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It is important to optimize the exposure dose when conducting interventional radiology, but optimization is difficult for medical centers to achieve independently. In 2005, we administered a questionnaire on the measurement of dose rates and awareness of exposure reduction when performing percutaneous coronary intervention. Ten years later, we conducted a follow-up survey of the same 31 centers to determine the current situation and identify trends. The results of the survey showed that the mean fluoroscopy dose rate decreased to 55% of the 2005 value, from 28.2 to 15.6 mGy/min, and the mean radiography dose rate decreased to 71% of the 2005 value, from 4.2 to 3.0 mGy/s. Dose rates for both fluoroscopy and radiography decreased by 84% of facilities. The results also indicated greater cooperation by physicians compared to 10 years ago. In particular, there was a considerable increase in the exchange of ideas with physicians regarding exposure, suggesting a stronger level of interest in exposure. The overall score for questionnaire items was 33% higher than that in the previous survey. These results show that in the past 10 years, awareness of exposure reduction has improved, and dose optimization has been a major factor in the downward trend in dose rates in radiography and fluoroscopy.

Purpose We conducted a multicenter study to investigate the current status of difference between the actual values at the patient entrance reference point (PERP) and display air kerma. Methods We exposure dose and fluoroscopy dose were measured by 32 apparatuses at 32 member institutions of the Japanese Society of Circulation Imaging Technology (CITEC) under unified conditions, and the actual measured values and display air kerma were compared. We entrance doses during fluoroscopy and imaging were measured at the PERP, with focus detector distance (FDD) 110 cm, a copper plate of 3.5 mm in thickness adhered to the front face of flat panel detector (FPD) as absorber, field-of-view (FOV) 18 cm, and the frame rate of 15 f/s, excluding the bed. Display air kerma were recorded at the same time. JIS (Z 4751-2-43: 2012) specify "The reference air kerma rate and the cumulative reference air kerma shall not deviate from their respective display air kerma by more than ±35% over the range of 6 mGy/min and 100 mGy to the maximum value." The number of apparatuses display air kerma deviated from this condition and its percentage were obtained. Results The mean difference percentage between actual measured values and display air kerma in 32 apparatuses was approximately 15.6%, with some apparatuses showing substantially different display air kerma. Conclusion In order to estimate patients' skin exposure dose from display air kerma more accurately, it is necessary to perform calibration of the apparatus by regular dose measurement or convert values.

We demonstrated the rapid effects of 10nM bisphenol A (BPA) on the spinogenesis of adult rat hippocampal slices. The density of spines was analyzed by imaging Lucifer Yellow-injected CA1 neurons in slices. Not only the total spine density but also the head diameter distribution of spine was quantitatively analyzed. Spinogenesis was significantly enhanced by BPA within 2h. In particular, the density of middle-head spine (with head diameter of 0.4-0.5μm) was significantly increased. Hydroxytamoxifen, an antagonist of both estrogen-related receptor gamma (ERRγ) and estrogen receptors (ERα/ERβ), blocked the BPA-induced enhancement of the spine density. However, ICI 182,780, an antagonist of ERα/ERβ, did not suppress the BPA effects. Therefore, ERRγ is deduced to be a high affinity receptor of BPA, responsible for modulation of spinogenesis. The BPA-induced enhancement of spinogenesis was also suppressed by MAP kinase inhibitor, PD98059, and the blocker of NMDA receptors, MK-801. Washout of BPA for additional 2h after 2h BPA treatment abolished the BPA-induced enhancement of spinogenesis, suggesting that the BPA effect was reversible. ERRγ was localized at synapses as well as cell bodies of principal neurons. ERRγ at synapses may contribute to the observed rapid effect. The level of BPA in the hippocampal slices was determined by mass-spectrometric analysis.

Estrogen modulates memory-related synaptic plasticity not only slowly but also rapidly in the hippocampus. However, molecular mechanisms of the rapid action are yet largely unknown. We here describe rapid modulation of representative synaptic plasticity, i.e., long-term depression (LTD), long-term potentiation (LTP) and spinogenesis, by 17beta-estradiol, selective estrogen agonists as well as endocrine disrupters. The authors demonstrated that 1-10 nM estradiol induced rapid enhancement of LTD within 1 h in not only CA1 but also CA3 and dentate gyrus (DG). On the other hand, the modulation of LTP by estradiol was not statistically significant. The total density of spines was increased in CA1 pyramidal neurons, within 2 h after application of estradiol. The total density of thorns (postsynaptic spine-like structure) was, however, decreased by estradiol in CA3 pyramidal neurons. Both the increase of spines in CA1 and the decrease of thorns in CA3 were completely suppressed by Erk MAP kinase inhibitor. Only ERalpha agonist PPT induced the same enhancement/suppression effect as estradiol on both LTD and spinogenesis in CA1 and CA3. ERbeta agonist DPN induced completely different results. ERalpha localized in spines and presynapses of principal glutamatergic neurons in CA1, CA3 and DG. The same ERalpha was also located in nuclei and cytoplasm. Identification of ERalpha was successfully performed using purified RC-19 antibody. Non-purified ERalpha antisera, however, reacted significantly with unknown proteins, resulting in wrong immunostaining different from real ERalpha distribution. An issue of 'endocrine disrupters' (1-100 nM low dose of environmental chemicals), which are artificial xenoestrogenic or anti-xenoestrogenic substances, has emerged as a social and environmental problem. Endocrine disrupters were found to significantly modulate LTD and spinogenesis. Bisphenol A (BPA) and diethylstilbestrol (DES) enhanced LTD in CA1 and CA3. The total spine density was significantly increased by BPA and DES in CA1. Most probable receptors for BPA and DES may be Ralpha; however, other receptors might also be involved.

Aim: The expression of the telomerase subunits such as human telomerase reverse transcriptase (hTERT) and human telomerase RNA component (hTR) may be associated with tumor development and progression. We evaluated the relationship between mRNA quantification of both hTERT and hTR and clinicopathologic parameters in bladder cancer. Methods: We examined the mRNA expression of hTERT and hTR in 29 specimens with bladder cancer (Grade: Grade I, 9 cases; Grade II, 13 cases and Grade III, 7 cases. Stage: pTa-pT1, 18 cases; pT2-T4, 11 cases). We immediately froze all of specimens obtained during TUR-Bt and isolated the total RNA from each specimen. We measured the quantity of hTERT, hTR and GAPDH mRNA by a real-time reverse transcription–polymerase chain reaction method based on TaqMan technology. Results: The hTERT/GAPDH mRNA ratio and hTERT mRNA/total RNA in superficial bladder tumor was significantly lower than in invasive bladder tumor. The hTR/GAPDH mRNA ratio and hTR mRNA/total RNA in superficial tumor were significantly lower than in invasive bladder tumor. The hTERT mRNA expression significantly correlated with tumor grade, but the hTR mRNA expression did not correlate with tumor grade. There was no significant difference in the hTERT/GAPDH mRNA ratio and hTR mRNA/total RNA according to multiplicity of bladder tumor. Conclusions: Our results demonstrated that the expression of hTERT mRNA correlated with the progression of stage and grade in bladder cancer. The quantitative analysis of hTERT and hTR mRNA might be a marker for clinicopathologic parameters in bladder cancer.

Hippocampal pyramidal neurons and granule neurons of adult male rats are equipped with a complete machinery for the synthesis of pregnenolone, dehydroepiandrosterone, testosterone, dihydrotestosterone and 17beta-estradiol. Both estrogens and androgens are synthesized in male hippocampus. These brain steroids are synthesized by cytochrome P450s (P450scc, P45017alpha and P450arom), hydroxysteroid dehydrogenases and reductases from endogenous cholesterol. The expression levels of enzymes are as low as 1/300-1/1000 of those in endocrine organs. Synthesis is dependent on the acute Ca(2+) influx upon neuron-neuron communication via NMDA receptors. Estradiol is particularly important because estradiol rapidly modulates neuronal synaptic transmission such as long-term potentiation via synaptic estrogen receptors. Xenoestrogens may also act via estrogen-driven signaling pathways.

In the hippocampus, the center for learning and memory, cytochrome P450s (P450scc, P450(17alpha), and P450arom) as well as 17beta-, 3beta-hydroxysteroid dehydrogenases, and 5alpha-reductase participate in the synthesis of brain steroids from endogenous cholesterol. These brain steroids include pregnenolone, dehydroepiandrosterone, testosterone, dihydrotestosterone, and 17beta-estradiol. Both estrogens and androgens are synthesized in the adult male hippocampal neurons. Although the expression levels of steroidogenic enzymes are as low as 1/200 to 1/50,000 of those in testis or ovary, the levels of synthesized steroids are sufficient for the local usage within small neurons (i.e., intracrine system). This intracrine system contrasts with the endocrine system in which high expression levels of steroidogenic enzymes are necessary in endocrine organs in order to supply steroids to many other organs via blood circulation. Endogenous synthesis of sex steroids in the hypothalamus is also discussed. Rapid modulation by estrogens and xenoestrogens is discussed concerning synaptic plasticity such as the long-term potentiation, the long-term depression, or spinogenesis. Synaptic expression of P450(17alpha), P450arom, and estrogen receptors suggests "synaptocrine" mechanisms of brain steroids, which are synthesized at synapses and act as synaptic modulators.

Modulation of hippocampal synaptic plasticity by glucocorticoids has been attracting much attention, due to its importance in stress responses. Dendritic spines are essential for memory storage processes. Here, we investigated the effect of dexamethasone (DEX), a specific agonist of glucocorticoid receptor (GR), on density and morphology of dendritic spines in adult male rat hippocampus by imaging of Lucifer Yellow-injected spines in slices. The application of 100 nM DEX (stressful high concentration) induced rapid modulation of the density and morphology of dendritic spines in CA1 pyramidal neurons within 1h. The total spine density increased from 0.88 spines/microm (control) to 1.36 spines/microm (DEX-treated). DEX significantly increased the density of thin and mushroom type spines, however only a slight increase was observed for stubby and filopodium type spines. Because the presence of 10 microM cycloheximide, an inhibitor of protein synthesis, did not suppress the DEX effect, these responses are probably non-genomic. Western immunoblot analysis demonstrated the localization of classical type GR in Triton-insoluble synaptosomal fractions (enriched in postsynaptic membranes) from hippocampal slices, suggesting a possible action site of DEX at spines.

わが国の透析患者数は年々増加しており, 2003年には23万人を超え, さらに増加しているが, それに比較して腎移植件数はほとんど増加していない. その原因として, 腎提供者の不足もあるが, 腎移植希望患者数が増えないことも-因と考えられる. 山梨県においても, 腎移植件数および献腎移植希望登録者数はあまり増えていない. そこで, 透析患者に対して腎移植に関する意識調査を施行した. 回答患者は723名で, 移植について考えたことがある者352名, 移植希望者171名, 臓器移植ネットワークに登録している者は70名で, 全体の1割以下であった. 登録しない理由は, 移植の意思がない32.5%, 年齢的なもの28.2%, ネットワークの存在を知らない13.4%, 無駄だから登録しない11.1%であった. 移植希望者が171名もいること, ネットワークの存在を知らない者が93名もいることより, 移植に対する啓蒙活動がさらに必要と思われた.

Hippocampal pyramidal neurons and granule neurons of adult male rats are equipped with a complete machinery for the synthesis of pregnenolone, dehydroepiandrosterone, 17beta-estradiol and testosterone as well as their sulfate esters. These brain neurosteroids are synthesized by cytochrome P450s (P450scc, P45017alpha and P450arom) from endogenous cholesterol. Synthesis is acutely dependent on the Ca(2+) influx attendant upon neuron-neuron communication via N-methyl-D-aspartate (NMDA) receptors. Pregnenolone sulfate, estradiol and corticosterone rapidly modulate neuronal signal transduction and the induction of long-term potentiation via NMDA receptors and putative membrane steroid receptors. Brain neurosteroids are therefore promising neuromodulators that may either activate or inactivate neuron-neuron communication, thereby mediating learning and memory in the hippocampus.

Between 1996 and 2003, ten patients with small renal tumors underwent retroperitoneoscopic partial nephrectomy without renal ischemia, nine patients with small renal tumors underwent open partial nephrectomy via a retroperitoneal approach. Both groups were operated on using a microwave tissue coagulator. We compared the results of retroperitoneoscopic group with those of a retroperitoneal open surgery group. Retroperitoneoscopic partial nephrectomy without renal ischemia was performed without any major or minor complications in any patient. The mean operation time for retroperitoneoscopic surgery significantly longer than that for open partial nephrectomy. However, the mean estimated blood loss for retroperitoneoscopic surgery was less than that for open partial nephrectomy. In addition, the retroperitoneoscopic group seemed to recover more rapidly than the open surgery group. This endoscopic surgery is feasible as minimally invasive procedure. It results in saving renal function, minimal blood loss and rapid recovery.

This work reports the first demonstration that corticosterone (CORT) has a rapid and transient effect on NMDA receptor-mediated Ca2+ signaling in cultured rat hippocampal neurons. Using single cell Ca2+ imaging, CORT and agonists of glucocorticoid receptors were observed to modulate the NMDA receptor-mediated Ca2+ signals in a completely different fashion from pregnenolone sulfate. In the absence of steroids, 100 µm NMDA induced a transient Ca2+ signal that lasted for 30–70 s in 86.1% of the neurons prepared from postnatal rats (3–5 days old). After pre-treatment with 0.1–100 µm CORT for 10–20 min, NMDA induced extremely prolonged Ca2+ elevation. This prolonged Ca2+ elevation was terminated by the application of MK-801 and followed by washing out of CORT. The proportion of CORT-modulated neurons within the NMDA-responsive cells increased from 25.1 to 95.5% when the concentration of CORT was raised from 0.1 to 50 µm. Substitution of BSA-conjugated CORT produced essentially the same results. When hippocampal neurons were preincubated with 10 µm cortisol and 1 µm dexamethasone for 20 min, a very prolonged Ca2+ elevation was also observed upon NMDA stimulation. The CORT-prolonged Ca2+ elevation caused a long-lasting depolarization of the mitochondrial membrane, as observed with rhodamine 123. In contrast, incubation with 100 µm pregnenolone sulfate did not considerably alter the time duration of NMDA-induced transient Ca2+ elevation, but caused a significant increase in the peak amplitude of Ca2+ elevation in hippocampal neurons. These results imply that high levels of CORT induce a rapid and non-genomic prolongation of NMDA receptor-mediated Ca2+ elevation, probably via putative membrane surface receptors for CORT in the hippocampal neurons.

血液透析において安定した維持透析療法を施行するためには, 内シャントをいかに維持していくかが大きな鍵になる. しかし手術時の血管剥離に伴う外膜損傷や非生理的な血流負荷, 穿刺による機械的な損傷などにより, いくら注意深く管理しても狭窄や閉塞などは起きうる. これに対してblood access intervention therapy (BAIVT) が, 各種デバイスの進歩に伴い近年普及してきている. しかし高耐圧のバルーンカテーテルを使用しても “くびれ (balloon indentation)” が残存し不十分な拡張になってしまうことも時に経験する. 我々はこのような高度狭窄症例に対して, 冠動脈形成術の技術として考案されたparallel wire technique (PWT) に若干の改良を加えて施行している.通常のPWTではカテーテルのガイドに用いたワイヤー以外にさらに1本必要であるが, 変法である自己反転式PWT (self reversed PWT: SRPWT) は1本のみで可能な方法である. この方法によりシースはバルーンの適応シースで十分となり, 元法で問題となる施行中の血液ロスもなく施行可能となった. またさらに簡便にSRPWTを施行するため, 先端柔軟長3cmの通常ガイドワイヤーを改良し, 柔軟長5cmを作成し現在施行している. これによって反転させたワイヤーのループ部分がバルーンの拡張長より十分長く得られるようになり, 容易に施行可能となった. PWTは高耐圧バルーン拡張に抵抗するような強固な狭窄に対しても拡張可能であり, さらに簡便に行えるSRPWT本方法は, 手技を断念する前に試行してみる有用な手段であるものと思われた.

This study was conducted to evaluate effects of the aldose reductase inhibitor ONO-2235 on the contractile response to acetylcholine of the urinary bladder dome of streptozotocin-induced diabetes mellitus (DM) rats and simultaneously observe the changes in the function and number of muscarinic receptors and the sorbitol content of the bladder. The contractile response to acetylcholine increased 51% in the DM rat bladder dome compared to the normal rats; however, this was attenuated to a 10% increase by administration of 100 mg/kg ONO-2235 for 2 weeks. Treatment with ONO-2235 significantly decreased the specific [3H]quinuclidinyl benzilate binding in DM rats. However there was no significant dose-dependency among the ONO-2235-treated groups. The sorbitol levels of the sciatic nerve and the bladder were higher in the DM rats compared to the control rats; ONO-2235 decreased the level, although it did not completely reverse them to the control level. These results suggest that an aldose reductase inhibitor attenuates the increase of the muscarinic receptor number and normalizes the enhanced contractile response to acetylcholine caused by hyperglycemia and diuresis, probably through suppression of the polyol-pathway in the DM rat bladder dome.

Low dose exposure to endocrine disrupters (environmental chemicals) may induce hormone-like effects on wildlife and humans. bisphenol A (BPA) might disturb the neuronal signaling regulated by endogenous estrogens. We investigated the rapid modulation effects of 10nM BPA, a typical endocrine disruptor, on long-term depression (LTD) of adult rat hippocampal slices.LTD was induced by a transient perfusion of 30 µM NMDA for 3 min. And measured with multielectrode probes.A 30 min perfusion of 10 nM BPA rapidly enhanced LTD in CA1, however, BPA suppressed LTD in dentate gyrus (DG). An ERRγ antagonist, 4-OH-tamoxifen, suppressed LTD in CA1 and DG. Inhibitor of estrogen receptor ICI 182,780 did not disturb BPA effects. On the other hand, tributyltin (TBT), another endocrine disruptor, did not have any effect on LTD in CA1 and DG.ERRγ, but not estrogen receptors, is a high affinity BPA receptor in LTD processes, since the effect of BPA on LTD was suppressed by an ERRγ antagonist. A possible mechanisms of BPA-induced enhancement of LTD could be described with ERRγ, MAPK activation and phosphorylation of MMDA receptors.

In interventional X-ray for cardiology of flat panel digital detector (FPD), the phenomenon that exposure dose was suddenly increased when a subject thickness was thickened was recognized. At that time, variable metal built-in filters in FPD were all off. Therefore, we examined whether dose reduction was possible without affecting a clinical image using metal filter (filter) which we have been conventionally using for dose reduction. About 45% dose reduction was achieved when we measured an exposure dose at 30 cm of acrylic thickness in the presence of a filter. In addition, we measured signal to noise ratio/contrast to noise ratio/a resolution limit by the visual evaluation, and there was no influence by filter usage. In the clinical examination, visual evaluation of image quality of coronary angiography (40 cases) using a 5-point evaluation scale by a physician was performed. As a result, filter usage did not influence the image quality (p=NS). Therefore, reduction of sudden increase of exposure dose was achieved without influencing an image quality by adding filter to FPD.

Editor: For patients undergoing hemodialysis treatment who have a rigid stricture of an arteriovenous fistula, it is extremely difficult to achieve sufficient dilation even if a highpressure resistant balloon catheter is used. In such cases, the parallel wire technique (1,2) has been a better alternative to achieve arteriovenous fistula dilation. The effectiveness of the parallel wire technique has been explained as being a result of the guide wire indwelling between the balloon and the stricture causing a cracked or cut intima, by which the vessel is extended. In other words, the cutting balloon’s blade is replaced with the guide wire. Eventually, the intimal injury is limited to the cracked area. It is speculated that the recurrence of strictures at these points will be less frequent. In the parallel wire technique, there are three alternative ways to indwell the guide wire, as shown in Figure 1: the conventional method passes another wire through the sheath of larger size (Fig 1a); the wire can also be passed through another puncture (Fig 1b); and finally, the selfreversed parallel wire technique, described herein, can be used (Fig 1c). Disadvantages of the conventional technique are that the sheath is required to be thicker than the optimum size and that blood is lost from the point at which the sheath is applied (2). It was reported that 200 mL of blood is generally lost with this method, and use of a Y-shaped connector was recommended (2). The disadvantage of the second method is that a new vein puncture is required and another guide wire is needed. To improve upon these techniques, we chose the method illustrated in Figure 1c: the self-reversed parallel wire technique. In this method, only one guide wire is passed through the sheath, so a sheath of appropriate size is sufficient and a connector preventing blood loss will not be needed. In our hospital, initial implementation of this method used two wires for conventional parallel wire technique (1,2), but this method presented problems such as blood loss from the sheath and required the use of an oversized sheath. Self-reversed parallel wire technique is a simple modification of the conventional one. Details of its implementation and effectiveness are reported herein. Between January 1999 and September 2001, blood access intervention therapy was carried out in 163 patients undergoing hemodialysis treatment. All these patients also had native arteriovenous fistulae. For these cases, we usually used noncompliant balloon catheters (balloon diameter: 4–6 mm) with a rated burst pressure of 15 atm and inflation times of 2 minutes for each dilation. Ultra-short braidedtype sheaths were used (5 F, 3 cm long; Medikit, Tokyo, Japan). In our experience, insufficient dilation was achieved in 22 cases (13%) in which only the high-pressure resistant balloon was used. The self-reversed parallel wire technique was applied in these cases. Figure 2 shows the self-reversed parallel wire technique procedure. A sheath of the required size (5 F) was inserted, through which a flexible-tipped guide-wire with an angleshaped tip (Radifocus; Terumo, Tokyo, Japan) was passed. The tip was then turned in a 180° curve by pushing the tip Figure 1. There are three alternative parallel wire techniques. (a) The conventional method requires an oversized sheath; (b) another puncture can be made to insert the guide wire; or (c) the self-reversed parallel wire technique can be employed.

Angiotensin II (Ang II) receptors in the rat urinary bladder smooth muscle were investigated by in vitro responses of smooth muscle strips to exogenous Ang II stimulation and in radioligand binding assays. Ang II (10(-10) M. to 10(-5) M.) caused a potent contractile response in a concentration-dependent manner. Using the recently developed nonpeptide subtype-selective antagonists, the Ang II-induced contractile response was further characterized. The Ang II-induced contractile response was inhibited weakly by the type 2 subtype (AT2)-selective antagonist PD123319 but was potently inhibited by the type 1 subtype (AT1)-selective antagonist DuP 753 with a pA2 value of 9.03, suggesting that the response is mediated predominantly by AT1 receptors. [125I]Ang II was used to specifically label a single class of binding sites with a dissociation constant of 0.31 nM. and a maximal binding capacity of 41.5 fmol./mg. of protein. DuP 753 could completely antagonize the binding of Ang II in a particulate fraction of rat bladder (Ki = 14 nM), whereas PD123319 did not have any effect in the concentration range of 10(-9) to 10(-5) M. The results suggest that AT1 receptors rather than AT2 receptors predominantly mediate Ang II-induced contraction in the rat urinary bladder.

The value of lymphadenectomy in the treatment of renal cell carcinoma remains controversial. The precise location of nodal metastasis and method of lymphadenectomy had seldom been mentioned. We report 2 patients with right renal cell carcinoma who had regional lymph node involvement without blood-borne metastasis. The involved lymph nodes were demonstrated by CT scan just behind the inferior vena cava at the level of renal hilus. These nodes seemed to be the first sites of nodal involvement from the right renal cell carcinoma. Elevation of the inferior vena cava by dividing its small branches, including a few lumbar veins, was necessary for complete removal of these nodes en bloc with the right kidney.

Rapid modulation of hippocampal synaptic plasticity by estrogen has long been a hot topic, but analysis of molecular mechanisms via synaptic estrogen receptors has been seriously difficult. Here, two types of independent synaptic plasticity, long-term depression (LTD) and spinogenesis, were investigated, in response to 17beta-estradiol and agonists of estrogen receptors using hippocampal slices from adult male rats. Multi-electrode investigations demonstrated that estradiol rapidly enhanced LTD not only in CA1 but also in CA3 and dentate gyrus. Dendritic spine morphology analysis demonstrated that the density of thin type spines was selectively increased in CA1 pyramidal neurons within 2 h after application of 1 nm estradiol. This enhancement of spinogenesis was completely suppressed by mitogen-activated protein (MAP) kinase inhibitor. Only the estrogen receptor (ER) alpha agonist, (propyl-pyrazole-trinyl)tris-phenol (PPT), induced the same enhancing effect as estradiol on both LTD and spinogenesis in the CA1. The ERbeta agonist, (4-hydroxyphenyl)-propionitrile (DPN), suppressed LTD and did not affect spinogenesis. Because the mode of synaptic modulations by estradiol was mostly the same as that by the ERalpha agonist, a search was made for synaptic ERalpha using purified RC-19 antibody qualified using ERalpha knockout (KO) mice. Localization of ERalpha in spines of principal glutamatergic neurons was demonstrated using immunogold electron microscopy and immunohistochemistry. ERalpha was also located in nuclei, cytoplasm and presynapses.

Modulation of hippocampal synaptic plasticity by estrogen has been attracting much attention. Here, we demonstrated the rapid effect of 17b-estradiol on the density and morphology of spines in the stratum oriens (s.o., basal side) and in the stratum lacunosummoleculare (s.l.m., apical side) by imaging Lucifer Yellow-injected CA1 neurons in adult male rat hippocampal slices, because spines in s.o. and s.l.m. have been poorly understood as compared with spines in the stratum radiatum. The application of 1 nM estradiol-induced a rapid increase in the density of spines of pyramidal neurons within 2 h. This increase by estradiol was blocked by Erk MAP kinase inhibitor and estrogen receptor inhibitor in both regions. Effect of blockade by agonists of AMPA receptors and NMDA receptors was different between s.o. and s.l.m. In both regions, ERa agonist PPT induced the same enhancing effect of spinogenesis as that induced by estradiol. � 2006 Published by Elsevier Inc.

The expression of the telomerase subunits such as human telomerase reverse transcriptase (hTERT) and human telomerase RNA component (hTR) may be associated with tumor development and progression. We evaluated the relationship between mRNA quantification of both hTERT and hTR and clinicopathologic parameters in bladder cancer.We examined the mRNA expression of hTERT and hTR in 29 specimens with bladder cancer (Grade: Grade I, 9 cases; Grade II, 13 cases and Grade III, 7 cases. Stage: pTa-pT1, 18 cases; pT2-T4, 11 cases). We immediately froze all of specimens obtained during TUR-Bt and isolated the total RNA from each specimen. We measured the quantity of hTERT, hTR and GAPDH mRNA by a real-time reverse transcription-polymerase chain reaction method based on TaqMan technology.The hTERT/GAPDH mRNA ratio and hTERT mRNA/total RNA in superficial bladder tumor was significantly lower than in invasive bladder tumor. The hTR/GAPDH mRNA ratio and hTR mRNA/total RNA in superficial tumor were significantly lower than in invasive bladder tumor. The hTERT mRNA expression significantly correlated with tumor grade, but the hTR mRNA expression did not correlate with tumor grade. There was no significant difference in the hTERT/GAPDH mRNA ratio and hTR mRNA/total RNA according to multiplicity of bladder tumor.Our results demonstrated that the expression of hTERT mRNA correlated with the progression of stage and grade in bladder cancer. The quantitative analysis of hTERT and hTR mRNA might be a marker for clinicopathologic parameters in bladder cancer.

Bisphenol A (BPA) is a typical endocrine disrupter. We investigated the mechanisms of rapid Ca(2+) signaling induced by a low dose BPA application in cultured hippocampal neurons.The primary culture of hippocampal neurons were prepared from postnatal 3 to 5-day-old rats. Cells were loaded with Calcium Green-1 fluorophore. Ca(2+) imaging and analysis were performed by Argus system.The application of BPA at 10-100 nM induced a transient increase in the intracellular Ca(2+) of N-methyl-D-aspartate (NMDA)-responsive neurons. The Ca(2+) transient occurred within 30 sec after the BPA application. The proportion of BPA-responsive neurons was 9.6 % and 8.5 % of the total NMDA-responsive neurons, respectively, upon 10 nM and 100 nM BPA application. The pre-treatment of neurons with Ca(2+) channel blockers, thapsigargin and nifedipine, considerably decreased the proportion of BPA-responsive neurons to 0.7 % and 3.7%, respectively. The treatment of neurons with an antagonist of estrogen receptor, ICI 182,780, also significantly decreased the proportion of BPA-responsive neurons down to 1.1 %.These results suggest that a low dose BPA application rapidly drives the Ca(2+) signaling system via activation of non-genomic pathway including estrogen receptors.

Modulation of hippocampal synaptic plasticity by estrogen has been attracting much attention. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. Here we demonstrated the rapid effect of estradiol on the density of thorns of thorny excrescences, by imaging Lucifer Yellow-injected CA3 neurons in adult male rat hippocampal slices. The application of 1nM estradiol induced rapid decrease in the density of thorns on pyramidal neurons within 2h. The estradiol-mediated decrease in the density of thorns was blocked by CNQX (AMPA receptor antagonist) and PD98059 (MAP kinase inhibitor), but not by MK-801 (NMDA receptor antagonist). ERalpha agonist PPT induced the same suppressive effect as that induced by estradiol on the density of thorns, but ERbeta agonist DPN did not affect the density of thorns. Note that a 1nM estradiol treatment did not affect the density of spines in the stratum radiatum and stratum oriens. A search for synaptic ERalpha was performed using purified RC-19 antibody. The localization of ERalpha (67kDa) in the CA3 mossy fiber terminals and thorns was demonstrated using immunogold electron microscopy. These results imply that estradiol drives the signaling pathway including ERalpha and MAP kinase.

We have developed a novel modification of previous approaches to donor nephrectomy and herein review our original operative procedure. First, the posterior aspect of the kidney was dissected retroperitoneoscopically and dissection of the renal artery, ureter and gonadal vein was almost completed. Second, the anterior aspect of the kidney was dissected with transperitoneal hand-assistance, and dissection of the renal pedicle from the anterior surface was accomplished easily and safely. This operative procedure was successfully performed for two donors with no intraoperative or postoperative complications. Our modified endoscopic donor nephrectomy is feasible as a minimally invasive procedure because of its safety, and its ability to preserve renal function and establish an excellent operative field for both posterior and anterior aspects of the kidney.

A 69-year-old-man undergoing hemodialysis for 8 years developed metastatic urothelial carcinoma and received combination chemotherapy with paclitaxel and carboplatin. Paclitaxel 175 mg/m2 was given as a 3-hour intravenous infusion, and carboplatin was dosed to the area under the plasma concentration-time curve (AUC) of 5 mg.min/ml calculated according to the Calvert formula as a 30-minute intravenous infusion immediately after paclitaxel. Hemodialysis was started 1 hour after carboplatin, then their pharmacokinetics was determined in the patient. The AUC of paclitaxel and carboplatin were 15.2 and 64.56 micrograms.h/ml, respectively. The metastatic tumor size was reduced by more than 20% after 3 courses of this chemotherapy. Grade 3 neutropenia and grade 1 thrombopenia were observed. This is the first report that the combination of paclitaxel and carboplatin is feasible in a patient with metastatic urothelial carcinoma undergoing hemodialysis, with low toxicity and safety.

It is ideal to use not a transperitoneal but a retroperitoneal approach for both open and endoscopic partial nephrectomy. We compared the results of retroperitoneoscopic nephron-sparing surgery for small renal tumors using a microwave tissue coagulator without renal pedicle clamping with those of a retroperitoneal open procedure.Between 1996 and 2002, eight patients with small renal tumors underwent retroperitoneoscopic partial nephrectomy without renal ischemia, and nine patients with small renal tumors underwent open partial nephrectomy via a retroperitoneal approach. Both groups were operated on using a microwave tissue coagulator.Retroperitoneoscopic partial nephrectomy without renal ischemia was performed without any major or minor complications in any patient. The mean operation time for retroperitoneoscopic surgery was significantly longer than that for open partial nephrectomy (221.9 minutes v 145.9 minutes; P = 0.0004). However, the mean estimated blood loss for retroperitoneoscopic surgery was less than that for open partial nephrectomy (137.5 mL v 334.8 mL; P = 0.012). In addition, the retroperitoneoscopic group seemed to recover more rapidly than the open surgery group.Retroperitoneoscopic nephron-sparing surgery of small renal tumors using a microwave tissue coagulator without renal ischemia is feasible as minimally invasive procedure. It results in saving renal function, minimal blood loss, and rapid recovery.

This work reports the first demonstration that corticosterone (CORT) has a rapid and transient effect on NMDA receptor-mediated Ca2+ signaling in cultured rat hippocampal neurons. Using single cell Ca2+ imaging, CORT and agonists of glucocorticoid receptors were observed to modulate the NMDA receptor-mediated Ca2+ signals in a completely different fashion from pregnenolone sulfate. In the absence of steroids, 100 micro m NMDA induced a transient Ca2+ signal that lasted for 30-70 s in 86.1% of the neurons prepared from postnatal rats (3-5 days old). After pre-treatment with 0.1-100 micro m CORT for 10-20 min, NMDA induced extremely prolonged Ca2+ elevation. This prolonged Ca2+ elevation was terminated by the application of MK-801 and followed by washing out of CORT. The proportion of CORT-modulated neurons within the NMDA-responsive cells increased from 25.1 to 95.5% when the concentration of CORT was raised from 0.1 to 50 micro m. Substitution of BSA-conjugated CORT produced essentially the same results. When hippocampal neurons were preincubated with 10 micro m cortisol and 1 micro m dexamethasone for 20 min, a very prolonged Ca2+ elevation was also observed upon NMDA stimulation. The CORT-prolonged Ca2+ elevation caused a long-lasting depolarization of the mitochondrial membrane, as observed with rhodamine 123. In contrast, incubation with 100 micro m pregnenolone sulfate did not considerably alter the time duration of NMDA-induced transient Ca2+ elevation, but caused a significant increase in the peak amplitude of Ca2+ elevation in hippocampal neurons. These results imply that high levels of CORT induce a rapid and non-genomic prolongation of NMDA receptor-mediated Ca2+ elevation, probably via putative membrane surface receptors for CORT in the hippocampal neurons.

We evaluated the efficacy of lymphadenectomy in conjunction with nephroureterectomy in patients with transitional cell carcinoma of the upper urinary tract.Data were evaluated retrospectively in 21 consecutive men and 15 women (mean age 67 years) who underwent total nephroureterectomy with lymphadenectomy between January 1985 and December 1993.Of the 36 patients 11 (31%) had lymph node metastases. Of 20 patients with stages pT3 to 4 or pN+ tumors 12 received cisplatin based chemotherapy (11 postoperatively and 1 preoperatively). Followup ranged from 3 to 135 months (mean 55). Among 13 patients who died by May 1996 tumor was the cause of death in 8, while 5 died of unrelated causes. The probability of a cause specific survival at 5 years was 100% in patients with stages pTa to 1, 80% with stage pT2, 59% with stage pT3 and 0% with stage pT4 cancer. The probability of a cause specific survival at 5 years in patients with nodal metastasis was 21%. No patient without nodal metastasis died of tumor related causes.Lymphadenectomy may provide therapeutic benefit in select patients with lymph node metastasis. It also may be a useful indicator of candidates for adjuvant chemotherapy if an effective regimen is established because lymph node metastasis is common in patients with carcinoma of the upper urinary tract and is critical in establishing the prognosis.

BACKGROUND The benefits and adverse effects of post-operative irradiation for advanced bladder cancer patients were investigated. METHODS Ten patients with pT3b, pT4 or pN+ bladder cancer who underwent radical cystectomy at Yamanashi Medical University hospital during 7 years and 3 months from October 1983 to December 1991 received adjuvant chemotherapy and radiotherapy (Group 1). During the same period, six patients with recurrent tumor after radical cystectomy were treated by radiotherapy (Group II). Stages of the primary tumors were pT2 in 1, pT3a in 2, pT3b in 6 and pT4 in 7 cases. In addition, 10 of 16 patients (63%) had positive nodes. RESULTS During the follow up period, seven patients died of cancer, and one died of other cause. As a result eight patients (5 in Group I, 3 in Group II) are alive. The cumulative 5-year survival rate is 50%. However, nine of the 16 patients (56%) suffered from the small bowel obstruction as an adverse effect of irradiation. Six patients required resection of the small bowel or bypass surgery. CONCLUSIONS Radiation after radical cystectomy seemed to be effective for the local control of the tumor, but the adverse effect to the digestive system was very severe and common.

During 7 years and 3 months from October 1983 to December 1990, 68 patients underwent radical cystectomy for primary bladder cancer at Yamanashi Medical College. Of these 68 bladder cancers, 16 were superficial and 52 were invasive. Among the 52 patients with invasive cancer, a combination chemotherapy of methotrexate and cisplatin and/or radiotherapy were given in 18 as an adjuvant therapy. All the adjuvant therapies were performed after the operation except for 2 patients with T4 bladder cancer who received chemotherapy before the operation. There were 23 recurrences and 25 deaths, 20 from bladder cancer and 5 from other causes. Of 20 bladder cancer deaths, 17 deaths (85%) were observed within 2 years after the operation. The 5-year survival rates were 92% for stage pTa-pT1, 83% for stage pT2, 80% for stage pT3a, 24% for stage pT3b and 43% for stage pT4-T4, respectively. A significant difference (p < 0.05) in survival curve was observed between pT3a and pT3b. The 5-year survival rate for pT2-pT3a without nodal metastases was as high as 89% (95% confidence limits 75 to 100%) although 18 out of 19 patients received no adjuvant therapy. On the other hand, the 5-year survival rate for pT3b-pT4 without nodal metastases (25%) was as low as that of patients for any T category with nodal metastases (35%). Most patients with tumor confined within bladder wall seemed to be cured by surgery only. Therefore, any adjuvant chemotherapy with severe side effects seemed not to be justified for these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

We report a case of a right adrenal pheochromocytoma with prominent anterolateral displacement of the inferior vena cava. A right ipsilateral anterior subcostal incision extending from the xiphoid process to the 11th intercostal space allowed for wide upward retraction of the right costal arch. This incision is useful for easy mobilization of the liver and manipulation of the inferior vena cava without thoracotomy.

To study the limitations of lymphangiography in the detection of early lymphatic spread of pelvic malignancies, we evaluated 587 lymph nodes from 23 patients with stages pNO to 2 carcinoma of the bladder or prostate. Pelvic lymphadenectomy was performed 5 to 10 days after bipedal lymphangiography. Excised lymph nodes were separated one by one and an x-ray of each node was taken (lymphnodegram). The individual lymphnodegram was compared to the histological findings. Interpretations of lymphnodegrams from all 17 nodes with metastases were positive in 5, suspicious in 1, negative in 9 and radiolucent in 2. False negative judgments occurred chiefly because metastatic foci were microscopic. Two lymph nodes without metastasis were interpreted as positive for disease because of fat replacement of the nodes. These results indicated that lymphangiography is not suitable for the detection of early lymphatic metastases of carcinoma of the bladder or prostate.