved after 2 months of treatment, and he was discharged from our hospital. However, since urinary frequency, urge incontinence and weak urinary stream persisted, he was referred to us for further examination. A pressure-flow study examination showed a decreased maximum urinary flow rate and the findings of detrusor sphincter dyssnergia. We diagnosed him with uninhibited bladder and detrusor sphincter dyssnergia. We administered propiverine hydrochloride and imipramine hydrochloride, and his symptoms subsided significantly. Now, (8 months) after this medication, he still has incontinence at night.

We treated a case of prostate cancer with cyst formation in an 80-year-old Japanese man presenting with constipation. Fist-sized elastic soft mass was palpable by digital rectal examination. Computed tomography and magnetic resonance imaging demonstrated a retrovesical cystic mass arisen from the prostate. Serum prostate-specific antigen (PSA) was elevated to 15.7 ng/ml. Transrectal prostate needle biopsy revealed moderately differentiated adenocarcinoma and puncture of the cyst yielded aseptic bloody fluid. With a clinical diagnosis of prostate cancer (T2b N0 M1b) with cystic formation, hormonal therapy with a luteinizing hormone releasing hormone analogue and bicalutamide significantly lowered the serum PSA level. One year later, the cyst was reduced in volume and constipation had resolved. A total of 57 cases of prostate cancer with cyst formation are reviewed.